pmcid
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6853670
|
{'1. Case Description': 'A 28-year-old man with classic salt-wasting CAH due to 21-hydroxylase deficiency presented with subfertility. For the past 6 months, he described a minimal coital frequency of 2 or 3 times per week without the use of contraception. He had been receiving prednisone 5 mg each morning and fludrocortisone 50 μg twice daily over the last decade. He had known bilateral TARTs, first noted at age 18 and occupying 1.2% of his total testicular volume (0.38 mL of 30.68 mL) ( Fig. 1 ). A recent testicular ultrasound showed increased TART volume, now occupying 16% of his total testicular volume (5.01 mL of 32.30 mL testicular volume), and semen analysis showed azoospermia. On examination, the patient was short-statured, with a standing height of 153.4 cm ( z score: −3.1); midparental height was 174.1 cm ( z score: −0.4). Testicular volume was 25 mL bilaterally. Biochemical evaluation at 0800 before medication showed 17-hydroxyprogesterone 13,060 ng/dL (reference: 13 to 120 ng/dL), androstenedione (A4) 1025 ng/dL (reference: 26 to 125 ng/dL), ACTH 866 pg/mL (reference: 5 to 46 pg/mL), plasma renin activity (PRA) 7.1 ng/mL/h (reference: 0.6 to 4.3 ng/mL/h), FSH 1.7 U/L (reference: 1 to 11 U/L), LH 1.3 U/L (reference: 1 to 8 U/L), and total testosterone (T) 473 ng/ dL (reference: 240 to 950 ng/dL). His A4/T ratio of 2.2 (>0.5) with low LH and FSH was suggestive of a mostly adrenal origin of his T. His glucocorticoid therapy was switched from prednisone 5 mg daily to dexamethasone 250 μg at bedtime to suppress the nocturnal ACTH surge. At his 5-month follow-up visit, he reported a weight gain of 5 kg and insomnia. Physical examination revealed supraclavicular fullness with predominantly central weight gain and the presence of abdominal striae, not present on previous exam. Testicular volume was stable at 25 mL. Repeat ultrasound showed 91% decrease in total TART volume (0.47 mL) ( Fig. 1 ). Follow-up semen analysis showed a sperm count of 132 × 10 6 /mL (reference range: >14 × 10 6 /mL), with 7 × 10 6 /mL being morphologically normal (reference range: >3 × 10 6 /mL) and 35% motile (normal >39%). Biochemical evaluation showed significant improvement in CAH control, with 0800 evaluation before medication revealing 17-hydroxyprogesterone 66 ng/dL, A4 16 ng/dL, ACTH 13.5 pg/mL, PRA 11 ng/mL/h, FSH 5.4 U/L, LH 1 U/L, and T 287 ng/dL ( Table 1 ). The patient’s wife was confirmed to be pregnant 9 months after the initiation of dexamethasone and delivered a healthy full-term baby girl. CYP21A2 genotyping was performed. Our patient had a 30-kb deletion (CH-1 chimera subtype) in one allele and IVS2-13A/C>G (In2G) mutation in the second allele; his wife was negative for any known CYP21A2 variants, and his daughter was found to carry a 30-kb deletion (CH-1 chimera subtype) in one allele. Given his weight gain and insomnia, the patient’s therapy was switched to prednisone 3 mg twice daily. He lost 3 kg, and his insomnia resolved. His TART volume, parameters of semen analysis, and biochemical markers of CAH control have remained stable 2 and a half years hence, and he is currently expecting his second child.'}
|
{'1. Case Description': 'A 28-year-old man with classic salt-wasting CAH due to 21-hydroxylase deficiency presented with subfertility. For the past 6 months, he described a minimal coital frequency of 2 or 3 times per week without the use of contraception. He had been receiving prednisone 5 mg each morning and fludrocortisone 50 μg twice daily over the last decade. He had known bilateral TARTs, first noted at age 18 and occupying 1.2% of his total testicular volume (0.38 mL of 30.68 mL) ( Fig. 1 ). A recent testicular ultrasound showed increased TART volume, now occupying 16% of his total testicular volume (5.01 mL of 32.30 mL testicular volume), and semen analysis showed azoospermia. On examination, the patient was short-statured, with a standing height of 153.4 cm ( z score: −3.1); midparental height was 174.1 cm ( z score: −0.4). Testicular volume was 25 mL bilaterally. Biochemical evaluation at 0800 before medication showed 17-hydroxyprogesterone 13,060 ng/dL (reference: 13 to 120 ng/dL), androstenedione (A4) 1025 ng/dL (reference: 26 to 125 ng/dL), ACTH 866 pg/mL (reference: 5 to 46 pg/mL), plasma renin activity (PRA) 7.1 ng/mL/h (reference: 0.6 to 4.3 ng/mL/h), FSH 1.7 U/L (reference: 1 to 11 U/L), LH 1.3 U/L (reference: 1 to 8 U/L), and total testosterone (T) 473 ng/ dL (reference: 240 to 950 ng/dL). His A4/T ratio of 2.2 (>0.5) with low LH and FSH was suggestive of a mostly adrenal origin of his T. His glucocorticoid therapy was switched from prednisone 5 mg daily to dexamethasone 250 μg at bedtime to suppress the nocturnal ACTH surge. At his 5-month follow-up visit, he reported a weight gain of 5 kg and insomnia. Physical examination revealed supraclavicular fullness with predominantly central weight gain and the presence of abdominal striae, not present on previous exam. Testicular volume was stable at 25 mL. Repeat ultrasound showed 91% decrease in total TART volume (0.47 mL) ( Fig. 1 ). Follow-up semen analysis showed a sperm count of 132 × 10 6 /mL (reference range: >14 × 10 6 /mL), with 7 × 10 6 /mL being morphologically normal (reference range: >3 × 10 6 /mL) and 35% motile (normal >39%). Biochemical evaluation showed significant improvement in CAH control, with 0800 evaluation before medication revealing 17-hydroxyprogesterone 66 ng/dL, A4 16 ng/dL, ACTH 13.5 pg/mL, PRA 11 ng/mL/h, FSH 5.4 U/L, LH 1 U/L, and T 287 ng/dL ( Table 1 ). The patient’s wife was confirmed to be pregnant 9 months after the initiation of dexamethasone and delivered a healthy full-term baby girl. CYP21A2 genotyping was performed. Our patient had a 30-kb deletion (CH-1 chimera subtype) in one allele and IVS2-13A/C>G (In2G) mutation in the second allele; his wife was negative for any known CYP21A2 variants, and his daughter was found to carry a 30-kb deletion (CH-1 chimera subtype) in one allele. Given his weight gain and insomnia, the patient’s therapy was switched to prednisone 3 mg twice daily. He lost 3 kg, and his insomnia resolved. His TART volume, parameters of semen analysis, and biochemical markers of CAH control have remained stable 2 and a half years hence, and he is currently expecting his second child.'}
|
Vitals-and-Hematology
|
Vitals_Hema
|
[
"standing height of 153.4 cm ( z score : −3.1 )"
] |
6853670
|
{'1. Case Description': 'A 28-year-old man with classic salt-wasting CAH due to 21-hydroxylase deficiency presented with subfertility. For the past 6 months, he described a minimal coital frequency of 2 or 3 times per week without the use of contraception. He had been receiving prednisone 5 mg each morning and fludrocortisone 50 μg twice daily over the last decade. He had known bilateral TARTs, first noted at age 18 and occupying 1.2% of his total testicular volume (0.38 mL of 30.68 mL) ( Fig. 1 ). A recent testicular ultrasound showed increased TART volume, now occupying 16% of his total testicular volume (5.01 mL of 32.30 mL testicular volume), and semen analysis showed azoospermia. On examination, the patient was short-statured, with a standing height of 153.4 cm ( z score: −3.1); midparental height was 174.1 cm ( z score: −0.4). Testicular volume was 25 mL bilaterally. Biochemical evaluation at 0800 before medication showed 17-hydroxyprogesterone 13,060 ng/dL (reference: 13 to 120 ng/dL), androstenedione (A4) 1025 ng/dL (reference: 26 to 125 ng/dL), ACTH 866 pg/mL (reference: 5 to 46 pg/mL), plasma renin activity (PRA) 7.1 ng/mL/h (reference: 0.6 to 4.3 ng/mL/h), FSH 1.7 U/L (reference: 1 to 11 U/L), LH 1.3 U/L (reference: 1 to 8 U/L), and total testosterone (T) 473 ng/ dL (reference: 240 to 950 ng/dL). His A4/T ratio of 2.2 (>0.5) with low LH and FSH was suggestive of a mostly adrenal origin of his T. His glucocorticoid therapy was switched from prednisone 5 mg daily to dexamethasone 250 μg at bedtime to suppress the nocturnal ACTH surge. At his 5-month follow-up visit, he reported a weight gain of 5 kg and insomnia. Physical examination revealed supraclavicular fullness with predominantly central weight gain and the presence of abdominal striae, not present on previous exam. Testicular volume was stable at 25 mL. Repeat ultrasound showed 91% decrease in total TART volume (0.47 mL) ( Fig. 1 ). Follow-up semen analysis showed a sperm count of 132 × 10 6 /mL (reference range: >14 × 10 6 /mL), with 7 × 10 6 /mL being morphologically normal (reference range: >3 × 10 6 /mL) and 35% motile (normal >39%). Biochemical evaluation showed significant improvement in CAH control, with 0800 evaluation before medication revealing 17-hydroxyprogesterone 66 ng/dL, A4 16 ng/dL, ACTH 13.5 pg/mL, PRA 11 ng/mL/h, FSH 5.4 U/L, LH 1 U/L, and T 287 ng/dL ( Table 1 ). The patient’s wife was confirmed to be pregnant 9 months after the initiation of dexamethasone and delivered a healthy full-term baby girl. CYP21A2 genotyping was performed. Our patient had a 30-kb deletion (CH-1 chimera subtype) in one allele and IVS2-13A/C>G (In2G) mutation in the second allele; his wife was negative for any known CYP21A2 variants, and his daughter was found to carry a 30-kb deletion (CH-1 chimera subtype) in one allele. Given his weight gain and insomnia, the patient’s therapy was switched to prednisone 3 mg twice daily. He lost 3 kg, and his insomnia resolved. His TART volume, parameters of semen analysis, and biochemical markers of CAH control have remained stable 2 and a half years hence, and he is currently expecting his second child.'}
|
{'1. Case Description': 'A 28-year-old man with classic salt-wasting CAH due to 21-hydroxylase deficiency presented with subfertility. For the past 6 months, he described a minimal coital frequency of 2 or 3 times per week without the use of contraception. He had been receiving prednisone 5 mg each morning and fludrocortisone 50 μg twice daily over the last decade. He had known bilateral TARTs, first noted at age 18 and occupying 1.2% of his total testicular volume (0.38 mL of 30.68 mL) ( Fig. 1 ). A recent testicular ultrasound showed increased TART volume, now occupying 16% of his total testicular volume (5.01 mL of 32.30 mL testicular volume), and semen analysis showed azoospermia. On examination, the patient was short-statured, with a standing height of 153.4 cm ( z score: −3.1); midparental height was 174.1 cm ( z score: −0.4). Testicular volume was 25 mL bilaterally. Biochemical evaluation at 0800 before medication showed 17-hydroxyprogesterone 13,060 ng/dL (reference: 13 to 120 ng/dL), androstenedione (A4) 1025 ng/dL (reference: 26 to 125 ng/dL), ACTH 866 pg/mL (reference: 5 to 46 pg/mL), plasma renin activity (PRA) 7.1 ng/mL/h (reference: 0.6 to 4.3 ng/mL/h), FSH 1.7 U/L (reference: 1 to 11 U/L), LH 1.3 U/L (reference: 1 to 8 U/L), and total testosterone (T) 473 ng/ dL (reference: 240 to 950 ng/dL). His A4/T ratio of 2.2 (>0.5) with low LH and FSH was suggestive of a mostly adrenal origin of his T. His glucocorticoid therapy was switched from prednisone 5 mg daily to dexamethasone 250 μg at bedtime to suppress the nocturnal ACTH surge. At his 5-month follow-up visit, he reported a weight gain of 5 kg and insomnia. Physical examination revealed supraclavicular fullness with predominantly central weight gain and the presence of abdominal striae, not present on previous exam. Testicular volume was stable at 25 mL. Repeat ultrasound showed 91% decrease in total TART volume (0.47 mL) ( Fig. 1 ). Follow-up semen analysis showed a sperm count of 132 × 10 6 /mL (reference range: >14 × 10 6 /mL), with 7 × 10 6 /mL being morphologically normal (reference range: >3 × 10 6 /mL) and 35% motile (normal >39%). Biochemical evaluation showed significant improvement in CAH control, with 0800 evaluation before medication revealing 17-hydroxyprogesterone 66 ng/dL, A4 16 ng/dL, ACTH 13.5 pg/mL, PRA 11 ng/mL/h, FSH 5.4 U/L, LH 1 U/L, and T 287 ng/dL ( Table 1 ). The patient’s wife was confirmed to be pregnant 9 months after the initiation of dexamethasone and delivered a healthy full-term baby girl. CYP21A2 genotyping was performed. Our patient had a 30-kb deletion (CH-1 chimera subtype) in one allele and IVS2-13A/C>G (In2G) mutation in the second allele; his wife was negative for any known CYP21A2 variants, and his daughter was found to carry a 30-kb deletion (CH-1 chimera subtype) in one allele. Given his weight gain and insomnia, the patient’s therapy was switched to prednisone 3 mg twice daily. He lost 3 kg, and his insomnia resolved. His TART volume, parameters of semen analysis, and biochemical markers of CAH control have remained stable 2 and a half years hence, and he is currently expecting his second child.'}
|
Gastrointestinal-System
|
GI
|
[] |
6853670
|
{'1. Case Description': 'A 28-year-old man with classic salt-wasting CAH due to 21-hydroxylase deficiency presented with subfertility. For the past 6 months, he described a minimal coital frequency of 2 or 3 times per week without the use of contraception. He had been receiving prednisone 5 mg each morning and fludrocortisone 50 μg twice daily over the last decade. He had known bilateral TARTs, first noted at age 18 and occupying 1.2% of his total testicular volume (0.38 mL of 30.68 mL) ( Fig. 1 ). A recent testicular ultrasound showed increased TART volume, now occupying 16% of his total testicular volume (5.01 mL of 32.30 mL testicular volume), and semen analysis showed azoospermia. On examination, the patient was short-statured, with a standing height of 153.4 cm ( z score: −3.1); midparental height was 174.1 cm ( z score: −0.4). Testicular volume was 25 mL bilaterally. Biochemical evaluation at 0800 before medication showed 17-hydroxyprogesterone 13,060 ng/dL (reference: 13 to 120 ng/dL), androstenedione (A4) 1025 ng/dL (reference: 26 to 125 ng/dL), ACTH 866 pg/mL (reference: 5 to 46 pg/mL), plasma renin activity (PRA) 7.1 ng/mL/h (reference: 0.6 to 4.3 ng/mL/h), FSH 1.7 U/L (reference: 1 to 11 U/L), LH 1.3 U/L (reference: 1 to 8 U/L), and total testosterone (T) 473 ng/ dL (reference: 240 to 950 ng/dL). His A4/T ratio of 2.2 (>0.5) with low LH and FSH was suggestive of a mostly adrenal origin of his T. His glucocorticoid therapy was switched from prednisone 5 mg daily to dexamethasone 250 μg at bedtime to suppress the nocturnal ACTH surge. At his 5-month follow-up visit, he reported a weight gain of 5 kg and insomnia. Physical examination revealed supraclavicular fullness with predominantly central weight gain and the presence of abdominal striae, not present on previous exam. Testicular volume was stable at 25 mL. Repeat ultrasound showed 91% decrease in total TART volume (0.47 mL) ( Fig. 1 ). Follow-up semen analysis showed a sperm count of 132 × 10 6 /mL (reference range: >14 × 10 6 /mL), with 7 × 10 6 /mL being morphologically normal (reference range: >3 × 10 6 /mL) and 35% motile (normal >39%). Biochemical evaluation showed significant improvement in CAH control, with 0800 evaluation before medication revealing 17-hydroxyprogesterone 66 ng/dL, A4 16 ng/dL, ACTH 13.5 pg/mL, PRA 11 ng/mL/h, FSH 5.4 U/L, LH 1 U/L, and T 287 ng/dL ( Table 1 ). The patient’s wife was confirmed to be pregnant 9 months after the initiation of dexamethasone and delivered a healthy full-term baby girl. CYP21A2 genotyping was performed. Our patient had a 30-kb deletion (CH-1 chimera subtype) in one allele and IVS2-13A/C>G (In2G) mutation in the second allele; his wife was negative for any known CYP21A2 variants, and his daughter was found to carry a 30-kb deletion (CH-1 chimera subtype) in one allele. Given his weight gain and insomnia, the patient’s therapy was switched to prednisone 3 mg twice daily. He lost 3 kg, and his insomnia resolved. His TART volume, parameters of semen analysis, and biochemical markers of CAH control have remained stable 2 and a half years hence, and he is currently expecting his second child.'}
|
{'1. Case Description': 'A 28-year-old man with classic salt-wasting CAH due to 21-hydroxylase deficiency presented with subfertility. For the past 6 months, he described a minimal coital frequency of 2 or 3 times per week without the use of contraception. He had been receiving prednisone 5 mg each morning and fludrocortisone 50 μg twice daily over the last decade. He had known bilateral TARTs, first noted at age 18 and occupying 1.2% of his total testicular volume (0.38 mL of 30.68 mL) ( Fig. 1 ). A recent testicular ultrasound showed increased TART volume, now occupying 16% of his total testicular volume (5.01 mL of 32.30 mL testicular volume), and semen analysis showed azoospermia. On examination, the patient was short-statured, with a standing height of 153.4 cm ( z score: −3.1); midparental height was 174.1 cm ( z score: −0.4). Testicular volume was 25 mL bilaterally. Biochemical evaluation at 0800 before medication showed 17-hydroxyprogesterone 13,060 ng/dL (reference: 13 to 120 ng/dL), androstenedione (A4) 1025 ng/dL (reference: 26 to 125 ng/dL), ACTH 866 pg/mL (reference: 5 to 46 pg/mL), plasma renin activity (PRA) 7.1 ng/mL/h (reference: 0.6 to 4.3 ng/mL/h), FSH 1.7 U/L (reference: 1 to 11 U/L), LH 1.3 U/L (reference: 1 to 8 U/L), and total testosterone (T) 473 ng/ dL (reference: 240 to 950 ng/dL). His A4/T ratio of 2.2 (>0.5) with low LH and FSH was suggestive of a mostly adrenal origin of his T. His glucocorticoid therapy was switched from prednisone 5 mg daily to dexamethasone 250 μg at bedtime to suppress the nocturnal ACTH surge. At his 5-month follow-up visit, he reported a weight gain of 5 kg and insomnia. Physical examination revealed supraclavicular fullness with predominantly central weight gain and the presence of abdominal striae, not present on previous exam. Testicular volume was stable at 25 mL. Repeat ultrasound showed 91% decrease in total TART volume (0.47 mL) ( Fig. 1 ). Follow-up semen analysis showed a sperm count of 132 × 10 6 /mL (reference range: >14 × 10 6 /mL), with 7 × 10 6 /mL being morphologically normal (reference range: >3 × 10 6 /mL) and 35% motile (normal >39%). Biochemical evaluation showed significant improvement in CAH control, with 0800 evaluation before medication revealing 17-hydroxyprogesterone 66 ng/dL, A4 16 ng/dL, ACTH 13.5 pg/mL, PRA 11 ng/mL/h, FSH 5.4 U/L, LH 1 U/L, and T 287 ng/dL ( Table 1 ). The patient’s wife was confirmed to be pregnant 9 months after the initiation of dexamethasone and delivered a healthy full-term baby girl. CYP21A2 genotyping was performed. Our patient had a 30-kb deletion (CH-1 chimera subtype) in one allele and IVS2-13A/C>G (In2G) mutation in the second allele; his wife was negative for any known CYP21A2 variants, and his daughter was found to carry a 30-kb deletion (CH-1 chimera subtype) in one allele. Given his weight gain and insomnia, the patient’s therapy was switched to prednisone 3 mg twice daily. He lost 3 kg, and his insomnia resolved. His TART volume, parameters of semen analysis, and biochemical markers of CAH control have remained stable 2 and a half years hence, and he is currently expecting his second child.'}
|
Patient-History
|
History
|
[
"A 28 - year - old man with classic salt - wasting CAH due to 21 - hydroxylase deficiency presented with subfertility. He had known bilateral TARTs"
] |
6853670
|
{'1. Case Description': 'A 28-year-old man with classic salt-wasting CAH due to 21-hydroxylase deficiency presented with subfertility. For the past 6 months, he described a minimal coital frequency of 2 or 3 times per week without the use of contraception. He had been receiving prednisone 5 mg each morning and fludrocortisone 50 μg twice daily over the last decade. He had known bilateral TARTs, first noted at age 18 and occupying 1.2% of his total testicular volume (0.38 mL of 30.68 mL) ( Fig. 1 ). A recent testicular ultrasound showed increased TART volume, now occupying 16% of his total testicular volume (5.01 mL of 32.30 mL testicular volume), and semen analysis showed azoospermia. On examination, the patient was short-statured, with a standing height of 153.4 cm ( z score: −3.1); midparental height was 174.1 cm ( z score: −0.4). Testicular volume was 25 mL bilaterally. Biochemical evaluation at 0800 before medication showed 17-hydroxyprogesterone 13,060 ng/dL (reference: 13 to 120 ng/dL), androstenedione (A4) 1025 ng/dL (reference: 26 to 125 ng/dL), ACTH 866 pg/mL (reference: 5 to 46 pg/mL), plasma renin activity (PRA) 7.1 ng/mL/h (reference: 0.6 to 4.3 ng/mL/h), FSH 1.7 U/L (reference: 1 to 11 U/L), LH 1.3 U/L (reference: 1 to 8 U/L), and total testosterone (T) 473 ng/ dL (reference: 240 to 950 ng/dL). His A4/T ratio of 2.2 (>0.5) with low LH and FSH was suggestive of a mostly adrenal origin of his T. His glucocorticoid therapy was switched from prednisone 5 mg daily to dexamethasone 250 μg at bedtime to suppress the nocturnal ACTH surge. At his 5-month follow-up visit, he reported a weight gain of 5 kg and insomnia. Physical examination revealed supraclavicular fullness with predominantly central weight gain and the presence of abdominal striae, not present on previous exam. Testicular volume was stable at 25 mL. Repeat ultrasound showed 91% decrease in total TART volume (0.47 mL) ( Fig. 1 ). Follow-up semen analysis showed a sperm count of 132 × 10 6 /mL (reference range: >14 × 10 6 /mL), with 7 × 10 6 /mL being morphologically normal (reference range: >3 × 10 6 /mL) and 35% motile (normal >39%). Biochemical evaluation showed significant improvement in CAH control, with 0800 evaluation before medication revealing 17-hydroxyprogesterone 66 ng/dL, A4 16 ng/dL, ACTH 13.5 pg/mL, PRA 11 ng/mL/h, FSH 5.4 U/L, LH 1 U/L, and T 287 ng/dL ( Table 1 ). The patient’s wife was confirmed to be pregnant 9 months after the initiation of dexamethasone and delivered a healthy full-term baby girl. CYP21A2 genotyping was performed. Our patient had a 30-kb deletion (CH-1 chimera subtype) in one allele and IVS2-13A/C>G (In2G) mutation in the second allele; his wife was negative for any known CYP21A2 variants, and his daughter was found to carry a 30-kb deletion (CH-1 chimera subtype) in one allele. Given his weight gain and insomnia, the patient’s therapy was switched to prednisone 3 mg twice daily. He lost 3 kg, and his insomnia resolved. His TART volume, parameters of semen analysis, and biochemical markers of CAH control have remained stable 2 and a half years hence, and he is currently expecting his second child.'}
|
{'1. Case Description': 'A 28-year-old man with classic salt-wasting CAH due to 21-hydroxylase deficiency presented with subfertility. For the past 6 months, he described a minimal coital frequency of 2 or 3 times per week without the use of contraception. He had been receiving prednisone 5 mg each morning and fludrocortisone 50 μg twice daily over the last decade. He had known bilateral TARTs, first noted at age 18 and occupying 1.2% of his total testicular volume (0.38 mL of 30.68 mL) ( Fig. 1 ). A recent testicular ultrasound showed increased TART volume, now occupying 16% of his total testicular volume (5.01 mL of 32.30 mL testicular volume), and semen analysis showed azoospermia. On examination, the patient was short-statured, with a standing height of 153.4 cm ( z score: −3.1); midparental height was 174.1 cm ( z score: −0.4). Testicular volume was 25 mL bilaterally. Biochemical evaluation at 0800 before medication showed 17-hydroxyprogesterone 13,060 ng/dL (reference: 13 to 120 ng/dL), androstenedione (A4) 1025 ng/dL (reference: 26 to 125 ng/dL), ACTH 866 pg/mL (reference: 5 to 46 pg/mL), plasma renin activity (PRA) 7.1 ng/mL/h (reference: 0.6 to 4.3 ng/mL/h), FSH 1.7 U/L (reference: 1 to 11 U/L), LH 1.3 U/L (reference: 1 to 8 U/L), and total testosterone (T) 473 ng/ dL (reference: 240 to 950 ng/dL). His A4/T ratio of 2.2 (>0.5) with low LH and FSH was suggestive of a mostly adrenal origin of his T. His glucocorticoid therapy was switched from prednisone 5 mg daily to dexamethasone 250 μg at bedtime to suppress the nocturnal ACTH surge. At his 5-month follow-up visit, he reported a weight gain of 5 kg and insomnia. Physical examination revealed supraclavicular fullness with predominantly central weight gain and the presence of abdominal striae, not present on previous exam. Testicular volume was stable at 25 mL. Repeat ultrasound showed 91% decrease in total TART volume (0.47 mL) ( Fig. 1 ). Follow-up semen analysis showed a sperm count of 132 × 10 6 /mL (reference range: >14 × 10 6 /mL), with 7 × 10 6 /mL being morphologically normal (reference range: >3 × 10 6 /mL) and 35% motile (normal >39%). Biochemical evaluation showed significant improvement in CAH control, with 0800 evaluation before medication revealing 17-hydroxyprogesterone 66 ng/dL, A4 16 ng/dL, ACTH 13.5 pg/mL, PRA 11 ng/mL/h, FSH 5.4 U/L, LH 1 U/L, and T 287 ng/dL ( Table 1 ). The patient’s wife was confirmed to be pregnant 9 months after the initiation of dexamethasone and delivered a healthy full-term baby girl. CYP21A2 genotyping was performed. Our patient had a 30-kb deletion (CH-1 chimera subtype) in one allele and IVS2-13A/C>G (In2G) mutation in the second allele; his wife was negative for any known CYP21A2 variants, and his daughter was found to carry a 30-kb deletion (CH-1 chimera subtype) in one allele. Given his weight gain and insomnia, the patient’s therapy was switched to prednisone 3 mg twice daily. He lost 3 kg, and his insomnia resolved. His TART volume, parameters of semen analysis, and biochemical markers of CAH control have remained stable 2 and a half years hence, and he is currently expecting his second child.'}
|
Neurology
|
Neuro
|
[
"insomnia"
] |
6853670
|
{'1. Case Description': 'A 28-year-old man with classic salt-wasting CAH due to 21-hydroxylase deficiency presented with subfertility. For the past 6 months, he described a minimal coital frequency of 2 or 3 times per week without the use of contraception. He had been receiving prednisone 5 mg each morning and fludrocortisone 50 μg twice daily over the last decade. He had known bilateral TARTs, first noted at age 18 and occupying 1.2% of his total testicular volume (0.38 mL of 30.68 mL) ( Fig. 1 ). A recent testicular ultrasound showed increased TART volume, now occupying 16% of his total testicular volume (5.01 mL of 32.30 mL testicular volume), and semen analysis showed azoospermia. On examination, the patient was short-statured, with a standing height of 153.4 cm ( z score: −3.1); midparental height was 174.1 cm ( z score: −0.4). Testicular volume was 25 mL bilaterally. Biochemical evaluation at 0800 before medication showed 17-hydroxyprogesterone 13,060 ng/dL (reference: 13 to 120 ng/dL), androstenedione (A4) 1025 ng/dL (reference: 26 to 125 ng/dL), ACTH 866 pg/mL (reference: 5 to 46 pg/mL), plasma renin activity (PRA) 7.1 ng/mL/h (reference: 0.6 to 4.3 ng/mL/h), FSH 1.7 U/L (reference: 1 to 11 U/L), LH 1.3 U/L (reference: 1 to 8 U/L), and total testosterone (T) 473 ng/ dL (reference: 240 to 950 ng/dL). His A4/T ratio of 2.2 (>0.5) with low LH and FSH was suggestive of a mostly adrenal origin of his T. His glucocorticoid therapy was switched from prednisone 5 mg daily to dexamethasone 250 μg at bedtime to suppress the nocturnal ACTH surge. At his 5-month follow-up visit, he reported a weight gain of 5 kg and insomnia. Physical examination revealed supraclavicular fullness with predominantly central weight gain and the presence of abdominal striae, not present on previous exam. Testicular volume was stable at 25 mL. Repeat ultrasound showed 91% decrease in total TART volume (0.47 mL) ( Fig. 1 ). Follow-up semen analysis showed a sperm count of 132 × 10 6 /mL (reference range: >14 × 10 6 /mL), with 7 × 10 6 /mL being morphologically normal (reference range: >3 × 10 6 /mL) and 35% motile (normal >39%). Biochemical evaluation showed significant improvement in CAH control, with 0800 evaluation before medication revealing 17-hydroxyprogesterone 66 ng/dL, A4 16 ng/dL, ACTH 13.5 pg/mL, PRA 11 ng/mL/h, FSH 5.4 U/L, LH 1 U/L, and T 287 ng/dL ( Table 1 ). The patient’s wife was confirmed to be pregnant 9 months after the initiation of dexamethasone and delivered a healthy full-term baby girl. CYP21A2 genotyping was performed. Our patient had a 30-kb deletion (CH-1 chimera subtype) in one allele and IVS2-13A/C>G (In2G) mutation in the second allele; his wife was negative for any known CYP21A2 variants, and his daughter was found to carry a 30-kb deletion (CH-1 chimera subtype) in one allele. Given his weight gain and insomnia, the patient’s therapy was switched to prednisone 3 mg twice daily. He lost 3 kg, and his insomnia resolved. His TART volume, parameters of semen analysis, and biochemical markers of CAH control have remained stable 2 and a half years hence, and he is currently expecting his second child.'}
|
{'1. Case Description': 'A 28-year-old man with classic salt-wasting CAH due to 21-hydroxylase deficiency presented with subfertility. For the past 6 months, he described a minimal coital frequency of 2 or 3 times per week without the use of contraception. He had been receiving prednisone 5 mg each morning and fludrocortisone 50 μg twice daily over the last decade. He had known bilateral TARTs, first noted at age 18 and occupying 1.2% of his total testicular volume (0.38 mL of 30.68 mL) ( Fig. 1 ). A recent testicular ultrasound showed increased TART volume, now occupying 16% of his total testicular volume (5.01 mL of 32.30 mL testicular volume), and semen analysis showed azoospermia. On examination, the patient was short-statured, with a standing height of 153.4 cm ( z score: −3.1); midparental height was 174.1 cm ( z score: −0.4). Testicular volume was 25 mL bilaterally. Biochemical evaluation at 0800 before medication showed 17-hydroxyprogesterone 13,060 ng/dL (reference: 13 to 120 ng/dL), androstenedione (A4) 1025 ng/dL (reference: 26 to 125 ng/dL), ACTH 866 pg/mL (reference: 5 to 46 pg/mL), plasma renin activity (PRA) 7.1 ng/mL/h (reference: 0.6 to 4.3 ng/mL/h), FSH 1.7 U/L (reference: 1 to 11 U/L), LH 1.3 U/L (reference: 1 to 8 U/L), and total testosterone (T) 473 ng/ dL (reference: 240 to 950 ng/dL). His A4/T ratio of 2.2 (>0.5) with low LH and FSH was suggestive of a mostly adrenal origin of his T. His glucocorticoid therapy was switched from prednisone 5 mg daily to dexamethasone 250 μg at bedtime to suppress the nocturnal ACTH surge. At his 5-month follow-up visit, he reported a weight gain of 5 kg and insomnia. Physical examination revealed supraclavicular fullness with predominantly central weight gain and the presence of abdominal striae, not present on previous exam. Testicular volume was stable at 25 mL. Repeat ultrasound showed 91% decrease in total TART volume (0.47 mL) ( Fig. 1 ). Follow-up semen analysis showed a sperm count of 132 × 10 6 /mL (reference range: >14 × 10 6 /mL), with 7 × 10 6 /mL being morphologically normal (reference range: >3 × 10 6 /mL) and 35% motile (normal >39%). Biochemical evaluation showed significant improvement in CAH control, with 0800 evaluation before medication revealing 17-hydroxyprogesterone 66 ng/dL, A4 16 ng/dL, ACTH 13.5 pg/mL, PRA 11 ng/mL/h, FSH 5.4 U/L, LH 1 U/L, and T 287 ng/dL ( Table 1 ). The patient’s wife was confirmed to be pregnant 9 months after the initiation of dexamethasone and delivered a healthy full-term baby girl. CYP21A2 genotyping was performed. Our patient had a 30-kb deletion (CH-1 chimera subtype) in one allele and IVS2-13A/C>G (In2G) mutation in the second allele; his wife was negative for any known CYP21A2 variants, and his daughter was found to carry a 30-kb deletion (CH-1 chimera subtype) in one allele. Given his weight gain and insomnia, the patient’s therapy was switched to prednisone 3 mg twice daily. He lost 3 kg, and his insomnia resolved. His TART volume, parameters of semen analysis, and biochemical markers of CAH control have remained stable 2 and a half years hence, and he is currently expecting his second child.'}
|
Laboratory-and-Imaging
|
Lab_Image
|
[
"A recent testicular ultrasound showed increased TART volume, now occupying 16 % of his total testicular volume ( 5.01 mL of 32.30 mL testicular volume ), and semen analysis showed azoospermia.",
"Biochemical evaluation at 0800 before medication showed 17 - hydroxyprogesterone 13,060 ng / dL ( reference : 13 to 120 ng / dL ), androstenedione ( A4 ) 1025 ng / dL ( reference : 26 to 125 ng / dL ), ACTH 866 pg / mL ( reference : 5 to 46 pg / mL ), plasma renin activity ( PRA ) 7.1 ng / mL / h ( reference : 0.6 to 4.3 ng / mL / h ), FSH 1.7 U / L ( reference : 1 to 11 U / L ), LH 1.3 U / L ( reference : 1 to 8 U / L ), and total testosterone ( T ) 473 ng/ dL ( reference : 240 to 950 ng / dL ). His A4 / T ratio of 2.2 ( > 0.5 ) with low LH and FSH was suggestive of a mostly adrenal origin of his T.",
"Repeat ultrasound showed 91 % decrease in total TART volume ( 0.47 mL ) ( Fig. 1 ). Follow - up semen analysis showed a sperm count of 132 × 10 6 /mL ( reference range : > 14 × 10 6 /mL ), with 7 × 10 6 /mL being morphologically normal ( reference range : > 3 × 10 6 /mL ) and 35 % motile ( normal > 39 % ). Biochemical evaluation showed significant improvement in CAH control, with 0800 evaluation before medication revealing 17 - hydroxyprogesterone 66 ng / dL, A4 16 ng / dL, ACTH 13.5 pg / mL, PRA 11 ng / mL / h, FSH 5.4 U / L, LH 1 U / L, and T 287 ng / dL",
"CYP21A2 genotyping was performed. Our patient had a 30 - kb deletion ( CH-1 chimera subtype ) in one allele and IVS2 - 13A / C > G ( In2 G ) mutation in the second allele"
] |
6853670
|
{'1. Case Description': 'A 28-year-old man with classic salt-wasting CAH due to 21-hydroxylase deficiency presented with subfertility. For the past 6 months, he described a minimal coital frequency of 2 or 3 times per week without the use of contraception. He had been receiving prednisone 5 mg each morning and fludrocortisone 50 μg twice daily over the last decade. He had known bilateral TARTs, first noted at age 18 and occupying 1.2% of his total testicular volume (0.38 mL of 30.68 mL) ( Fig. 1 ). A recent testicular ultrasound showed increased TART volume, now occupying 16% of his total testicular volume (5.01 mL of 32.30 mL testicular volume), and semen analysis showed azoospermia. On examination, the patient was short-statured, with a standing height of 153.4 cm ( z score: −3.1); midparental height was 174.1 cm ( z score: −0.4). Testicular volume was 25 mL bilaterally. Biochemical evaluation at 0800 before medication showed 17-hydroxyprogesterone 13,060 ng/dL (reference: 13 to 120 ng/dL), androstenedione (A4) 1025 ng/dL (reference: 26 to 125 ng/dL), ACTH 866 pg/mL (reference: 5 to 46 pg/mL), plasma renin activity (PRA) 7.1 ng/mL/h (reference: 0.6 to 4.3 ng/mL/h), FSH 1.7 U/L (reference: 1 to 11 U/L), LH 1.3 U/L (reference: 1 to 8 U/L), and total testosterone (T) 473 ng/ dL (reference: 240 to 950 ng/dL). His A4/T ratio of 2.2 (>0.5) with low LH and FSH was suggestive of a mostly adrenal origin of his T. His glucocorticoid therapy was switched from prednisone 5 mg daily to dexamethasone 250 μg at bedtime to suppress the nocturnal ACTH surge. At his 5-month follow-up visit, he reported a weight gain of 5 kg and insomnia. Physical examination revealed supraclavicular fullness with predominantly central weight gain and the presence of abdominal striae, not present on previous exam. Testicular volume was stable at 25 mL. Repeat ultrasound showed 91% decrease in total TART volume (0.47 mL) ( Fig. 1 ). Follow-up semen analysis showed a sperm count of 132 × 10 6 /mL (reference range: >14 × 10 6 /mL), with 7 × 10 6 /mL being morphologically normal (reference range: >3 × 10 6 /mL) and 35% motile (normal >39%). Biochemical evaluation showed significant improvement in CAH control, with 0800 evaluation before medication revealing 17-hydroxyprogesterone 66 ng/dL, A4 16 ng/dL, ACTH 13.5 pg/mL, PRA 11 ng/mL/h, FSH 5.4 U/L, LH 1 U/L, and T 287 ng/dL ( Table 1 ). The patient’s wife was confirmed to be pregnant 9 months after the initiation of dexamethasone and delivered a healthy full-term baby girl. CYP21A2 genotyping was performed. Our patient had a 30-kb deletion (CH-1 chimera subtype) in one allele and IVS2-13A/C>G (In2G) mutation in the second allele; his wife was negative for any known CYP21A2 variants, and his daughter was found to carry a 30-kb deletion (CH-1 chimera subtype) in one allele. Given his weight gain and insomnia, the patient’s therapy was switched to prednisone 3 mg twice daily. He lost 3 kg, and his insomnia resolved. His TART volume, parameters of semen analysis, and biochemical markers of CAH control have remained stable 2 and a half years hence, and he is currently expecting his second child.'}
|
{'1. Case Description': 'A 28-year-old man with classic salt-wasting CAH due to 21-hydroxylase deficiency presented with subfertility. For the past 6 months, he described a minimal coital frequency of 2 or 3 times per week without the use of contraception. He had been receiving prednisone 5 mg each morning and fludrocortisone 50 μg twice daily over the last decade. He had known bilateral TARTs, first noted at age 18 and occupying 1.2% of his total testicular volume (0.38 mL of 30.68 mL) ( Fig. 1 ). A recent testicular ultrasound showed increased TART volume, now occupying 16% of his total testicular volume (5.01 mL of 32.30 mL testicular volume), and semen analysis showed azoospermia. On examination, the patient was short-statured, with a standing height of 153.4 cm ( z score: −3.1); midparental height was 174.1 cm ( z score: −0.4). Testicular volume was 25 mL bilaterally. Biochemical evaluation at 0800 before medication showed 17-hydroxyprogesterone 13,060 ng/dL (reference: 13 to 120 ng/dL), androstenedione (A4) 1025 ng/dL (reference: 26 to 125 ng/dL), ACTH 866 pg/mL (reference: 5 to 46 pg/mL), plasma renin activity (PRA) 7.1 ng/mL/h (reference: 0.6 to 4.3 ng/mL/h), FSH 1.7 U/L (reference: 1 to 11 U/L), LH 1.3 U/L (reference: 1 to 8 U/L), and total testosterone (T) 473 ng/ dL (reference: 240 to 950 ng/dL). His A4/T ratio of 2.2 (>0.5) with low LH and FSH was suggestive of a mostly adrenal origin of his T. His glucocorticoid therapy was switched from prednisone 5 mg daily to dexamethasone 250 μg at bedtime to suppress the nocturnal ACTH surge. At his 5-month follow-up visit, he reported a weight gain of 5 kg and insomnia. Physical examination revealed supraclavicular fullness with predominantly central weight gain and the presence of abdominal striae, not present on previous exam. Testicular volume was stable at 25 mL. Repeat ultrasound showed 91% decrease in total TART volume (0.47 mL) ( Fig. 1 ). Follow-up semen analysis showed a sperm count of 132 × 10 6 /mL (reference range: >14 × 10 6 /mL), with 7 × 10 6 /mL being morphologically normal (reference range: >3 × 10 6 /mL) and 35% motile (normal >39%). Biochemical evaluation showed significant improvement in CAH control, with 0800 evaluation before medication revealing 17-hydroxyprogesterone 66 ng/dL, A4 16 ng/dL, ACTH 13.5 pg/mL, PRA 11 ng/mL/h, FSH 5.4 U/L, LH 1 U/L, and T 287 ng/dL ( Table 1 ). The patient’s wife was confirmed to be pregnant 9 months after the initiation of dexamethasone and delivered a healthy full-term baby girl. CYP21A2 genotyping was performed. Our patient had a 30-kb deletion (CH-1 chimera subtype) in one allele and IVS2-13A/C>G (In2G) mutation in the second allele; his wife was negative for any known CYP21A2 variants, and his daughter was found to carry a 30-kb deletion (CH-1 chimera subtype) in one allele. Given his weight gain and insomnia, the patient’s therapy was switched to prednisone 3 mg twice daily. He lost 3 kg, and his insomnia resolved. His TART volume, parameters of semen analysis, and biochemical markers of CAH control have remained stable 2 and a half years hence, and he is currently expecting his second child.'}
|
Cardiovascular-System
|
CVS
|
[] |
6853670
|
{'1. Case Description': 'A 28-year-old man with classic salt-wasting CAH due to 21-hydroxylase deficiency presented with subfertility. For the past 6 months, he described a minimal coital frequency of 2 or 3 times per week without the use of contraception. He had been receiving prednisone 5 mg each morning and fludrocortisone 50 μg twice daily over the last decade. He had known bilateral TARTs, first noted at age 18 and occupying 1.2% of his total testicular volume (0.38 mL of 30.68 mL) ( Fig. 1 ). A recent testicular ultrasound showed increased TART volume, now occupying 16% of his total testicular volume (5.01 mL of 32.30 mL testicular volume), and semen analysis showed azoospermia. On examination, the patient was short-statured, with a standing height of 153.4 cm ( z score: −3.1); midparental height was 174.1 cm ( z score: −0.4). Testicular volume was 25 mL bilaterally. Biochemical evaluation at 0800 before medication showed 17-hydroxyprogesterone 13,060 ng/dL (reference: 13 to 120 ng/dL), androstenedione (A4) 1025 ng/dL (reference: 26 to 125 ng/dL), ACTH 866 pg/mL (reference: 5 to 46 pg/mL), plasma renin activity (PRA) 7.1 ng/mL/h (reference: 0.6 to 4.3 ng/mL/h), FSH 1.7 U/L (reference: 1 to 11 U/L), LH 1.3 U/L (reference: 1 to 8 U/L), and total testosterone (T) 473 ng/ dL (reference: 240 to 950 ng/dL). His A4/T ratio of 2.2 (>0.5) with low LH and FSH was suggestive of a mostly adrenal origin of his T. His glucocorticoid therapy was switched from prednisone 5 mg daily to dexamethasone 250 μg at bedtime to suppress the nocturnal ACTH surge. At his 5-month follow-up visit, he reported a weight gain of 5 kg and insomnia. Physical examination revealed supraclavicular fullness with predominantly central weight gain and the presence of abdominal striae, not present on previous exam. Testicular volume was stable at 25 mL. Repeat ultrasound showed 91% decrease in total TART volume (0.47 mL) ( Fig. 1 ). Follow-up semen analysis showed a sperm count of 132 × 10 6 /mL (reference range: >14 × 10 6 /mL), with 7 × 10 6 /mL being morphologically normal (reference range: >3 × 10 6 /mL) and 35% motile (normal >39%). Biochemical evaluation showed significant improvement in CAH control, with 0800 evaluation before medication revealing 17-hydroxyprogesterone 66 ng/dL, A4 16 ng/dL, ACTH 13.5 pg/mL, PRA 11 ng/mL/h, FSH 5.4 U/L, LH 1 U/L, and T 287 ng/dL ( Table 1 ). The patient’s wife was confirmed to be pregnant 9 months after the initiation of dexamethasone and delivered a healthy full-term baby girl. CYP21A2 genotyping was performed. Our patient had a 30-kb deletion (CH-1 chimera subtype) in one allele and IVS2-13A/C>G (In2G) mutation in the second allele; his wife was negative for any known CYP21A2 variants, and his daughter was found to carry a 30-kb deletion (CH-1 chimera subtype) in one allele. Given his weight gain and insomnia, the patient’s therapy was switched to prednisone 3 mg twice daily. He lost 3 kg, and his insomnia resolved. His TART volume, parameters of semen analysis, and biochemical markers of CAH control have remained stable 2 and a half years hence, and he is currently expecting his second child.'}
|
{'1. Case Description': 'A 28-year-old man with classic salt-wasting CAH due to 21-hydroxylase deficiency presented with subfertility. For the past 6 months, he described a minimal coital frequency of 2 or 3 times per week without the use of contraception. He had been receiving prednisone 5 mg each morning and fludrocortisone 50 μg twice daily over the last decade. He had known bilateral TARTs, first noted at age 18 and occupying 1.2% of his total testicular volume (0.38 mL of 30.68 mL) ( Fig. 1 ). A recent testicular ultrasound showed increased TART volume, now occupying 16% of his total testicular volume (5.01 mL of 32.30 mL testicular volume), and semen analysis showed azoospermia. On examination, the patient was short-statured, with a standing height of 153.4 cm ( z score: −3.1); midparental height was 174.1 cm ( z score: −0.4). Testicular volume was 25 mL bilaterally. Biochemical evaluation at 0800 before medication showed 17-hydroxyprogesterone 13,060 ng/dL (reference: 13 to 120 ng/dL), androstenedione (A4) 1025 ng/dL (reference: 26 to 125 ng/dL), ACTH 866 pg/mL (reference: 5 to 46 pg/mL), plasma renin activity (PRA) 7.1 ng/mL/h (reference: 0.6 to 4.3 ng/mL/h), FSH 1.7 U/L (reference: 1 to 11 U/L), LH 1.3 U/L (reference: 1 to 8 U/L), and total testosterone (T) 473 ng/ dL (reference: 240 to 950 ng/dL). His A4/T ratio of 2.2 (>0.5) with low LH and FSH was suggestive of a mostly adrenal origin of his T. His glucocorticoid therapy was switched from prednisone 5 mg daily to dexamethasone 250 μg at bedtime to suppress the nocturnal ACTH surge. At his 5-month follow-up visit, he reported a weight gain of 5 kg and insomnia. Physical examination revealed supraclavicular fullness with predominantly central weight gain and the presence of abdominal striae, not present on previous exam. Testicular volume was stable at 25 mL. Repeat ultrasound showed 91% decrease in total TART volume (0.47 mL) ( Fig. 1 ). Follow-up semen analysis showed a sperm count of 132 × 10 6 /mL (reference range: >14 × 10 6 /mL), with 7 × 10 6 /mL being morphologically normal (reference range: >3 × 10 6 /mL) and 35% motile (normal >39%). Biochemical evaluation showed significant improvement in CAH control, with 0800 evaluation before medication revealing 17-hydroxyprogesterone 66 ng/dL, A4 16 ng/dL, ACTH 13.5 pg/mL, PRA 11 ng/mL/h, FSH 5.4 U/L, LH 1 U/L, and T 287 ng/dL ( Table 1 ). The patient’s wife was confirmed to be pregnant 9 months after the initiation of dexamethasone and delivered a healthy full-term baby girl. CYP21A2 genotyping was performed. Our patient had a 30-kb deletion (CH-1 chimera subtype) in one allele and IVS2-13A/C>G (In2G) mutation in the second allele; his wife was negative for any known CYP21A2 variants, and his daughter was found to carry a 30-kb deletion (CH-1 chimera subtype) in one allele. Given his weight gain and insomnia, the patient’s therapy was switched to prednisone 3 mg twice daily. He lost 3 kg, and his insomnia resolved. His TART volume, parameters of semen analysis, and biochemical markers of CAH control have remained stable 2 and a half years hence, and he is currently expecting his second child.'}
|
Endocrinology
|
ENDO
|
[
"subfertility",
"bilateral TARTs, first noted at age 18 and occupying 1.2 % of his total testicular volume ( 0.38 mL of 30.68 mL )",
"A recent testicular ultrasound showed increased TART volume, now occupying 16 % of his total testicular volume ( 5.01 mL of 32.30 mL testicular volume ),",
"short - statured",
"17 - hydroxyprogesterone 13,060 ng / dL ( reference : 13 to 120 ng / dL ), androstenedione ( A4 ) 1025 ng / dL ( reference : 26 to 125 ng / dL ), ACTH 866 pg / mL ( reference : 5 to 46 pg / mL ), plasma renin activity ( PRA ) 7.1 ng / mL / h ( reference : 0.6 to 4.3 ng / mL / h ), FSH 1.7 U / L ( reference : 1 to 11 U / L ), LH 1.3 U / L ( reference : 1 to 8 U / L ), and total testosterone ( T ) 473 ng/ dL ( reference : 240 to 950 ng / dL ). His A4 / T ratio of 2.2 ( > 0.5 ) with low LH and FSH",
"weight gain of 5 kg",
"91 % decrease in total TART volume ( 0.47 mL )",
"17 - hydroxyprogesterone 66 ng / dL, A4 16 ng / dL, ACTH 13.5 pg / mL, PRA 11 ng / mL / h, FSH 5.4 U / L, LH 1 U / L, and T 287 ng / dL",
"weight gain",
"lost 3 kg"
] |
6853670
|
{'1. Case Description': 'A 28-year-old man with classic salt-wasting CAH due to 21-hydroxylase deficiency presented with subfertility. For the past 6 months, he described a minimal coital frequency of 2 or 3 times per week without the use of contraception. He had been receiving prednisone 5 mg each morning and fludrocortisone 50 μg twice daily over the last decade. He had known bilateral TARTs, first noted at age 18 and occupying 1.2% of his total testicular volume (0.38 mL of 30.68 mL) ( Fig. 1 ). A recent testicular ultrasound showed increased TART volume, now occupying 16% of his total testicular volume (5.01 mL of 32.30 mL testicular volume), and semen analysis showed azoospermia. On examination, the patient was short-statured, with a standing height of 153.4 cm ( z score: −3.1); midparental height was 174.1 cm ( z score: −0.4). Testicular volume was 25 mL bilaterally. Biochemical evaluation at 0800 before medication showed 17-hydroxyprogesterone 13,060 ng/dL (reference: 13 to 120 ng/dL), androstenedione (A4) 1025 ng/dL (reference: 26 to 125 ng/dL), ACTH 866 pg/mL (reference: 5 to 46 pg/mL), plasma renin activity (PRA) 7.1 ng/mL/h (reference: 0.6 to 4.3 ng/mL/h), FSH 1.7 U/L (reference: 1 to 11 U/L), LH 1.3 U/L (reference: 1 to 8 U/L), and total testosterone (T) 473 ng/ dL (reference: 240 to 950 ng/dL). His A4/T ratio of 2.2 (>0.5) with low LH and FSH was suggestive of a mostly adrenal origin of his T. His glucocorticoid therapy was switched from prednisone 5 mg daily to dexamethasone 250 μg at bedtime to suppress the nocturnal ACTH surge. At his 5-month follow-up visit, he reported a weight gain of 5 kg and insomnia. Physical examination revealed supraclavicular fullness with predominantly central weight gain and the presence of abdominal striae, not present on previous exam. Testicular volume was stable at 25 mL. Repeat ultrasound showed 91% decrease in total TART volume (0.47 mL) ( Fig. 1 ). Follow-up semen analysis showed a sperm count of 132 × 10 6 /mL (reference range: >14 × 10 6 /mL), with 7 × 10 6 /mL being morphologically normal (reference range: >3 × 10 6 /mL) and 35% motile (normal >39%). Biochemical evaluation showed significant improvement in CAH control, with 0800 evaluation before medication revealing 17-hydroxyprogesterone 66 ng/dL, A4 16 ng/dL, ACTH 13.5 pg/mL, PRA 11 ng/mL/h, FSH 5.4 U/L, LH 1 U/L, and T 287 ng/dL ( Table 1 ). The patient’s wife was confirmed to be pregnant 9 months after the initiation of dexamethasone and delivered a healthy full-term baby girl. CYP21A2 genotyping was performed. Our patient had a 30-kb deletion (CH-1 chimera subtype) in one allele and IVS2-13A/C>G (In2G) mutation in the second allele; his wife was negative for any known CYP21A2 variants, and his daughter was found to carry a 30-kb deletion (CH-1 chimera subtype) in one allele. Given his weight gain and insomnia, the patient’s therapy was switched to prednisone 3 mg twice daily. He lost 3 kg, and his insomnia resolved. His TART volume, parameters of semen analysis, and biochemical markers of CAH control have remained stable 2 and a half years hence, and he is currently expecting his second child.'}
|
{'1. Case Description': 'A 28-year-old man with classic salt-wasting CAH due to 21-hydroxylase deficiency presented with subfertility. For the past 6 months, he described a minimal coital frequency of 2 or 3 times per week without the use of contraception. He had been receiving prednisone 5 mg each morning and fludrocortisone 50 μg twice daily over the last decade. He had known bilateral TARTs, first noted at age 18 and occupying 1.2% of his total testicular volume (0.38 mL of 30.68 mL) ( Fig. 1 ). A recent testicular ultrasound showed increased TART volume, now occupying 16% of his total testicular volume (5.01 mL of 32.30 mL testicular volume), and semen analysis showed azoospermia. On examination, the patient was short-statured, with a standing height of 153.4 cm ( z score: −3.1); midparental height was 174.1 cm ( z score: −0.4). Testicular volume was 25 mL bilaterally. Biochemical evaluation at 0800 before medication showed 17-hydroxyprogesterone 13,060 ng/dL (reference: 13 to 120 ng/dL), androstenedione (A4) 1025 ng/dL (reference: 26 to 125 ng/dL), ACTH 866 pg/mL (reference: 5 to 46 pg/mL), plasma renin activity (PRA) 7.1 ng/mL/h (reference: 0.6 to 4.3 ng/mL/h), FSH 1.7 U/L (reference: 1 to 11 U/L), LH 1.3 U/L (reference: 1 to 8 U/L), and total testosterone (T) 473 ng/ dL (reference: 240 to 950 ng/dL). His A4/T ratio of 2.2 (>0.5) with low LH and FSH was suggestive of a mostly adrenal origin of his T. His glucocorticoid therapy was switched from prednisone 5 mg daily to dexamethasone 250 μg at bedtime to suppress the nocturnal ACTH surge. At his 5-month follow-up visit, he reported a weight gain of 5 kg and insomnia. Physical examination revealed supraclavicular fullness with predominantly central weight gain and the presence of abdominal striae, not present on previous exam. Testicular volume was stable at 25 mL. Repeat ultrasound showed 91% decrease in total TART volume (0.47 mL) ( Fig. 1 ). Follow-up semen analysis showed a sperm count of 132 × 10 6 /mL (reference range: >14 × 10 6 /mL), with 7 × 10 6 /mL being morphologically normal (reference range: >3 × 10 6 /mL) and 35% motile (normal >39%). Biochemical evaluation showed significant improvement in CAH control, with 0800 evaluation before medication revealing 17-hydroxyprogesterone 66 ng/dL, A4 16 ng/dL, ACTH 13.5 pg/mL, PRA 11 ng/mL/h, FSH 5.4 U/L, LH 1 U/L, and T 287 ng/dL ( Table 1 ). The patient’s wife was confirmed to be pregnant 9 months after the initiation of dexamethasone and delivered a healthy full-term baby girl. CYP21A2 genotyping was performed. Our patient had a 30-kb deletion (CH-1 chimera subtype) in one allele and IVS2-13A/C>G (In2G) mutation in the second allele; his wife was negative for any known CYP21A2 variants, and his daughter was found to carry a 30-kb deletion (CH-1 chimera subtype) in one allele. Given his weight gain and insomnia, the patient’s therapy was switched to prednisone 3 mg twice daily. He lost 3 kg, and his insomnia resolved. His TART volume, parameters of semen analysis, and biochemical markers of CAH control have remained stable 2 and a half years hence, and he is currently expecting his second child.'}
|
Genitourinary-System
|
GU
|
[
"subfertility",
"bilateral TARTs, first noted at age 18 and occupying 1.2 % of his total testicular volume ( 0.38 mL of 30.68 mL )",
"A recent testicular ultrasound showed increased TART volume, now occupying 16 % of his total testicular volume ( 5.01 mL of 32.30 mL testicular volume ), and semen analysis showed azoospermia.",
"Testicular volume was 25 mL bilaterally",
"Testicular volume was stable at 25 mL.",
"91 % decrease in total TART volume ( 0.47 mL ) ( Fig. 1 ). Follow - up semen analysis showed a sperm count of 132 × 10 6 /mL ( reference range : > 14 × 10 6 /mL ), with 7 × 10 6 /mL being morphologically normal ( reference range : > 3 × 10 6 /mL ) and 35 % motile ( normal > 39 % )."
] |
6853670
|
{'1. Case Description': 'A 28-year-old man with classic salt-wasting CAH due to 21-hydroxylase deficiency presented with subfertility. For the past 6 months, he described a minimal coital frequency of 2 or 3 times per week without the use of contraception. He had been receiving prednisone 5 mg each morning and fludrocortisone 50 μg twice daily over the last decade. He had known bilateral TARTs, first noted at age 18 and occupying 1.2% of his total testicular volume (0.38 mL of 30.68 mL) ( Fig. 1 ). A recent testicular ultrasound showed increased TART volume, now occupying 16% of his total testicular volume (5.01 mL of 32.30 mL testicular volume), and semen analysis showed azoospermia. On examination, the patient was short-statured, with a standing height of 153.4 cm ( z score: −3.1); midparental height was 174.1 cm ( z score: −0.4). Testicular volume was 25 mL bilaterally. Biochemical evaluation at 0800 before medication showed 17-hydroxyprogesterone 13,060 ng/dL (reference: 13 to 120 ng/dL), androstenedione (A4) 1025 ng/dL (reference: 26 to 125 ng/dL), ACTH 866 pg/mL (reference: 5 to 46 pg/mL), plasma renin activity (PRA) 7.1 ng/mL/h (reference: 0.6 to 4.3 ng/mL/h), FSH 1.7 U/L (reference: 1 to 11 U/L), LH 1.3 U/L (reference: 1 to 8 U/L), and total testosterone (T) 473 ng/ dL (reference: 240 to 950 ng/dL). His A4/T ratio of 2.2 (>0.5) with low LH and FSH was suggestive of a mostly adrenal origin of his T. His glucocorticoid therapy was switched from prednisone 5 mg daily to dexamethasone 250 μg at bedtime to suppress the nocturnal ACTH surge. At his 5-month follow-up visit, he reported a weight gain of 5 kg and insomnia. Physical examination revealed supraclavicular fullness with predominantly central weight gain and the presence of abdominal striae, not present on previous exam. Testicular volume was stable at 25 mL. Repeat ultrasound showed 91% decrease in total TART volume (0.47 mL) ( Fig. 1 ). Follow-up semen analysis showed a sperm count of 132 × 10 6 /mL (reference range: >14 × 10 6 /mL), with 7 × 10 6 /mL being morphologically normal (reference range: >3 × 10 6 /mL) and 35% motile (normal >39%). Biochemical evaluation showed significant improvement in CAH control, with 0800 evaluation before medication revealing 17-hydroxyprogesterone 66 ng/dL, A4 16 ng/dL, ACTH 13.5 pg/mL, PRA 11 ng/mL/h, FSH 5.4 U/L, LH 1 U/L, and T 287 ng/dL ( Table 1 ). The patient’s wife was confirmed to be pregnant 9 months after the initiation of dexamethasone and delivered a healthy full-term baby girl. CYP21A2 genotyping was performed. Our patient had a 30-kb deletion (CH-1 chimera subtype) in one allele and IVS2-13A/C>G (In2G) mutation in the second allele; his wife was negative for any known CYP21A2 variants, and his daughter was found to carry a 30-kb deletion (CH-1 chimera subtype) in one allele. Given his weight gain and insomnia, the patient’s therapy was switched to prednisone 3 mg twice daily. He lost 3 kg, and his insomnia resolved. His TART volume, parameters of semen analysis, and biochemical markers of CAH control have remained stable 2 and a half years hence, and he is currently expecting his second child.'}
|
{'1. Case Description': 'A 28-year-old man with classic salt-wasting CAH due to 21-hydroxylase deficiency presented with subfertility. For the past 6 months, he described a minimal coital frequency of 2 or 3 times per week without the use of contraception. He had been receiving prednisone 5 mg each morning and fludrocortisone 50 μg twice daily over the last decade. He had known bilateral TARTs, first noted at age 18 and occupying 1.2% of his total testicular volume (0.38 mL of 30.68 mL) ( Fig. 1 ). A recent testicular ultrasound showed increased TART volume, now occupying 16% of his total testicular volume (5.01 mL of 32.30 mL testicular volume), and semen analysis showed azoospermia. On examination, the patient was short-statured, with a standing height of 153.4 cm ( z score: −3.1); midparental height was 174.1 cm ( z score: −0.4). Testicular volume was 25 mL bilaterally. Biochemical evaluation at 0800 before medication showed 17-hydroxyprogesterone 13,060 ng/dL (reference: 13 to 120 ng/dL), androstenedione (A4) 1025 ng/dL (reference: 26 to 125 ng/dL), ACTH 866 pg/mL (reference: 5 to 46 pg/mL), plasma renin activity (PRA) 7.1 ng/mL/h (reference: 0.6 to 4.3 ng/mL/h), FSH 1.7 U/L (reference: 1 to 11 U/L), LH 1.3 U/L (reference: 1 to 8 U/L), and total testosterone (T) 473 ng/ dL (reference: 240 to 950 ng/dL). His A4/T ratio of 2.2 (>0.5) with low LH and FSH was suggestive of a mostly adrenal origin of his T. His glucocorticoid therapy was switched from prednisone 5 mg daily to dexamethasone 250 μg at bedtime to suppress the nocturnal ACTH surge. At his 5-month follow-up visit, he reported a weight gain of 5 kg and insomnia. Physical examination revealed supraclavicular fullness with predominantly central weight gain and the presence of abdominal striae, not present on previous exam. Testicular volume was stable at 25 mL. Repeat ultrasound showed 91% decrease in total TART volume (0.47 mL) ( Fig. 1 ). Follow-up semen analysis showed a sperm count of 132 × 10 6 /mL (reference range: >14 × 10 6 /mL), with 7 × 10 6 /mL being morphologically normal (reference range: >3 × 10 6 /mL) and 35% motile (normal >39%). Biochemical evaluation showed significant improvement in CAH control, with 0800 evaluation before medication revealing 17-hydroxyprogesterone 66 ng/dL, A4 16 ng/dL, ACTH 13.5 pg/mL, PRA 11 ng/mL/h, FSH 5.4 U/L, LH 1 U/L, and T 287 ng/dL ( Table 1 ). The patient’s wife was confirmed to be pregnant 9 months after the initiation of dexamethasone and delivered a healthy full-term baby girl. CYP21A2 genotyping was performed. Our patient had a 30-kb deletion (CH-1 chimera subtype) in one allele and IVS2-13A/C>G (In2G) mutation in the second allele; his wife was negative for any known CYP21A2 variants, and his daughter was found to carry a 30-kb deletion (CH-1 chimera subtype) in one allele. Given his weight gain and insomnia, the patient’s therapy was switched to prednisone 3 mg twice daily. He lost 3 kg, and his insomnia resolved. His TART volume, parameters of semen analysis, and biochemical markers of CAH control have remained stable 2 and a half years hence, and he is currently expecting his second child.'}
|
Respiratory-System
|
RESP
|
[] |
6853670
|
{'1. Case Description': 'A 28-year-old man with classic salt-wasting CAH due to 21-hydroxylase deficiency presented with subfertility. For the past 6 months, he described a minimal coital frequency of 2 or 3 times per week without the use of contraception. He had been receiving prednisone 5 mg each morning and fludrocortisone 50 μg twice daily over the last decade. He had known bilateral TARTs, first noted at age 18 and occupying 1.2% of his total testicular volume (0.38 mL of 30.68 mL) ( Fig. 1 ). A recent testicular ultrasound showed increased TART volume, now occupying 16% of his total testicular volume (5.01 mL of 32.30 mL testicular volume), and semen analysis showed azoospermia. On examination, the patient was short-statured, with a standing height of 153.4 cm ( z score: −3.1); midparental height was 174.1 cm ( z score: −0.4). Testicular volume was 25 mL bilaterally. Biochemical evaluation at 0800 before medication showed 17-hydroxyprogesterone 13,060 ng/dL (reference: 13 to 120 ng/dL), androstenedione (A4) 1025 ng/dL (reference: 26 to 125 ng/dL), ACTH 866 pg/mL (reference: 5 to 46 pg/mL), plasma renin activity (PRA) 7.1 ng/mL/h (reference: 0.6 to 4.3 ng/mL/h), FSH 1.7 U/L (reference: 1 to 11 U/L), LH 1.3 U/L (reference: 1 to 8 U/L), and total testosterone (T) 473 ng/ dL (reference: 240 to 950 ng/dL). His A4/T ratio of 2.2 (>0.5) with low LH and FSH was suggestive of a mostly adrenal origin of his T. His glucocorticoid therapy was switched from prednisone 5 mg daily to dexamethasone 250 μg at bedtime to suppress the nocturnal ACTH surge. At his 5-month follow-up visit, he reported a weight gain of 5 kg and insomnia. Physical examination revealed supraclavicular fullness with predominantly central weight gain and the presence of abdominal striae, not present on previous exam. Testicular volume was stable at 25 mL. Repeat ultrasound showed 91% decrease in total TART volume (0.47 mL) ( Fig. 1 ). Follow-up semen analysis showed a sperm count of 132 × 10 6 /mL (reference range: >14 × 10 6 /mL), with 7 × 10 6 /mL being morphologically normal (reference range: >3 × 10 6 /mL) and 35% motile (normal >39%). Biochemical evaluation showed significant improvement in CAH control, with 0800 evaluation before medication revealing 17-hydroxyprogesterone 66 ng/dL, A4 16 ng/dL, ACTH 13.5 pg/mL, PRA 11 ng/mL/h, FSH 5.4 U/L, LH 1 U/L, and T 287 ng/dL ( Table 1 ). The patient’s wife was confirmed to be pregnant 9 months after the initiation of dexamethasone and delivered a healthy full-term baby girl. CYP21A2 genotyping was performed. Our patient had a 30-kb deletion (CH-1 chimera subtype) in one allele and IVS2-13A/C>G (In2G) mutation in the second allele; his wife was negative for any known CYP21A2 variants, and his daughter was found to carry a 30-kb deletion (CH-1 chimera subtype) in one allele. Given his weight gain and insomnia, the patient’s therapy was switched to prednisone 3 mg twice daily. He lost 3 kg, and his insomnia resolved. His TART volume, parameters of semen analysis, and biochemical markers of CAH control have remained stable 2 and a half years hence, and he is currently expecting his second child.'}
|
{'1. Case Description': 'A 28-year-old man with classic salt-wasting CAH due to 21-hydroxylase deficiency presented with subfertility. For the past 6 months, he described a minimal coital frequency of 2 or 3 times per week without the use of contraception. He had been receiving prednisone 5 mg each morning and fludrocortisone 50 μg twice daily over the last decade. He had known bilateral TARTs, first noted at age 18 and occupying 1.2% of his total testicular volume (0.38 mL of 30.68 mL) ( Fig. 1 ). A recent testicular ultrasound showed increased TART volume, now occupying 16% of his total testicular volume (5.01 mL of 32.30 mL testicular volume), and semen analysis showed azoospermia. On examination, the patient was short-statured, with a standing height of 153.4 cm ( z score: −3.1); midparental height was 174.1 cm ( z score: −0.4). Testicular volume was 25 mL bilaterally. Biochemical evaluation at 0800 before medication showed 17-hydroxyprogesterone 13,060 ng/dL (reference: 13 to 120 ng/dL), androstenedione (A4) 1025 ng/dL (reference: 26 to 125 ng/dL), ACTH 866 pg/mL (reference: 5 to 46 pg/mL), plasma renin activity (PRA) 7.1 ng/mL/h (reference: 0.6 to 4.3 ng/mL/h), FSH 1.7 U/L (reference: 1 to 11 U/L), LH 1.3 U/L (reference: 1 to 8 U/L), and total testosterone (T) 473 ng/ dL (reference: 240 to 950 ng/dL). His A4/T ratio of 2.2 (>0.5) with low LH and FSH was suggestive of a mostly adrenal origin of his T. His glucocorticoid therapy was switched from prednisone 5 mg daily to dexamethasone 250 μg at bedtime to suppress the nocturnal ACTH surge. At his 5-month follow-up visit, he reported a weight gain of 5 kg and insomnia. Physical examination revealed supraclavicular fullness with predominantly central weight gain and the presence of abdominal striae, not present on previous exam. Testicular volume was stable at 25 mL. Repeat ultrasound showed 91% decrease in total TART volume (0.47 mL) ( Fig. 1 ). Follow-up semen analysis showed a sperm count of 132 × 10 6 /mL (reference range: >14 × 10 6 /mL), with 7 × 10 6 /mL being morphologically normal (reference range: >3 × 10 6 /mL) and 35% motile (normal >39%). Biochemical evaluation showed significant improvement in CAH control, with 0800 evaluation before medication revealing 17-hydroxyprogesterone 66 ng/dL, A4 16 ng/dL, ACTH 13.5 pg/mL, PRA 11 ng/mL/h, FSH 5.4 U/L, LH 1 U/L, and T 287 ng/dL ( Table 1 ). The patient’s wife was confirmed to be pregnant 9 months after the initiation of dexamethasone and delivered a healthy full-term baby girl. CYP21A2 genotyping was performed. Our patient had a 30-kb deletion (CH-1 chimera subtype) in one allele and IVS2-13A/C>G (In2G) mutation in the second allele; his wife was negative for any known CYP21A2 variants, and his daughter was found to carry a 30-kb deletion (CH-1 chimera subtype) in one allele. Given his weight gain and insomnia, the patient’s therapy was switched to prednisone 3 mg twice daily. He lost 3 kg, and his insomnia resolved. His TART volume, parameters of semen analysis, and biochemical markers of CAH control have remained stable 2 and a half years hence, and he is currently expecting his second child.'}
|
Musculoskeletal-System
|
MSK
|
[
"On examination, the patient was short - statured, with a standing height of 153.4 cm ( z score : −3.1 ); midparental height was 174.1 cm ( z score : −0.4 )."
] |
6853670
|
{'1. Case Description': 'A 28-year-old man with classic salt-wasting CAH due to 21-hydroxylase deficiency presented with subfertility. For the past 6 months, he described a minimal coital frequency of 2 or 3 times per week without the use of contraception. He had been receiving prednisone 5 mg each morning and fludrocortisone 50 μg twice daily over the last decade. He had known bilateral TARTs, first noted at age 18 and occupying 1.2% of his total testicular volume (0.38 mL of 30.68 mL) ( Fig. 1 ). A recent testicular ultrasound showed increased TART volume, now occupying 16% of his total testicular volume (5.01 mL of 32.30 mL testicular volume), and semen analysis showed azoospermia. On examination, the patient was short-statured, with a standing height of 153.4 cm ( z score: −3.1); midparental height was 174.1 cm ( z score: −0.4). Testicular volume was 25 mL bilaterally. Biochemical evaluation at 0800 before medication showed 17-hydroxyprogesterone 13,060 ng/dL (reference: 13 to 120 ng/dL), androstenedione (A4) 1025 ng/dL (reference: 26 to 125 ng/dL), ACTH 866 pg/mL (reference: 5 to 46 pg/mL), plasma renin activity (PRA) 7.1 ng/mL/h (reference: 0.6 to 4.3 ng/mL/h), FSH 1.7 U/L (reference: 1 to 11 U/L), LH 1.3 U/L (reference: 1 to 8 U/L), and total testosterone (T) 473 ng/ dL (reference: 240 to 950 ng/dL). His A4/T ratio of 2.2 (>0.5) with low LH and FSH was suggestive of a mostly adrenal origin of his T. His glucocorticoid therapy was switched from prednisone 5 mg daily to dexamethasone 250 μg at bedtime to suppress the nocturnal ACTH surge. At his 5-month follow-up visit, he reported a weight gain of 5 kg and insomnia. Physical examination revealed supraclavicular fullness with predominantly central weight gain and the presence of abdominal striae, not present on previous exam. Testicular volume was stable at 25 mL. Repeat ultrasound showed 91% decrease in total TART volume (0.47 mL) ( Fig. 1 ). Follow-up semen analysis showed a sperm count of 132 × 10 6 /mL (reference range: >14 × 10 6 /mL), with 7 × 10 6 /mL being morphologically normal (reference range: >3 × 10 6 /mL) and 35% motile (normal >39%). Biochemical evaluation showed significant improvement in CAH control, with 0800 evaluation before medication revealing 17-hydroxyprogesterone 66 ng/dL, A4 16 ng/dL, ACTH 13.5 pg/mL, PRA 11 ng/mL/h, FSH 5.4 U/L, LH 1 U/L, and T 287 ng/dL ( Table 1 ). The patient’s wife was confirmed to be pregnant 9 months after the initiation of dexamethasone and delivered a healthy full-term baby girl. CYP21A2 genotyping was performed. Our patient had a 30-kb deletion (CH-1 chimera subtype) in one allele and IVS2-13A/C>G (In2G) mutation in the second allele; his wife was negative for any known CYP21A2 variants, and his daughter was found to carry a 30-kb deletion (CH-1 chimera subtype) in one allele. Given his weight gain and insomnia, the patient’s therapy was switched to prednisone 3 mg twice daily. He lost 3 kg, and his insomnia resolved. His TART volume, parameters of semen analysis, and biochemical markers of CAH control have remained stable 2 and a half years hence, and he is currently expecting his second child.'}
|
{'1. Case Description': 'A 28-year-old man with classic salt-wasting CAH due to 21-hydroxylase deficiency presented with subfertility. For the past 6 months, he described a minimal coital frequency of 2 or 3 times per week without the use of contraception. He had been receiving prednisone 5 mg each morning and fludrocortisone 50 μg twice daily over the last decade. He had known bilateral TARTs, first noted at age 18 and occupying 1.2% of his total testicular volume (0.38 mL of 30.68 mL) ( Fig. 1 ). A recent testicular ultrasound showed increased TART volume, now occupying 16% of his total testicular volume (5.01 mL of 32.30 mL testicular volume), and semen analysis showed azoospermia. On examination, the patient was short-statured, with a standing height of 153.4 cm ( z score: −3.1); midparental height was 174.1 cm ( z score: −0.4). Testicular volume was 25 mL bilaterally. Biochemical evaluation at 0800 before medication showed 17-hydroxyprogesterone 13,060 ng/dL (reference: 13 to 120 ng/dL), androstenedione (A4) 1025 ng/dL (reference: 26 to 125 ng/dL), ACTH 866 pg/mL (reference: 5 to 46 pg/mL), plasma renin activity (PRA) 7.1 ng/mL/h (reference: 0.6 to 4.3 ng/mL/h), FSH 1.7 U/L (reference: 1 to 11 U/L), LH 1.3 U/L (reference: 1 to 8 U/L), and total testosterone (T) 473 ng/ dL (reference: 240 to 950 ng/dL). His A4/T ratio of 2.2 (>0.5) with low LH and FSH was suggestive of a mostly adrenal origin of his T. His glucocorticoid therapy was switched from prednisone 5 mg daily to dexamethasone 250 μg at bedtime to suppress the nocturnal ACTH surge. At his 5-month follow-up visit, he reported a weight gain of 5 kg and insomnia. Physical examination revealed supraclavicular fullness with predominantly central weight gain and the presence of abdominal striae, not present on previous exam. Testicular volume was stable at 25 mL. Repeat ultrasound showed 91% decrease in total TART volume (0.47 mL) ( Fig. 1 ). Follow-up semen analysis showed a sperm count of 132 × 10 6 /mL (reference range: >14 × 10 6 /mL), with 7 × 10 6 /mL being morphologically normal (reference range: >3 × 10 6 /mL) and 35% motile (normal >39%). Biochemical evaluation showed significant improvement in CAH control, with 0800 evaluation before medication revealing 17-hydroxyprogesterone 66 ng/dL, A4 16 ng/dL, ACTH 13.5 pg/mL, PRA 11 ng/mL/h, FSH 5.4 U/L, LH 1 U/L, and T 287 ng/dL ( Table 1 ). The patient’s wife was confirmed to be pregnant 9 months after the initiation of dexamethasone and delivered a healthy full-term baby girl. CYP21A2 genotyping was performed. Our patient had a 30-kb deletion (CH-1 chimera subtype) in one allele and IVS2-13A/C>G (In2G) mutation in the second allele; his wife was negative for any known CYP21A2 variants, and his daughter was found to carry a 30-kb deletion (CH-1 chimera subtype) in one allele. Given his weight gain and insomnia, the patient’s therapy was switched to prednisone 3 mg twice daily. He lost 3 kg, and his insomnia resolved. His TART volume, parameters of semen analysis, and biochemical markers of CAH control have remained stable 2 and a half years hence, and he is currently expecting his second child.'}
|
Eyes-Ears-Nose-Throat
|
EENT
|
[] |
6853670
|
{'1. Case Description': 'A 28-year-old man with classic salt-wasting CAH due to 21-hydroxylase deficiency presented with subfertility. For the past 6 months, he described a minimal coital frequency of 2 or 3 times per week without the use of contraception. He had been receiving prednisone 5 mg each morning and fludrocortisone 50 μg twice daily over the last decade. He had known bilateral TARTs, first noted at age 18 and occupying 1.2% of his total testicular volume (0.38 mL of 30.68 mL) ( Fig. 1 ). A recent testicular ultrasound showed increased TART volume, now occupying 16% of his total testicular volume (5.01 mL of 32.30 mL testicular volume), and semen analysis showed azoospermia. On examination, the patient was short-statured, with a standing height of 153.4 cm ( z score: −3.1); midparental height was 174.1 cm ( z score: −0.4). Testicular volume was 25 mL bilaterally. Biochemical evaluation at 0800 before medication showed 17-hydroxyprogesterone 13,060 ng/dL (reference: 13 to 120 ng/dL), androstenedione (A4) 1025 ng/dL (reference: 26 to 125 ng/dL), ACTH 866 pg/mL (reference: 5 to 46 pg/mL), plasma renin activity (PRA) 7.1 ng/mL/h (reference: 0.6 to 4.3 ng/mL/h), FSH 1.7 U/L (reference: 1 to 11 U/L), LH 1.3 U/L (reference: 1 to 8 U/L), and total testosterone (T) 473 ng/ dL (reference: 240 to 950 ng/dL). His A4/T ratio of 2.2 (>0.5) with low LH and FSH was suggestive of a mostly adrenal origin of his T. His glucocorticoid therapy was switched from prednisone 5 mg daily to dexamethasone 250 μg at bedtime to suppress the nocturnal ACTH surge. At his 5-month follow-up visit, he reported a weight gain of 5 kg and insomnia. Physical examination revealed supraclavicular fullness with predominantly central weight gain and the presence of abdominal striae, not present on previous exam. Testicular volume was stable at 25 mL. Repeat ultrasound showed 91% decrease in total TART volume (0.47 mL) ( Fig. 1 ). Follow-up semen analysis showed a sperm count of 132 × 10 6 /mL (reference range: >14 × 10 6 /mL), with 7 × 10 6 /mL being morphologically normal (reference range: >3 × 10 6 /mL) and 35% motile (normal >39%). Biochemical evaluation showed significant improvement in CAH control, with 0800 evaluation before medication revealing 17-hydroxyprogesterone 66 ng/dL, A4 16 ng/dL, ACTH 13.5 pg/mL, PRA 11 ng/mL/h, FSH 5.4 U/L, LH 1 U/L, and T 287 ng/dL ( Table 1 ). The patient’s wife was confirmed to be pregnant 9 months after the initiation of dexamethasone and delivered a healthy full-term baby girl. CYP21A2 genotyping was performed. Our patient had a 30-kb deletion (CH-1 chimera subtype) in one allele and IVS2-13A/C>G (In2G) mutation in the second allele; his wife was negative for any known CYP21A2 variants, and his daughter was found to carry a 30-kb deletion (CH-1 chimera subtype) in one allele. Given his weight gain and insomnia, the patient’s therapy was switched to prednisone 3 mg twice daily. He lost 3 kg, and his insomnia resolved. His TART volume, parameters of semen analysis, and biochemical markers of CAH control have remained stable 2 and a half years hence, and he is currently expecting his second child.'}
|
{'1. Case Description': 'A 28-year-old man with classic salt-wasting CAH due to 21-hydroxylase deficiency presented with subfertility. For the past 6 months, he described a minimal coital frequency of 2 or 3 times per week without the use of contraception. He had been receiving prednisone 5 mg each morning and fludrocortisone 50 μg twice daily over the last decade. He had known bilateral TARTs, first noted at age 18 and occupying 1.2% of his total testicular volume (0.38 mL of 30.68 mL) ( Fig. 1 ). A recent testicular ultrasound showed increased TART volume, now occupying 16% of his total testicular volume (5.01 mL of 32.30 mL testicular volume), and semen analysis showed azoospermia. On examination, the patient was short-statured, with a standing height of 153.4 cm ( z score: −3.1); midparental height was 174.1 cm ( z score: −0.4). Testicular volume was 25 mL bilaterally. Biochemical evaluation at 0800 before medication showed 17-hydroxyprogesterone 13,060 ng/dL (reference: 13 to 120 ng/dL), androstenedione (A4) 1025 ng/dL (reference: 26 to 125 ng/dL), ACTH 866 pg/mL (reference: 5 to 46 pg/mL), plasma renin activity (PRA) 7.1 ng/mL/h (reference: 0.6 to 4.3 ng/mL/h), FSH 1.7 U/L (reference: 1 to 11 U/L), LH 1.3 U/L (reference: 1 to 8 U/L), and total testosterone (T) 473 ng/ dL (reference: 240 to 950 ng/dL). His A4/T ratio of 2.2 (>0.5) with low LH and FSH was suggestive of a mostly adrenal origin of his T. His glucocorticoid therapy was switched from prednisone 5 mg daily to dexamethasone 250 μg at bedtime to suppress the nocturnal ACTH surge. At his 5-month follow-up visit, he reported a weight gain of 5 kg and insomnia. Physical examination revealed supraclavicular fullness with predominantly central weight gain and the presence of abdominal striae, not present on previous exam. Testicular volume was stable at 25 mL. Repeat ultrasound showed 91% decrease in total TART volume (0.47 mL) ( Fig. 1 ). Follow-up semen analysis showed a sperm count of 132 × 10 6 /mL (reference range: >14 × 10 6 /mL), with 7 × 10 6 /mL being morphologically normal (reference range: >3 × 10 6 /mL) and 35% motile (normal >39%). Biochemical evaluation showed significant improvement in CAH control, with 0800 evaluation before medication revealing 17-hydroxyprogesterone 66 ng/dL, A4 16 ng/dL, ACTH 13.5 pg/mL, PRA 11 ng/mL/h, FSH 5.4 U/L, LH 1 U/L, and T 287 ng/dL ( Table 1 ). The patient’s wife was confirmed to be pregnant 9 months after the initiation of dexamethasone and delivered a healthy full-term baby girl. CYP21A2 genotyping was performed. Our patient had a 30-kb deletion (CH-1 chimera subtype) in one allele and IVS2-13A/C>G (In2G) mutation in the second allele; his wife was negative for any known CYP21A2 variants, and his daughter was found to carry a 30-kb deletion (CH-1 chimera subtype) in one allele. Given his weight gain and insomnia, the patient’s therapy was switched to prednisone 3 mg twice daily. He lost 3 kg, and his insomnia resolved. His TART volume, parameters of semen analysis, and biochemical markers of CAH control have remained stable 2 and a half years hence, and he is currently expecting his second child.'}
|
Dermatology
|
DERM
|
[
"supraclavicular fullness with predominantly central weight gain and the presence of abdominal striae"
] |
6853670
|
{'1. Case Description': 'A 28-year-old man with classic salt-wasting CAH due to 21-hydroxylase deficiency presented with subfertility. For the past 6 months, he described a minimal coital frequency of 2 or 3 times per week without the use of contraception. He had been receiving prednisone 5 mg each morning and fludrocortisone 50 μg twice daily over the last decade. He had known bilateral TARTs, first noted at age 18 and occupying 1.2% of his total testicular volume (0.38 mL of 30.68 mL) ( Fig. 1 ). A recent testicular ultrasound showed increased TART volume, now occupying 16% of his total testicular volume (5.01 mL of 32.30 mL testicular volume), and semen analysis showed azoospermia. On examination, the patient was short-statured, with a standing height of 153.4 cm ( z score: −3.1); midparental height was 174.1 cm ( z score: −0.4). Testicular volume was 25 mL bilaterally. Biochemical evaluation at 0800 before medication showed 17-hydroxyprogesterone 13,060 ng/dL (reference: 13 to 120 ng/dL), androstenedione (A4) 1025 ng/dL (reference: 26 to 125 ng/dL), ACTH 866 pg/mL (reference: 5 to 46 pg/mL), plasma renin activity (PRA) 7.1 ng/mL/h (reference: 0.6 to 4.3 ng/mL/h), FSH 1.7 U/L (reference: 1 to 11 U/L), LH 1.3 U/L (reference: 1 to 8 U/L), and total testosterone (T) 473 ng/ dL (reference: 240 to 950 ng/dL). His A4/T ratio of 2.2 (>0.5) with low LH and FSH was suggestive of a mostly adrenal origin of his T. His glucocorticoid therapy was switched from prednisone 5 mg daily to dexamethasone 250 μg at bedtime to suppress the nocturnal ACTH surge. At his 5-month follow-up visit, he reported a weight gain of 5 kg and insomnia. Physical examination revealed supraclavicular fullness with predominantly central weight gain and the presence of abdominal striae, not present on previous exam. Testicular volume was stable at 25 mL. Repeat ultrasound showed 91% decrease in total TART volume (0.47 mL) ( Fig. 1 ). Follow-up semen analysis showed a sperm count of 132 × 10 6 /mL (reference range: >14 × 10 6 /mL), with 7 × 10 6 /mL being morphologically normal (reference range: >3 × 10 6 /mL) and 35% motile (normal >39%). Biochemical evaluation showed significant improvement in CAH control, with 0800 evaluation before medication revealing 17-hydroxyprogesterone 66 ng/dL, A4 16 ng/dL, ACTH 13.5 pg/mL, PRA 11 ng/mL/h, FSH 5.4 U/L, LH 1 U/L, and T 287 ng/dL ( Table 1 ). The patient’s wife was confirmed to be pregnant 9 months after the initiation of dexamethasone and delivered a healthy full-term baby girl. CYP21A2 genotyping was performed. Our patient had a 30-kb deletion (CH-1 chimera subtype) in one allele and IVS2-13A/C>G (In2G) mutation in the second allele; his wife was negative for any known CYP21A2 variants, and his daughter was found to carry a 30-kb deletion (CH-1 chimera subtype) in one allele. Given his weight gain and insomnia, the patient’s therapy was switched to prednisone 3 mg twice daily. He lost 3 kg, and his insomnia resolved. His TART volume, parameters of semen analysis, and biochemical markers of CAH control have remained stable 2 and a half years hence, and he is currently expecting his second child.'}
|
{'1. Case Description': 'A 28-year-old man with classic salt-wasting CAH due to 21-hydroxylase deficiency presented with subfertility. For the past 6 months, he described a minimal coital frequency of 2 or 3 times per week without the use of contraception. He had been receiving prednisone 5 mg each morning and fludrocortisone 50 μg twice daily over the last decade. He had known bilateral TARTs, first noted at age 18 and occupying 1.2% of his total testicular volume (0.38 mL of 30.68 mL) ( Fig. 1 ). A recent testicular ultrasound showed increased TART volume, now occupying 16% of his total testicular volume (5.01 mL of 32.30 mL testicular volume), and semen analysis showed azoospermia. On examination, the patient was short-statured, with a standing height of 153.4 cm ( z score: −3.1); midparental height was 174.1 cm ( z score: −0.4). Testicular volume was 25 mL bilaterally. Biochemical evaluation at 0800 before medication showed 17-hydroxyprogesterone 13,060 ng/dL (reference: 13 to 120 ng/dL), androstenedione (A4) 1025 ng/dL (reference: 26 to 125 ng/dL), ACTH 866 pg/mL (reference: 5 to 46 pg/mL), plasma renin activity (PRA) 7.1 ng/mL/h (reference: 0.6 to 4.3 ng/mL/h), FSH 1.7 U/L (reference: 1 to 11 U/L), LH 1.3 U/L (reference: 1 to 8 U/L), and total testosterone (T) 473 ng/ dL (reference: 240 to 950 ng/dL). His A4/T ratio of 2.2 (>0.5) with low LH and FSH was suggestive of a mostly adrenal origin of his T. His glucocorticoid therapy was switched from prednisone 5 mg daily to dexamethasone 250 μg at bedtime to suppress the nocturnal ACTH surge. At his 5-month follow-up visit, he reported a weight gain of 5 kg and insomnia. Physical examination revealed supraclavicular fullness with predominantly central weight gain and the presence of abdominal striae, not present on previous exam. Testicular volume was stable at 25 mL. Repeat ultrasound showed 91% decrease in total TART volume (0.47 mL) ( Fig. 1 ). Follow-up semen analysis showed a sperm count of 132 × 10 6 /mL (reference range: >14 × 10 6 /mL), with 7 × 10 6 /mL being morphologically normal (reference range: >3 × 10 6 /mL) and 35% motile (normal >39%). Biochemical evaluation showed significant improvement in CAH control, with 0800 evaluation before medication revealing 17-hydroxyprogesterone 66 ng/dL, A4 16 ng/dL, ACTH 13.5 pg/mL, PRA 11 ng/mL/h, FSH 5.4 U/L, LH 1 U/L, and T 287 ng/dL ( Table 1 ). The patient’s wife was confirmed to be pregnant 9 months after the initiation of dexamethasone and delivered a healthy full-term baby girl. CYP21A2 genotyping was performed. Our patient had a 30-kb deletion (CH-1 chimera subtype) in one allele and IVS2-13A/C>G (In2G) mutation in the second allele; his wife was negative for any known CYP21A2 variants, and his daughter was found to carry a 30-kb deletion (CH-1 chimera subtype) in one allele. Given his weight gain and insomnia, the patient’s therapy was switched to prednisone 3 mg twice daily. He lost 3 kg, and his insomnia resolved. His TART volume, parameters of semen analysis, and biochemical markers of CAH control have remained stable 2 and a half years hence, and he is currently expecting his second child.'}
|
Pregnancy
|
Pregnancy
|
[] |
6853670
|
{'1. Case Description': 'A 28-year-old man with classic salt-wasting CAH due to 21-hydroxylase deficiency presented with subfertility. For the past 6 months, he described a minimal coital frequency of 2 or 3 times per week without the use of contraception. He had been receiving prednisone 5 mg each morning and fludrocortisone 50 μg twice daily over the last decade. He had known bilateral TARTs, first noted at age 18 and occupying 1.2% of his total testicular volume (0.38 mL of 30.68 mL) ( Fig. 1 ). A recent testicular ultrasound showed increased TART volume, now occupying 16% of his total testicular volume (5.01 mL of 32.30 mL testicular volume), and semen analysis showed azoospermia. On examination, the patient was short-statured, with a standing height of 153.4 cm ( z score: −3.1); midparental height was 174.1 cm ( z score: −0.4). Testicular volume was 25 mL bilaterally. Biochemical evaluation at 0800 before medication showed 17-hydroxyprogesterone 13,060 ng/dL (reference: 13 to 120 ng/dL), androstenedione (A4) 1025 ng/dL (reference: 26 to 125 ng/dL), ACTH 866 pg/mL (reference: 5 to 46 pg/mL), plasma renin activity (PRA) 7.1 ng/mL/h (reference: 0.6 to 4.3 ng/mL/h), FSH 1.7 U/L (reference: 1 to 11 U/L), LH 1.3 U/L (reference: 1 to 8 U/L), and total testosterone (T) 473 ng/ dL (reference: 240 to 950 ng/dL). His A4/T ratio of 2.2 (>0.5) with low LH and FSH was suggestive of a mostly adrenal origin of his T. His glucocorticoid therapy was switched from prednisone 5 mg daily to dexamethasone 250 μg at bedtime to suppress the nocturnal ACTH surge. At his 5-month follow-up visit, he reported a weight gain of 5 kg and insomnia. Physical examination revealed supraclavicular fullness with predominantly central weight gain and the presence of abdominal striae, not present on previous exam. Testicular volume was stable at 25 mL. Repeat ultrasound showed 91% decrease in total TART volume (0.47 mL) ( Fig. 1 ). Follow-up semen analysis showed a sperm count of 132 × 10 6 /mL (reference range: >14 × 10 6 /mL), with 7 × 10 6 /mL being morphologically normal (reference range: >3 × 10 6 /mL) and 35% motile (normal >39%). Biochemical evaluation showed significant improvement in CAH control, with 0800 evaluation before medication revealing 17-hydroxyprogesterone 66 ng/dL, A4 16 ng/dL, ACTH 13.5 pg/mL, PRA 11 ng/mL/h, FSH 5.4 U/L, LH 1 U/L, and T 287 ng/dL ( Table 1 ). The patient’s wife was confirmed to be pregnant 9 months after the initiation of dexamethasone and delivered a healthy full-term baby girl. CYP21A2 genotyping was performed. Our patient had a 30-kb deletion (CH-1 chimera subtype) in one allele and IVS2-13A/C>G (In2G) mutation in the second allele; his wife was negative for any known CYP21A2 variants, and his daughter was found to carry a 30-kb deletion (CH-1 chimera subtype) in one allele. Given his weight gain and insomnia, the patient’s therapy was switched to prednisone 3 mg twice daily. He lost 3 kg, and his insomnia resolved. His TART volume, parameters of semen analysis, and biochemical markers of CAH control have remained stable 2 and a half years hence, and he is currently expecting his second child.'}
|
{'1. Case Description': 'A 28-year-old man with classic salt-wasting CAH due to 21-hydroxylase deficiency presented with subfertility. For the past 6 months, he described a minimal coital frequency of 2 or 3 times per week without the use of contraception. He had been receiving prednisone 5 mg each morning and fludrocortisone 50 μg twice daily over the last decade. He had known bilateral TARTs, first noted at age 18 and occupying 1.2% of his total testicular volume (0.38 mL of 30.68 mL) ( Fig. 1 ). A recent testicular ultrasound showed increased TART volume, now occupying 16% of his total testicular volume (5.01 mL of 32.30 mL testicular volume), and semen analysis showed azoospermia. On examination, the patient was short-statured, with a standing height of 153.4 cm ( z score: −3.1); midparental height was 174.1 cm ( z score: −0.4). Testicular volume was 25 mL bilaterally. Biochemical evaluation at 0800 before medication showed 17-hydroxyprogesterone 13,060 ng/dL (reference: 13 to 120 ng/dL), androstenedione (A4) 1025 ng/dL (reference: 26 to 125 ng/dL), ACTH 866 pg/mL (reference: 5 to 46 pg/mL), plasma renin activity (PRA) 7.1 ng/mL/h (reference: 0.6 to 4.3 ng/mL/h), FSH 1.7 U/L (reference: 1 to 11 U/L), LH 1.3 U/L (reference: 1 to 8 U/L), and total testosterone (T) 473 ng/ dL (reference: 240 to 950 ng/dL). His A4/T ratio of 2.2 (>0.5) with low LH and FSH was suggestive of a mostly adrenal origin of his T. His glucocorticoid therapy was switched from prednisone 5 mg daily to dexamethasone 250 μg at bedtime to suppress the nocturnal ACTH surge. At his 5-month follow-up visit, he reported a weight gain of 5 kg and insomnia. Physical examination revealed supraclavicular fullness with predominantly central weight gain and the presence of abdominal striae, not present on previous exam. Testicular volume was stable at 25 mL. Repeat ultrasound showed 91% decrease in total TART volume (0.47 mL) ( Fig. 1 ). Follow-up semen analysis showed a sperm count of 132 × 10 6 /mL (reference range: >14 × 10 6 /mL), with 7 × 10 6 /mL being morphologically normal (reference range: >3 × 10 6 /mL) and 35% motile (normal >39%). Biochemical evaluation showed significant improvement in CAH control, with 0800 evaluation before medication revealing 17-hydroxyprogesterone 66 ng/dL, A4 16 ng/dL, ACTH 13.5 pg/mL, PRA 11 ng/mL/h, FSH 5.4 U/L, LH 1 U/L, and T 287 ng/dL ( Table 1 ). The patient’s wife was confirmed to be pregnant 9 months after the initiation of dexamethasone and delivered a healthy full-term baby girl. CYP21A2 genotyping was performed. Our patient had a 30-kb deletion (CH-1 chimera subtype) in one allele and IVS2-13A/C>G (In2G) mutation in the second allele; his wife was negative for any known CYP21A2 variants, and his daughter was found to carry a 30-kb deletion (CH-1 chimera subtype) in one allele. Given his weight gain and insomnia, the patient’s therapy was switched to prednisone 3 mg twice daily. He lost 3 kg, and his insomnia resolved. His TART volume, parameters of semen analysis, and biochemical markers of CAH control have remained stable 2 and a half years hence, and he is currently expecting his second child.'}
|
Lymphatic-System
|
LYMPH
|
[] |
6853670
|
{'1. Case Description': 'A 28-year-old man with classic salt-wasting CAH due to 21-hydroxylase deficiency presented with subfertility. For the past 6 months, he described a minimal coital frequency of 2 or 3 times per week without the use of contraception. He had been receiving prednisone 5 mg each morning and fludrocortisone 50 μg twice daily over the last decade. He had known bilateral TARTs, first noted at age 18 and occupying 1.2% of his total testicular volume (0.38 mL of 30.68 mL) ( Fig. 1 ). A recent testicular ultrasound showed increased TART volume, now occupying 16% of his total testicular volume (5.01 mL of 32.30 mL testicular volume), and semen analysis showed azoospermia. On examination, the patient was short-statured, with a standing height of 153.4 cm ( z score: −3.1); midparental height was 174.1 cm ( z score: −0.4). Testicular volume was 25 mL bilaterally. Biochemical evaluation at 0800 before medication showed 17-hydroxyprogesterone 13,060 ng/dL (reference: 13 to 120 ng/dL), androstenedione (A4) 1025 ng/dL (reference: 26 to 125 ng/dL), ACTH 866 pg/mL (reference: 5 to 46 pg/mL), plasma renin activity (PRA) 7.1 ng/mL/h (reference: 0.6 to 4.3 ng/mL/h), FSH 1.7 U/L (reference: 1 to 11 U/L), LH 1.3 U/L (reference: 1 to 8 U/L), and total testosterone (T) 473 ng/ dL (reference: 240 to 950 ng/dL). His A4/T ratio of 2.2 (>0.5) with low LH and FSH was suggestive of a mostly adrenal origin of his T. His glucocorticoid therapy was switched from prednisone 5 mg daily to dexamethasone 250 μg at bedtime to suppress the nocturnal ACTH surge. At his 5-month follow-up visit, he reported a weight gain of 5 kg and insomnia. Physical examination revealed supraclavicular fullness with predominantly central weight gain and the presence of abdominal striae, not present on previous exam. Testicular volume was stable at 25 mL. Repeat ultrasound showed 91% decrease in total TART volume (0.47 mL) ( Fig. 1 ). Follow-up semen analysis showed a sperm count of 132 × 10 6 /mL (reference range: >14 × 10 6 /mL), with 7 × 10 6 /mL being morphologically normal (reference range: >3 × 10 6 /mL) and 35% motile (normal >39%). Biochemical evaluation showed significant improvement in CAH control, with 0800 evaluation before medication revealing 17-hydroxyprogesterone 66 ng/dL, A4 16 ng/dL, ACTH 13.5 pg/mL, PRA 11 ng/mL/h, FSH 5.4 U/L, LH 1 U/L, and T 287 ng/dL ( Table 1 ). The patient’s wife was confirmed to be pregnant 9 months after the initiation of dexamethasone and delivered a healthy full-term baby girl. CYP21A2 genotyping was performed. Our patient had a 30-kb deletion (CH-1 chimera subtype) in one allele and IVS2-13A/C>G (In2G) mutation in the second allele; his wife was negative for any known CYP21A2 variants, and his daughter was found to carry a 30-kb deletion (CH-1 chimera subtype) in one allele. Given his weight gain and insomnia, the patient’s therapy was switched to prednisone 3 mg twice daily. He lost 3 kg, and his insomnia resolved. His TART volume, parameters of semen analysis, and biochemical markers of CAH control have remained stable 2 and a half years hence, and he is currently expecting his second child.'}
|
{'1. Case Description': 'A 28-year-old man with classic salt-wasting CAH due to 21-hydroxylase deficiency presented with subfertility. For the past 6 months, he described a minimal coital frequency of 2 or 3 times per week without the use of contraception. He had been receiving prednisone 5 mg each morning and fludrocortisone 50 μg twice daily over the last decade. He had known bilateral TARTs, first noted at age 18 and occupying 1.2% of his total testicular volume (0.38 mL of 30.68 mL) ( Fig. 1 ). A recent testicular ultrasound showed increased TART volume, now occupying 16% of his total testicular volume (5.01 mL of 32.30 mL testicular volume), and semen analysis showed azoospermia. On examination, the patient was short-statured, with a standing height of 153.4 cm ( z score: −3.1); midparental height was 174.1 cm ( z score: −0.4). Testicular volume was 25 mL bilaterally. Biochemical evaluation at 0800 before medication showed 17-hydroxyprogesterone 13,060 ng/dL (reference: 13 to 120 ng/dL), androstenedione (A4) 1025 ng/dL (reference: 26 to 125 ng/dL), ACTH 866 pg/mL (reference: 5 to 46 pg/mL), plasma renin activity (PRA) 7.1 ng/mL/h (reference: 0.6 to 4.3 ng/mL/h), FSH 1.7 U/L (reference: 1 to 11 U/L), LH 1.3 U/L (reference: 1 to 8 U/L), and total testosterone (T) 473 ng/ dL (reference: 240 to 950 ng/dL). His A4/T ratio of 2.2 (>0.5) with low LH and FSH was suggestive of a mostly adrenal origin of his T. His glucocorticoid therapy was switched from prednisone 5 mg daily to dexamethasone 250 μg at bedtime to suppress the nocturnal ACTH surge. At his 5-month follow-up visit, he reported a weight gain of 5 kg and insomnia. Physical examination revealed supraclavicular fullness with predominantly central weight gain and the presence of abdominal striae, not present on previous exam. Testicular volume was stable at 25 mL. Repeat ultrasound showed 91% decrease in total TART volume (0.47 mL) ( Fig. 1 ). Follow-up semen analysis showed a sperm count of 132 × 10 6 /mL (reference range: >14 × 10 6 /mL), with 7 × 10 6 /mL being morphologically normal (reference range: >3 × 10 6 /mL) and 35% motile (normal >39%). Biochemical evaluation showed significant improvement in CAH control, with 0800 evaluation before medication revealing 17-hydroxyprogesterone 66 ng/dL, A4 16 ng/dL, ACTH 13.5 pg/mL, PRA 11 ng/mL/h, FSH 5.4 U/L, LH 1 U/L, and T 287 ng/dL ( Table 1 ). The patient’s wife was confirmed to be pregnant 9 months after the initiation of dexamethasone and delivered a healthy full-term baby girl. CYP21A2 genotyping was performed. Our patient had a 30-kb deletion (CH-1 chimera subtype) in one allele and IVS2-13A/C>G (In2G) mutation in the second allele; his wife was negative for any known CYP21A2 variants, and his daughter was found to carry a 30-kb deletion (CH-1 chimera subtype) in one allele. Given his weight gain and insomnia, the patient’s therapy was switched to prednisone 3 mg twice daily. He lost 3 kg, and his insomnia resolved. His TART volume, parameters of semen analysis, and biochemical markers of CAH control have remained stable 2 and a half years hence, and he is currently expecting his second child.'}
|
Age-at-Presentation
|
Age (at case presentation)
|
[
"28 - year - old"
] |
6853670
|
{'1. Case Description': 'A 28-year-old man with classic salt-wasting CAH due to 21-hydroxylase deficiency presented with subfertility. For the past 6 months, he described a minimal coital frequency of 2 or 3 times per week without the use of contraception. He had been receiving prednisone 5 mg each morning and fludrocortisone 50 μg twice daily over the last decade. He had known bilateral TARTs, first noted at age 18 and occupying 1.2% of his total testicular volume (0.38 mL of 30.68 mL) ( Fig. 1 ). A recent testicular ultrasound showed increased TART volume, now occupying 16% of his total testicular volume (5.01 mL of 32.30 mL testicular volume), and semen analysis showed azoospermia. On examination, the patient was short-statured, with a standing height of 153.4 cm ( z score: −3.1); midparental height was 174.1 cm ( z score: −0.4). Testicular volume was 25 mL bilaterally. Biochemical evaluation at 0800 before medication showed 17-hydroxyprogesterone 13,060 ng/dL (reference: 13 to 120 ng/dL), androstenedione (A4) 1025 ng/dL (reference: 26 to 125 ng/dL), ACTH 866 pg/mL (reference: 5 to 46 pg/mL), plasma renin activity (PRA) 7.1 ng/mL/h (reference: 0.6 to 4.3 ng/mL/h), FSH 1.7 U/L (reference: 1 to 11 U/L), LH 1.3 U/L (reference: 1 to 8 U/L), and total testosterone (T) 473 ng/ dL (reference: 240 to 950 ng/dL). His A4/T ratio of 2.2 (>0.5) with low LH and FSH was suggestive of a mostly adrenal origin of his T. His glucocorticoid therapy was switched from prednisone 5 mg daily to dexamethasone 250 μg at bedtime to suppress the nocturnal ACTH surge. At his 5-month follow-up visit, he reported a weight gain of 5 kg and insomnia. Physical examination revealed supraclavicular fullness with predominantly central weight gain and the presence of abdominal striae, not present on previous exam. Testicular volume was stable at 25 mL. Repeat ultrasound showed 91% decrease in total TART volume (0.47 mL) ( Fig. 1 ). Follow-up semen analysis showed a sperm count of 132 × 10 6 /mL (reference range: >14 × 10 6 /mL), with 7 × 10 6 /mL being morphologically normal (reference range: >3 × 10 6 /mL) and 35% motile (normal >39%). Biochemical evaluation showed significant improvement in CAH control, with 0800 evaluation before medication revealing 17-hydroxyprogesterone 66 ng/dL, A4 16 ng/dL, ACTH 13.5 pg/mL, PRA 11 ng/mL/h, FSH 5.4 U/L, LH 1 U/L, and T 287 ng/dL ( Table 1 ). The patient’s wife was confirmed to be pregnant 9 months after the initiation of dexamethasone and delivered a healthy full-term baby girl. CYP21A2 genotyping was performed. Our patient had a 30-kb deletion (CH-1 chimera subtype) in one allele and IVS2-13A/C>G (In2G) mutation in the second allele; his wife was negative for any known CYP21A2 variants, and his daughter was found to carry a 30-kb deletion (CH-1 chimera subtype) in one allele. Given his weight gain and insomnia, the patient’s therapy was switched to prednisone 3 mg twice daily. He lost 3 kg, and his insomnia resolved. His TART volume, parameters of semen analysis, and biochemical markers of CAH control have remained stable 2 and a half years hence, and he is currently expecting his second child.'}
|
{'1. Case Description': 'A 28-year-old man with classic salt-wasting CAH due to 21-hydroxylase deficiency presented with subfertility. For the past 6 months, he described a minimal coital frequency of 2 or 3 times per week without the use of contraception. He had been receiving prednisone 5 mg each morning and fludrocortisone 50 μg twice daily over the last decade. He had known bilateral TARTs, first noted at age 18 and occupying 1.2% of his total testicular volume (0.38 mL of 30.68 mL) ( Fig. 1 ). A recent testicular ultrasound showed increased TART volume, now occupying 16% of his total testicular volume (5.01 mL of 32.30 mL testicular volume), and semen analysis showed azoospermia. On examination, the patient was short-statured, with a standing height of 153.4 cm ( z score: −3.1); midparental height was 174.1 cm ( z score: −0.4). Testicular volume was 25 mL bilaterally. Biochemical evaluation at 0800 before medication showed 17-hydroxyprogesterone 13,060 ng/dL (reference: 13 to 120 ng/dL), androstenedione (A4) 1025 ng/dL (reference: 26 to 125 ng/dL), ACTH 866 pg/mL (reference: 5 to 46 pg/mL), plasma renin activity (PRA) 7.1 ng/mL/h (reference: 0.6 to 4.3 ng/mL/h), FSH 1.7 U/L (reference: 1 to 11 U/L), LH 1.3 U/L (reference: 1 to 8 U/L), and total testosterone (T) 473 ng/ dL (reference: 240 to 950 ng/dL). His A4/T ratio of 2.2 (>0.5) with low LH and FSH was suggestive of a mostly adrenal origin of his T. His glucocorticoid therapy was switched from prednisone 5 mg daily to dexamethasone 250 μg at bedtime to suppress the nocturnal ACTH surge. At his 5-month follow-up visit, he reported a weight gain of 5 kg and insomnia. Physical examination revealed supraclavicular fullness with predominantly central weight gain and the presence of abdominal striae, not present on previous exam. Testicular volume was stable at 25 mL. Repeat ultrasound showed 91% decrease in total TART volume (0.47 mL) ( Fig. 1 ). Follow-up semen analysis showed a sperm count of 132 × 10 6 /mL (reference range: >14 × 10 6 /mL), with 7 × 10 6 /mL being morphologically normal (reference range: >3 × 10 6 /mL) and 35% motile (normal >39%). Biochemical evaluation showed significant improvement in CAH control, with 0800 evaluation before medication revealing 17-hydroxyprogesterone 66 ng/dL, A4 16 ng/dL, ACTH 13.5 pg/mL, PRA 11 ng/mL/h, FSH 5.4 U/L, LH 1 U/L, and T 287 ng/dL ( Table 1 ). The patient’s wife was confirmed to be pregnant 9 months after the initiation of dexamethasone and delivered a healthy full-term baby girl. CYP21A2 genotyping was performed. Our patient had a 30-kb deletion (CH-1 chimera subtype) in one allele and IVS2-13A/C>G (In2G) mutation in the second allele; his wife was negative for any known CYP21A2 variants, and his daughter was found to carry a 30-kb deletion (CH-1 chimera subtype) in one allele. Given his weight gain and insomnia, the patient’s therapy was switched to prednisone 3 mg twice daily. He lost 3 kg, and his insomnia resolved. His TART volume, parameters of semen analysis, and biochemical markers of CAH control have remained stable 2 and a half years hence, and he is currently expecting his second child.'}
|
Age-of-Onset
|
Age (of onset)
|
[] |
6853670
|
{'1. Case Description': 'A 28-year-old man with classic salt-wasting CAH due to 21-hydroxylase deficiency presented with subfertility. For the past 6 months, he described a minimal coital frequency of 2 or 3 times per week without the use of contraception. He had been receiving prednisone 5 mg each morning and fludrocortisone 50 μg twice daily over the last decade. He had known bilateral TARTs, first noted at age 18 and occupying 1.2% of his total testicular volume (0.38 mL of 30.68 mL) ( Fig. 1 ). A recent testicular ultrasound showed increased TART volume, now occupying 16% of his total testicular volume (5.01 mL of 32.30 mL testicular volume), and semen analysis showed azoospermia. On examination, the patient was short-statured, with a standing height of 153.4 cm ( z score: −3.1); midparental height was 174.1 cm ( z score: −0.4). Testicular volume was 25 mL bilaterally. Biochemical evaluation at 0800 before medication showed 17-hydroxyprogesterone 13,060 ng/dL (reference: 13 to 120 ng/dL), androstenedione (A4) 1025 ng/dL (reference: 26 to 125 ng/dL), ACTH 866 pg/mL (reference: 5 to 46 pg/mL), plasma renin activity (PRA) 7.1 ng/mL/h (reference: 0.6 to 4.3 ng/mL/h), FSH 1.7 U/L (reference: 1 to 11 U/L), LH 1.3 U/L (reference: 1 to 8 U/L), and total testosterone (T) 473 ng/ dL (reference: 240 to 950 ng/dL). His A4/T ratio of 2.2 (>0.5) with low LH and FSH was suggestive of a mostly adrenal origin of his T. His glucocorticoid therapy was switched from prednisone 5 mg daily to dexamethasone 250 μg at bedtime to suppress the nocturnal ACTH surge. At his 5-month follow-up visit, he reported a weight gain of 5 kg and insomnia. Physical examination revealed supraclavicular fullness with predominantly central weight gain and the presence of abdominal striae, not present on previous exam. Testicular volume was stable at 25 mL. Repeat ultrasound showed 91% decrease in total TART volume (0.47 mL) ( Fig. 1 ). Follow-up semen analysis showed a sperm count of 132 × 10 6 /mL (reference range: >14 × 10 6 /mL), with 7 × 10 6 /mL being morphologically normal (reference range: >3 × 10 6 /mL) and 35% motile (normal >39%). Biochemical evaluation showed significant improvement in CAH control, with 0800 evaluation before medication revealing 17-hydroxyprogesterone 66 ng/dL, A4 16 ng/dL, ACTH 13.5 pg/mL, PRA 11 ng/mL/h, FSH 5.4 U/L, LH 1 U/L, and T 287 ng/dL ( Table 1 ). The patient’s wife was confirmed to be pregnant 9 months after the initiation of dexamethasone and delivered a healthy full-term baby girl. CYP21A2 genotyping was performed. Our patient had a 30-kb deletion (CH-1 chimera subtype) in one allele and IVS2-13A/C>G (In2G) mutation in the second allele; his wife was negative for any known CYP21A2 variants, and his daughter was found to carry a 30-kb deletion (CH-1 chimera subtype) in one allele. Given his weight gain and insomnia, the patient’s therapy was switched to prednisone 3 mg twice daily. He lost 3 kg, and his insomnia resolved. His TART volume, parameters of semen analysis, and biochemical markers of CAH control have remained stable 2 and a half years hence, and he is currently expecting his second child.'}
|
{'1. Case Description': 'A 28-year-old man with classic salt-wasting CAH due to 21-hydroxylase deficiency presented with subfertility. For the past 6 months, he described a minimal coital frequency of 2 or 3 times per week without the use of contraception. He had been receiving prednisone 5 mg each morning and fludrocortisone 50 μg twice daily over the last decade. He had known bilateral TARTs, first noted at age 18 and occupying 1.2% of his total testicular volume (0.38 mL of 30.68 mL) ( Fig. 1 ). A recent testicular ultrasound showed increased TART volume, now occupying 16% of his total testicular volume (5.01 mL of 32.30 mL testicular volume), and semen analysis showed azoospermia. On examination, the patient was short-statured, with a standing height of 153.4 cm ( z score: −3.1); midparental height was 174.1 cm ( z score: −0.4). Testicular volume was 25 mL bilaterally. Biochemical evaluation at 0800 before medication showed 17-hydroxyprogesterone 13,060 ng/dL (reference: 13 to 120 ng/dL), androstenedione (A4) 1025 ng/dL (reference: 26 to 125 ng/dL), ACTH 866 pg/mL (reference: 5 to 46 pg/mL), plasma renin activity (PRA) 7.1 ng/mL/h (reference: 0.6 to 4.3 ng/mL/h), FSH 1.7 U/L (reference: 1 to 11 U/L), LH 1.3 U/L (reference: 1 to 8 U/L), and total testosterone (T) 473 ng/ dL (reference: 240 to 950 ng/dL). His A4/T ratio of 2.2 (>0.5) with low LH and FSH was suggestive of a mostly adrenal origin of his T. His glucocorticoid therapy was switched from prednisone 5 mg daily to dexamethasone 250 μg at bedtime to suppress the nocturnal ACTH surge. At his 5-month follow-up visit, he reported a weight gain of 5 kg and insomnia. Physical examination revealed supraclavicular fullness with predominantly central weight gain and the presence of abdominal striae, not present on previous exam. Testicular volume was stable at 25 mL. Repeat ultrasound showed 91% decrease in total TART volume (0.47 mL) ( Fig. 1 ). Follow-up semen analysis showed a sperm count of 132 × 10 6 /mL (reference range: >14 × 10 6 /mL), with 7 × 10 6 /mL being morphologically normal (reference range: >3 × 10 6 /mL) and 35% motile (normal >39%). Biochemical evaluation showed significant improvement in CAH control, with 0800 evaluation before medication revealing 17-hydroxyprogesterone 66 ng/dL, A4 16 ng/dL, ACTH 13.5 pg/mL, PRA 11 ng/mL/h, FSH 5.4 U/L, LH 1 U/L, and T 287 ng/dL ( Table 1 ). The patient’s wife was confirmed to be pregnant 9 months after the initiation of dexamethasone and delivered a healthy full-term baby girl. CYP21A2 genotyping was performed. Our patient had a 30-kb deletion (CH-1 chimera subtype) in one allele and IVS2-13A/C>G (In2G) mutation in the second allele; his wife was negative for any known CYP21A2 variants, and his daughter was found to carry a 30-kb deletion (CH-1 chimera subtype) in one allele. Given his weight gain and insomnia, the patient’s therapy was switched to prednisone 3 mg twice daily. He lost 3 kg, and his insomnia resolved. His TART volume, parameters of semen analysis, and biochemical markers of CAH control have remained stable 2 and a half years hence, and he is currently expecting his second child.'}
|
Confirmed-Diagnosis-IEM
|
Confirmed_Diagnosis(IEM)
|
[
"with classic salt - wasting CAH due to 21 - hydroxylase deficiency"
] |
6853670
|
{'1. Case Description': 'A 28-year-old man with classic salt-wasting CAH due to 21-hydroxylase deficiency presented with subfertility. For the past 6 months, he described a minimal coital frequency of 2 or 3 times per week without the use of contraception. He had been receiving prednisone 5 mg each morning and fludrocortisone 50 μg twice daily over the last decade. He had known bilateral TARTs, first noted at age 18 and occupying 1.2% of his total testicular volume (0.38 mL of 30.68 mL) ( Fig. 1 ). A recent testicular ultrasound showed increased TART volume, now occupying 16% of his total testicular volume (5.01 mL of 32.30 mL testicular volume), and semen analysis showed azoospermia. On examination, the patient was short-statured, with a standing height of 153.4 cm ( z score: −3.1); midparental height was 174.1 cm ( z score: −0.4). Testicular volume was 25 mL bilaterally. Biochemical evaluation at 0800 before medication showed 17-hydroxyprogesterone 13,060 ng/dL (reference: 13 to 120 ng/dL), androstenedione (A4) 1025 ng/dL (reference: 26 to 125 ng/dL), ACTH 866 pg/mL (reference: 5 to 46 pg/mL), plasma renin activity (PRA) 7.1 ng/mL/h (reference: 0.6 to 4.3 ng/mL/h), FSH 1.7 U/L (reference: 1 to 11 U/L), LH 1.3 U/L (reference: 1 to 8 U/L), and total testosterone (T) 473 ng/ dL (reference: 240 to 950 ng/dL). His A4/T ratio of 2.2 (>0.5) with low LH and FSH was suggestive of a mostly adrenal origin of his T. His glucocorticoid therapy was switched from prednisone 5 mg daily to dexamethasone 250 μg at bedtime to suppress the nocturnal ACTH surge. At his 5-month follow-up visit, he reported a weight gain of 5 kg and insomnia. Physical examination revealed supraclavicular fullness with predominantly central weight gain and the presence of abdominal striae, not present on previous exam. Testicular volume was stable at 25 mL. Repeat ultrasound showed 91% decrease in total TART volume (0.47 mL) ( Fig. 1 ). Follow-up semen analysis showed a sperm count of 132 × 10 6 /mL (reference range: >14 × 10 6 /mL), with 7 × 10 6 /mL being morphologically normal (reference range: >3 × 10 6 /mL) and 35% motile (normal >39%). Biochemical evaluation showed significant improvement in CAH control, with 0800 evaluation before medication revealing 17-hydroxyprogesterone 66 ng/dL, A4 16 ng/dL, ACTH 13.5 pg/mL, PRA 11 ng/mL/h, FSH 5.4 U/L, LH 1 U/L, and T 287 ng/dL ( Table 1 ). The patient’s wife was confirmed to be pregnant 9 months after the initiation of dexamethasone and delivered a healthy full-term baby girl. CYP21A2 genotyping was performed. Our patient had a 30-kb deletion (CH-1 chimera subtype) in one allele and IVS2-13A/C>G (In2G) mutation in the second allele; his wife was negative for any known CYP21A2 variants, and his daughter was found to carry a 30-kb deletion (CH-1 chimera subtype) in one allele. Given his weight gain and insomnia, the patient’s therapy was switched to prednisone 3 mg twice daily. He lost 3 kg, and his insomnia resolved. His TART volume, parameters of semen analysis, and biochemical markers of CAH control have remained stable 2 and a half years hence, and he is currently expecting his second child.'}
|
{'1. Case Description': 'A 28-year-old man with classic salt-wasting CAH due to 21-hydroxylase deficiency presented with subfertility. For the past 6 months, he described a minimal coital frequency of 2 or 3 times per week without the use of contraception. He had been receiving prednisone 5 mg each morning and fludrocortisone 50 μg twice daily over the last decade. He had known bilateral TARTs, first noted at age 18 and occupying 1.2% of his total testicular volume (0.38 mL of 30.68 mL) ( Fig. 1 ). A recent testicular ultrasound showed increased TART volume, now occupying 16% of his total testicular volume (5.01 mL of 32.30 mL testicular volume), and semen analysis showed azoospermia. On examination, the patient was short-statured, with a standing height of 153.4 cm ( z score: −3.1); midparental height was 174.1 cm ( z score: −0.4). Testicular volume was 25 mL bilaterally. Biochemical evaluation at 0800 before medication showed 17-hydroxyprogesterone 13,060 ng/dL (reference: 13 to 120 ng/dL), androstenedione (A4) 1025 ng/dL (reference: 26 to 125 ng/dL), ACTH 866 pg/mL (reference: 5 to 46 pg/mL), plasma renin activity (PRA) 7.1 ng/mL/h (reference: 0.6 to 4.3 ng/mL/h), FSH 1.7 U/L (reference: 1 to 11 U/L), LH 1.3 U/L (reference: 1 to 8 U/L), and total testosterone (T) 473 ng/ dL (reference: 240 to 950 ng/dL). His A4/T ratio of 2.2 (>0.5) with low LH and FSH was suggestive of a mostly adrenal origin of his T. His glucocorticoid therapy was switched from prednisone 5 mg daily to dexamethasone 250 μg at bedtime to suppress the nocturnal ACTH surge. At his 5-month follow-up visit, he reported a weight gain of 5 kg and insomnia. Physical examination revealed supraclavicular fullness with predominantly central weight gain and the presence of abdominal striae, not present on previous exam. Testicular volume was stable at 25 mL. Repeat ultrasound showed 91% decrease in total TART volume (0.47 mL) ( Fig. 1 ). Follow-up semen analysis showed a sperm count of 132 × 10 6 /mL (reference range: >14 × 10 6 /mL), with 7 × 10 6 /mL being morphologically normal (reference range: >3 × 10 6 /mL) and 35% motile (normal >39%). Biochemical evaluation showed significant improvement in CAH control, with 0800 evaluation before medication revealing 17-hydroxyprogesterone 66 ng/dL, A4 16 ng/dL, ACTH 13.5 pg/mL, PRA 11 ng/mL/h, FSH 5.4 U/L, LH 1 U/L, and T 287 ng/dL ( Table 1 ). The patient’s wife was confirmed to be pregnant 9 months after the initiation of dexamethasone and delivered a healthy full-term baby girl. CYP21A2 genotyping was performed. Our patient had a 30-kb deletion (CH-1 chimera subtype) in one allele and IVS2-13A/C>G (In2G) mutation in the second allele; his wife was negative for any known CYP21A2 variants, and his daughter was found to carry a 30-kb deletion (CH-1 chimera subtype) in one allele. Given his weight gain and insomnia, the patient’s therapy was switched to prednisone 3 mg twice daily. He lost 3 kg, and his insomnia resolved. His TART volume, parameters of semen analysis, and biochemical markers of CAH control have remained stable 2 and a half years hence, and he is currently expecting his second child.'}
|
IEM-Treatment
|
IEM_Treatment
|
[
"He had been receiving prednisone 5 mg each morning and fludrocortisone 50 μg twice daily over the last decade",
"His glucocorticoid therapy was switched from prednisone 5 mg daily to dexamethasone 250 μg at bedtime to suppress the nocturnal ACTH surge ."
] |
6340697
|
{'CASE': 'A 32-year-old woman with Turner syndrome (143 cm/49 kg, body surface area 1.37 m 2 ) was admitted to Kyungpook National University Hospital center with complaint of sudden-onset back pain. She had been diagnosed with Turner syndrome twenty years prior following examination for her short stature. She was regularly treated with hormone replacement therapy as an outpatient of the obstetrics and gynecology. She felt well, worked as a kindergarten teacher, and was unmarried. On admission, her initial systolic blood pressure and heart rate were 131 mmHg and 68 beats per minute, respectively. Her blood pressures were almost equal in the upper and lower extremities. Her initial hemoglobin level was 11.8 g/dL, and electrocardiography revealed a normal sinus rhythm. An initial computed tomography (CT) scan revealed intimal dissection on aortic isthmus level and a dissected flap extending from the left subclavian artery to the descending aorta. An elongated transverse aortic arch (ETA) and an aberrant right subclavian artery (ARSA) branching into the aortic isthmus as unusual anatomic location were seen. Periaortic hematoma formation was suspected of possible extravasation. In addition, a partial anomalous pulmonary venous connection (PAPVC) showed that the vertical vein connected to the left upper lobe drained into the left bra-chiocephalic vein ( Fig. 1A, B ). We planned an arch and descending aorta replacement surgery via an anterolateral thoracotomy under cardiopulmonary bypass. However, the patient was hesitant with regard to invasive surgery owing to her cosmetic concerns as a single woman. Her back pain gradually improved with analgesics, however, 3 days later, she again complained of acute sharp back pain. Subsequent CT scan revealed active aggravation of ruptured aortic dissection and aneurysmal dilatation on dissected aorta. The false lumen had increased in size to 10% of the aortic maximum diameter, measuring 3.9 cm, and left pleural fluid collection suspicious to hemothorax and periaortic hematoma had increased ( Fig. 2A, B ). We decided to perform an emergency operation for the recurrent back pain, enlarging periaortic hematoma and hemothorax. After consultation with the patient, we initially planned an anterolateral thoracotomy with left heart bypass. However, we determined that it would be too dangerous to clamp on the aortic isthmus near the ARSA owing to the frailty of the aneurysmal dilatation on the dissected aorta. In addition, the vertical vein running directly above the dissecting flap might have interfered with the operative field. Instead of open surgery, we decided to perform emergency thoracic endovascular aortic repair (TEVAR). However, because the patients had the ARSA with a dominant vertebral artery, we decided to perform a carotid to subclavian artery bypass with the dominant vertebral artery before TEVAR. Under general anesthesia, a right carotid and subclavian artery bypass was performed via supraclavicular transverse incision. A 7 mm Gore-Tex polytetrafluoroethylene Stretch graft was placed between the right carotid and subclavian arteries. After bypass, we exposed the patient’s right common femoral artery (CFA) through a longitudinal incision. Through the left CFA, a sizing catheter was inserted with angiography guidance for checking the length. Pre-deploying aortogram revealed ARCA branching from the aortic isthmus and aneurysmal dilatation on the dissected aorta including the left subclavian artery ( Fig. 3A ). An S&G SEAL thoracic stent graft (24×24×110 mm; S&G Biotech, Seongnam, Korea) was advanced through the right CFA. During stent graft insertion, a slightly strong resistance was encountered; however, post-procedural aortogram revealed no peripheral arterial injury. After stent graft deployment, aortography showed laminar blood flow through the devices and the thoracic aorta with complete exclusion of the dissecting aneurysm ( Fig. 3B ). There were no complications during the procedure, and the oversizing of stent grafts relative to the aorta did not exceed 10% to provide adequate radial force to keep the deployed stent grafts in place. The total operative time was 245 minutes, and the total contrast agent volume was 90 mL. Postoperatively, the blood pressure in both arms was nearly same and there was no evidence of ischemia. After postoperative day (POD) 5, CT scan revealed a well-functioning aortic isthmus stent graft without endoleaks, and complete occlusion of both subclavian artery orifices with distal run-off reserved from collateral flow ( Fig. 4A, B ). The patient was discharged on POD 6 without complications and is planning follow-up examination of the PAPVC at the cardiac and cardiovascular clinics.'}
|
{'CASE': 'A 32-year-old woman with Turner syndrome (143 cm/49 kg, body surface area 1.37 m 2 ) was admitted to Kyungpook National University Hospital center with complaint of sudden-onset back pain. She had been diagnosed with Turner syndrome twenty years prior following examination for her short stature. She was regularly treated with hormone replacement therapy as an outpatient of the obstetrics and gynecology. She felt well, worked as a kindergarten teacher, and was unmarried. On admission, her initial systolic blood pressure and heart rate were 131 mmHg and 68 beats per minute, respectively. Her blood pressures were almost equal in the upper and lower extremities. Her initial hemoglobin level was 11.8 g/dL, and electrocardiography revealed a normal sinus rhythm. An initial computed tomography (CT) scan revealed intimal dissection on aortic isthmus level and a dissected flap extending from the left subclavian artery to the descending aorta. An elongated transverse aortic arch (ETA) and an aberrant right subclavian artery (ARSA) branching into the aortic isthmus as unusual anatomic location were seen. Periaortic hematoma formation was suspected of possible extravasation. In addition, a partial anomalous pulmonary venous connection (PAPVC) showed that the vertical vein connected to the left upper lobe drained into the left bra-chiocephalic vein ( Fig. 1A, B ). We planned an arch and descending aorta replacement surgery via an anterolateral thoracotomy under cardiopulmonary bypass. However, the patient was hesitant with regard to invasive surgery owing to her cosmetic concerns as a single woman. Her back pain gradually improved with analgesics, however, 3 days later, she again complained of acute sharp back pain. Subsequent CT scan revealed active aggravation of ruptured aortic dissection and aneurysmal dilatation on dissected aorta. The false lumen had increased in size to 10% of the aortic maximum diameter, measuring 3.9 cm, and left pleural fluid collection suspicious to hemothorax and periaortic hematoma had increased ( Fig. 2A, B ). We decided to perform an emergency operation for the recurrent back pain, enlarging periaortic hematoma and hemothorax. After consultation with the patient, we initially planned an anterolateral thoracotomy with left heart bypass. However, we determined that it would be too dangerous to clamp on the aortic isthmus near the ARSA owing to the frailty of the aneurysmal dilatation on the dissected aorta. In addition, the vertical vein running directly above the dissecting flap might have interfered with the operative field. Instead of open surgery, we decided to perform emergency thoracic endovascular aortic repair (TEVAR). However, because the patients had the ARSA with a dominant vertebral artery, we decided to perform a carotid to subclavian artery bypass with the dominant vertebral artery before TEVAR. Under general anesthesia, a right carotid and subclavian artery bypass was performed via supraclavicular transverse incision. A 7 mm Gore-Tex polytetrafluoroethylene Stretch graft was placed between the right carotid and subclavian arteries. After bypass, we exposed the patient’s right common femoral artery (CFA) through a longitudinal incision. Through the left CFA, a sizing catheter was inserted with angiography guidance for checking the length. Pre-deploying aortogram revealed ARCA branching from the aortic isthmus and aneurysmal dilatation on the dissected aorta including the left subclavian artery ( Fig. 3A ). An S&G SEAL thoracic stent graft (24×24×110 mm; S&G Biotech, Seongnam, Korea) was advanced through the right CFA. During stent graft insertion, a slightly strong resistance was encountered; however, post-procedural aortogram revealed no peripheral arterial injury. After stent graft deployment, aortography showed laminar blood flow through the devices and the thoracic aorta with complete exclusion of the dissecting aneurysm ( Fig. 3B ). There were no complications during the procedure, and the oversizing of stent grafts relative to the aorta did not exceed 10% to provide adequate radial force to keep the deployed stent grafts in place. The total operative time was 245 minutes, and the total contrast agent volume was 90 mL. Postoperatively, the blood pressure in both arms was nearly same and there was no evidence of ischemia. After postoperative day (POD) 5, CT scan revealed a well-functioning aortic isthmus stent graft without endoleaks, and complete occlusion of both subclavian artery orifices with distal run-off reserved from collateral flow ( Fig. 4A, B ). The patient was discharged on POD 6 without complications and is planning follow-up examination of the PAPVC at the cardiac and cardiovascular clinics.'}
|
Vitals-and-Hematology
|
Vitals_Hema
|
[
"143 cm/49 kg, body surface area 1.37 m 2",
"her initial systolic blood pressure and heart rate were 131 mmHg and 68 beats per minute, respectively. Her blood pressures were almost equal in the upper and lower extremities",
"Her initial hemoglobin level was 11.8 g / dL"
] |
6340697
|
{'CASE': 'A 32-year-old woman with Turner syndrome (143 cm/49 kg, body surface area 1.37 m 2 ) was admitted to Kyungpook National University Hospital center with complaint of sudden-onset back pain. She had been diagnosed with Turner syndrome twenty years prior following examination for her short stature. She was regularly treated with hormone replacement therapy as an outpatient of the obstetrics and gynecology. She felt well, worked as a kindergarten teacher, and was unmarried. On admission, her initial systolic blood pressure and heart rate were 131 mmHg and 68 beats per minute, respectively. Her blood pressures were almost equal in the upper and lower extremities. Her initial hemoglobin level was 11.8 g/dL, and electrocardiography revealed a normal sinus rhythm. An initial computed tomography (CT) scan revealed intimal dissection on aortic isthmus level and a dissected flap extending from the left subclavian artery to the descending aorta. An elongated transverse aortic arch (ETA) and an aberrant right subclavian artery (ARSA) branching into the aortic isthmus as unusual anatomic location were seen. Periaortic hematoma formation was suspected of possible extravasation. In addition, a partial anomalous pulmonary venous connection (PAPVC) showed that the vertical vein connected to the left upper lobe drained into the left bra-chiocephalic vein ( Fig. 1A, B ). We planned an arch and descending aorta replacement surgery via an anterolateral thoracotomy under cardiopulmonary bypass. However, the patient was hesitant with regard to invasive surgery owing to her cosmetic concerns as a single woman. Her back pain gradually improved with analgesics, however, 3 days later, she again complained of acute sharp back pain. Subsequent CT scan revealed active aggravation of ruptured aortic dissection and aneurysmal dilatation on dissected aorta. The false lumen had increased in size to 10% of the aortic maximum diameter, measuring 3.9 cm, and left pleural fluid collection suspicious to hemothorax and periaortic hematoma had increased ( Fig. 2A, B ). We decided to perform an emergency operation for the recurrent back pain, enlarging periaortic hematoma and hemothorax. After consultation with the patient, we initially planned an anterolateral thoracotomy with left heart bypass. However, we determined that it would be too dangerous to clamp on the aortic isthmus near the ARSA owing to the frailty of the aneurysmal dilatation on the dissected aorta. In addition, the vertical vein running directly above the dissecting flap might have interfered with the operative field. Instead of open surgery, we decided to perform emergency thoracic endovascular aortic repair (TEVAR). However, because the patients had the ARSA with a dominant vertebral artery, we decided to perform a carotid to subclavian artery bypass with the dominant vertebral artery before TEVAR. Under general anesthesia, a right carotid and subclavian artery bypass was performed via supraclavicular transverse incision. A 7 mm Gore-Tex polytetrafluoroethylene Stretch graft was placed between the right carotid and subclavian arteries. After bypass, we exposed the patient’s right common femoral artery (CFA) through a longitudinal incision. Through the left CFA, a sizing catheter was inserted with angiography guidance for checking the length. Pre-deploying aortogram revealed ARCA branching from the aortic isthmus and aneurysmal dilatation on the dissected aorta including the left subclavian artery ( Fig. 3A ). An S&G SEAL thoracic stent graft (24×24×110 mm; S&G Biotech, Seongnam, Korea) was advanced through the right CFA. During stent graft insertion, a slightly strong resistance was encountered; however, post-procedural aortogram revealed no peripheral arterial injury. After stent graft deployment, aortography showed laminar blood flow through the devices and the thoracic aorta with complete exclusion of the dissecting aneurysm ( Fig. 3B ). There were no complications during the procedure, and the oversizing of stent grafts relative to the aorta did not exceed 10% to provide adequate radial force to keep the deployed stent grafts in place. The total operative time was 245 minutes, and the total contrast agent volume was 90 mL. Postoperatively, the blood pressure in both arms was nearly same and there was no evidence of ischemia. After postoperative day (POD) 5, CT scan revealed a well-functioning aortic isthmus stent graft without endoleaks, and complete occlusion of both subclavian artery orifices with distal run-off reserved from collateral flow ( Fig. 4A, B ). The patient was discharged on POD 6 without complications and is planning follow-up examination of the PAPVC at the cardiac and cardiovascular clinics.'}
|
{'CASE': 'A 32-year-old woman with Turner syndrome (143 cm/49 kg, body surface area 1.37 m 2 ) was admitted to Kyungpook National University Hospital center with complaint of sudden-onset back pain. She had been diagnosed with Turner syndrome twenty years prior following examination for her short stature. She was regularly treated with hormone replacement therapy as an outpatient of the obstetrics and gynecology. She felt well, worked as a kindergarten teacher, and was unmarried. On admission, her initial systolic blood pressure and heart rate were 131 mmHg and 68 beats per minute, respectively. Her blood pressures were almost equal in the upper and lower extremities. Her initial hemoglobin level was 11.8 g/dL, and electrocardiography revealed a normal sinus rhythm. An initial computed tomography (CT) scan revealed intimal dissection on aortic isthmus level and a dissected flap extending from the left subclavian artery to the descending aorta. An elongated transverse aortic arch (ETA) and an aberrant right subclavian artery (ARSA) branching into the aortic isthmus as unusual anatomic location were seen. Periaortic hematoma formation was suspected of possible extravasation. In addition, a partial anomalous pulmonary venous connection (PAPVC) showed that the vertical vein connected to the left upper lobe drained into the left bra-chiocephalic vein ( Fig. 1A, B ). We planned an arch and descending aorta replacement surgery via an anterolateral thoracotomy under cardiopulmonary bypass. However, the patient was hesitant with regard to invasive surgery owing to her cosmetic concerns as a single woman. Her back pain gradually improved with analgesics, however, 3 days later, she again complained of acute sharp back pain. Subsequent CT scan revealed active aggravation of ruptured aortic dissection and aneurysmal dilatation on dissected aorta. The false lumen had increased in size to 10% of the aortic maximum diameter, measuring 3.9 cm, and left pleural fluid collection suspicious to hemothorax and periaortic hematoma had increased ( Fig. 2A, B ). We decided to perform an emergency operation for the recurrent back pain, enlarging periaortic hematoma and hemothorax. After consultation with the patient, we initially planned an anterolateral thoracotomy with left heart bypass. However, we determined that it would be too dangerous to clamp on the aortic isthmus near the ARSA owing to the frailty of the aneurysmal dilatation on the dissected aorta. In addition, the vertical vein running directly above the dissecting flap might have interfered with the operative field. Instead of open surgery, we decided to perform emergency thoracic endovascular aortic repair (TEVAR). However, because the patients had the ARSA with a dominant vertebral artery, we decided to perform a carotid to subclavian artery bypass with the dominant vertebral artery before TEVAR. Under general anesthesia, a right carotid and subclavian artery bypass was performed via supraclavicular transverse incision. A 7 mm Gore-Tex polytetrafluoroethylene Stretch graft was placed between the right carotid and subclavian arteries. After bypass, we exposed the patient’s right common femoral artery (CFA) through a longitudinal incision. Through the left CFA, a sizing catheter was inserted with angiography guidance for checking the length. Pre-deploying aortogram revealed ARCA branching from the aortic isthmus and aneurysmal dilatation on the dissected aorta including the left subclavian artery ( Fig. 3A ). An S&G SEAL thoracic stent graft (24×24×110 mm; S&G Biotech, Seongnam, Korea) was advanced through the right CFA. During stent graft insertion, a slightly strong resistance was encountered; however, post-procedural aortogram revealed no peripheral arterial injury. After stent graft deployment, aortography showed laminar blood flow through the devices and the thoracic aorta with complete exclusion of the dissecting aneurysm ( Fig. 3B ). There were no complications during the procedure, and the oversizing of stent grafts relative to the aorta did not exceed 10% to provide adequate radial force to keep the deployed stent grafts in place. The total operative time was 245 minutes, and the total contrast agent volume was 90 mL. Postoperatively, the blood pressure in both arms was nearly same and there was no evidence of ischemia. After postoperative day (POD) 5, CT scan revealed a well-functioning aortic isthmus stent graft without endoleaks, and complete occlusion of both subclavian artery orifices with distal run-off reserved from collateral flow ( Fig. 4A, B ). The patient was discharged on POD 6 without complications and is planning follow-up examination of the PAPVC at the cardiac and cardiovascular clinics.'}
|
Gastrointestinal-System
|
GI
|
[] |
6340697
|
{'CASE': 'A 32-year-old woman with Turner syndrome (143 cm/49 kg, body surface area 1.37 m 2 ) was admitted to Kyungpook National University Hospital center with complaint of sudden-onset back pain. She had been diagnosed with Turner syndrome twenty years prior following examination for her short stature. She was regularly treated with hormone replacement therapy as an outpatient of the obstetrics and gynecology. She felt well, worked as a kindergarten teacher, and was unmarried. On admission, her initial systolic blood pressure and heart rate were 131 mmHg and 68 beats per minute, respectively. Her blood pressures were almost equal in the upper and lower extremities. Her initial hemoglobin level was 11.8 g/dL, and electrocardiography revealed a normal sinus rhythm. An initial computed tomography (CT) scan revealed intimal dissection on aortic isthmus level and a dissected flap extending from the left subclavian artery to the descending aorta. An elongated transverse aortic arch (ETA) and an aberrant right subclavian artery (ARSA) branching into the aortic isthmus as unusual anatomic location were seen. Periaortic hematoma formation was suspected of possible extravasation. In addition, a partial anomalous pulmonary venous connection (PAPVC) showed that the vertical vein connected to the left upper lobe drained into the left bra-chiocephalic vein ( Fig. 1A, B ). We planned an arch and descending aorta replacement surgery via an anterolateral thoracotomy under cardiopulmonary bypass. However, the patient was hesitant with regard to invasive surgery owing to her cosmetic concerns as a single woman. Her back pain gradually improved with analgesics, however, 3 days later, she again complained of acute sharp back pain. Subsequent CT scan revealed active aggravation of ruptured aortic dissection and aneurysmal dilatation on dissected aorta. The false lumen had increased in size to 10% of the aortic maximum diameter, measuring 3.9 cm, and left pleural fluid collection suspicious to hemothorax and periaortic hematoma had increased ( Fig. 2A, B ). We decided to perform an emergency operation for the recurrent back pain, enlarging periaortic hematoma and hemothorax. After consultation with the patient, we initially planned an anterolateral thoracotomy with left heart bypass. However, we determined that it would be too dangerous to clamp on the aortic isthmus near the ARSA owing to the frailty of the aneurysmal dilatation on the dissected aorta. In addition, the vertical vein running directly above the dissecting flap might have interfered with the operative field. Instead of open surgery, we decided to perform emergency thoracic endovascular aortic repair (TEVAR). However, because the patients had the ARSA with a dominant vertebral artery, we decided to perform a carotid to subclavian artery bypass with the dominant vertebral artery before TEVAR. Under general anesthesia, a right carotid and subclavian artery bypass was performed via supraclavicular transverse incision. A 7 mm Gore-Tex polytetrafluoroethylene Stretch graft was placed between the right carotid and subclavian arteries. After bypass, we exposed the patient’s right common femoral artery (CFA) through a longitudinal incision. Through the left CFA, a sizing catheter was inserted with angiography guidance for checking the length. Pre-deploying aortogram revealed ARCA branching from the aortic isthmus and aneurysmal dilatation on the dissected aorta including the left subclavian artery ( Fig. 3A ). An S&G SEAL thoracic stent graft (24×24×110 mm; S&G Biotech, Seongnam, Korea) was advanced through the right CFA. During stent graft insertion, a slightly strong resistance was encountered; however, post-procedural aortogram revealed no peripheral arterial injury. After stent graft deployment, aortography showed laminar blood flow through the devices and the thoracic aorta with complete exclusion of the dissecting aneurysm ( Fig. 3B ). There were no complications during the procedure, and the oversizing of stent grafts relative to the aorta did not exceed 10% to provide adequate radial force to keep the deployed stent grafts in place. The total operative time was 245 minutes, and the total contrast agent volume was 90 mL. Postoperatively, the blood pressure in both arms was nearly same and there was no evidence of ischemia. After postoperative day (POD) 5, CT scan revealed a well-functioning aortic isthmus stent graft without endoleaks, and complete occlusion of both subclavian artery orifices with distal run-off reserved from collateral flow ( Fig. 4A, B ). The patient was discharged on POD 6 without complications and is planning follow-up examination of the PAPVC at the cardiac and cardiovascular clinics.'}
|
{'CASE': 'A 32-year-old woman with Turner syndrome (143 cm/49 kg, body surface area 1.37 m 2 ) was admitted to Kyungpook National University Hospital center with complaint of sudden-onset back pain. She had been diagnosed with Turner syndrome twenty years prior following examination for her short stature. She was regularly treated with hormone replacement therapy as an outpatient of the obstetrics and gynecology. She felt well, worked as a kindergarten teacher, and was unmarried. On admission, her initial systolic blood pressure and heart rate were 131 mmHg and 68 beats per minute, respectively. Her blood pressures were almost equal in the upper and lower extremities. Her initial hemoglobin level was 11.8 g/dL, and electrocardiography revealed a normal sinus rhythm. An initial computed tomography (CT) scan revealed intimal dissection on aortic isthmus level and a dissected flap extending from the left subclavian artery to the descending aorta. An elongated transverse aortic arch (ETA) and an aberrant right subclavian artery (ARSA) branching into the aortic isthmus as unusual anatomic location were seen. Periaortic hematoma formation was suspected of possible extravasation. In addition, a partial anomalous pulmonary venous connection (PAPVC) showed that the vertical vein connected to the left upper lobe drained into the left bra-chiocephalic vein ( Fig. 1A, B ). We planned an arch and descending aorta replacement surgery via an anterolateral thoracotomy under cardiopulmonary bypass. However, the patient was hesitant with regard to invasive surgery owing to her cosmetic concerns as a single woman. Her back pain gradually improved with analgesics, however, 3 days later, she again complained of acute sharp back pain. Subsequent CT scan revealed active aggravation of ruptured aortic dissection and aneurysmal dilatation on dissected aorta. The false lumen had increased in size to 10% of the aortic maximum diameter, measuring 3.9 cm, and left pleural fluid collection suspicious to hemothorax and periaortic hematoma had increased ( Fig. 2A, B ). We decided to perform an emergency operation for the recurrent back pain, enlarging periaortic hematoma and hemothorax. After consultation with the patient, we initially planned an anterolateral thoracotomy with left heart bypass. However, we determined that it would be too dangerous to clamp on the aortic isthmus near the ARSA owing to the frailty of the aneurysmal dilatation on the dissected aorta. In addition, the vertical vein running directly above the dissecting flap might have interfered with the operative field. Instead of open surgery, we decided to perform emergency thoracic endovascular aortic repair (TEVAR). However, because the patients had the ARSA with a dominant vertebral artery, we decided to perform a carotid to subclavian artery bypass with the dominant vertebral artery before TEVAR. Under general anesthesia, a right carotid and subclavian artery bypass was performed via supraclavicular transverse incision. A 7 mm Gore-Tex polytetrafluoroethylene Stretch graft was placed between the right carotid and subclavian arteries. After bypass, we exposed the patient’s right common femoral artery (CFA) through a longitudinal incision. Through the left CFA, a sizing catheter was inserted with angiography guidance for checking the length. Pre-deploying aortogram revealed ARCA branching from the aortic isthmus and aneurysmal dilatation on the dissected aorta including the left subclavian artery ( Fig. 3A ). An S&G SEAL thoracic stent graft (24×24×110 mm; S&G Biotech, Seongnam, Korea) was advanced through the right CFA. During stent graft insertion, a slightly strong resistance was encountered; however, post-procedural aortogram revealed no peripheral arterial injury. After stent graft deployment, aortography showed laminar blood flow through the devices and the thoracic aorta with complete exclusion of the dissecting aneurysm ( Fig. 3B ). There were no complications during the procedure, and the oversizing of stent grafts relative to the aorta did not exceed 10% to provide adequate radial force to keep the deployed stent grafts in place. The total operative time was 245 minutes, and the total contrast agent volume was 90 mL. Postoperatively, the blood pressure in both arms was nearly same and there was no evidence of ischemia. After postoperative day (POD) 5, CT scan revealed a well-functioning aortic isthmus stent graft without endoleaks, and complete occlusion of both subclavian artery orifices with distal run-off reserved from collateral flow ( Fig. 4A, B ). The patient was discharged on POD 6 without complications and is planning follow-up examination of the PAPVC at the cardiac and cardiovascular clinics.'}
|
Patient-History
|
History
|
[
"A 32 - year - old woman with Turner syndrome ( 143 cm/49 kg, body surface area 1.37 m 2 ) was admitted to Kyungpook National University Hospital center with complaint of sudden - onset back pain"
] |
6340697
|
{'CASE': 'A 32-year-old woman with Turner syndrome (143 cm/49 kg, body surface area 1.37 m 2 ) was admitted to Kyungpook National University Hospital center with complaint of sudden-onset back pain. She had been diagnosed with Turner syndrome twenty years prior following examination for her short stature. She was regularly treated with hormone replacement therapy as an outpatient of the obstetrics and gynecology. She felt well, worked as a kindergarten teacher, and was unmarried. On admission, her initial systolic blood pressure and heart rate were 131 mmHg and 68 beats per minute, respectively. Her blood pressures were almost equal in the upper and lower extremities. Her initial hemoglobin level was 11.8 g/dL, and electrocardiography revealed a normal sinus rhythm. An initial computed tomography (CT) scan revealed intimal dissection on aortic isthmus level and a dissected flap extending from the left subclavian artery to the descending aorta. An elongated transverse aortic arch (ETA) and an aberrant right subclavian artery (ARSA) branching into the aortic isthmus as unusual anatomic location were seen. Periaortic hematoma formation was suspected of possible extravasation. In addition, a partial anomalous pulmonary venous connection (PAPVC) showed that the vertical vein connected to the left upper lobe drained into the left bra-chiocephalic vein ( Fig. 1A, B ). We planned an arch and descending aorta replacement surgery via an anterolateral thoracotomy under cardiopulmonary bypass. However, the patient was hesitant with regard to invasive surgery owing to her cosmetic concerns as a single woman. Her back pain gradually improved with analgesics, however, 3 days later, she again complained of acute sharp back pain. Subsequent CT scan revealed active aggravation of ruptured aortic dissection and aneurysmal dilatation on dissected aorta. The false lumen had increased in size to 10% of the aortic maximum diameter, measuring 3.9 cm, and left pleural fluid collection suspicious to hemothorax and periaortic hematoma had increased ( Fig. 2A, B ). We decided to perform an emergency operation for the recurrent back pain, enlarging periaortic hematoma and hemothorax. After consultation with the patient, we initially planned an anterolateral thoracotomy with left heart bypass. However, we determined that it would be too dangerous to clamp on the aortic isthmus near the ARSA owing to the frailty of the aneurysmal dilatation on the dissected aorta. In addition, the vertical vein running directly above the dissecting flap might have interfered with the operative field. Instead of open surgery, we decided to perform emergency thoracic endovascular aortic repair (TEVAR). However, because the patients had the ARSA with a dominant vertebral artery, we decided to perform a carotid to subclavian artery bypass with the dominant vertebral artery before TEVAR. Under general anesthesia, a right carotid and subclavian artery bypass was performed via supraclavicular transverse incision. A 7 mm Gore-Tex polytetrafluoroethylene Stretch graft was placed between the right carotid and subclavian arteries. After bypass, we exposed the patient’s right common femoral artery (CFA) through a longitudinal incision. Through the left CFA, a sizing catheter was inserted with angiography guidance for checking the length. Pre-deploying aortogram revealed ARCA branching from the aortic isthmus and aneurysmal dilatation on the dissected aorta including the left subclavian artery ( Fig. 3A ). An S&G SEAL thoracic stent graft (24×24×110 mm; S&G Biotech, Seongnam, Korea) was advanced through the right CFA. During stent graft insertion, a slightly strong resistance was encountered; however, post-procedural aortogram revealed no peripheral arterial injury. After stent graft deployment, aortography showed laminar blood flow through the devices and the thoracic aorta with complete exclusion of the dissecting aneurysm ( Fig. 3B ). There were no complications during the procedure, and the oversizing of stent grafts relative to the aorta did not exceed 10% to provide adequate radial force to keep the deployed stent grafts in place. The total operative time was 245 minutes, and the total contrast agent volume was 90 mL. Postoperatively, the blood pressure in both arms was nearly same and there was no evidence of ischemia. After postoperative day (POD) 5, CT scan revealed a well-functioning aortic isthmus stent graft without endoleaks, and complete occlusion of both subclavian artery orifices with distal run-off reserved from collateral flow ( Fig. 4A, B ). The patient was discharged on POD 6 without complications and is planning follow-up examination of the PAPVC at the cardiac and cardiovascular clinics.'}
|
{'CASE': 'A 32-year-old woman with Turner syndrome (143 cm/49 kg, body surface area 1.37 m 2 ) was admitted to Kyungpook National University Hospital center with complaint of sudden-onset back pain. She had been diagnosed with Turner syndrome twenty years prior following examination for her short stature. She was regularly treated with hormone replacement therapy as an outpatient of the obstetrics and gynecology. She felt well, worked as a kindergarten teacher, and was unmarried. On admission, her initial systolic blood pressure and heart rate were 131 mmHg and 68 beats per minute, respectively. Her blood pressures were almost equal in the upper and lower extremities. Her initial hemoglobin level was 11.8 g/dL, and electrocardiography revealed a normal sinus rhythm. An initial computed tomography (CT) scan revealed intimal dissection on aortic isthmus level and a dissected flap extending from the left subclavian artery to the descending aorta. An elongated transverse aortic arch (ETA) and an aberrant right subclavian artery (ARSA) branching into the aortic isthmus as unusual anatomic location were seen. Periaortic hematoma formation was suspected of possible extravasation. In addition, a partial anomalous pulmonary venous connection (PAPVC) showed that the vertical vein connected to the left upper lobe drained into the left bra-chiocephalic vein ( Fig. 1A, B ). We planned an arch and descending aorta replacement surgery via an anterolateral thoracotomy under cardiopulmonary bypass. However, the patient was hesitant with regard to invasive surgery owing to her cosmetic concerns as a single woman. Her back pain gradually improved with analgesics, however, 3 days later, she again complained of acute sharp back pain. Subsequent CT scan revealed active aggravation of ruptured aortic dissection and aneurysmal dilatation on dissected aorta. The false lumen had increased in size to 10% of the aortic maximum diameter, measuring 3.9 cm, and left pleural fluid collection suspicious to hemothorax and periaortic hematoma had increased ( Fig. 2A, B ). We decided to perform an emergency operation for the recurrent back pain, enlarging periaortic hematoma and hemothorax. After consultation with the patient, we initially planned an anterolateral thoracotomy with left heart bypass. However, we determined that it would be too dangerous to clamp on the aortic isthmus near the ARSA owing to the frailty of the aneurysmal dilatation on the dissected aorta. In addition, the vertical vein running directly above the dissecting flap might have interfered with the operative field. Instead of open surgery, we decided to perform emergency thoracic endovascular aortic repair (TEVAR). However, because the patients had the ARSA with a dominant vertebral artery, we decided to perform a carotid to subclavian artery bypass with the dominant vertebral artery before TEVAR. Under general anesthesia, a right carotid and subclavian artery bypass was performed via supraclavicular transverse incision. A 7 mm Gore-Tex polytetrafluoroethylene Stretch graft was placed between the right carotid and subclavian arteries. After bypass, we exposed the patient’s right common femoral artery (CFA) through a longitudinal incision. Through the left CFA, a sizing catheter was inserted with angiography guidance for checking the length. Pre-deploying aortogram revealed ARCA branching from the aortic isthmus and aneurysmal dilatation on the dissected aorta including the left subclavian artery ( Fig. 3A ). An S&G SEAL thoracic stent graft (24×24×110 mm; S&G Biotech, Seongnam, Korea) was advanced through the right CFA. During stent graft insertion, a slightly strong resistance was encountered; however, post-procedural aortogram revealed no peripheral arterial injury. After stent graft deployment, aortography showed laminar blood flow through the devices and the thoracic aorta with complete exclusion of the dissecting aneurysm ( Fig. 3B ). There were no complications during the procedure, and the oversizing of stent grafts relative to the aorta did not exceed 10% to provide adequate radial force to keep the deployed stent grafts in place. The total operative time was 245 minutes, and the total contrast agent volume was 90 mL. Postoperatively, the blood pressure in both arms was nearly same and there was no evidence of ischemia. After postoperative day (POD) 5, CT scan revealed a well-functioning aortic isthmus stent graft without endoleaks, and complete occlusion of both subclavian artery orifices with distal run-off reserved from collateral flow ( Fig. 4A, B ). The patient was discharged on POD 6 without complications and is planning follow-up examination of the PAPVC at the cardiac and cardiovascular clinics.'}
|
Neurology
|
Neuro
|
[] |
6340697
|
{'CASE': 'A 32-year-old woman with Turner syndrome (143 cm/49 kg, body surface area 1.37 m 2 ) was admitted to Kyungpook National University Hospital center with complaint of sudden-onset back pain. She had been diagnosed with Turner syndrome twenty years prior following examination for her short stature. She was regularly treated with hormone replacement therapy as an outpatient of the obstetrics and gynecology. She felt well, worked as a kindergarten teacher, and was unmarried. On admission, her initial systolic blood pressure and heart rate were 131 mmHg and 68 beats per minute, respectively. Her blood pressures were almost equal in the upper and lower extremities. Her initial hemoglobin level was 11.8 g/dL, and electrocardiography revealed a normal sinus rhythm. An initial computed tomography (CT) scan revealed intimal dissection on aortic isthmus level and a dissected flap extending from the left subclavian artery to the descending aorta. An elongated transverse aortic arch (ETA) and an aberrant right subclavian artery (ARSA) branching into the aortic isthmus as unusual anatomic location were seen. Periaortic hematoma formation was suspected of possible extravasation. In addition, a partial anomalous pulmonary venous connection (PAPVC) showed that the vertical vein connected to the left upper lobe drained into the left bra-chiocephalic vein ( Fig. 1A, B ). We planned an arch and descending aorta replacement surgery via an anterolateral thoracotomy under cardiopulmonary bypass. However, the patient was hesitant with regard to invasive surgery owing to her cosmetic concerns as a single woman. Her back pain gradually improved with analgesics, however, 3 days later, she again complained of acute sharp back pain. Subsequent CT scan revealed active aggravation of ruptured aortic dissection and aneurysmal dilatation on dissected aorta. The false lumen had increased in size to 10% of the aortic maximum diameter, measuring 3.9 cm, and left pleural fluid collection suspicious to hemothorax and periaortic hematoma had increased ( Fig. 2A, B ). We decided to perform an emergency operation for the recurrent back pain, enlarging periaortic hematoma and hemothorax. After consultation with the patient, we initially planned an anterolateral thoracotomy with left heart bypass. However, we determined that it would be too dangerous to clamp on the aortic isthmus near the ARSA owing to the frailty of the aneurysmal dilatation on the dissected aorta. In addition, the vertical vein running directly above the dissecting flap might have interfered with the operative field. Instead of open surgery, we decided to perform emergency thoracic endovascular aortic repair (TEVAR). However, because the patients had the ARSA with a dominant vertebral artery, we decided to perform a carotid to subclavian artery bypass with the dominant vertebral artery before TEVAR. Under general anesthesia, a right carotid and subclavian artery bypass was performed via supraclavicular transverse incision. A 7 mm Gore-Tex polytetrafluoroethylene Stretch graft was placed between the right carotid and subclavian arteries. After bypass, we exposed the patient’s right common femoral artery (CFA) through a longitudinal incision. Through the left CFA, a sizing catheter was inserted with angiography guidance for checking the length. Pre-deploying aortogram revealed ARCA branching from the aortic isthmus and aneurysmal dilatation on the dissected aorta including the left subclavian artery ( Fig. 3A ). An S&G SEAL thoracic stent graft (24×24×110 mm; S&G Biotech, Seongnam, Korea) was advanced through the right CFA. During stent graft insertion, a slightly strong resistance was encountered; however, post-procedural aortogram revealed no peripheral arterial injury. After stent graft deployment, aortography showed laminar blood flow through the devices and the thoracic aorta with complete exclusion of the dissecting aneurysm ( Fig. 3B ). There were no complications during the procedure, and the oversizing of stent grafts relative to the aorta did not exceed 10% to provide adequate radial force to keep the deployed stent grafts in place. The total operative time was 245 minutes, and the total contrast agent volume was 90 mL. Postoperatively, the blood pressure in both arms was nearly same and there was no evidence of ischemia. After postoperative day (POD) 5, CT scan revealed a well-functioning aortic isthmus stent graft without endoleaks, and complete occlusion of both subclavian artery orifices with distal run-off reserved from collateral flow ( Fig. 4A, B ). The patient was discharged on POD 6 without complications and is planning follow-up examination of the PAPVC at the cardiac and cardiovascular clinics.'}
|
{'CASE': 'A 32-year-old woman with Turner syndrome (143 cm/49 kg, body surface area 1.37 m 2 ) was admitted to Kyungpook National University Hospital center with complaint of sudden-onset back pain. She had been diagnosed with Turner syndrome twenty years prior following examination for her short stature. She was regularly treated with hormone replacement therapy as an outpatient of the obstetrics and gynecology. She felt well, worked as a kindergarten teacher, and was unmarried. On admission, her initial systolic blood pressure and heart rate were 131 mmHg and 68 beats per minute, respectively. Her blood pressures were almost equal in the upper and lower extremities. Her initial hemoglobin level was 11.8 g/dL, and electrocardiography revealed a normal sinus rhythm. An initial computed tomography (CT) scan revealed intimal dissection on aortic isthmus level and a dissected flap extending from the left subclavian artery to the descending aorta. An elongated transverse aortic arch (ETA) and an aberrant right subclavian artery (ARSA) branching into the aortic isthmus as unusual anatomic location were seen. Periaortic hematoma formation was suspected of possible extravasation. In addition, a partial anomalous pulmonary venous connection (PAPVC) showed that the vertical vein connected to the left upper lobe drained into the left bra-chiocephalic vein ( Fig. 1A, B ). We planned an arch and descending aorta replacement surgery via an anterolateral thoracotomy under cardiopulmonary bypass. However, the patient was hesitant with regard to invasive surgery owing to her cosmetic concerns as a single woman. Her back pain gradually improved with analgesics, however, 3 days later, she again complained of acute sharp back pain. Subsequent CT scan revealed active aggravation of ruptured aortic dissection and aneurysmal dilatation on dissected aorta. The false lumen had increased in size to 10% of the aortic maximum diameter, measuring 3.9 cm, and left pleural fluid collection suspicious to hemothorax and periaortic hematoma had increased ( Fig. 2A, B ). We decided to perform an emergency operation for the recurrent back pain, enlarging periaortic hematoma and hemothorax. After consultation with the patient, we initially planned an anterolateral thoracotomy with left heart bypass. However, we determined that it would be too dangerous to clamp on the aortic isthmus near the ARSA owing to the frailty of the aneurysmal dilatation on the dissected aorta. In addition, the vertical vein running directly above the dissecting flap might have interfered with the operative field. Instead of open surgery, we decided to perform emergency thoracic endovascular aortic repair (TEVAR). However, because the patients had the ARSA with a dominant vertebral artery, we decided to perform a carotid to subclavian artery bypass with the dominant vertebral artery before TEVAR. Under general anesthesia, a right carotid and subclavian artery bypass was performed via supraclavicular transverse incision. A 7 mm Gore-Tex polytetrafluoroethylene Stretch graft was placed between the right carotid and subclavian arteries. After bypass, we exposed the patient’s right common femoral artery (CFA) through a longitudinal incision. Through the left CFA, a sizing catheter was inserted with angiography guidance for checking the length. Pre-deploying aortogram revealed ARCA branching from the aortic isthmus and aneurysmal dilatation on the dissected aorta including the left subclavian artery ( Fig. 3A ). An S&G SEAL thoracic stent graft (24×24×110 mm; S&G Biotech, Seongnam, Korea) was advanced through the right CFA. During stent graft insertion, a slightly strong resistance was encountered; however, post-procedural aortogram revealed no peripheral arterial injury. After stent graft deployment, aortography showed laminar blood flow through the devices and the thoracic aorta with complete exclusion of the dissecting aneurysm ( Fig. 3B ). There were no complications during the procedure, and the oversizing of stent grafts relative to the aorta did not exceed 10% to provide adequate radial force to keep the deployed stent grafts in place. The total operative time was 245 minutes, and the total contrast agent volume was 90 mL. Postoperatively, the blood pressure in both arms was nearly same and there was no evidence of ischemia. After postoperative day (POD) 5, CT scan revealed a well-functioning aortic isthmus stent graft without endoleaks, and complete occlusion of both subclavian artery orifices with distal run-off reserved from collateral flow ( Fig. 4A, B ). The patient was discharged on POD 6 without complications and is planning follow-up examination of the PAPVC at the cardiac and cardiovascular clinics.'}
|
Laboratory-and-Imaging
|
Lab_Image
|
[
"Her initial hemoglobin level was 11.8 g / dL",
"An initial computed tomography ( CT ) scan revealed intimal dissection on aortic isthmus level and a dissected flap extending from the left subclavian artery to the descending aorta. An elongated transverse aortic arch ( ETA ) and an aberrant right subclavian artery ( ARSA ) branching into the aortic isthmus as unusual anatomic location were seen. Periaortic hematoma formation was suspected of possible extravasation. In addition, a partial anomalous pulmonary venous connection ( PAPVC ) showed that the vertical vein connected to the left upper lobe drained into the left bra - chiocephalic vein",
"Subsequent CT scan revealed active aggravation of ruptured aortic dissection and aneurysmal dilatation on dissected aorta. The false lumen had increased in size to 10 % of the aortic maximum diameter, measuring 3.9 cm, and left pleural fluid collection suspicious to hemothorax and periaortic hematoma had increased",
"CT scan revealed a well - functioning aortic isthmus stent graft without endoleaks, and complete occlusion of both subclavian artery orifices with distal run - off reserved from collateral flow"
] |
6340697
|
{'CASE': 'A 32-year-old woman with Turner syndrome (143 cm/49 kg, body surface area 1.37 m 2 ) was admitted to Kyungpook National University Hospital center with complaint of sudden-onset back pain. She had been diagnosed with Turner syndrome twenty years prior following examination for her short stature. She was regularly treated with hormone replacement therapy as an outpatient of the obstetrics and gynecology. She felt well, worked as a kindergarten teacher, and was unmarried. On admission, her initial systolic blood pressure and heart rate were 131 mmHg and 68 beats per minute, respectively. Her blood pressures were almost equal in the upper and lower extremities. Her initial hemoglobin level was 11.8 g/dL, and electrocardiography revealed a normal sinus rhythm. An initial computed tomography (CT) scan revealed intimal dissection on aortic isthmus level and a dissected flap extending from the left subclavian artery to the descending aorta. An elongated transverse aortic arch (ETA) and an aberrant right subclavian artery (ARSA) branching into the aortic isthmus as unusual anatomic location were seen. Periaortic hematoma formation was suspected of possible extravasation. In addition, a partial anomalous pulmonary venous connection (PAPVC) showed that the vertical vein connected to the left upper lobe drained into the left bra-chiocephalic vein ( Fig. 1A, B ). We planned an arch and descending aorta replacement surgery via an anterolateral thoracotomy under cardiopulmonary bypass. However, the patient was hesitant with regard to invasive surgery owing to her cosmetic concerns as a single woman. Her back pain gradually improved with analgesics, however, 3 days later, she again complained of acute sharp back pain. Subsequent CT scan revealed active aggravation of ruptured aortic dissection and aneurysmal dilatation on dissected aorta. The false lumen had increased in size to 10% of the aortic maximum diameter, measuring 3.9 cm, and left pleural fluid collection suspicious to hemothorax and periaortic hematoma had increased ( Fig. 2A, B ). We decided to perform an emergency operation for the recurrent back pain, enlarging periaortic hematoma and hemothorax. After consultation with the patient, we initially planned an anterolateral thoracotomy with left heart bypass. However, we determined that it would be too dangerous to clamp on the aortic isthmus near the ARSA owing to the frailty of the aneurysmal dilatation on the dissected aorta. In addition, the vertical vein running directly above the dissecting flap might have interfered with the operative field. Instead of open surgery, we decided to perform emergency thoracic endovascular aortic repair (TEVAR). However, because the patients had the ARSA with a dominant vertebral artery, we decided to perform a carotid to subclavian artery bypass with the dominant vertebral artery before TEVAR. Under general anesthesia, a right carotid and subclavian artery bypass was performed via supraclavicular transverse incision. A 7 mm Gore-Tex polytetrafluoroethylene Stretch graft was placed between the right carotid and subclavian arteries. After bypass, we exposed the patient’s right common femoral artery (CFA) through a longitudinal incision. Through the left CFA, a sizing catheter was inserted with angiography guidance for checking the length. Pre-deploying aortogram revealed ARCA branching from the aortic isthmus and aneurysmal dilatation on the dissected aorta including the left subclavian artery ( Fig. 3A ). An S&G SEAL thoracic stent graft (24×24×110 mm; S&G Biotech, Seongnam, Korea) was advanced through the right CFA. During stent graft insertion, a slightly strong resistance was encountered; however, post-procedural aortogram revealed no peripheral arterial injury. After stent graft deployment, aortography showed laminar blood flow through the devices and the thoracic aorta with complete exclusion of the dissecting aneurysm ( Fig. 3B ). There were no complications during the procedure, and the oversizing of stent grafts relative to the aorta did not exceed 10% to provide adequate radial force to keep the deployed stent grafts in place. The total operative time was 245 minutes, and the total contrast agent volume was 90 mL. Postoperatively, the blood pressure in both arms was nearly same and there was no evidence of ischemia. After postoperative day (POD) 5, CT scan revealed a well-functioning aortic isthmus stent graft without endoleaks, and complete occlusion of both subclavian artery orifices with distal run-off reserved from collateral flow ( Fig. 4A, B ). The patient was discharged on POD 6 without complications and is planning follow-up examination of the PAPVC at the cardiac and cardiovascular clinics.'}
|
{'CASE': 'A 32-year-old woman with Turner syndrome (143 cm/49 kg, body surface area 1.37 m 2 ) was admitted to Kyungpook National University Hospital center with complaint of sudden-onset back pain. She had been diagnosed with Turner syndrome twenty years prior following examination for her short stature. She was regularly treated with hormone replacement therapy as an outpatient of the obstetrics and gynecology. She felt well, worked as a kindergarten teacher, and was unmarried. On admission, her initial systolic blood pressure and heart rate were 131 mmHg and 68 beats per minute, respectively. Her blood pressures were almost equal in the upper and lower extremities. Her initial hemoglobin level was 11.8 g/dL, and electrocardiography revealed a normal sinus rhythm. An initial computed tomography (CT) scan revealed intimal dissection on aortic isthmus level and a dissected flap extending from the left subclavian artery to the descending aorta. An elongated transverse aortic arch (ETA) and an aberrant right subclavian artery (ARSA) branching into the aortic isthmus as unusual anatomic location were seen. Periaortic hematoma formation was suspected of possible extravasation. In addition, a partial anomalous pulmonary venous connection (PAPVC) showed that the vertical vein connected to the left upper lobe drained into the left bra-chiocephalic vein ( Fig. 1A, B ). We planned an arch and descending aorta replacement surgery via an anterolateral thoracotomy under cardiopulmonary bypass. However, the patient was hesitant with regard to invasive surgery owing to her cosmetic concerns as a single woman. Her back pain gradually improved with analgesics, however, 3 days later, she again complained of acute sharp back pain. Subsequent CT scan revealed active aggravation of ruptured aortic dissection and aneurysmal dilatation on dissected aorta. The false lumen had increased in size to 10% of the aortic maximum diameter, measuring 3.9 cm, and left pleural fluid collection suspicious to hemothorax and periaortic hematoma had increased ( Fig. 2A, B ). We decided to perform an emergency operation for the recurrent back pain, enlarging periaortic hematoma and hemothorax. After consultation with the patient, we initially planned an anterolateral thoracotomy with left heart bypass. However, we determined that it would be too dangerous to clamp on the aortic isthmus near the ARSA owing to the frailty of the aneurysmal dilatation on the dissected aorta. In addition, the vertical vein running directly above the dissecting flap might have interfered with the operative field. Instead of open surgery, we decided to perform emergency thoracic endovascular aortic repair (TEVAR). However, because the patients had the ARSA with a dominant vertebral artery, we decided to perform a carotid to subclavian artery bypass with the dominant vertebral artery before TEVAR. Under general anesthesia, a right carotid and subclavian artery bypass was performed via supraclavicular transverse incision. A 7 mm Gore-Tex polytetrafluoroethylene Stretch graft was placed between the right carotid and subclavian arteries. After bypass, we exposed the patient’s right common femoral artery (CFA) through a longitudinal incision. Through the left CFA, a sizing catheter was inserted with angiography guidance for checking the length. Pre-deploying aortogram revealed ARCA branching from the aortic isthmus and aneurysmal dilatation on the dissected aorta including the left subclavian artery ( Fig. 3A ). An S&G SEAL thoracic stent graft (24×24×110 mm; S&G Biotech, Seongnam, Korea) was advanced through the right CFA. During stent graft insertion, a slightly strong resistance was encountered; however, post-procedural aortogram revealed no peripheral arterial injury. After stent graft deployment, aortography showed laminar blood flow through the devices and the thoracic aorta with complete exclusion of the dissecting aneurysm ( Fig. 3B ). There were no complications during the procedure, and the oversizing of stent grafts relative to the aorta did not exceed 10% to provide adequate radial force to keep the deployed stent grafts in place. The total operative time was 245 minutes, and the total contrast agent volume was 90 mL. Postoperatively, the blood pressure in both arms was nearly same and there was no evidence of ischemia. After postoperative day (POD) 5, CT scan revealed a well-functioning aortic isthmus stent graft without endoleaks, and complete occlusion of both subclavian artery orifices with distal run-off reserved from collateral flow ( Fig. 4A, B ). The patient was discharged on POD 6 without complications and is planning follow-up examination of the PAPVC at the cardiac and cardiovascular clinics.'}
|
Cardiovascular-System
|
CVS
|
[
"sudden - onset back pain",
"electrocardiography revealed a normal sinus rhythm"
] |
6340697
|
{'CASE': 'A 32-year-old woman with Turner syndrome (143 cm/49 kg, body surface area 1.37 m 2 ) was admitted to Kyungpook National University Hospital center with complaint of sudden-onset back pain. She had been diagnosed with Turner syndrome twenty years prior following examination for her short stature. She was regularly treated with hormone replacement therapy as an outpatient of the obstetrics and gynecology. She felt well, worked as a kindergarten teacher, and was unmarried. On admission, her initial systolic blood pressure and heart rate were 131 mmHg and 68 beats per minute, respectively. Her blood pressures were almost equal in the upper and lower extremities. Her initial hemoglobin level was 11.8 g/dL, and electrocardiography revealed a normal sinus rhythm. An initial computed tomography (CT) scan revealed intimal dissection on aortic isthmus level and a dissected flap extending from the left subclavian artery to the descending aorta. An elongated transverse aortic arch (ETA) and an aberrant right subclavian artery (ARSA) branching into the aortic isthmus as unusual anatomic location were seen. Periaortic hematoma formation was suspected of possible extravasation. In addition, a partial anomalous pulmonary venous connection (PAPVC) showed that the vertical vein connected to the left upper lobe drained into the left bra-chiocephalic vein ( Fig. 1A, B ). We planned an arch and descending aorta replacement surgery via an anterolateral thoracotomy under cardiopulmonary bypass. However, the patient was hesitant with regard to invasive surgery owing to her cosmetic concerns as a single woman. Her back pain gradually improved with analgesics, however, 3 days later, she again complained of acute sharp back pain. Subsequent CT scan revealed active aggravation of ruptured aortic dissection and aneurysmal dilatation on dissected aorta. The false lumen had increased in size to 10% of the aortic maximum diameter, measuring 3.9 cm, and left pleural fluid collection suspicious to hemothorax and periaortic hematoma had increased ( Fig. 2A, B ). We decided to perform an emergency operation for the recurrent back pain, enlarging periaortic hematoma and hemothorax. After consultation with the patient, we initially planned an anterolateral thoracotomy with left heart bypass. However, we determined that it would be too dangerous to clamp on the aortic isthmus near the ARSA owing to the frailty of the aneurysmal dilatation on the dissected aorta. In addition, the vertical vein running directly above the dissecting flap might have interfered with the operative field. Instead of open surgery, we decided to perform emergency thoracic endovascular aortic repair (TEVAR). However, because the patients had the ARSA with a dominant vertebral artery, we decided to perform a carotid to subclavian artery bypass with the dominant vertebral artery before TEVAR. Under general anesthesia, a right carotid and subclavian artery bypass was performed via supraclavicular transverse incision. A 7 mm Gore-Tex polytetrafluoroethylene Stretch graft was placed between the right carotid and subclavian arteries. After bypass, we exposed the patient’s right common femoral artery (CFA) through a longitudinal incision. Through the left CFA, a sizing catheter was inserted with angiography guidance for checking the length. Pre-deploying aortogram revealed ARCA branching from the aortic isthmus and aneurysmal dilatation on the dissected aorta including the left subclavian artery ( Fig. 3A ). An S&G SEAL thoracic stent graft (24×24×110 mm; S&G Biotech, Seongnam, Korea) was advanced through the right CFA. During stent graft insertion, a slightly strong resistance was encountered; however, post-procedural aortogram revealed no peripheral arterial injury. After stent graft deployment, aortography showed laminar blood flow through the devices and the thoracic aorta with complete exclusion of the dissecting aneurysm ( Fig. 3B ). There were no complications during the procedure, and the oversizing of stent grafts relative to the aorta did not exceed 10% to provide adequate radial force to keep the deployed stent grafts in place. The total operative time was 245 minutes, and the total contrast agent volume was 90 mL. Postoperatively, the blood pressure in both arms was nearly same and there was no evidence of ischemia. After postoperative day (POD) 5, CT scan revealed a well-functioning aortic isthmus stent graft without endoleaks, and complete occlusion of both subclavian artery orifices with distal run-off reserved from collateral flow ( Fig. 4A, B ). The patient was discharged on POD 6 without complications and is planning follow-up examination of the PAPVC at the cardiac and cardiovascular clinics.'}
|
{'CASE': 'A 32-year-old woman with Turner syndrome (143 cm/49 kg, body surface area 1.37 m 2 ) was admitted to Kyungpook National University Hospital center with complaint of sudden-onset back pain. She had been diagnosed with Turner syndrome twenty years prior following examination for her short stature. She was regularly treated with hormone replacement therapy as an outpatient of the obstetrics and gynecology. She felt well, worked as a kindergarten teacher, and was unmarried. On admission, her initial systolic blood pressure and heart rate were 131 mmHg and 68 beats per minute, respectively. Her blood pressures were almost equal in the upper and lower extremities. Her initial hemoglobin level was 11.8 g/dL, and electrocardiography revealed a normal sinus rhythm. An initial computed tomography (CT) scan revealed intimal dissection on aortic isthmus level and a dissected flap extending from the left subclavian artery to the descending aorta. An elongated transverse aortic arch (ETA) and an aberrant right subclavian artery (ARSA) branching into the aortic isthmus as unusual anatomic location were seen. Periaortic hematoma formation was suspected of possible extravasation. In addition, a partial anomalous pulmonary venous connection (PAPVC) showed that the vertical vein connected to the left upper lobe drained into the left bra-chiocephalic vein ( Fig. 1A, B ). We planned an arch and descending aorta replacement surgery via an anterolateral thoracotomy under cardiopulmonary bypass. However, the patient was hesitant with regard to invasive surgery owing to her cosmetic concerns as a single woman. Her back pain gradually improved with analgesics, however, 3 days later, she again complained of acute sharp back pain. Subsequent CT scan revealed active aggravation of ruptured aortic dissection and aneurysmal dilatation on dissected aorta. The false lumen had increased in size to 10% of the aortic maximum diameter, measuring 3.9 cm, and left pleural fluid collection suspicious to hemothorax and periaortic hematoma had increased ( Fig. 2A, B ). We decided to perform an emergency operation for the recurrent back pain, enlarging periaortic hematoma and hemothorax. After consultation with the patient, we initially planned an anterolateral thoracotomy with left heart bypass. However, we determined that it would be too dangerous to clamp on the aortic isthmus near the ARSA owing to the frailty of the aneurysmal dilatation on the dissected aorta. In addition, the vertical vein running directly above the dissecting flap might have interfered with the operative field. Instead of open surgery, we decided to perform emergency thoracic endovascular aortic repair (TEVAR). However, because the patients had the ARSA with a dominant vertebral artery, we decided to perform a carotid to subclavian artery bypass with the dominant vertebral artery before TEVAR. Under general anesthesia, a right carotid and subclavian artery bypass was performed via supraclavicular transverse incision. A 7 mm Gore-Tex polytetrafluoroethylene Stretch graft was placed between the right carotid and subclavian arteries. After bypass, we exposed the patient’s right common femoral artery (CFA) through a longitudinal incision. Through the left CFA, a sizing catheter was inserted with angiography guidance for checking the length. Pre-deploying aortogram revealed ARCA branching from the aortic isthmus and aneurysmal dilatation on the dissected aorta including the left subclavian artery ( Fig. 3A ). An S&G SEAL thoracic stent graft (24×24×110 mm; S&G Biotech, Seongnam, Korea) was advanced through the right CFA. During stent graft insertion, a slightly strong resistance was encountered; however, post-procedural aortogram revealed no peripheral arterial injury. After stent graft deployment, aortography showed laminar blood flow through the devices and the thoracic aorta with complete exclusion of the dissecting aneurysm ( Fig. 3B ). There were no complications during the procedure, and the oversizing of stent grafts relative to the aorta did not exceed 10% to provide adequate radial force to keep the deployed stent grafts in place. The total operative time was 245 minutes, and the total contrast agent volume was 90 mL. Postoperatively, the blood pressure in both arms was nearly same and there was no evidence of ischemia. After postoperative day (POD) 5, CT scan revealed a well-functioning aortic isthmus stent graft without endoleaks, and complete occlusion of both subclavian artery orifices with distal run-off reserved from collateral flow ( Fig. 4A, B ). The patient was discharged on POD 6 without complications and is planning follow-up examination of the PAPVC at the cardiac and cardiovascular clinics.'}
|
Endocrinology
|
ENDO
|
[] |
6340697
|
{'CASE': 'A 32-year-old woman with Turner syndrome (143 cm/49 kg, body surface area 1.37 m 2 ) was admitted to Kyungpook National University Hospital center with complaint of sudden-onset back pain. She had been diagnosed with Turner syndrome twenty years prior following examination for her short stature. She was regularly treated with hormone replacement therapy as an outpatient of the obstetrics and gynecology. She felt well, worked as a kindergarten teacher, and was unmarried. On admission, her initial systolic blood pressure and heart rate were 131 mmHg and 68 beats per minute, respectively. Her blood pressures were almost equal in the upper and lower extremities. Her initial hemoglobin level was 11.8 g/dL, and electrocardiography revealed a normal sinus rhythm. An initial computed tomography (CT) scan revealed intimal dissection on aortic isthmus level and a dissected flap extending from the left subclavian artery to the descending aorta. An elongated transverse aortic arch (ETA) and an aberrant right subclavian artery (ARSA) branching into the aortic isthmus as unusual anatomic location were seen. Periaortic hematoma formation was suspected of possible extravasation. In addition, a partial anomalous pulmonary venous connection (PAPVC) showed that the vertical vein connected to the left upper lobe drained into the left bra-chiocephalic vein ( Fig. 1A, B ). We planned an arch and descending aorta replacement surgery via an anterolateral thoracotomy under cardiopulmonary bypass. However, the patient was hesitant with regard to invasive surgery owing to her cosmetic concerns as a single woman. Her back pain gradually improved with analgesics, however, 3 days later, she again complained of acute sharp back pain. Subsequent CT scan revealed active aggravation of ruptured aortic dissection and aneurysmal dilatation on dissected aorta. The false lumen had increased in size to 10% of the aortic maximum diameter, measuring 3.9 cm, and left pleural fluid collection suspicious to hemothorax and periaortic hematoma had increased ( Fig. 2A, B ). We decided to perform an emergency operation for the recurrent back pain, enlarging periaortic hematoma and hemothorax. After consultation with the patient, we initially planned an anterolateral thoracotomy with left heart bypass. However, we determined that it would be too dangerous to clamp on the aortic isthmus near the ARSA owing to the frailty of the aneurysmal dilatation on the dissected aorta. In addition, the vertical vein running directly above the dissecting flap might have interfered with the operative field. Instead of open surgery, we decided to perform emergency thoracic endovascular aortic repair (TEVAR). However, because the patients had the ARSA with a dominant vertebral artery, we decided to perform a carotid to subclavian artery bypass with the dominant vertebral artery before TEVAR. Under general anesthesia, a right carotid and subclavian artery bypass was performed via supraclavicular transverse incision. A 7 mm Gore-Tex polytetrafluoroethylene Stretch graft was placed between the right carotid and subclavian arteries. After bypass, we exposed the patient’s right common femoral artery (CFA) through a longitudinal incision. Through the left CFA, a sizing catheter was inserted with angiography guidance for checking the length. Pre-deploying aortogram revealed ARCA branching from the aortic isthmus and aneurysmal dilatation on the dissected aorta including the left subclavian artery ( Fig. 3A ). An S&G SEAL thoracic stent graft (24×24×110 mm; S&G Biotech, Seongnam, Korea) was advanced through the right CFA. During stent graft insertion, a slightly strong resistance was encountered; however, post-procedural aortogram revealed no peripheral arterial injury. After stent graft deployment, aortography showed laminar blood flow through the devices and the thoracic aorta with complete exclusion of the dissecting aneurysm ( Fig. 3B ). There were no complications during the procedure, and the oversizing of stent grafts relative to the aorta did not exceed 10% to provide adequate radial force to keep the deployed stent grafts in place. The total operative time was 245 minutes, and the total contrast agent volume was 90 mL. Postoperatively, the blood pressure in both arms was nearly same and there was no evidence of ischemia. After postoperative day (POD) 5, CT scan revealed a well-functioning aortic isthmus stent graft without endoleaks, and complete occlusion of both subclavian artery orifices with distal run-off reserved from collateral flow ( Fig. 4A, B ). The patient was discharged on POD 6 without complications and is planning follow-up examination of the PAPVC at the cardiac and cardiovascular clinics.'}
|
{'CASE': 'A 32-year-old woman with Turner syndrome (143 cm/49 kg, body surface area 1.37 m 2 ) was admitted to Kyungpook National University Hospital center with complaint of sudden-onset back pain. She had been diagnosed with Turner syndrome twenty years prior following examination for her short stature. She was regularly treated with hormone replacement therapy as an outpatient of the obstetrics and gynecology. She felt well, worked as a kindergarten teacher, and was unmarried. On admission, her initial systolic blood pressure and heart rate were 131 mmHg and 68 beats per minute, respectively. Her blood pressures were almost equal in the upper and lower extremities. Her initial hemoglobin level was 11.8 g/dL, and electrocardiography revealed a normal sinus rhythm. An initial computed tomography (CT) scan revealed intimal dissection on aortic isthmus level and a dissected flap extending from the left subclavian artery to the descending aorta. An elongated transverse aortic arch (ETA) and an aberrant right subclavian artery (ARSA) branching into the aortic isthmus as unusual anatomic location were seen. Periaortic hematoma formation was suspected of possible extravasation. In addition, a partial anomalous pulmonary venous connection (PAPVC) showed that the vertical vein connected to the left upper lobe drained into the left bra-chiocephalic vein ( Fig. 1A, B ). We planned an arch and descending aorta replacement surgery via an anterolateral thoracotomy under cardiopulmonary bypass. However, the patient was hesitant with regard to invasive surgery owing to her cosmetic concerns as a single woman. Her back pain gradually improved with analgesics, however, 3 days later, she again complained of acute sharp back pain. Subsequent CT scan revealed active aggravation of ruptured aortic dissection and aneurysmal dilatation on dissected aorta. The false lumen had increased in size to 10% of the aortic maximum diameter, measuring 3.9 cm, and left pleural fluid collection suspicious to hemothorax and periaortic hematoma had increased ( Fig. 2A, B ). We decided to perform an emergency operation for the recurrent back pain, enlarging periaortic hematoma and hemothorax. After consultation with the patient, we initially planned an anterolateral thoracotomy with left heart bypass. However, we determined that it would be too dangerous to clamp on the aortic isthmus near the ARSA owing to the frailty of the aneurysmal dilatation on the dissected aorta. In addition, the vertical vein running directly above the dissecting flap might have interfered with the operative field. Instead of open surgery, we decided to perform emergency thoracic endovascular aortic repair (TEVAR). However, because the patients had the ARSA with a dominant vertebral artery, we decided to perform a carotid to subclavian artery bypass with the dominant vertebral artery before TEVAR. Under general anesthesia, a right carotid and subclavian artery bypass was performed via supraclavicular transverse incision. A 7 mm Gore-Tex polytetrafluoroethylene Stretch graft was placed between the right carotid and subclavian arteries. After bypass, we exposed the patient’s right common femoral artery (CFA) through a longitudinal incision. Through the left CFA, a sizing catheter was inserted with angiography guidance for checking the length. Pre-deploying aortogram revealed ARCA branching from the aortic isthmus and aneurysmal dilatation on the dissected aorta including the left subclavian artery ( Fig. 3A ). An S&G SEAL thoracic stent graft (24×24×110 mm; S&G Biotech, Seongnam, Korea) was advanced through the right CFA. During stent graft insertion, a slightly strong resistance was encountered; however, post-procedural aortogram revealed no peripheral arterial injury. After stent graft deployment, aortography showed laminar blood flow through the devices and the thoracic aorta with complete exclusion of the dissecting aneurysm ( Fig. 3B ). There were no complications during the procedure, and the oversizing of stent grafts relative to the aorta did not exceed 10% to provide adequate radial force to keep the deployed stent grafts in place. The total operative time was 245 minutes, and the total contrast agent volume was 90 mL. Postoperatively, the blood pressure in both arms was nearly same and there was no evidence of ischemia. After postoperative day (POD) 5, CT scan revealed a well-functioning aortic isthmus stent graft without endoleaks, and complete occlusion of both subclavian artery orifices with distal run-off reserved from collateral flow ( Fig. 4A, B ). The patient was discharged on POD 6 without complications and is planning follow-up examination of the PAPVC at the cardiac and cardiovascular clinics.'}
|
Genitourinary-System
|
GU
|
[] |
6340697
|
{'CASE': 'A 32-year-old woman with Turner syndrome (143 cm/49 kg, body surface area 1.37 m 2 ) was admitted to Kyungpook National University Hospital center with complaint of sudden-onset back pain. She had been diagnosed with Turner syndrome twenty years prior following examination for her short stature. She was regularly treated with hormone replacement therapy as an outpatient of the obstetrics and gynecology. She felt well, worked as a kindergarten teacher, and was unmarried. On admission, her initial systolic blood pressure and heart rate were 131 mmHg and 68 beats per minute, respectively. Her blood pressures were almost equal in the upper and lower extremities. Her initial hemoglobin level was 11.8 g/dL, and electrocardiography revealed a normal sinus rhythm. An initial computed tomography (CT) scan revealed intimal dissection on aortic isthmus level and a dissected flap extending from the left subclavian artery to the descending aorta. An elongated transverse aortic arch (ETA) and an aberrant right subclavian artery (ARSA) branching into the aortic isthmus as unusual anatomic location were seen. Periaortic hematoma formation was suspected of possible extravasation. In addition, a partial anomalous pulmonary venous connection (PAPVC) showed that the vertical vein connected to the left upper lobe drained into the left bra-chiocephalic vein ( Fig. 1A, B ). We planned an arch and descending aorta replacement surgery via an anterolateral thoracotomy under cardiopulmonary bypass. However, the patient was hesitant with regard to invasive surgery owing to her cosmetic concerns as a single woman. Her back pain gradually improved with analgesics, however, 3 days later, she again complained of acute sharp back pain. Subsequent CT scan revealed active aggravation of ruptured aortic dissection and aneurysmal dilatation on dissected aorta. The false lumen had increased in size to 10% of the aortic maximum diameter, measuring 3.9 cm, and left pleural fluid collection suspicious to hemothorax and periaortic hematoma had increased ( Fig. 2A, B ). We decided to perform an emergency operation for the recurrent back pain, enlarging periaortic hematoma and hemothorax. After consultation with the patient, we initially planned an anterolateral thoracotomy with left heart bypass. However, we determined that it would be too dangerous to clamp on the aortic isthmus near the ARSA owing to the frailty of the aneurysmal dilatation on the dissected aorta. In addition, the vertical vein running directly above the dissecting flap might have interfered with the operative field. Instead of open surgery, we decided to perform emergency thoracic endovascular aortic repair (TEVAR). However, because the patients had the ARSA with a dominant vertebral artery, we decided to perform a carotid to subclavian artery bypass with the dominant vertebral artery before TEVAR. Under general anesthesia, a right carotid and subclavian artery bypass was performed via supraclavicular transverse incision. A 7 mm Gore-Tex polytetrafluoroethylene Stretch graft was placed between the right carotid and subclavian arteries. After bypass, we exposed the patient’s right common femoral artery (CFA) through a longitudinal incision. Through the left CFA, a sizing catheter was inserted with angiography guidance for checking the length. Pre-deploying aortogram revealed ARCA branching from the aortic isthmus and aneurysmal dilatation on the dissected aorta including the left subclavian artery ( Fig. 3A ). An S&G SEAL thoracic stent graft (24×24×110 mm; S&G Biotech, Seongnam, Korea) was advanced through the right CFA. During stent graft insertion, a slightly strong resistance was encountered; however, post-procedural aortogram revealed no peripheral arterial injury. After stent graft deployment, aortography showed laminar blood flow through the devices and the thoracic aorta with complete exclusion of the dissecting aneurysm ( Fig. 3B ). There were no complications during the procedure, and the oversizing of stent grafts relative to the aorta did not exceed 10% to provide adequate radial force to keep the deployed stent grafts in place. The total operative time was 245 minutes, and the total contrast agent volume was 90 mL. Postoperatively, the blood pressure in both arms was nearly same and there was no evidence of ischemia. After postoperative day (POD) 5, CT scan revealed a well-functioning aortic isthmus stent graft without endoleaks, and complete occlusion of both subclavian artery orifices with distal run-off reserved from collateral flow ( Fig. 4A, B ). The patient was discharged on POD 6 without complications and is planning follow-up examination of the PAPVC at the cardiac and cardiovascular clinics.'}
|
{'CASE': 'A 32-year-old woman with Turner syndrome (143 cm/49 kg, body surface area 1.37 m 2 ) was admitted to Kyungpook National University Hospital center with complaint of sudden-onset back pain. She had been diagnosed with Turner syndrome twenty years prior following examination for her short stature. She was regularly treated with hormone replacement therapy as an outpatient of the obstetrics and gynecology. She felt well, worked as a kindergarten teacher, and was unmarried. On admission, her initial systolic blood pressure and heart rate were 131 mmHg and 68 beats per minute, respectively. Her blood pressures were almost equal in the upper and lower extremities. Her initial hemoglobin level was 11.8 g/dL, and electrocardiography revealed a normal sinus rhythm. An initial computed tomography (CT) scan revealed intimal dissection on aortic isthmus level and a dissected flap extending from the left subclavian artery to the descending aorta. An elongated transverse aortic arch (ETA) and an aberrant right subclavian artery (ARSA) branching into the aortic isthmus as unusual anatomic location were seen. Periaortic hematoma formation was suspected of possible extravasation. In addition, a partial anomalous pulmonary venous connection (PAPVC) showed that the vertical vein connected to the left upper lobe drained into the left bra-chiocephalic vein ( Fig. 1A, B ). We planned an arch and descending aorta replacement surgery via an anterolateral thoracotomy under cardiopulmonary bypass. However, the patient was hesitant with regard to invasive surgery owing to her cosmetic concerns as a single woman. Her back pain gradually improved with analgesics, however, 3 days later, she again complained of acute sharp back pain. Subsequent CT scan revealed active aggravation of ruptured aortic dissection and aneurysmal dilatation on dissected aorta. The false lumen had increased in size to 10% of the aortic maximum diameter, measuring 3.9 cm, and left pleural fluid collection suspicious to hemothorax and periaortic hematoma had increased ( Fig. 2A, B ). We decided to perform an emergency operation for the recurrent back pain, enlarging periaortic hematoma and hemothorax. After consultation with the patient, we initially planned an anterolateral thoracotomy with left heart bypass. However, we determined that it would be too dangerous to clamp on the aortic isthmus near the ARSA owing to the frailty of the aneurysmal dilatation on the dissected aorta. In addition, the vertical vein running directly above the dissecting flap might have interfered with the operative field. Instead of open surgery, we decided to perform emergency thoracic endovascular aortic repair (TEVAR). However, because the patients had the ARSA with a dominant vertebral artery, we decided to perform a carotid to subclavian artery bypass with the dominant vertebral artery before TEVAR. Under general anesthesia, a right carotid and subclavian artery bypass was performed via supraclavicular transverse incision. A 7 mm Gore-Tex polytetrafluoroethylene Stretch graft was placed between the right carotid and subclavian arteries. After bypass, we exposed the patient’s right common femoral artery (CFA) through a longitudinal incision. Through the left CFA, a sizing catheter was inserted with angiography guidance for checking the length. Pre-deploying aortogram revealed ARCA branching from the aortic isthmus and aneurysmal dilatation on the dissected aorta including the left subclavian artery ( Fig. 3A ). An S&G SEAL thoracic stent graft (24×24×110 mm; S&G Biotech, Seongnam, Korea) was advanced through the right CFA. During stent graft insertion, a slightly strong resistance was encountered; however, post-procedural aortogram revealed no peripheral arterial injury. After stent graft deployment, aortography showed laminar blood flow through the devices and the thoracic aorta with complete exclusion of the dissecting aneurysm ( Fig. 3B ). There were no complications during the procedure, and the oversizing of stent grafts relative to the aorta did not exceed 10% to provide adequate radial force to keep the deployed stent grafts in place. The total operative time was 245 minutes, and the total contrast agent volume was 90 mL. Postoperatively, the blood pressure in both arms was nearly same and there was no evidence of ischemia. After postoperative day (POD) 5, CT scan revealed a well-functioning aortic isthmus stent graft without endoleaks, and complete occlusion of both subclavian artery orifices with distal run-off reserved from collateral flow ( Fig. 4A, B ). The patient was discharged on POD 6 without complications and is planning follow-up examination of the PAPVC at the cardiac and cardiovascular clinics.'}
|
Respiratory-System
|
RESP
|
[] |
6340697
|
{'CASE': 'A 32-year-old woman with Turner syndrome (143 cm/49 kg, body surface area 1.37 m 2 ) was admitted to Kyungpook National University Hospital center with complaint of sudden-onset back pain. She had been diagnosed with Turner syndrome twenty years prior following examination for her short stature. She was regularly treated with hormone replacement therapy as an outpatient of the obstetrics and gynecology. She felt well, worked as a kindergarten teacher, and was unmarried. On admission, her initial systolic blood pressure and heart rate were 131 mmHg and 68 beats per minute, respectively. Her blood pressures were almost equal in the upper and lower extremities. Her initial hemoglobin level was 11.8 g/dL, and electrocardiography revealed a normal sinus rhythm. An initial computed tomography (CT) scan revealed intimal dissection on aortic isthmus level and a dissected flap extending from the left subclavian artery to the descending aorta. An elongated transverse aortic arch (ETA) and an aberrant right subclavian artery (ARSA) branching into the aortic isthmus as unusual anatomic location were seen. Periaortic hematoma formation was suspected of possible extravasation. In addition, a partial anomalous pulmonary venous connection (PAPVC) showed that the vertical vein connected to the left upper lobe drained into the left bra-chiocephalic vein ( Fig. 1A, B ). We planned an arch and descending aorta replacement surgery via an anterolateral thoracotomy under cardiopulmonary bypass. However, the patient was hesitant with regard to invasive surgery owing to her cosmetic concerns as a single woman. Her back pain gradually improved with analgesics, however, 3 days later, she again complained of acute sharp back pain. Subsequent CT scan revealed active aggravation of ruptured aortic dissection and aneurysmal dilatation on dissected aorta. The false lumen had increased in size to 10% of the aortic maximum diameter, measuring 3.9 cm, and left pleural fluid collection suspicious to hemothorax and periaortic hematoma had increased ( Fig. 2A, B ). We decided to perform an emergency operation for the recurrent back pain, enlarging periaortic hematoma and hemothorax. After consultation with the patient, we initially planned an anterolateral thoracotomy with left heart bypass. However, we determined that it would be too dangerous to clamp on the aortic isthmus near the ARSA owing to the frailty of the aneurysmal dilatation on the dissected aorta. In addition, the vertical vein running directly above the dissecting flap might have interfered with the operative field. Instead of open surgery, we decided to perform emergency thoracic endovascular aortic repair (TEVAR). However, because the patients had the ARSA with a dominant vertebral artery, we decided to perform a carotid to subclavian artery bypass with the dominant vertebral artery before TEVAR. Under general anesthesia, a right carotid and subclavian artery bypass was performed via supraclavicular transverse incision. A 7 mm Gore-Tex polytetrafluoroethylene Stretch graft was placed between the right carotid and subclavian arteries. After bypass, we exposed the patient’s right common femoral artery (CFA) through a longitudinal incision. Through the left CFA, a sizing catheter was inserted with angiography guidance for checking the length. Pre-deploying aortogram revealed ARCA branching from the aortic isthmus and aneurysmal dilatation on the dissected aorta including the left subclavian artery ( Fig. 3A ). An S&G SEAL thoracic stent graft (24×24×110 mm; S&G Biotech, Seongnam, Korea) was advanced through the right CFA. During stent graft insertion, a slightly strong resistance was encountered; however, post-procedural aortogram revealed no peripheral arterial injury. After stent graft deployment, aortography showed laminar blood flow through the devices and the thoracic aorta with complete exclusion of the dissecting aneurysm ( Fig. 3B ). There were no complications during the procedure, and the oversizing of stent grafts relative to the aorta did not exceed 10% to provide adequate radial force to keep the deployed stent grafts in place. The total operative time was 245 minutes, and the total contrast agent volume was 90 mL. Postoperatively, the blood pressure in both arms was nearly same and there was no evidence of ischemia. After postoperative day (POD) 5, CT scan revealed a well-functioning aortic isthmus stent graft without endoleaks, and complete occlusion of both subclavian artery orifices with distal run-off reserved from collateral flow ( Fig. 4A, B ). The patient was discharged on POD 6 without complications and is planning follow-up examination of the PAPVC at the cardiac and cardiovascular clinics.'}
|
{'CASE': 'A 32-year-old woman with Turner syndrome (143 cm/49 kg, body surface area 1.37 m 2 ) was admitted to Kyungpook National University Hospital center with complaint of sudden-onset back pain. She had been diagnosed with Turner syndrome twenty years prior following examination for her short stature. She was regularly treated with hormone replacement therapy as an outpatient of the obstetrics and gynecology. She felt well, worked as a kindergarten teacher, and was unmarried. On admission, her initial systolic blood pressure and heart rate were 131 mmHg and 68 beats per minute, respectively. Her blood pressures were almost equal in the upper and lower extremities. Her initial hemoglobin level was 11.8 g/dL, and electrocardiography revealed a normal sinus rhythm. An initial computed tomography (CT) scan revealed intimal dissection on aortic isthmus level and a dissected flap extending from the left subclavian artery to the descending aorta. An elongated transverse aortic arch (ETA) and an aberrant right subclavian artery (ARSA) branching into the aortic isthmus as unusual anatomic location were seen. Periaortic hematoma formation was suspected of possible extravasation. In addition, a partial anomalous pulmonary venous connection (PAPVC) showed that the vertical vein connected to the left upper lobe drained into the left bra-chiocephalic vein ( Fig. 1A, B ). We planned an arch and descending aorta replacement surgery via an anterolateral thoracotomy under cardiopulmonary bypass. However, the patient was hesitant with regard to invasive surgery owing to her cosmetic concerns as a single woman. Her back pain gradually improved with analgesics, however, 3 days later, she again complained of acute sharp back pain. Subsequent CT scan revealed active aggravation of ruptured aortic dissection and aneurysmal dilatation on dissected aorta. The false lumen had increased in size to 10% of the aortic maximum diameter, measuring 3.9 cm, and left pleural fluid collection suspicious to hemothorax and periaortic hematoma had increased ( Fig. 2A, B ). We decided to perform an emergency operation for the recurrent back pain, enlarging periaortic hematoma and hemothorax. After consultation with the patient, we initially planned an anterolateral thoracotomy with left heart bypass. However, we determined that it would be too dangerous to clamp on the aortic isthmus near the ARSA owing to the frailty of the aneurysmal dilatation on the dissected aorta. In addition, the vertical vein running directly above the dissecting flap might have interfered with the operative field. Instead of open surgery, we decided to perform emergency thoracic endovascular aortic repair (TEVAR). However, because the patients had the ARSA with a dominant vertebral artery, we decided to perform a carotid to subclavian artery bypass with the dominant vertebral artery before TEVAR. Under general anesthesia, a right carotid and subclavian artery bypass was performed via supraclavicular transverse incision. A 7 mm Gore-Tex polytetrafluoroethylene Stretch graft was placed between the right carotid and subclavian arteries. After bypass, we exposed the patient’s right common femoral artery (CFA) through a longitudinal incision. Through the left CFA, a sizing catheter was inserted with angiography guidance for checking the length. Pre-deploying aortogram revealed ARCA branching from the aortic isthmus and aneurysmal dilatation on the dissected aorta including the left subclavian artery ( Fig. 3A ). An S&G SEAL thoracic stent graft (24×24×110 mm; S&G Biotech, Seongnam, Korea) was advanced through the right CFA. During stent graft insertion, a slightly strong resistance was encountered; however, post-procedural aortogram revealed no peripheral arterial injury. After stent graft deployment, aortography showed laminar blood flow through the devices and the thoracic aorta with complete exclusion of the dissecting aneurysm ( Fig. 3B ). There were no complications during the procedure, and the oversizing of stent grafts relative to the aorta did not exceed 10% to provide adequate radial force to keep the deployed stent grafts in place. The total operative time was 245 minutes, and the total contrast agent volume was 90 mL. Postoperatively, the blood pressure in both arms was nearly same and there was no evidence of ischemia. After postoperative day (POD) 5, CT scan revealed a well-functioning aortic isthmus stent graft without endoleaks, and complete occlusion of both subclavian artery orifices with distal run-off reserved from collateral flow ( Fig. 4A, B ). The patient was discharged on POD 6 without complications and is planning follow-up examination of the PAPVC at the cardiac and cardiovascular clinics.'}
|
Musculoskeletal-System
|
MSK
|
[
"short stature"
] |
6340697
|
{'CASE': 'A 32-year-old woman with Turner syndrome (143 cm/49 kg, body surface area 1.37 m 2 ) was admitted to Kyungpook National University Hospital center with complaint of sudden-onset back pain. She had been diagnosed with Turner syndrome twenty years prior following examination for her short stature. She was regularly treated with hormone replacement therapy as an outpatient of the obstetrics and gynecology. She felt well, worked as a kindergarten teacher, and was unmarried. On admission, her initial systolic blood pressure and heart rate were 131 mmHg and 68 beats per minute, respectively. Her blood pressures were almost equal in the upper and lower extremities. Her initial hemoglobin level was 11.8 g/dL, and electrocardiography revealed a normal sinus rhythm. An initial computed tomography (CT) scan revealed intimal dissection on aortic isthmus level and a dissected flap extending from the left subclavian artery to the descending aorta. An elongated transverse aortic arch (ETA) and an aberrant right subclavian artery (ARSA) branching into the aortic isthmus as unusual anatomic location were seen. Periaortic hematoma formation was suspected of possible extravasation. In addition, a partial anomalous pulmonary venous connection (PAPVC) showed that the vertical vein connected to the left upper lobe drained into the left bra-chiocephalic vein ( Fig. 1A, B ). We planned an arch and descending aorta replacement surgery via an anterolateral thoracotomy under cardiopulmonary bypass. However, the patient was hesitant with regard to invasive surgery owing to her cosmetic concerns as a single woman. Her back pain gradually improved with analgesics, however, 3 days later, she again complained of acute sharp back pain. Subsequent CT scan revealed active aggravation of ruptured aortic dissection and aneurysmal dilatation on dissected aorta. The false lumen had increased in size to 10% of the aortic maximum diameter, measuring 3.9 cm, and left pleural fluid collection suspicious to hemothorax and periaortic hematoma had increased ( Fig. 2A, B ). We decided to perform an emergency operation for the recurrent back pain, enlarging periaortic hematoma and hemothorax. After consultation with the patient, we initially planned an anterolateral thoracotomy with left heart bypass. However, we determined that it would be too dangerous to clamp on the aortic isthmus near the ARSA owing to the frailty of the aneurysmal dilatation on the dissected aorta. In addition, the vertical vein running directly above the dissecting flap might have interfered with the operative field. Instead of open surgery, we decided to perform emergency thoracic endovascular aortic repair (TEVAR). However, because the patients had the ARSA with a dominant vertebral artery, we decided to perform a carotid to subclavian artery bypass with the dominant vertebral artery before TEVAR. Under general anesthesia, a right carotid and subclavian artery bypass was performed via supraclavicular transverse incision. A 7 mm Gore-Tex polytetrafluoroethylene Stretch graft was placed between the right carotid and subclavian arteries. After bypass, we exposed the patient’s right common femoral artery (CFA) through a longitudinal incision. Through the left CFA, a sizing catheter was inserted with angiography guidance for checking the length. Pre-deploying aortogram revealed ARCA branching from the aortic isthmus and aneurysmal dilatation on the dissected aorta including the left subclavian artery ( Fig. 3A ). An S&G SEAL thoracic stent graft (24×24×110 mm; S&G Biotech, Seongnam, Korea) was advanced through the right CFA. During stent graft insertion, a slightly strong resistance was encountered; however, post-procedural aortogram revealed no peripheral arterial injury. After stent graft deployment, aortography showed laminar blood flow through the devices and the thoracic aorta with complete exclusion of the dissecting aneurysm ( Fig. 3B ). There were no complications during the procedure, and the oversizing of stent grafts relative to the aorta did not exceed 10% to provide adequate radial force to keep the deployed stent grafts in place. The total operative time was 245 minutes, and the total contrast agent volume was 90 mL. Postoperatively, the blood pressure in both arms was nearly same and there was no evidence of ischemia. After postoperative day (POD) 5, CT scan revealed a well-functioning aortic isthmus stent graft without endoleaks, and complete occlusion of both subclavian artery orifices with distal run-off reserved from collateral flow ( Fig. 4A, B ). The patient was discharged on POD 6 without complications and is planning follow-up examination of the PAPVC at the cardiac and cardiovascular clinics.'}
|
{'CASE': 'A 32-year-old woman with Turner syndrome (143 cm/49 kg, body surface area 1.37 m 2 ) was admitted to Kyungpook National University Hospital center with complaint of sudden-onset back pain. She had been diagnosed with Turner syndrome twenty years prior following examination for her short stature. She was regularly treated with hormone replacement therapy as an outpatient of the obstetrics and gynecology. She felt well, worked as a kindergarten teacher, and was unmarried. On admission, her initial systolic blood pressure and heart rate were 131 mmHg and 68 beats per minute, respectively. Her blood pressures were almost equal in the upper and lower extremities. Her initial hemoglobin level was 11.8 g/dL, and electrocardiography revealed a normal sinus rhythm. An initial computed tomography (CT) scan revealed intimal dissection on aortic isthmus level and a dissected flap extending from the left subclavian artery to the descending aorta. An elongated transverse aortic arch (ETA) and an aberrant right subclavian artery (ARSA) branching into the aortic isthmus as unusual anatomic location were seen. Periaortic hematoma formation was suspected of possible extravasation. In addition, a partial anomalous pulmonary venous connection (PAPVC) showed that the vertical vein connected to the left upper lobe drained into the left bra-chiocephalic vein ( Fig. 1A, B ). We planned an arch and descending aorta replacement surgery via an anterolateral thoracotomy under cardiopulmonary bypass. However, the patient was hesitant with regard to invasive surgery owing to her cosmetic concerns as a single woman. Her back pain gradually improved with analgesics, however, 3 days later, she again complained of acute sharp back pain. Subsequent CT scan revealed active aggravation of ruptured aortic dissection and aneurysmal dilatation on dissected aorta. The false lumen had increased in size to 10% of the aortic maximum diameter, measuring 3.9 cm, and left pleural fluid collection suspicious to hemothorax and periaortic hematoma had increased ( Fig. 2A, B ). We decided to perform an emergency operation for the recurrent back pain, enlarging periaortic hematoma and hemothorax. After consultation with the patient, we initially planned an anterolateral thoracotomy with left heart bypass. However, we determined that it would be too dangerous to clamp on the aortic isthmus near the ARSA owing to the frailty of the aneurysmal dilatation on the dissected aorta. In addition, the vertical vein running directly above the dissecting flap might have interfered with the operative field. Instead of open surgery, we decided to perform emergency thoracic endovascular aortic repair (TEVAR). However, because the patients had the ARSA with a dominant vertebral artery, we decided to perform a carotid to subclavian artery bypass with the dominant vertebral artery before TEVAR. Under general anesthesia, a right carotid and subclavian artery bypass was performed via supraclavicular transverse incision. A 7 mm Gore-Tex polytetrafluoroethylene Stretch graft was placed between the right carotid and subclavian arteries. After bypass, we exposed the patient’s right common femoral artery (CFA) through a longitudinal incision. Through the left CFA, a sizing catheter was inserted with angiography guidance for checking the length. Pre-deploying aortogram revealed ARCA branching from the aortic isthmus and aneurysmal dilatation on the dissected aorta including the left subclavian artery ( Fig. 3A ). An S&G SEAL thoracic stent graft (24×24×110 mm; S&G Biotech, Seongnam, Korea) was advanced through the right CFA. During stent graft insertion, a slightly strong resistance was encountered; however, post-procedural aortogram revealed no peripheral arterial injury. After stent graft deployment, aortography showed laminar blood flow through the devices and the thoracic aorta with complete exclusion of the dissecting aneurysm ( Fig. 3B ). There were no complications during the procedure, and the oversizing of stent grafts relative to the aorta did not exceed 10% to provide adequate radial force to keep the deployed stent grafts in place. The total operative time was 245 minutes, and the total contrast agent volume was 90 mL. Postoperatively, the blood pressure in both arms was nearly same and there was no evidence of ischemia. After postoperative day (POD) 5, CT scan revealed a well-functioning aortic isthmus stent graft without endoleaks, and complete occlusion of both subclavian artery orifices with distal run-off reserved from collateral flow ( Fig. 4A, B ). The patient was discharged on POD 6 without complications and is planning follow-up examination of the PAPVC at the cardiac and cardiovascular clinics.'}
|
Eyes-Ears-Nose-Throat
|
EENT
|
[] |
6340697
|
{'CASE': 'A 32-year-old woman with Turner syndrome (143 cm/49 kg, body surface area 1.37 m 2 ) was admitted to Kyungpook National University Hospital center with complaint of sudden-onset back pain. She had been diagnosed with Turner syndrome twenty years prior following examination for her short stature. She was regularly treated with hormone replacement therapy as an outpatient of the obstetrics and gynecology. She felt well, worked as a kindergarten teacher, and was unmarried. On admission, her initial systolic blood pressure and heart rate were 131 mmHg and 68 beats per minute, respectively. Her blood pressures were almost equal in the upper and lower extremities. Her initial hemoglobin level was 11.8 g/dL, and electrocardiography revealed a normal sinus rhythm. An initial computed tomography (CT) scan revealed intimal dissection on aortic isthmus level and a dissected flap extending from the left subclavian artery to the descending aorta. An elongated transverse aortic arch (ETA) and an aberrant right subclavian artery (ARSA) branching into the aortic isthmus as unusual anatomic location were seen. Periaortic hematoma formation was suspected of possible extravasation. In addition, a partial anomalous pulmonary venous connection (PAPVC) showed that the vertical vein connected to the left upper lobe drained into the left bra-chiocephalic vein ( Fig. 1A, B ). We planned an arch and descending aorta replacement surgery via an anterolateral thoracotomy under cardiopulmonary bypass. However, the patient was hesitant with regard to invasive surgery owing to her cosmetic concerns as a single woman. Her back pain gradually improved with analgesics, however, 3 days later, she again complained of acute sharp back pain. Subsequent CT scan revealed active aggravation of ruptured aortic dissection and aneurysmal dilatation on dissected aorta. The false lumen had increased in size to 10% of the aortic maximum diameter, measuring 3.9 cm, and left pleural fluid collection suspicious to hemothorax and periaortic hematoma had increased ( Fig. 2A, B ). We decided to perform an emergency operation for the recurrent back pain, enlarging periaortic hematoma and hemothorax. After consultation with the patient, we initially planned an anterolateral thoracotomy with left heart bypass. However, we determined that it would be too dangerous to clamp on the aortic isthmus near the ARSA owing to the frailty of the aneurysmal dilatation on the dissected aorta. In addition, the vertical vein running directly above the dissecting flap might have interfered with the operative field. Instead of open surgery, we decided to perform emergency thoracic endovascular aortic repair (TEVAR). However, because the patients had the ARSA with a dominant vertebral artery, we decided to perform a carotid to subclavian artery bypass with the dominant vertebral artery before TEVAR. Under general anesthesia, a right carotid and subclavian artery bypass was performed via supraclavicular transverse incision. A 7 mm Gore-Tex polytetrafluoroethylene Stretch graft was placed between the right carotid and subclavian arteries. After bypass, we exposed the patient’s right common femoral artery (CFA) through a longitudinal incision. Through the left CFA, a sizing catheter was inserted with angiography guidance for checking the length. Pre-deploying aortogram revealed ARCA branching from the aortic isthmus and aneurysmal dilatation on the dissected aorta including the left subclavian artery ( Fig. 3A ). An S&G SEAL thoracic stent graft (24×24×110 mm; S&G Biotech, Seongnam, Korea) was advanced through the right CFA. During stent graft insertion, a slightly strong resistance was encountered; however, post-procedural aortogram revealed no peripheral arterial injury. After stent graft deployment, aortography showed laminar blood flow through the devices and the thoracic aorta with complete exclusion of the dissecting aneurysm ( Fig. 3B ). There were no complications during the procedure, and the oversizing of stent grafts relative to the aorta did not exceed 10% to provide adequate radial force to keep the deployed stent grafts in place. The total operative time was 245 minutes, and the total contrast agent volume was 90 mL. Postoperatively, the blood pressure in both arms was nearly same and there was no evidence of ischemia. After postoperative day (POD) 5, CT scan revealed a well-functioning aortic isthmus stent graft without endoleaks, and complete occlusion of both subclavian artery orifices with distal run-off reserved from collateral flow ( Fig. 4A, B ). The patient was discharged on POD 6 without complications and is planning follow-up examination of the PAPVC at the cardiac and cardiovascular clinics.'}
|
{'CASE': 'A 32-year-old woman with Turner syndrome (143 cm/49 kg, body surface area 1.37 m 2 ) was admitted to Kyungpook National University Hospital center with complaint of sudden-onset back pain. She had been diagnosed with Turner syndrome twenty years prior following examination for her short stature. She was regularly treated with hormone replacement therapy as an outpatient of the obstetrics and gynecology. She felt well, worked as a kindergarten teacher, and was unmarried. On admission, her initial systolic blood pressure and heart rate were 131 mmHg and 68 beats per minute, respectively. Her blood pressures were almost equal in the upper and lower extremities. Her initial hemoglobin level was 11.8 g/dL, and electrocardiography revealed a normal sinus rhythm. An initial computed tomography (CT) scan revealed intimal dissection on aortic isthmus level and a dissected flap extending from the left subclavian artery to the descending aorta. An elongated transverse aortic arch (ETA) and an aberrant right subclavian artery (ARSA) branching into the aortic isthmus as unusual anatomic location were seen. Periaortic hematoma formation was suspected of possible extravasation. In addition, a partial anomalous pulmonary venous connection (PAPVC) showed that the vertical vein connected to the left upper lobe drained into the left bra-chiocephalic vein ( Fig. 1A, B ). We planned an arch and descending aorta replacement surgery via an anterolateral thoracotomy under cardiopulmonary bypass. However, the patient was hesitant with regard to invasive surgery owing to her cosmetic concerns as a single woman. Her back pain gradually improved with analgesics, however, 3 days later, she again complained of acute sharp back pain. Subsequent CT scan revealed active aggravation of ruptured aortic dissection and aneurysmal dilatation on dissected aorta. The false lumen had increased in size to 10% of the aortic maximum diameter, measuring 3.9 cm, and left pleural fluid collection suspicious to hemothorax and periaortic hematoma had increased ( Fig. 2A, B ). We decided to perform an emergency operation for the recurrent back pain, enlarging periaortic hematoma and hemothorax. After consultation with the patient, we initially planned an anterolateral thoracotomy with left heart bypass. However, we determined that it would be too dangerous to clamp on the aortic isthmus near the ARSA owing to the frailty of the aneurysmal dilatation on the dissected aorta. In addition, the vertical vein running directly above the dissecting flap might have interfered with the operative field. Instead of open surgery, we decided to perform emergency thoracic endovascular aortic repair (TEVAR). However, because the patients had the ARSA with a dominant vertebral artery, we decided to perform a carotid to subclavian artery bypass with the dominant vertebral artery before TEVAR. Under general anesthesia, a right carotid and subclavian artery bypass was performed via supraclavicular transverse incision. A 7 mm Gore-Tex polytetrafluoroethylene Stretch graft was placed between the right carotid and subclavian arteries. After bypass, we exposed the patient’s right common femoral artery (CFA) through a longitudinal incision. Through the left CFA, a sizing catheter was inserted with angiography guidance for checking the length. Pre-deploying aortogram revealed ARCA branching from the aortic isthmus and aneurysmal dilatation on the dissected aorta including the left subclavian artery ( Fig. 3A ). An S&G SEAL thoracic stent graft (24×24×110 mm; S&G Biotech, Seongnam, Korea) was advanced through the right CFA. During stent graft insertion, a slightly strong resistance was encountered; however, post-procedural aortogram revealed no peripheral arterial injury. After stent graft deployment, aortography showed laminar blood flow through the devices and the thoracic aorta with complete exclusion of the dissecting aneurysm ( Fig. 3B ). There were no complications during the procedure, and the oversizing of stent grafts relative to the aorta did not exceed 10% to provide adequate radial force to keep the deployed stent grafts in place. The total operative time was 245 minutes, and the total contrast agent volume was 90 mL. Postoperatively, the blood pressure in both arms was nearly same and there was no evidence of ischemia. After postoperative day (POD) 5, CT scan revealed a well-functioning aortic isthmus stent graft without endoleaks, and complete occlusion of both subclavian artery orifices with distal run-off reserved from collateral flow ( Fig. 4A, B ). The patient was discharged on POD 6 without complications and is planning follow-up examination of the PAPVC at the cardiac and cardiovascular clinics.'}
|
Dermatology
|
DERM
|
[] |
6340697
|
{'CASE': 'A 32-year-old woman with Turner syndrome (143 cm/49 kg, body surface area 1.37 m 2 ) was admitted to Kyungpook National University Hospital center with complaint of sudden-onset back pain. She had been diagnosed with Turner syndrome twenty years prior following examination for her short stature. She was regularly treated with hormone replacement therapy as an outpatient of the obstetrics and gynecology. She felt well, worked as a kindergarten teacher, and was unmarried. On admission, her initial systolic blood pressure and heart rate were 131 mmHg and 68 beats per minute, respectively. Her blood pressures were almost equal in the upper and lower extremities. Her initial hemoglobin level was 11.8 g/dL, and electrocardiography revealed a normal sinus rhythm. An initial computed tomography (CT) scan revealed intimal dissection on aortic isthmus level and a dissected flap extending from the left subclavian artery to the descending aorta. An elongated transverse aortic arch (ETA) and an aberrant right subclavian artery (ARSA) branching into the aortic isthmus as unusual anatomic location were seen. Periaortic hematoma formation was suspected of possible extravasation. In addition, a partial anomalous pulmonary venous connection (PAPVC) showed that the vertical vein connected to the left upper lobe drained into the left bra-chiocephalic vein ( Fig. 1A, B ). We planned an arch and descending aorta replacement surgery via an anterolateral thoracotomy under cardiopulmonary bypass. However, the patient was hesitant with regard to invasive surgery owing to her cosmetic concerns as a single woman. Her back pain gradually improved with analgesics, however, 3 days later, she again complained of acute sharp back pain. Subsequent CT scan revealed active aggravation of ruptured aortic dissection and aneurysmal dilatation on dissected aorta. The false lumen had increased in size to 10% of the aortic maximum diameter, measuring 3.9 cm, and left pleural fluid collection suspicious to hemothorax and periaortic hematoma had increased ( Fig. 2A, B ). We decided to perform an emergency operation for the recurrent back pain, enlarging periaortic hematoma and hemothorax. After consultation with the patient, we initially planned an anterolateral thoracotomy with left heart bypass. However, we determined that it would be too dangerous to clamp on the aortic isthmus near the ARSA owing to the frailty of the aneurysmal dilatation on the dissected aorta. In addition, the vertical vein running directly above the dissecting flap might have interfered with the operative field. Instead of open surgery, we decided to perform emergency thoracic endovascular aortic repair (TEVAR). However, because the patients had the ARSA with a dominant vertebral artery, we decided to perform a carotid to subclavian artery bypass with the dominant vertebral artery before TEVAR. Under general anesthesia, a right carotid and subclavian artery bypass was performed via supraclavicular transverse incision. A 7 mm Gore-Tex polytetrafluoroethylene Stretch graft was placed between the right carotid and subclavian arteries. After bypass, we exposed the patient’s right common femoral artery (CFA) through a longitudinal incision. Through the left CFA, a sizing catheter was inserted with angiography guidance for checking the length. Pre-deploying aortogram revealed ARCA branching from the aortic isthmus and aneurysmal dilatation on the dissected aorta including the left subclavian artery ( Fig. 3A ). An S&G SEAL thoracic stent graft (24×24×110 mm; S&G Biotech, Seongnam, Korea) was advanced through the right CFA. During stent graft insertion, a slightly strong resistance was encountered; however, post-procedural aortogram revealed no peripheral arterial injury. After stent graft deployment, aortography showed laminar blood flow through the devices and the thoracic aorta with complete exclusion of the dissecting aneurysm ( Fig. 3B ). There were no complications during the procedure, and the oversizing of stent grafts relative to the aorta did not exceed 10% to provide adequate radial force to keep the deployed stent grafts in place. The total operative time was 245 minutes, and the total contrast agent volume was 90 mL. Postoperatively, the blood pressure in both arms was nearly same and there was no evidence of ischemia. After postoperative day (POD) 5, CT scan revealed a well-functioning aortic isthmus stent graft without endoleaks, and complete occlusion of both subclavian artery orifices with distal run-off reserved from collateral flow ( Fig. 4A, B ). The patient was discharged on POD 6 without complications and is planning follow-up examination of the PAPVC at the cardiac and cardiovascular clinics.'}
|
{'CASE': 'A 32-year-old woman with Turner syndrome (143 cm/49 kg, body surface area 1.37 m 2 ) was admitted to Kyungpook National University Hospital center with complaint of sudden-onset back pain. She had been diagnosed with Turner syndrome twenty years prior following examination for her short stature. She was regularly treated with hormone replacement therapy as an outpatient of the obstetrics and gynecology. She felt well, worked as a kindergarten teacher, and was unmarried. On admission, her initial systolic blood pressure and heart rate were 131 mmHg and 68 beats per minute, respectively. Her blood pressures were almost equal in the upper and lower extremities. Her initial hemoglobin level was 11.8 g/dL, and electrocardiography revealed a normal sinus rhythm. An initial computed tomography (CT) scan revealed intimal dissection on aortic isthmus level and a dissected flap extending from the left subclavian artery to the descending aorta. An elongated transverse aortic arch (ETA) and an aberrant right subclavian artery (ARSA) branching into the aortic isthmus as unusual anatomic location were seen. Periaortic hematoma formation was suspected of possible extravasation. In addition, a partial anomalous pulmonary venous connection (PAPVC) showed that the vertical vein connected to the left upper lobe drained into the left bra-chiocephalic vein ( Fig. 1A, B ). We planned an arch and descending aorta replacement surgery via an anterolateral thoracotomy under cardiopulmonary bypass. However, the patient was hesitant with regard to invasive surgery owing to her cosmetic concerns as a single woman. Her back pain gradually improved with analgesics, however, 3 days later, she again complained of acute sharp back pain. Subsequent CT scan revealed active aggravation of ruptured aortic dissection and aneurysmal dilatation on dissected aorta. The false lumen had increased in size to 10% of the aortic maximum diameter, measuring 3.9 cm, and left pleural fluid collection suspicious to hemothorax and periaortic hematoma had increased ( Fig. 2A, B ). We decided to perform an emergency operation for the recurrent back pain, enlarging periaortic hematoma and hemothorax. After consultation with the patient, we initially planned an anterolateral thoracotomy with left heart bypass. However, we determined that it would be too dangerous to clamp on the aortic isthmus near the ARSA owing to the frailty of the aneurysmal dilatation on the dissected aorta. In addition, the vertical vein running directly above the dissecting flap might have interfered with the operative field. Instead of open surgery, we decided to perform emergency thoracic endovascular aortic repair (TEVAR). However, because the patients had the ARSA with a dominant vertebral artery, we decided to perform a carotid to subclavian artery bypass with the dominant vertebral artery before TEVAR. Under general anesthesia, a right carotid and subclavian artery bypass was performed via supraclavicular transverse incision. A 7 mm Gore-Tex polytetrafluoroethylene Stretch graft was placed between the right carotid and subclavian arteries. After bypass, we exposed the patient’s right common femoral artery (CFA) through a longitudinal incision. Through the left CFA, a sizing catheter was inserted with angiography guidance for checking the length. Pre-deploying aortogram revealed ARCA branching from the aortic isthmus and aneurysmal dilatation on the dissected aorta including the left subclavian artery ( Fig. 3A ). An S&G SEAL thoracic stent graft (24×24×110 mm; S&G Biotech, Seongnam, Korea) was advanced through the right CFA. During stent graft insertion, a slightly strong resistance was encountered; however, post-procedural aortogram revealed no peripheral arterial injury. After stent graft deployment, aortography showed laminar blood flow through the devices and the thoracic aorta with complete exclusion of the dissecting aneurysm ( Fig. 3B ). There were no complications during the procedure, and the oversizing of stent grafts relative to the aorta did not exceed 10% to provide adequate radial force to keep the deployed stent grafts in place. The total operative time was 245 minutes, and the total contrast agent volume was 90 mL. Postoperatively, the blood pressure in both arms was nearly same and there was no evidence of ischemia. After postoperative day (POD) 5, CT scan revealed a well-functioning aortic isthmus stent graft without endoleaks, and complete occlusion of both subclavian artery orifices with distal run-off reserved from collateral flow ( Fig. 4A, B ). The patient was discharged on POD 6 without complications and is planning follow-up examination of the PAPVC at the cardiac and cardiovascular clinics.'}
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Pregnancy
|
Pregnancy
|
[] |
6340697
|
{'CASE': 'A 32-year-old woman with Turner syndrome (143 cm/49 kg, body surface area 1.37 m 2 ) was admitted to Kyungpook National University Hospital center with complaint of sudden-onset back pain. She had been diagnosed with Turner syndrome twenty years prior following examination for her short stature. She was regularly treated with hormone replacement therapy as an outpatient of the obstetrics and gynecology. She felt well, worked as a kindergarten teacher, and was unmarried. On admission, her initial systolic blood pressure and heart rate were 131 mmHg and 68 beats per minute, respectively. Her blood pressures were almost equal in the upper and lower extremities. Her initial hemoglobin level was 11.8 g/dL, and electrocardiography revealed a normal sinus rhythm. An initial computed tomography (CT) scan revealed intimal dissection on aortic isthmus level and a dissected flap extending from the left subclavian artery to the descending aorta. An elongated transverse aortic arch (ETA) and an aberrant right subclavian artery (ARSA) branching into the aortic isthmus as unusual anatomic location were seen. Periaortic hematoma formation was suspected of possible extravasation. In addition, a partial anomalous pulmonary venous connection (PAPVC) showed that the vertical vein connected to the left upper lobe drained into the left bra-chiocephalic vein ( Fig. 1A, B ). We planned an arch and descending aorta replacement surgery via an anterolateral thoracotomy under cardiopulmonary bypass. However, the patient was hesitant with regard to invasive surgery owing to her cosmetic concerns as a single woman. Her back pain gradually improved with analgesics, however, 3 days later, she again complained of acute sharp back pain. Subsequent CT scan revealed active aggravation of ruptured aortic dissection and aneurysmal dilatation on dissected aorta. The false lumen had increased in size to 10% of the aortic maximum diameter, measuring 3.9 cm, and left pleural fluid collection suspicious to hemothorax and periaortic hematoma had increased ( Fig. 2A, B ). We decided to perform an emergency operation for the recurrent back pain, enlarging periaortic hematoma and hemothorax. After consultation with the patient, we initially planned an anterolateral thoracotomy with left heart bypass. However, we determined that it would be too dangerous to clamp on the aortic isthmus near the ARSA owing to the frailty of the aneurysmal dilatation on the dissected aorta. In addition, the vertical vein running directly above the dissecting flap might have interfered with the operative field. Instead of open surgery, we decided to perform emergency thoracic endovascular aortic repair (TEVAR). However, because the patients had the ARSA with a dominant vertebral artery, we decided to perform a carotid to subclavian artery bypass with the dominant vertebral artery before TEVAR. Under general anesthesia, a right carotid and subclavian artery bypass was performed via supraclavicular transverse incision. A 7 mm Gore-Tex polytetrafluoroethylene Stretch graft was placed between the right carotid and subclavian arteries. After bypass, we exposed the patient’s right common femoral artery (CFA) through a longitudinal incision. Through the left CFA, a sizing catheter was inserted with angiography guidance for checking the length. Pre-deploying aortogram revealed ARCA branching from the aortic isthmus and aneurysmal dilatation on the dissected aorta including the left subclavian artery ( Fig. 3A ). An S&G SEAL thoracic stent graft (24×24×110 mm; S&G Biotech, Seongnam, Korea) was advanced through the right CFA. During stent graft insertion, a slightly strong resistance was encountered; however, post-procedural aortogram revealed no peripheral arterial injury. After stent graft deployment, aortography showed laminar blood flow through the devices and the thoracic aorta with complete exclusion of the dissecting aneurysm ( Fig. 3B ). There were no complications during the procedure, and the oversizing of stent grafts relative to the aorta did not exceed 10% to provide adequate radial force to keep the deployed stent grafts in place. The total operative time was 245 minutes, and the total contrast agent volume was 90 mL. Postoperatively, the blood pressure in both arms was nearly same and there was no evidence of ischemia. After postoperative day (POD) 5, CT scan revealed a well-functioning aortic isthmus stent graft without endoleaks, and complete occlusion of both subclavian artery orifices with distal run-off reserved from collateral flow ( Fig. 4A, B ). The patient was discharged on POD 6 without complications and is planning follow-up examination of the PAPVC at the cardiac and cardiovascular clinics.'}
|
{'CASE': 'A 32-year-old woman with Turner syndrome (143 cm/49 kg, body surface area 1.37 m 2 ) was admitted to Kyungpook National University Hospital center with complaint of sudden-onset back pain. She had been diagnosed with Turner syndrome twenty years prior following examination for her short stature. She was regularly treated with hormone replacement therapy as an outpatient of the obstetrics and gynecology. She felt well, worked as a kindergarten teacher, and was unmarried. On admission, her initial systolic blood pressure and heart rate were 131 mmHg and 68 beats per minute, respectively. Her blood pressures were almost equal in the upper and lower extremities. Her initial hemoglobin level was 11.8 g/dL, and electrocardiography revealed a normal sinus rhythm. An initial computed tomography (CT) scan revealed intimal dissection on aortic isthmus level and a dissected flap extending from the left subclavian artery to the descending aorta. An elongated transverse aortic arch (ETA) and an aberrant right subclavian artery (ARSA) branching into the aortic isthmus as unusual anatomic location were seen. Periaortic hematoma formation was suspected of possible extravasation. In addition, a partial anomalous pulmonary venous connection (PAPVC) showed that the vertical vein connected to the left upper lobe drained into the left bra-chiocephalic vein ( Fig. 1A, B ). We planned an arch and descending aorta replacement surgery via an anterolateral thoracotomy under cardiopulmonary bypass. However, the patient was hesitant with regard to invasive surgery owing to her cosmetic concerns as a single woman. Her back pain gradually improved with analgesics, however, 3 days later, she again complained of acute sharp back pain. Subsequent CT scan revealed active aggravation of ruptured aortic dissection and aneurysmal dilatation on dissected aorta. The false lumen had increased in size to 10% of the aortic maximum diameter, measuring 3.9 cm, and left pleural fluid collection suspicious to hemothorax and periaortic hematoma had increased ( Fig. 2A, B ). We decided to perform an emergency operation for the recurrent back pain, enlarging periaortic hematoma and hemothorax. After consultation with the patient, we initially planned an anterolateral thoracotomy with left heart bypass. However, we determined that it would be too dangerous to clamp on the aortic isthmus near the ARSA owing to the frailty of the aneurysmal dilatation on the dissected aorta. In addition, the vertical vein running directly above the dissecting flap might have interfered with the operative field. Instead of open surgery, we decided to perform emergency thoracic endovascular aortic repair (TEVAR). However, because the patients had the ARSA with a dominant vertebral artery, we decided to perform a carotid to subclavian artery bypass with the dominant vertebral artery before TEVAR. Under general anesthesia, a right carotid and subclavian artery bypass was performed via supraclavicular transverse incision. A 7 mm Gore-Tex polytetrafluoroethylene Stretch graft was placed between the right carotid and subclavian arteries. After bypass, we exposed the patient’s right common femoral artery (CFA) through a longitudinal incision. Through the left CFA, a sizing catheter was inserted with angiography guidance for checking the length. Pre-deploying aortogram revealed ARCA branching from the aortic isthmus and aneurysmal dilatation on the dissected aorta including the left subclavian artery ( Fig. 3A ). An S&G SEAL thoracic stent graft (24×24×110 mm; S&G Biotech, Seongnam, Korea) was advanced through the right CFA. During stent graft insertion, a slightly strong resistance was encountered; however, post-procedural aortogram revealed no peripheral arterial injury. After stent graft deployment, aortography showed laminar blood flow through the devices and the thoracic aorta with complete exclusion of the dissecting aneurysm ( Fig. 3B ). There were no complications during the procedure, and the oversizing of stent grafts relative to the aorta did not exceed 10% to provide adequate radial force to keep the deployed stent grafts in place. The total operative time was 245 minutes, and the total contrast agent volume was 90 mL. Postoperatively, the blood pressure in both arms was nearly same and there was no evidence of ischemia. After postoperative day (POD) 5, CT scan revealed a well-functioning aortic isthmus stent graft without endoleaks, and complete occlusion of both subclavian artery orifices with distal run-off reserved from collateral flow ( Fig. 4A, B ). The patient was discharged on POD 6 without complications and is planning follow-up examination of the PAPVC at the cardiac and cardiovascular clinics.'}
|
Lymphatic-System
|
LYMPH
|
[] |
6340697
|
{'CASE': 'A 32-year-old woman with Turner syndrome (143 cm/49 kg, body surface area 1.37 m 2 ) was admitted to Kyungpook National University Hospital center with complaint of sudden-onset back pain. She had been diagnosed with Turner syndrome twenty years prior following examination for her short stature. She was regularly treated with hormone replacement therapy as an outpatient of the obstetrics and gynecology. She felt well, worked as a kindergarten teacher, and was unmarried. On admission, her initial systolic blood pressure and heart rate were 131 mmHg and 68 beats per minute, respectively. Her blood pressures were almost equal in the upper and lower extremities. Her initial hemoglobin level was 11.8 g/dL, and electrocardiography revealed a normal sinus rhythm. An initial computed tomography (CT) scan revealed intimal dissection on aortic isthmus level and a dissected flap extending from the left subclavian artery to the descending aorta. An elongated transverse aortic arch (ETA) and an aberrant right subclavian artery (ARSA) branching into the aortic isthmus as unusual anatomic location were seen. Periaortic hematoma formation was suspected of possible extravasation. In addition, a partial anomalous pulmonary venous connection (PAPVC) showed that the vertical vein connected to the left upper lobe drained into the left bra-chiocephalic vein ( Fig. 1A, B ). We planned an arch and descending aorta replacement surgery via an anterolateral thoracotomy under cardiopulmonary bypass. However, the patient was hesitant with regard to invasive surgery owing to her cosmetic concerns as a single woman. Her back pain gradually improved with analgesics, however, 3 days later, she again complained of acute sharp back pain. Subsequent CT scan revealed active aggravation of ruptured aortic dissection and aneurysmal dilatation on dissected aorta. The false lumen had increased in size to 10% of the aortic maximum diameter, measuring 3.9 cm, and left pleural fluid collection suspicious to hemothorax and periaortic hematoma had increased ( Fig. 2A, B ). We decided to perform an emergency operation for the recurrent back pain, enlarging periaortic hematoma and hemothorax. After consultation with the patient, we initially planned an anterolateral thoracotomy with left heart bypass. However, we determined that it would be too dangerous to clamp on the aortic isthmus near the ARSA owing to the frailty of the aneurysmal dilatation on the dissected aorta. In addition, the vertical vein running directly above the dissecting flap might have interfered with the operative field. Instead of open surgery, we decided to perform emergency thoracic endovascular aortic repair (TEVAR). However, because the patients had the ARSA with a dominant vertebral artery, we decided to perform a carotid to subclavian artery bypass with the dominant vertebral artery before TEVAR. Under general anesthesia, a right carotid and subclavian artery bypass was performed via supraclavicular transverse incision. A 7 mm Gore-Tex polytetrafluoroethylene Stretch graft was placed between the right carotid and subclavian arteries. After bypass, we exposed the patient’s right common femoral artery (CFA) through a longitudinal incision. Through the left CFA, a sizing catheter was inserted with angiography guidance for checking the length. Pre-deploying aortogram revealed ARCA branching from the aortic isthmus and aneurysmal dilatation on the dissected aorta including the left subclavian artery ( Fig. 3A ). An S&G SEAL thoracic stent graft (24×24×110 mm; S&G Biotech, Seongnam, Korea) was advanced through the right CFA. During stent graft insertion, a slightly strong resistance was encountered; however, post-procedural aortogram revealed no peripheral arterial injury. After stent graft deployment, aortography showed laminar blood flow through the devices and the thoracic aorta with complete exclusion of the dissecting aneurysm ( Fig. 3B ). There were no complications during the procedure, and the oversizing of stent grafts relative to the aorta did not exceed 10% to provide adequate radial force to keep the deployed stent grafts in place. The total operative time was 245 minutes, and the total contrast agent volume was 90 mL. Postoperatively, the blood pressure in both arms was nearly same and there was no evidence of ischemia. After postoperative day (POD) 5, CT scan revealed a well-functioning aortic isthmus stent graft without endoleaks, and complete occlusion of both subclavian artery orifices with distal run-off reserved from collateral flow ( Fig. 4A, B ). The patient was discharged on POD 6 without complications and is planning follow-up examination of the PAPVC at the cardiac and cardiovascular clinics.'}
|
{'CASE': 'A 32-year-old woman with Turner syndrome (143 cm/49 kg, body surface area 1.37 m 2 ) was admitted to Kyungpook National University Hospital center with complaint of sudden-onset back pain. She had been diagnosed with Turner syndrome twenty years prior following examination for her short stature. She was regularly treated with hormone replacement therapy as an outpatient of the obstetrics and gynecology. She felt well, worked as a kindergarten teacher, and was unmarried. On admission, her initial systolic blood pressure and heart rate were 131 mmHg and 68 beats per minute, respectively. Her blood pressures were almost equal in the upper and lower extremities. Her initial hemoglobin level was 11.8 g/dL, and electrocardiography revealed a normal sinus rhythm. An initial computed tomography (CT) scan revealed intimal dissection on aortic isthmus level and a dissected flap extending from the left subclavian artery to the descending aorta. An elongated transverse aortic arch (ETA) and an aberrant right subclavian artery (ARSA) branching into the aortic isthmus as unusual anatomic location were seen. Periaortic hematoma formation was suspected of possible extravasation. In addition, a partial anomalous pulmonary venous connection (PAPVC) showed that the vertical vein connected to the left upper lobe drained into the left bra-chiocephalic vein ( Fig. 1A, B ). We planned an arch and descending aorta replacement surgery via an anterolateral thoracotomy under cardiopulmonary bypass. However, the patient was hesitant with regard to invasive surgery owing to her cosmetic concerns as a single woman. Her back pain gradually improved with analgesics, however, 3 days later, she again complained of acute sharp back pain. Subsequent CT scan revealed active aggravation of ruptured aortic dissection and aneurysmal dilatation on dissected aorta. The false lumen had increased in size to 10% of the aortic maximum diameter, measuring 3.9 cm, and left pleural fluid collection suspicious to hemothorax and periaortic hematoma had increased ( Fig. 2A, B ). We decided to perform an emergency operation for the recurrent back pain, enlarging periaortic hematoma and hemothorax. After consultation with the patient, we initially planned an anterolateral thoracotomy with left heart bypass. However, we determined that it would be too dangerous to clamp on the aortic isthmus near the ARSA owing to the frailty of the aneurysmal dilatation on the dissected aorta. In addition, the vertical vein running directly above the dissecting flap might have interfered with the operative field. Instead of open surgery, we decided to perform emergency thoracic endovascular aortic repair (TEVAR). However, because the patients had the ARSA with a dominant vertebral artery, we decided to perform a carotid to subclavian artery bypass with the dominant vertebral artery before TEVAR. Under general anesthesia, a right carotid and subclavian artery bypass was performed via supraclavicular transverse incision. A 7 mm Gore-Tex polytetrafluoroethylene Stretch graft was placed between the right carotid and subclavian arteries. After bypass, we exposed the patient’s right common femoral artery (CFA) through a longitudinal incision. Through the left CFA, a sizing catheter was inserted with angiography guidance for checking the length. Pre-deploying aortogram revealed ARCA branching from the aortic isthmus and aneurysmal dilatation on the dissected aorta including the left subclavian artery ( Fig. 3A ). An S&G SEAL thoracic stent graft (24×24×110 mm; S&G Biotech, Seongnam, Korea) was advanced through the right CFA. During stent graft insertion, a slightly strong resistance was encountered; however, post-procedural aortogram revealed no peripheral arterial injury. After stent graft deployment, aortography showed laminar blood flow through the devices and the thoracic aorta with complete exclusion of the dissecting aneurysm ( Fig. 3B ). There were no complications during the procedure, and the oversizing of stent grafts relative to the aorta did not exceed 10% to provide adequate radial force to keep the deployed stent grafts in place. The total operative time was 245 minutes, and the total contrast agent volume was 90 mL. Postoperatively, the blood pressure in both arms was nearly same and there was no evidence of ischemia. After postoperative day (POD) 5, CT scan revealed a well-functioning aortic isthmus stent graft without endoleaks, and complete occlusion of both subclavian artery orifices with distal run-off reserved from collateral flow ( Fig. 4A, B ). The patient was discharged on POD 6 without complications and is planning follow-up examination of the PAPVC at the cardiac and cardiovascular clinics.'}
|
Age-at-Presentation
|
Age (at case presentation)
|
[
"32 - year - old"
] |
6340697
|
{'CASE': 'A 32-year-old woman with Turner syndrome (143 cm/49 kg, body surface area 1.37 m 2 ) was admitted to Kyungpook National University Hospital center with complaint of sudden-onset back pain. She had been diagnosed with Turner syndrome twenty years prior following examination for her short stature. She was regularly treated with hormone replacement therapy as an outpatient of the obstetrics and gynecology. She felt well, worked as a kindergarten teacher, and was unmarried. On admission, her initial systolic blood pressure and heart rate were 131 mmHg and 68 beats per minute, respectively. Her blood pressures were almost equal in the upper and lower extremities. Her initial hemoglobin level was 11.8 g/dL, and electrocardiography revealed a normal sinus rhythm. An initial computed tomography (CT) scan revealed intimal dissection on aortic isthmus level and a dissected flap extending from the left subclavian artery to the descending aorta. An elongated transverse aortic arch (ETA) and an aberrant right subclavian artery (ARSA) branching into the aortic isthmus as unusual anatomic location were seen. Periaortic hematoma formation was suspected of possible extravasation. In addition, a partial anomalous pulmonary venous connection (PAPVC) showed that the vertical vein connected to the left upper lobe drained into the left bra-chiocephalic vein ( Fig. 1A, B ). We planned an arch and descending aorta replacement surgery via an anterolateral thoracotomy under cardiopulmonary bypass. However, the patient was hesitant with regard to invasive surgery owing to her cosmetic concerns as a single woman. Her back pain gradually improved with analgesics, however, 3 days later, she again complained of acute sharp back pain. Subsequent CT scan revealed active aggravation of ruptured aortic dissection and aneurysmal dilatation on dissected aorta. The false lumen had increased in size to 10% of the aortic maximum diameter, measuring 3.9 cm, and left pleural fluid collection suspicious to hemothorax and periaortic hematoma had increased ( Fig. 2A, B ). We decided to perform an emergency operation for the recurrent back pain, enlarging periaortic hematoma and hemothorax. After consultation with the patient, we initially planned an anterolateral thoracotomy with left heart bypass. However, we determined that it would be too dangerous to clamp on the aortic isthmus near the ARSA owing to the frailty of the aneurysmal dilatation on the dissected aorta. In addition, the vertical vein running directly above the dissecting flap might have interfered with the operative field. Instead of open surgery, we decided to perform emergency thoracic endovascular aortic repair (TEVAR). However, because the patients had the ARSA with a dominant vertebral artery, we decided to perform a carotid to subclavian artery bypass with the dominant vertebral artery before TEVAR. Under general anesthesia, a right carotid and subclavian artery bypass was performed via supraclavicular transverse incision. A 7 mm Gore-Tex polytetrafluoroethylene Stretch graft was placed between the right carotid and subclavian arteries. After bypass, we exposed the patient’s right common femoral artery (CFA) through a longitudinal incision. Through the left CFA, a sizing catheter was inserted with angiography guidance for checking the length. Pre-deploying aortogram revealed ARCA branching from the aortic isthmus and aneurysmal dilatation on the dissected aorta including the left subclavian artery ( Fig. 3A ). An S&G SEAL thoracic stent graft (24×24×110 mm; S&G Biotech, Seongnam, Korea) was advanced through the right CFA. During stent graft insertion, a slightly strong resistance was encountered; however, post-procedural aortogram revealed no peripheral arterial injury. After stent graft deployment, aortography showed laminar blood flow through the devices and the thoracic aorta with complete exclusion of the dissecting aneurysm ( Fig. 3B ). There were no complications during the procedure, and the oversizing of stent grafts relative to the aorta did not exceed 10% to provide adequate radial force to keep the deployed stent grafts in place. The total operative time was 245 minutes, and the total contrast agent volume was 90 mL. Postoperatively, the blood pressure in both arms was nearly same and there was no evidence of ischemia. After postoperative day (POD) 5, CT scan revealed a well-functioning aortic isthmus stent graft without endoleaks, and complete occlusion of both subclavian artery orifices with distal run-off reserved from collateral flow ( Fig. 4A, B ). The patient was discharged on POD 6 without complications and is planning follow-up examination of the PAPVC at the cardiac and cardiovascular clinics.'}
|
{'CASE': 'A 32-year-old woman with Turner syndrome (143 cm/49 kg, body surface area 1.37 m 2 ) was admitted to Kyungpook National University Hospital center with complaint of sudden-onset back pain. She had been diagnosed with Turner syndrome twenty years prior following examination for her short stature. She was regularly treated with hormone replacement therapy as an outpatient of the obstetrics and gynecology. She felt well, worked as a kindergarten teacher, and was unmarried. On admission, her initial systolic blood pressure and heart rate were 131 mmHg and 68 beats per minute, respectively. Her blood pressures were almost equal in the upper and lower extremities. Her initial hemoglobin level was 11.8 g/dL, and electrocardiography revealed a normal sinus rhythm. An initial computed tomography (CT) scan revealed intimal dissection on aortic isthmus level and a dissected flap extending from the left subclavian artery to the descending aorta. An elongated transverse aortic arch (ETA) and an aberrant right subclavian artery (ARSA) branching into the aortic isthmus as unusual anatomic location were seen. Periaortic hematoma formation was suspected of possible extravasation. In addition, a partial anomalous pulmonary venous connection (PAPVC) showed that the vertical vein connected to the left upper lobe drained into the left bra-chiocephalic vein ( Fig. 1A, B ). We planned an arch and descending aorta replacement surgery via an anterolateral thoracotomy under cardiopulmonary bypass. However, the patient was hesitant with regard to invasive surgery owing to her cosmetic concerns as a single woman. Her back pain gradually improved with analgesics, however, 3 days later, she again complained of acute sharp back pain. Subsequent CT scan revealed active aggravation of ruptured aortic dissection and aneurysmal dilatation on dissected aorta. The false lumen had increased in size to 10% of the aortic maximum diameter, measuring 3.9 cm, and left pleural fluid collection suspicious to hemothorax and periaortic hematoma had increased ( Fig. 2A, B ). We decided to perform an emergency operation for the recurrent back pain, enlarging periaortic hematoma and hemothorax. After consultation with the patient, we initially planned an anterolateral thoracotomy with left heart bypass. However, we determined that it would be too dangerous to clamp on the aortic isthmus near the ARSA owing to the frailty of the aneurysmal dilatation on the dissected aorta. In addition, the vertical vein running directly above the dissecting flap might have interfered with the operative field. Instead of open surgery, we decided to perform emergency thoracic endovascular aortic repair (TEVAR). However, because the patients had the ARSA with a dominant vertebral artery, we decided to perform a carotid to subclavian artery bypass with the dominant vertebral artery before TEVAR. Under general anesthesia, a right carotid and subclavian artery bypass was performed via supraclavicular transverse incision. A 7 mm Gore-Tex polytetrafluoroethylene Stretch graft was placed between the right carotid and subclavian arteries. After bypass, we exposed the patient’s right common femoral artery (CFA) through a longitudinal incision. Through the left CFA, a sizing catheter was inserted with angiography guidance for checking the length. Pre-deploying aortogram revealed ARCA branching from the aortic isthmus and aneurysmal dilatation on the dissected aorta including the left subclavian artery ( Fig. 3A ). An S&G SEAL thoracic stent graft (24×24×110 mm; S&G Biotech, Seongnam, Korea) was advanced through the right CFA. During stent graft insertion, a slightly strong resistance was encountered; however, post-procedural aortogram revealed no peripheral arterial injury. After stent graft deployment, aortography showed laminar blood flow through the devices and the thoracic aorta with complete exclusion of the dissecting aneurysm ( Fig. 3B ). There were no complications during the procedure, and the oversizing of stent grafts relative to the aorta did not exceed 10% to provide adequate radial force to keep the deployed stent grafts in place. The total operative time was 245 minutes, and the total contrast agent volume was 90 mL. Postoperatively, the blood pressure in both arms was nearly same and there was no evidence of ischemia. After postoperative day (POD) 5, CT scan revealed a well-functioning aortic isthmus stent graft without endoleaks, and complete occlusion of both subclavian artery orifices with distal run-off reserved from collateral flow ( Fig. 4A, B ). The patient was discharged on POD 6 without complications and is planning follow-up examination of the PAPVC at the cardiac and cardiovascular clinics.'}
|
Age-of-Onset
|
Age (of onset)
|
[] |
6340697
|
{'CASE': 'A 32-year-old woman with Turner syndrome (143 cm/49 kg, body surface area 1.37 m 2 ) was admitted to Kyungpook National University Hospital center with complaint of sudden-onset back pain. She had been diagnosed with Turner syndrome twenty years prior following examination for her short stature. She was regularly treated with hormone replacement therapy as an outpatient of the obstetrics and gynecology. She felt well, worked as a kindergarten teacher, and was unmarried. On admission, her initial systolic blood pressure and heart rate were 131 mmHg and 68 beats per minute, respectively. Her blood pressures were almost equal in the upper and lower extremities. Her initial hemoglobin level was 11.8 g/dL, and electrocardiography revealed a normal sinus rhythm. An initial computed tomography (CT) scan revealed intimal dissection on aortic isthmus level and a dissected flap extending from the left subclavian artery to the descending aorta. An elongated transverse aortic arch (ETA) and an aberrant right subclavian artery (ARSA) branching into the aortic isthmus as unusual anatomic location were seen. Periaortic hematoma formation was suspected of possible extravasation. In addition, a partial anomalous pulmonary venous connection (PAPVC) showed that the vertical vein connected to the left upper lobe drained into the left bra-chiocephalic vein ( Fig. 1A, B ). We planned an arch and descending aorta replacement surgery via an anterolateral thoracotomy under cardiopulmonary bypass. However, the patient was hesitant with regard to invasive surgery owing to her cosmetic concerns as a single woman. Her back pain gradually improved with analgesics, however, 3 days later, she again complained of acute sharp back pain. Subsequent CT scan revealed active aggravation of ruptured aortic dissection and aneurysmal dilatation on dissected aorta. The false lumen had increased in size to 10% of the aortic maximum diameter, measuring 3.9 cm, and left pleural fluid collection suspicious to hemothorax and periaortic hematoma had increased ( Fig. 2A, B ). We decided to perform an emergency operation for the recurrent back pain, enlarging periaortic hematoma and hemothorax. After consultation with the patient, we initially planned an anterolateral thoracotomy with left heart bypass. However, we determined that it would be too dangerous to clamp on the aortic isthmus near the ARSA owing to the frailty of the aneurysmal dilatation on the dissected aorta. In addition, the vertical vein running directly above the dissecting flap might have interfered with the operative field. Instead of open surgery, we decided to perform emergency thoracic endovascular aortic repair (TEVAR). However, because the patients had the ARSA with a dominant vertebral artery, we decided to perform a carotid to subclavian artery bypass with the dominant vertebral artery before TEVAR. Under general anesthesia, a right carotid and subclavian artery bypass was performed via supraclavicular transverse incision. A 7 mm Gore-Tex polytetrafluoroethylene Stretch graft was placed between the right carotid and subclavian arteries. After bypass, we exposed the patient’s right common femoral artery (CFA) through a longitudinal incision. Through the left CFA, a sizing catheter was inserted with angiography guidance for checking the length. Pre-deploying aortogram revealed ARCA branching from the aortic isthmus and aneurysmal dilatation on the dissected aorta including the left subclavian artery ( Fig. 3A ). An S&G SEAL thoracic stent graft (24×24×110 mm; S&G Biotech, Seongnam, Korea) was advanced through the right CFA. During stent graft insertion, a slightly strong resistance was encountered; however, post-procedural aortogram revealed no peripheral arterial injury. After stent graft deployment, aortography showed laminar blood flow through the devices and the thoracic aorta with complete exclusion of the dissecting aneurysm ( Fig. 3B ). There were no complications during the procedure, and the oversizing of stent grafts relative to the aorta did not exceed 10% to provide adequate radial force to keep the deployed stent grafts in place. The total operative time was 245 minutes, and the total contrast agent volume was 90 mL. Postoperatively, the blood pressure in both arms was nearly same and there was no evidence of ischemia. After postoperative day (POD) 5, CT scan revealed a well-functioning aortic isthmus stent graft without endoleaks, and complete occlusion of both subclavian artery orifices with distal run-off reserved from collateral flow ( Fig. 4A, B ). The patient was discharged on POD 6 without complications and is planning follow-up examination of the PAPVC at the cardiac and cardiovascular clinics.'}
|
{'CASE': 'A 32-year-old woman with Turner syndrome (143 cm/49 kg, body surface area 1.37 m 2 ) was admitted to Kyungpook National University Hospital center with complaint of sudden-onset back pain. She had been diagnosed with Turner syndrome twenty years prior following examination for her short stature. She was regularly treated with hormone replacement therapy as an outpatient of the obstetrics and gynecology. She felt well, worked as a kindergarten teacher, and was unmarried. On admission, her initial systolic blood pressure and heart rate were 131 mmHg and 68 beats per minute, respectively. Her blood pressures were almost equal in the upper and lower extremities. Her initial hemoglobin level was 11.8 g/dL, and electrocardiography revealed a normal sinus rhythm. An initial computed tomography (CT) scan revealed intimal dissection on aortic isthmus level and a dissected flap extending from the left subclavian artery to the descending aorta. An elongated transverse aortic arch (ETA) and an aberrant right subclavian artery (ARSA) branching into the aortic isthmus as unusual anatomic location were seen. Periaortic hematoma formation was suspected of possible extravasation. In addition, a partial anomalous pulmonary venous connection (PAPVC) showed that the vertical vein connected to the left upper lobe drained into the left bra-chiocephalic vein ( Fig. 1A, B ). We planned an arch and descending aorta replacement surgery via an anterolateral thoracotomy under cardiopulmonary bypass. However, the patient was hesitant with regard to invasive surgery owing to her cosmetic concerns as a single woman. Her back pain gradually improved with analgesics, however, 3 days later, she again complained of acute sharp back pain. Subsequent CT scan revealed active aggravation of ruptured aortic dissection and aneurysmal dilatation on dissected aorta. The false lumen had increased in size to 10% of the aortic maximum diameter, measuring 3.9 cm, and left pleural fluid collection suspicious to hemothorax and periaortic hematoma had increased ( Fig. 2A, B ). We decided to perform an emergency operation for the recurrent back pain, enlarging periaortic hematoma and hemothorax. After consultation with the patient, we initially planned an anterolateral thoracotomy with left heart bypass. However, we determined that it would be too dangerous to clamp on the aortic isthmus near the ARSA owing to the frailty of the aneurysmal dilatation on the dissected aorta. In addition, the vertical vein running directly above the dissecting flap might have interfered with the operative field. Instead of open surgery, we decided to perform emergency thoracic endovascular aortic repair (TEVAR). However, because the patients had the ARSA with a dominant vertebral artery, we decided to perform a carotid to subclavian artery bypass with the dominant vertebral artery before TEVAR. Under general anesthesia, a right carotid and subclavian artery bypass was performed via supraclavicular transverse incision. A 7 mm Gore-Tex polytetrafluoroethylene Stretch graft was placed between the right carotid and subclavian arteries. After bypass, we exposed the patient’s right common femoral artery (CFA) through a longitudinal incision. Through the left CFA, a sizing catheter was inserted with angiography guidance for checking the length. Pre-deploying aortogram revealed ARCA branching from the aortic isthmus and aneurysmal dilatation on the dissected aorta including the left subclavian artery ( Fig. 3A ). An S&G SEAL thoracic stent graft (24×24×110 mm; S&G Biotech, Seongnam, Korea) was advanced through the right CFA. During stent graft insertion, a slightly strong resistance was encountered; however, post-procedural aortogram revealed no peripheral arterial injury. After stent graft deployment, aortography showed laminar blood flow through the devices and the thoracic aorta with complete exclusion of the dissecting aneurysm ( Fig. 3B ). There were no complications during the procedure, and the oversizing of stent grafts relative to the aorta did not exceed 10% to provide adequate radial force to keep the deployed stent grafts in place. The total operative time was 245 minutes, and the total contrast agent volume was 90 mL. Postoperatively, the blood pressure in both arms was nearly same and there was no evidence of ischemia. After postoperative day (POD) 5, CT scan revealed a well-functioning aortic isthmus stent graft without endoleaks, and complete occlusion of both subclavian artery orifices with distal run-off reserved from collateral flow ( Fig. 4A, B ). The patient was discharged on POD 6 without complications and is planning follow-up examination of the PAPVC at the cardiac and cardiovascular clinics.'}
|
Confirmed-Diagnosis-IEM
|
Confirmed_Diagnosis(IEM)
|
[
"Turner syndrome"
] |
6340697
|
{'CASE': 'A 32-year-old woman with Turner syndrome (143 cm/49 kg, body surface area 1.37 m 2 ) was admitted to Kyungpook National University Hospital center with complaint of sudden-onset back pain. She had been diagnosed with Turner syndrome twenty years prior following examination for her short stature. She was regularly treated with hormone replacement therapy as an outpatient of the obstetrics and gynecology. She felt well, worked as a kindergarten teacher, and was unmarried. On admission, her initial systolic blood pressure and heart rate were 131 mmHg and 68 beats per minute, respectively. Her blood pressures were almost equal in the upper and lower extremities. Her initial hemoglobin level was 11.8 g/dL, and electrocardiography revealed a normal sinus rhythm. An initial computed tomography (CT) scan revealed intimal dissection on aortic isthmus level and a dissected flap extending from the left subclavian artery to the descending aorta. An elongated transverse aortic arch (ETA) and an aberrant right subclavian artery (ARSA) branching into the aortic isthmus as unusual anatomic location were seen. Periaortic hematoma formation was suspected of possible extravasation. In addition, a partial anomalous pulmonary venous connection (PAPVC) showed that the vertical vein connected to the left upper lobe drained into the left bra-chiocephalic vein ( Fig. 1A, B ). We planned an arch and descending aorta replacement surgery via an anterolateral thoracotomy under cardiopulmonary bypass. However, the patient was hesitant with regard to invasive surgery owing to her cosmetic concerns as a single woman. Her back pain gradually improved with analgesics, however, 3 days later, she again complained of acute sharp back pain. Subsequent CT scan revealed active aggravation of ruptured aortic dissection and aneurysmal dilatation on dissected aorta. The false lumen had increased in size to 10% of the aortic maximum diameter, measuring 3.9 cm, and left pleural fluid collection suspicious to hemothorax and periaortic hematoma had increased ( Fig. 2A, B ). We decided to perform an emergency operation for the recurrent back pain, enlarging periaortic hematoma and hemothorax. After consultation with the patient, we initially planned an anterolateral thoracotomy with left heart bypass. However, we determined that it would be too dangerous to clamp on the aortic isthmus near the ARSA owing to the frailty of the aneurysmal dilatation on the dissected aorta. In addition, the vertical vein running directly above the dissecting flap might have interfered with the operative field. Instead of open surgery, we decided to perform emergency thoracic endovascular aortic repair (TEVAR). However, because the patients had the ARSA with a dominant vertebral artery, we decided to perform a carotid to subclavian artery bypass with the dominant vertebral artery before TEVAR. Under general anesthesia, a right carotid and subclavian artery bypass was performed via supraclavicular transverse incision. A 7 mm Gore-Tex polytetrafluoroethylene Stretch graft was placed between the right carotid and subclavian arteries. After bypass, we exposed the patient’s right common femoral artery (CFA) through a longitudinal incision. Through the left CFA, a sizing catheter was inserted with angiography guidance for checking the length. Pre-deploying aortogram revealed ARCA branching from the aortic isthmus and aneurysmal dilatation on the dissected aorta including the left subclavian artery ( Fig. 3A ). An S&G SEAL thoracic stent graft (24×24×110 mm; S&G Biotech, Seongnam, Korea) was advanced through the right CFA. During stent graft insertion, a slightly strong resistance was encountered; however, post-procedural aortogram revealed no peripheral arterial injury. After stent graft deployment, aortography showed laminar blood flow through the devices and the thoracic aorta with complete exclusion of the dissecting aneurysm ( Fig. 3B ). There were no complications during the procedure, and the oversizing of stent grafts relative to the aorta did not exceed 10% to provide adequate radial force to keep the deployed stent grafts in place. The total operative time was 245 minutes, and the total contrast agent volume was 90 mL. Postoperatively, the blood pressure in both arms was nearly same and there was no evidence of ischemia. After postoperative day (POD) 5, CT scan revealed a well-functioning aortic isthmus stent graft without endoleaks, and complete occlusion of both subclavian artery orifices with distal run-off reserved from collateral flow ( Fig. 4A, B ). The patient was discharged on POD 6 without complications and is planning follow-up examination of the PAPVC at the cardiac and cardiovascular clinics.'}
|
{'CASE': 'A 32-year-old woman with Turner syndrome (143 cm/49 kg, body surface area 1.37 m 2 ) was admitted to Kyungpook National University Hospital center with complaint of sudden-onset back pain. She had been diagnosed with Turner syndrome twenty years prior following examination for her short stature. She was regularly treated with hormone replacement therapy as an outpatient of the obstetrics and gynecology. She felt well, worked as a kindergarten teacher, and was unmarried. On admission, her initial systolic blood pressure and heart rate were 131 mmHg and 68 beats per minute, respectively. Her blood pressures were almost equal in the upper and lower extremities. Her initial hemoglobin level was 11.8 g/dL, and electrocardiography revealed a normal sinus rhythm. An initial computed tomography (CT) scan revealed intimal dissection on aortic isthmus level and a dissected flap extending from the left subclavian artery to the descending aorta. An elongated transverse aortic arch (ETA) and an aberrant right subclavian artery (ARSA) branching into the aortic isthmus as unusual anatomic location were seen. Periaortic hematoma formation was suspected of possible extravasation. In addition, a partial anomalous pulmonary venous connection (PAPVC) showed that the vertical vein connected to the left upper lobe drained into the left bra-chiocephalic vein ( Fig. 1A, B ). We planned an arch and descending aorta replacement surgery via an anterolateral thoracotomy under cardiopulmonary bypass. However, the patient was hesitant with regard to invasive surgery owing to her cosmetic concerns as a single woman. Her back pain gradually improved with analgesics, however, 3 days later, she again complained of acute sharp back pain. Subsequent CT scan revealed active aggravation of ruptured aortic dissection and aneurysmal dilatation on dissected aorta. The false lumen had increased in size to 10% of the aortic maximum diameter, measuring 3.9 cm, and left pleural fluid collection suspicious to hemothorax and periaortic hematoma had increased ( Fig. 2A, B ). We decided to perform an emergency operation for the recurrent back pain, enlarging periaortic hematoma and hemothorax. After consultation with the patient, we initially planned an anterolateral thoracotomy with left heart bypass. However, we determined that it would be too dangerous to clamp on the aortic isthmus near the ARSA owing to the frailty of the aneurysmal dilatation on the dissected aorta. In addition, the vertical vein running directly above the dissecting flap might have interfered with the operative field. Instead of open surgery, we decided to perform emergency thoracic endovascular aortic repair (TEVAR). However, because the patients had the ARSA with a dominant vertebral artery, we decided to perform a carotid to subclavian artery bypass with the dominant vertebral artery before TEVAR. Under general anesthesia, a right carotid and subclavian artery bypass was performed via supraclavicular transverse incision. A 7 mm Gore-Tex polytetrafluoroethylene Stretch graft was placed between the right carotid and subclavian arteries. After bypass, we exposed the patient’s right common femoral artery (CFA) through a longitudinal incision. Through the left CFA, a sizing catheter was inserted with angiography guidance for checking the length. Pre-deploying aortogram revealed ARCA branching from the aortic isthmus and aneurysmal dilatation on the dissected aorta including the left subclavian artery ( Fig. 3A ). An S&G SEAL thoracic stent graft (24×24×110 mm; S&G Biotech, Seongnam, Korea) was advanced through the right CFA. During stent graft insertion, a slightly strong resistance was encountered; however, post-procedural aortogram revealed no peripheral arterial injury. After stent graft deployment, aortography showed laminar blood flow through the devices and the thoracic aorta with complete exclusion of the dissecting aneurysm ( Fig. 3B ). There were no complications during the procedure, and the oversizing of stent grafts relative to the aorta did not exceed 10% to provide adequate radial force to keep the deployed stent grafts in place. The total operative time was 245 minutes, and the total contrast agent volume was 90 mL. Postoperatively, the blood pressure in both arms was nearly same and there was no evidence of ischemia. After postoperative day (POD) 5, CT scan revealed a well-functioning aortic isthmus stent graft without endoleaks, and complete occlusion of both subclavian artery orifices with distal run-off reserved from collateral flow ( Fig. 4A, B ). The patient was discharged on POD 6 without complications and is planning follow-up examination of the PAPVC at the cardiac and cardiovascular clinics.'}
|
IEM-Treatment
|
IEM_Treatment
|
[] |
6144612
|
{'Observation': 'This child presented with encephalopathy, fatigue, muscle weakness, ketonuria, and lipid storage in muscles. His tandem mass spectroscopy showed elevated medium-chain acylcarnitine and long-chain acylcarnitine suggestive of MADD. His urine showed elevated excretion of 2HG, adipate, and arabitol.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.', 'Patient and methods': 'Our patient is a 13-year-old boy who was the second child born to non-consanguineous parents. He noticed tiredness and pain in muscles on walking. Patient had about 6 episodes of weakness of all four limbs presenting as difficulty in getting up from sitting posture and falls while walking. He also had vomiting and brown colored urine after exertion. Examination revealed thin built child with a small goiter. Wasting of supraspinatus, infraspinatus, deltoid, and pectoralis muscles was reported with winging of scapula. Power was 4/5 in proximal muscles of upper limbs and 2 to 3/5 in lower limbs. All reflexes were preserved and sensations were normal. Investigations showed severe ketonuria (creatine kinase, 1271 IU/L, lactate dehydrogenase, 2622 IU/L). Liver and renal function tests were normal (aspartate transaminase, 1214 IU/L; alalnine transaminase, 307 IU/L; potential of Hydrogen, 7.4; partial pressure of Carbon Dioxide, 39.9; partial pressure of Oxygen, 77.4; lactate, 2.8 µmol/L). Ultrasonography of abdomen was normal. Estimation of blood levels of free acylcarnitines by tandem mass spectrometry showed significant elevation of short, medium and long-chain acylcarnitines suggestive of multiple acyl-CoA dehydrogenase deficiency. The following levels were obtained from the estimation: hexanoylcarnitine (C6)- 0.67 μmol/L (normal range 0–0.23 μmol/L); adipylcarnitine (C6DC)- 0.52 μmol/L (normal range 0.01–0.33 μmol/L); octanylcarnitine (C8) I-1.2 μmol/L (normal range 0.01–0.39 μmol/L); decanoylcarnitine (C10)-1.71 μmol/L (normal range 0–0.5 μmol/L); dodecanoylcarnitine (C12)-0.63 μmol/L (normal range 0.02–0.42 μmol/L); tetradecanoylcarnitine (C14)- 0.56 μmol/L (normal range 0.03–0.41 μmol/L) and tetradecanoylcarnitine (C14)- 0.59 μmol/L (normal range 0.01–0.28 μmol/L). Profiling of urine organic acids showed increased excretion of 2-hydroxyglutarate (2HG), adipate, arabitol, and 3-hydroxy butyrate. Muscle biopsy was carried out and histopathological analysis of transversely cut skeletal muscle tissue showed mild variation in fiber diameter and multiple fine vacuoles in hematoxylin and eosin–stained material. Modified Gomori trichrome stain showed vacuolated fibers with red granular material consistent with ragged red fibers. Oil Red O stain showed vacuolated fibers with Oil Red O–positive material suggesting lipid storage. The patient was started on high carbohydrate diet with restriction on protein, fat and started on riboflavin (200 mg) and carnitine (1.5 g) per day. He was also given symptomatic treatment. He steadily improved and became fully symptom free at 3 months. Figure 2 shows the patient at 3 months of follow-up. The pictures at admission could not be taken as patient’s relatives were unwilling to give permission as the child was very ill.'}
|
{'Observation': 'This child presented with encephalopathy, fatigue, muscle weakness, ketonuria, and lipid storage in muscles. His tandem mass spectroscopy showed elevated medium-chain acylcarnitine and long-chain acylcarnitine suggestive of MADD. His urine showed elevated excretion of 2HG, adipate, and arabitol.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.', 'Patient and methods': 'Our patient is a 13-year-old boy who was the second child born to non-consanguineous parents. He noticed tiredness and pain in muscles on walking. Patient had about 6 episodes of weakness of all four limbs presenting as difficulty in getting up from sitting posture and falls while walking. He also had vomiting and brown colored urine after exertion. Examination revealed thin built child with a small goiter. Wasting of supraspinatus, infraspinatus, deltoid, and pectoralis muscles was reported with winging of scapula. Power was 4/5 in proximal muscles of upper limbs and 2 to 3/5 in lower limbs. All reflexes were preserved and sensations were normal. Investigations showed severe ketonuria (creatine kinase, 1271 IU/L, lactate dehydrogenase, 2622 IU/L). Liver and renal function tests were normal (aspartate transaminase, 1214 IU/L; alalnine transaminase, 307 IU/L; potential of Hydrogen, 7.4; partial pressure of Carbon Dioxide, 39.9; partial pressure of Oxygen, 77.4; lactate, 2.8 µmol/L). Ultrasonography of abdomen was normal. Estimation of blood levels of free acylcarnitines by tandem mass spectrometry showed significant elevation of short, medium and long-chain acylcarnitines suggestive of multiple acyl-CoA dehydrogenase deficiency. The following levels were obtained from the estimation: hexanoylcarnitine (C6)- 0.67 μmol/L (normal range 0–0.23 μmol/L); adipylcarnitine (C6DC)- 0.52 μmol/L (normal range 0.01–0.33 μmol/L); octanylcarnitine (C8) I-1.2 μmol/L (normal range 0.01–0.39 μmol/L); decanoylcarnitine (C10)-1.71 μmol/L (normal range 0–0.5 μmol/L); dodecanoylcarnitine (C12)-0.63 μmol/L (normal range 0.02–0.42 μmol/L); tetradecanoylcarnitine (C14)- 0.56 μmol/L (normal range 0.03–0.41 μmol/L) and tetradecanoylcarnitine (C14)- 0.59 μmol/L (normal range 0.01–0.28 μmol/L). Profiling of urine organic acids showed increased excretion of 2-hydroxyglutarate (2HG), adipate, arabitol, and 3-hydroxy butyrate. Muscle biopsy was carried out and histopathological analysis of transversely cut skeletal muscle tissue showed mild variation in fiber diameter and multiple fine vacuoles in hematoxylin and eosin–stained material. Modified Gomori trichrome stain showed vacuolated fibers with red granular material consistent with ragged red fibers. Oil Red O stain showed vacuolated fibers with Oil Red O–positive material suggesting lipid storage. The patient was started on high carbohydrate diet with restriction on protein, fat and started on riboflavin (200 mg) and carnitine (1.5 g) per day. He was also given symptomatic treatment. He steadily improved and became fully symptom free at 3 months. Figure 2 shows the patient at 3 months of follow-up. The pictures at admission could not be taken as patient’s relatives were unwilling to give permission as the child was very ill.'}
|
Vitals-and-Hematology
|
Vitals_Hema
|
[] |
6144612
|
{'Observation': 'This child presented with encephalopathy, fatigue, muscle weakness, ketonuria, and lipid storage in muscles. His tandem mass spectroscopy showed elevated medium-chain acylcarnitine and long-chain acylcarnitine suggestive of MADD. His urine showed elevated excretion of 2HG, adipate, and arabitol.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.', 'Patient and methods': 'Our patient is a 13-year-old boy who was the second child born to non-consanguineous parents. He noticed tiredness and pain in muscles on walking. Patient had about 6 episodes of weakness of all four limbs presenting as difficulty in getting up from sitting posture and falls while walking. He also had vomiting and brown colored urine after exertion. Examination revealed thin built child with a small goiter. Wasting of supraspinatus, infraspinatus, deltoid, and pectoralis muscles was reported with winging of scapula. Power was 4/5 in proximal muscles of upper limbs and 2 to 3/5 in lower limbs. All reflexes were preserved and sensations were normal. Investigations showed severe ketonuria (creatine kinase, 1271 IU/L, lactate dehydrogenase, 2622 IU/L). Liver and renal function tests were normal (aspartate transaminase, 1214 IU/L; alalnine transaminase, 307 IU/L; potential of Hydrogen, 7.4; partial pressure of Carbon Dioxide, 39.9; partial pressure of Oxygen, 77.4; lactate, 2.8 µmol/L). Ultrasonography of abdomen was normal. Estimation of blood levels of free acylcarnitines by tandem mass spectrometry showed significant elevation of short, medium and long-chain acylcarnitines suggestive of multiple acyl-CoA dehydrogenase deficiency. The following levels were obtained from the estimation: hexanoylcarnitine (C6)- 0.67 μmol/L (normal range 0–0.23 μmol/L); adipylcarnitine (C6DC)- 0.52 μmol/L (normal range 0.01–0.33 μmol/L); octanylcarnitine (C8) I-1.2 μmol/L (normal range 0.01–0.39 μmol/L); decanoylcarnitine (C10)-1.71 μmol/L (normal range 0–0.5 μmol/L); dodecanoylcarnitine (C12)-0.63 μmol/L (normal range 0.02–0.42 μmol/L); tetradecanoylcarnitine (C14)- 0.56 μmol/L (normal range 0.03–0.41 μmol/L) and tetradecanoylcarnitine (C14)- 0.59 μmol/L (normal range 0.01–0.28 μmol/L). Profiling of urine organic acids showed increased excretion of 2-hydroxyglutarate (2HG), adipate, arabitol, and 3-hydroxy butyrate. Muscle biopsy was carried out and histopathological analysis of transversely cut skeletal muscle tissue showed mild variation in fiber diameter and multiple fine vacuoles in hematoxylin and eosin–stained material. Modified Gomori trichrome stain showed vacuolated fibers with red granular material consistent with ragged red fibers. Oil Red O stain showed vacuolated fibers with Oil Red O–positive material suggesting lipid storage. The patient was started on high carbohydrate diet with restriction on protein, fat and started on riboflavin (200 mg) and carnitine (1.5 g) per day. He was also given symptomatic treatment. He steadily improved and became fully symptom free at 3 months. Figure 2 shows the patient at 3 months of follow-up. The pictures at admission could not be taken as patient’s relatives were unwilling to give permission as the child was very ill.'}
|
{'Observation': 'This child presented with encephalopathy, fatigue, muscle weakness, ketonuria, and lipid storage in muscles. His tandem mass spectroscopy showed elevated medium-chain acylcarnitine and long-chain acylcarnitine suggestive of MADD. His urine showed elevated excretion of 2HG, adipate, and arabitol.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.', 'Patient and methods': 'Our patient is a 13-year-old boy who was the second child born to non-consanguineous parents. He noticed tiredness and pain in muscles on walking. Patient had about 6 episodes of weakness of all four limbs presenting as difficulty in getting up from sitting posture and falls while walking. He also had vomiting and brown colored urine after exertion. Examination revealed thin built child with a small goiter. Wasting of supraspinatus, infraspinatus, deltoid, and pectoralis muscles was reported with winging of scapula. Power was 4/5 in proximal muscles of upper limbs and 2 to 3/5 in lower limbs. All reflexes were preserved and sensations were normal. Investigations showed severe ketonuria (creatine kinase, 1271 IU/L, lactate dehydrogenase, 2622 IU/L). Liver and renal function tests were normal (aspartate transaminase, 1214 IU/L; alalnine transaminase, 307 IU/L; potential of Hydrogen, 7.4; partial pressure of Carbon Dioxide, 39.9; partial pressure of Oxygen, 77.4; lactate, 2.8 µmol/L). Ultrasonography of abdomen was normal. Estimation of blood levels of free acylcarnitines by tandem mass spectrometry showed significant elevation of short, medium and long-chain acylcarnitines suggestive of multiple acyl-CoA dehydrogenase deficiency. The following levels were obtained from the estimation: hexanoylcarnitine (C6)- 0.67 μmol/L (normal range 0–0.23 μmol/L); adipylcarnitine (C6DC)- 0.52 μmol/L (normal range 0.01–0.33 μmol/L); octanylcarnitine (C8) I-1.2 μmol/L (normal range 0.01–0.39 μmol/L); decanoylcarnitine (C10)-1.71 μmol/L (normal range 0–0.5 μmol/L); dodecanoylcarnitine (C12)-0.63 μmol/L (normal range 0.02–0.42 μmol/L); tetradecanoylcarnitine (C14)- 0.56 μmol/L (normal range 0.03–0.41 μmol/L) and tetradecanoylcarnitine (C14)- 0.59 μmol/L (normal range 0.01–0.28 μmol/L). Profiling of urine organic acids showed increased excretion of 2-hydroxyglutarate (2HG), adipate, arabitol, and 3-hydroxy butyrate. Muscle biopsy was carried out and histopathological analysis of transversely cut skeletal muscle tissue showed mild variation in fiber diameter and multiple fine vacuoles in hematoxylin and eosin–stained material. Modified Gomori trichrome stain showed vacuolated fibers with red granular material consistent with ragged red fibers. Oil Red O stain showed vacuolated fibers with Oil Red O–positive material suggesting lipid storage. The patient was started on high carbohydrate diet with restriction on protein, fat and started on riboflavin (200 mg) and carnitine (1.5 g) per day. He was also given symptomatic treatment. He steadily improved and became fully symptom free at 3 months. Figure 2 shows the patient at 3 months of follow-up. The pictures at admission could not be taken as patient’s relatives were unwilling to give permission as the child was very ill.'}
|
Gastrointestinal-System
|
GI
|
[
"vomiting"
] |
6144612
|
{'Observation': 'This child presented with encephalopathy, fatigue, muscle weakness, ketonuria, and lipid storage in muscles. His tandem mass spectroscopy showed elevated medium-chain acylcarnitine and long-chain acylcarnitine suggestive of MADD. His urine showed elevated excretion of 2HG, adipate, and arabitol.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.', 'Patient and methods': 'Our patient is a 13-year-old boy who was the second child born to non-consanguineous parents. He noticed tiredness and pain in muscles on walking. Patient had about 6 episodes of weakness of all four limbs presenting as difficulty in getting up from sitting posture and falls while walking. He also had vomiting and brown colored urine after exertion. Examination revealed thin built child with a small goiter. Wasting of supraspinatus, infraspinatus, deltoid, and pectoralis muscles was reported with winging of scapula. Power was 4/5 in proximal muscles of upper limbs and 2 to 3/5 in lower limbs. All reflexes were preserved and sensations were normal. Investigations showed severe ketonuria (creatine kinase, 1271 IU/L, lactate dehydrogenase, 2622 IU/L). Liver and renal function tests were normal (aspartate transaminase, 1214 IU/L; alalnine transaminase, 307 IU/L; potential of Hydrogen, 7.4; partial pressure of Carbon Dioxide, 39.9; partial pressure of Oxygen, 77.4; lactate, 2.8 µmol/L). Ultrasonography of abdomen was normal. Estimation of blood levels of free acylcarnitines by tandem mass spectrometry showed significant elevation of short, medium and long-chain acylcarnitines suggestive of multiple acyl-CoA dehydrogenase deficiency. The following levels were obtained from the estimation: hexanoylcarnitine (C6)- 0.67 μmol/L (normal range 0–0.23 μmol/L); adipylcarnitine (C6DC)- 0.52 μmol/L (normal range 0.01–0.33 μmol/L); octanylcarnitine (C8) I-1.2 μmol/L (normal range 0.01–0.39 μmol/L); decanoylcarnitine (C10)-1.71 μmol/L (normal range 0–0.5 μmol/L); dodecanoylcarnitine (C12)-0.63 μmol/L (normal range 0.02–0.42 μmol/L); tetradecanoylcarnitine (C14)- 0.56 μmol/L (normal range 0.03–0.41 μmol/L) and tetradecanoylcarnitine (C14)- 0.59 μmol/L (normal range 0.01–0.28 μmol/L). Profiling of urine organic acids showed increased excretion of 2-hydroxyglutarate (2HG), adipate, arabitol, and 3-hydroxy butyrate. Muscle biopsy was carried out and histopathological analysis of transversely cut skeletal muscle tissue showed mild variation in fiber diameter and multiple fine vacuoles in hematoxylin and eosin–stained material. Modified Gomori trichrome stain showed vacuolated fibers with red granular material consistent with ragged red fibers. Oil Red O stain showed vacuolated fibers with Oil Red O–positive material suggesting lipid storage. The patient was started on high carbohydrate diet with restriction on protein, fat and started on riboflavin (200 mg) and carnitine (1.5 g) per day. He was also given symptomatic treatment. He steadily improved and became fully symptom free at 3 months. Figure 2 shows the patient at 3 months of follow-up. The pictures at admission could not be taken as patient’s relatives were unwilling to give permission as the child was very ill.'}
|
{'Observation': 'This child presented with encephalopathy, fatigue, muscle weakness, ketonuria, and lipid storage in muscles. His tandem mass spectroscopy showed elevated medium-chain acylcarnitine and long-chain acylcarnitine suggestive of MADD. His urine showed elevated excretion of 2HG, adipate, and arabitol.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.', 'Patient and methods': 'Our patient is a 13-year-old boy who was the second child born to non-consanguineous parents. He noticed tiredness and pain in muscles on walking. Patient had about 6 episodes of weakness of all four limbs presenting as difficulty in getting up from sitting posture and falls while walking. He also had vomiting and brown colored urine after exertion. Examination revealed thin built child with a small goiter. Wasting of supraspinatus, infraspinatus, deltoid, and pectoralis muscles was reported with winging of scapula. Power was 4/5 in proximal muscles of upper limbs and 2 to 3/5 in lower limbs. All reflexes were preserved and sensations were normal. Investigations showed severe ketonuria (creatine kinase, 1271 IU/L, lactate dehydrogenase, 2622 IU/L). Liver and renal function tests were normal (aspartate transaminase, 1214 IU/L; alalnine transaminase, 307 IU/L; potential of Hydrogen, 7.4; partial pressure of Carbon Dioxide, 39.9; partial pressure of Oxygen, 77.4; lactate, 2.8 µmol/L). Ultrasonography of abdomen was normal. Estimation of blood levels of free acylcarnitines by tandem mass spectrometry showed significant elevation of short, medium and long-chain acylcarnitines suggestive of multiple acyl-CoA dehydrogenase deficiency. The following levels were obtained from the estimation: hexanoylcarnitine (C6)- 0.67 μmol/L (normal range 0–0.23 μmol/L); adipylcarnitine (C6DC)- 0.52 μmol/L (normal range 0.01–0.33 μmol/L); octanylcarnitine (C8) I-1.2 μmol/L (normal range 0.01–0.39 μmol/L); decanoylcarnitine (C10)-1.71 μmol/L (normal range 0–0.5 μmol/L); dodecanoylcarnitine (C12)-0.63 μmol/L (normal range 0.02–0.42 μmol/L); tetradecanoylcarnitine (C14)- 0.56 μmol/L (normal range 0.03–0.41 μmol/L) and tetradecanoylcarnitine (C14)- 0.59 μmol/L (normal range 0.01–0.28 μmol/L). Profiling of urine organic acids showed increased excretion of 2-hydroxyglutarate (2HG), adipate, arabitol, and 3-hydroxy butyrate. Muscle biopsy was carried out and histopathological analysis of transversely cut skeletal muscle tissue showed mild variation in fiber diameter and multiple fine vacuoles in hematoxylin and eosin–stained material. Modified Gomori trichrome stain showed vacuolated fibers with red granular material consistent with ragged red fibers. Oil Red O stain showed vacuolated fibers with Oil Red O–positive material suggesting lipid storage. The patient was started on high carbohydrate diet with restriction on protein, fat and started on riboflavin (200 mg) and carnitine (1.5 g) per day. He was also given symptomatic treatment. He steadily improved and became fully symptom free at 3 months. Figure 2 shows the patient at 3 months of follow-up. The pictures at admission could not be taken as patient’s relatives were unwilling to give permission as the child was very ill.'}
|
Patient-History
|
History
|
[
"This child presented with encephalopathy, fatigue, muscle weakness, ketonuria, and lipid storage in muscles",
"Our patient is a 13 - year - old boy who was the second child born to non - consanguineous parents. He noticed tiredness and pain in muscles on walking. Patient had about 6 episodes of weakness of all four limbs presenting as difficulty in getting up from sitting posture and falls while walking. He also had vomiting and brown colored urine after exertion"
] |
6144612
|
{'Observation': 'This child presented with encephalopathy, fatigue, muscle weakness, ketonuria, and lipid storage in muscles. His tandem mass spectroscopy showed elevated medium-chain acylcarnitine and long-chain acylcarnitine suggestive of MADD. His urine showed elevated excretion of 2HG, adipate, and arabitol.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.', 'Patient and methods': 'Our patient is a 13-year-old boy who was the second child born to non-consanguineous parents. He noticed tiredness and pain in muscles on walking. Patient had about 6 episodes of weakness of all four limbs presenting as difficulty in getting up from sitting posture and falls while walking. He also had vomiting and brown colored urine after exertion. Examination revealed thin built child with a small goiter. Wasting of supraspinatus, infraspinatus, deltoid, and pectoralis muscles was reported with winging of scapula. Power was 4/5 in proximal muscles of upper limbs and 2 to 3/5 in lower limbs. All reflexes were preserved and sensations were normal. Investigations showed severe ketonuria (creatine kinase, 1271 IU/L, lactate dehydrogenase, 2622 IU/L). Liver and renal function tests were normal (aspartate transaminase, 1214 IU/L; alalnine transaminase, 307 IU/L; potential of Hydrogen, 7.4; partial pressure of Carbon Dioxide, 39.9; partial pressure of Oxygen, 77.4; lactate, 2.8 µmol/L). Ultrasonography of abdomen was normal. Estimation of blood levels of free acylcarnitines by tandem mass spectrometry showed significant elevation of short, medium and long-chain acylcarnitines suggestive of multiple acyl-CoA dehydrogenase deficiency. The following levels were obtained from the estimation: hexanoylcarnitine (C6)- 0.67 μmol/L (normal range 0–0.23 μmol/L); adipylcarnitine (C6DC)- 0.52 μmol/L (normal range 0.01–0.33 μmol/L); octanylcarnitine (C8) I-1.2 μmol/L (normal range 0.01–0.39 μmol/L); decanoylcarnitine (C10)-1.71 μmol/L (normal range 0–0.5 μmol/L); dodecanoylcarnitine (C12)-0.63 μmol/L (normal range 0.02–0.42 μmol/L); tetradecanoylcarnitine (C14)- 0.56 μmol/L (normal range 0.03–0.41 μmol/L) and tetradecanoylcarnitine (C14)- 0.59 μmol/L (normal range 0.01–0.28 μmol/L). Profiling of urine organic acids showed increased excretion of 2-hydroxyglutarate (2HG), adipate, arabitol, and 3-hydroxy butyrate. Muscle biopsy was carried out and histopathological analysis of transversely cut skeletal muscle tissue showed mild variation in fiber diameter and multiple fine vacuoles in hematoxylin and eosin–stained material. Modified Gomori trichrome stain showed vacuolated fibers with red granular material consistent with ragged red fibers. Oil Red O stain showed vacuolated fibers with Oil Red O–positive material suggesting lipid storage. The patient was started on high carbohydrate diet with restriction on protein, fat and started on riboflavin (200 mg) and carnitine (1.5 g) per day. He was also given symptomatic treatment. He steadily improved and became fully symptom free at 3 months. Figure 2 shows the patient at 3 months of follow-up. The pictures at admission could not be taken as patient’s relatives were unwilling to give permission as the child was very ill.'}
|
{'Observation': 'This child presented with encephalopathy, fatigue, muscle weakness, ketonuria, and lipid storage in muscles. His tandem mass spectroscopy showed elevated medium-chain acylcarnitine and long-chain acylcarnitine suggestive of MADD. His urine showed elevated excretion of 2HG, adipate, and arabitol.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.', 'Patient and methods': 'Our patient is a 13-year-old boy who was the second child born to non-consanguineous parents. He noticed tiredness and pain in muscles on walking. Patient had about 6 episodes of weakness of all four limbs presenting as difficulty in getting up from sitting posture and falls while walking. He also had vomiting and brown colored urine after exertion. Examination revealed thin built child with a small goiter. Wasting of supraspinatus, infraspinatus, deltoid, and pectoralis muscles was reported with winging of scapula. Power was 4/5 in proximal muscles of upper limbs and 2 to 3/5 in lower limbs. All reflexes were preserved and sensations were normal. Investigations showed severe ketonuria (creatine kinase, 1271 IU/L, lactate dehydrogenase, 2622 IU/L). Liver and renal function tests were normal (aspartate transaminase, 1214 IU/L; alalnine transaminase, 307 IU/L; potential of Hydrogen, 7.4; partial pressure of Carbon Dioxide, 39.9; partial pressure of Oxygen, 77.4; lactate, 2.8 µmol/L). Ultrasonography of abdomen was normal. Estimation of blood levels of free acylcarnitines by tandem mass spectrometry showed significant elevation of short, medium and long-chain acylcarnitines suggestive of multiple acyl-CoA dehydrogenase deficiency. The following levels were obtained from the estimation: hexanoylcarnitine (C6)- 0.67 μmol/L (normal range 0–0.23 μmol/L); adipylcarnitine (C6DC)- 0.52 μmol/L (normal range 0.01–0.33 μmol/L); octanylcarnitine (C8) I-1.2 μmol/L (normal range 0.01–0.39 μmol/L); decanoylcarnitine (C10)-1.71 μmol/L (normal range 0–0.5 μmol/L); dodecanoylcarnitine (C12)-0.63 μmol/L (normal range 0.02–0.42 μmol/L); tetradecanoylcarnitine (C14)- 0.56 μmol/L (normal range 0.03–0.41 μmol/L) and tetradecanoylcarnitine (C14)- 0.59 μmol/L (normal range 0.01–0.28 μmol/L). Profiling of urine organic acids showed increased excretion of 2-hydroxyglutarate (2HG), adipate, arabitol, and 3-hydroxy butyrate. Muscle biopsy was carried out and histopathological analysis of transversely cut skeletal muscle tissue showed mild variation in fiber diameter and multiple fine vacuoles in hematoxylin and eosin–stained material. Modified Gomori trichrome stain showed vacuolated fibers with red granular material consistent with ragged red fibers. Oil Red O stain showed vacuolated fibers with Oil Red O–positive material suggesting lipid storage. The patient was started on high carbohydrate diet with restriction on protein, fat and started on riboflavin (200 mg) and carnitine (1.5 g) per day. He was also given symptomatic treatment. He steadily improved and became fully symptom free at 3 months. Figure 2 shows the patient at 3 months of follow-up. The pictures at admission could not be taken as patient’s relatives were unwilling to give permission as the child was very ill.'}
|
Neurology
|
Neuro
|
[
"encephalopathy, fatigue, muscle weakness",
"All reflexes were preserved and sensations were normal"
] |
6144612
|
{'Observation': 'This child presented with encephalopathy, fatigue, muscle weakness, ketonuria, and lipid storage in muscles. His tandem mass spectroscopy showed elevated medium-chain acylcarnitine and long-chain acylcarnitine suggestive of MADD. His urine showed elevated excretion of 2HG, adipate, and arabitol.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.', 'Patient and methods': 'Our patient is a 13-year-old boy who was the second child born to non-consanguineous parents. He noticed tiredness and pain in muscles on walking. Patient had about 6 episodes of weakness of all four limbs presenting as difficulty in getting up from sitting posture and falls while walking. He also had vomiting and brown colored urine after exertion. Examination revealed thin built child with a small goiter. Wasting of supraspinatus, infraspinatus, deltoid, and pectoralis muscles was reported with winging of scapula. Power was 4/5 in proximal muscles of upper limbs and 2 to 3/5 in lower limbs. All reflexes were preserved and sensations were normal. Investigations showed severe ketonuria (creatine kinase, 1271 IU/L, lactate dehydrogenase, 2622 IU/L). Liver and renal function tests were normal (aspartate transaminase, 1214 IU/L; alalnine transaminase, 307 IU/L; potential of Hydrogen, 7.4; partial pressure of Carbon Dioxide, 39.9; partial pressure of Oxygen, 77.4; lactate, 2.8 µmol/L). Ultrasonography of abdomen was normal. Estimation of blood levels of free acylcarnitines by tandem mass spectrometry showed significant elevation of short, medium and long-chain acylcarnitines suggestive of multiple acyl-CoA dehydrogenase deficiency. The following levels were obtained from the estimation: hexanoylcarnitine (C6)- 0.67 μmol/L (normal range 0–0.23 μmol/L); adipylcarnitine (C6DC)- 0.52 μmol/L (normal range 0.01–0.33 μmol/L); octanylcarnitine (C8) I-1.2 μmol/L (normal range 0.01–0.39 μmol/L); decanoylcarnitine (C10)-1.71 μmol/L (normal range 0–0.5 μmol/L); dodecanoylcarnitine (C12)-0.63 μmol/L (normal range 0.02–0.42 μmol/L); tetradecanoylcarnitine (C14)- 0.56 μmol/L (normal range 0.03–0.41 μmol/L) and tetradecanoylcarnitine (C14)- 0.59 μmol/L (normal range 0.01–0.28 μmol/L). Profiling of urine organic acids showed increased excretion of 2-hydroxyglutarate (2HG), adipate, arabitol, and 3-hydroxy butyrate. Muscle biopsy was carried out and histopathological analysis of transversely cut skeletal muscle tissue showed mild variation in fiber diameter and multiple fine vacuoles in hematoxylin and eosin–stained material. Modified Gomori trichrome stain showed vacuolated fibers with red granular material consistent with ragged red fibers. Oil Red O stain showed vacuolated fibers with Oil Red O–positive material suggesting lipid storage. The patient was started on high carbohydrate diet with restriction on protein, fat and started on riboflavin (200 mg) and carnitine (1.5 g) per day. He was also given symptomatic treatment. He steadily improved and became fully symptom free at 3 months. Figure 2 shows the patient at 3 months of follow-up. The pictures at admission could not be taken as patient’s relatives were unwilling to give permission as the child was very ill.'}
|
{'Observation': 'This child presented with encephalopathy, fatigue, muscle weakness, ketonuria, and lipid storage in muscles. His tandem mass spectroscopy showed elevated medium-chain acylcarnitine and long-chain acylcarnitine suggestive of MADD. His urine showed elevated excretion of 2HG, adipate, and arabitol.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.', 'Patient and methods': 'Our patient is a 13-year-old boy who was the second child born to non-consanguineous parents. He noticed tiredness and pain in muscles on walking. Patient had about 6 episodes of weakness of all four limbs presenting as difficulty in getting up from sitting posture and falls while walking. He also had vomiting and brown colored urine after exertion. Examination revealed thin built child with a small goiter. Wasting of supraspinatus, infraspinatus, deltoid, and pectoralis muscles was reported with winging of scapula. Power was 4/5 in proximal muscles of upper limbs and 2 to 3/5 in lower limbs. All reflexes were preserved and sensations were normal. Investigations showed severe ketonuria (creatine kinase, 1271 IU/L, lactate dehydrogenase, 2622 IU/L). Liver and renal function tests were normal (aspartate transaminase, 1214 IU/L; alalnine transaminase, 307 IU/L; potential of Hydrogen, 7.4; partial pressure of Carbon Dioxide, 39.9; partial pressure of Oxygen, 77.4; lactate, 2.8 µmol/L). Ultrasonography of abdomen was normal. Estimation of blood levels of free acylcarnitines by tandem mass spectrometry showed significant elevation of short, medium and long-chain acylcarnitines suggestive of multiple acyl-CoA dehydrogenase deficiency. The following levels were obtained from the estimation: hexanoylcarnitine (C6)- 0.67 μmol/L (normal range 0–0.23 μmol/L); adipylcarnitine (C6DC)- 0.52 μmol/L (normal range 0.01–0.33 μmol/L); octanylcarnitine (C8) I-1.2 μmol/L (normal range 0.01–0.39 μmol/L); decanoylcarnitine (C10)-1.71 μmol/L (normal range 0–0.5 μmol/L); dodecanoylcarnitine (C12)-0.63 μmol/L (normal range 0.02–0.42 μmol/L); tetradecanoylcarnitine (C14)- 0.56 μmol/L (normal range 0.03–0.41 μmol/L) and tetradecanoylcarnitine (C14)- 0.59 μmol/L (normal range 0.01–0.28 μmol/L). Profiling of urine organic acids showed increased excretion of 2-hydroxyglutarate (2HG), adipate, arabitol, and 3-hydroxy butyrate. Muscle biopsy was carried out and histopathological analysis of transversely cut skeletal muscle tissue showed mild variation in fiber diameter and multiple fine vacuoles in hematoxylin and eosin–stained material. Modified Gomori trichrome stain showed vacuolated fibers with red granular material consistent with ragged red fibers. Oil Red O stain showed vacuolated fibers with Oil Red O–positive material suggesting lipid storage. The patient was started on high carbohydrate diet with restriction on protein, fat and started on riboflavin (200 mg) and carnitine (1.5 g) per day. He was also given symptomatic treatment. He steadily improved and became fully symptom free at 3 months. Figure 2 shows the patient at 3 months of follow-up. The pictures at admission could not be taken as patient’s relatives were unwilling to give permission as the child was very ill.'}
|
Laboratory-and-Imaging
|
Lab_Image
|
[
"ketonuria",
"His tandem mass spectroscopy showed elevated medium - chain acylcarnitine and long - chain acylcarnitine suggestive of MADD. His urine showed elevated excretion of 2HG, adipate, and arabitol",
"Investigations showed severe ketonuria ( creatine kinase, 1271 IU / L, lactate dehydrogenase, 2622 IU / L ). Liver and renal function tests were normal ( aspartate transaminase, 1214 IU / L; alalnine transaminase, 307 IU / L; potential of Hydrogen, 7.4; partial pressure of Carbon Dioxide, 39.9; partial pressure of Oxygen, 77.4; lactate, 2.8 µmol / L ). Ultrasonography of abdomen was normal. Estimation of blood levels of free acylcarnitines by tandem mass spectrometry showed significant elevation of short, medium and long - chain acylcarnitines suggestive of multiple acyl - CoA dehydrogenase deficiency. The following levels were obtained from the estimation : hexanoylcarnitine ( C6)- 0.67 μmol / L ( normal range 0–0.23 μmol / L ); adipylcarnitine ( C6DC)- 0.52 μmol / L ( normal range 0.01–0.33 μmol / L ); octanylcarnitine ( C8 ) I-1.2 μmol / L ( normal range 0.01–0.39 μmol / L ); decanoylcarnitine ( C10)-1.71 μmol / L ( normal range 0–0.5 μmol / L ); dodecanoylcarnitine ( C12)-0.63 μmol / L ( normal range 0.02–0.42 μmol / L ); tetradecanoylcarnitine ( C14)- 0.56 μmol / L ( normal range 0.03–0.41 μmol / L ) and tetradecanoylcarnitine ( C14)- 0.59 μmol / L ( normal range 0.01–0.28 μmol / L ). Profiling of urine organic acids showed increased excretion of 2 - hydroxyglutarate ( 2HG ), adipate, arabitol, and 3 - hydroxy butyrate. Muscle biopsy was carried out and histopathological analysis of transversely cut skeletal muscle tissue showed mild variation in fiber diameter and multiple fine vacuoles in hematoxylin and eosin – stained material. Modified Gomori trichrome stain showed vacuolated fibers with red granular material consistent with ragged red fibers. Oil Red O stain showed vacuolated fibers with Oil Red O – positive material suggesting lipid storage."
] |
6144612
|
{'Observation': 'This child presented with encephalopathy, fatigue, muscle weakness, ketonuria, and lipid storage in muscles. His tandem mass spectroscopy showed elevated medium-chain acylcarnitine and long-chain acylcarnitine suggestive of MADD. His urine showed elevated excretion of 2HG, adipate, and arabitol.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.', 'Patient and methods': 'Our patient is a 13-year-old boy who was the second child born to non-consanguineous parents. He noticed tiredness and pain in muscles on walking. Patient had about 6 episodes of weakness of all four limbs presenting as difficulty in getting up from sitting posture and falls while walking. He also had vomiting and brown colored urine after exertion. Examination revealed thin built child with a small goiter. Wasting of supraspinatus, infraspinatus, deltoid, and pectoralis muscles was reported with winging of scapula. Power was 4/5 in proximal muscles of upper limbs and 2 to 3/5 in lower limbs. All reflexes were preserved and sensations were normal. Investigations showed severe ketonuria (creatine kinase, 1271 IU/L, lactate dehydrogenase, 2622 IU/L). Liver and renal function tests were normal (aspartate transaminase, 1214 IU/L; alalnine transaminase, 307 IU/L; potential of Hydrogen, 7.4; partial pressure of Carbon Dioxide, 39.9; partial pressure of Oxygen, 77.4; lactate, 2.8 µmol/L). Ultrasonography of abdomen was normal. Estimation of blood levels of free acylcarnitines by tandem mass spectrometry showed significant elevation of short, medium and long-chain acylcarnitines suggestive of multiple acyl-CoA dehydrogenase deficiency. The following levels were obtained from the estimation: hexanoylcarnitine (C6)- 0.67 μmol/L (normal range 0–0.23 μmol/L); adipylcarnitine (C6DC)- 0.52 μmol/L (normal range 0.01–0.33 μmol/L); octanylcarnitine (C8) I-1.2 μmol/L (normal range 0.01–0.39 μmol/L); decanoylcarnitine (C10)-1.71 μmol/L (normal range 0–0.5 μmol/L); dodecanoylcarnitine (C12)-0.63 μmol/L (normal range 0.02–0.42 μmol/L); tetradecanoylcarnitine (C14)- 0.56 μmol/L (normal range 0.03–0.41 μmol/L) and tetradecanoylcarnitine (C14)- 0.59 μmol/L (normal range 0.01–0.28 μmol/L). Profiling of urine organic acids showed increased excretion of 2-hydroxyglutarate (2HG), adipate, arabitol, and 3-hydroxy butyrate. Muscle biopsy was carried out and histopathological analysis of transversely cut skeletal muscle tissue showed mild variation in fiber diameter and multiple fine vacuoles in hematoxylin and eosin–stained material. Modified Gomori trichrome stain showed vacuolated fibers with red granular material consistent with ragged red fibers. Oil Red O stain showed vacuolated fibers with Oil Red O–positive material suggesting lipid storage. The patient was started on high carbohydrate diet with restriction on protein, fat and started on riboflavin (200 mg) and carnitine (1.5 g) per day. He was also given symptomatic treatment. He steadily improved and became fully symptom free at 3 months. Figure 2 shows the patient at 3 months of follow-up. The pictures at admission could not be taken as patient’s relatives were unwilling to give permission as the child was very ill.'}
|
{'Observation': 'This child presented with encephalopathy, fatigue, muscle weakness, ketonuria, and lipid storage in muscles. His tandem mass spectroscopy showed elevated medium-chain acylcarnitine and long-chain acylcarnitine suggestive of MADD. His urine showed elevated excretion of 2HG, adipate, and arabitol.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.', 'Patient and methods': 'Our patient is a 13-year-old boy who was the second child born to non-consanguineous parents. He noticed tiredness and pain in muscles on walking. Patient had about 6 episodes of weakness of all four limbs presenting as difficulty in getting up from sitting posture and falls while walking. He also had vomiting and brown colored urine after exertion. Examination revealed thin built child with a small goiter. Wasting of supraspinatus, infraspinatus, deltoid, and pectoralis muscles was reported with winging of scapula. Power was 4/5 in proximal muscles of upper limbs and 2 to 3/5 in lower limbs. All reflexes were preserved and sensations were normal. Investigations showed severe ketonuria (creatine kinase, 1271 IU/L, lactate dehydrogenase, 2622 IU/L). Liver and renal function tests were normal (aspartate transaminase, 1214 IU/L; alalnine transaminase, 307 IU/L; potential of Hydrogen, 7.4; partial pressure of Carbon Dioxide, 39.9; partial pressure of Oxygen, 77.4; lactate, 2.8 µmol/L). Ultrasonography of abdomen was normal. Estimation of blood levels of free acylcarnitines by tandem mass spectrometry showed significant elevation of short, medium and long-chain acylcarnitines suggestive of multiple acyl-CoA dehydrogenase deficiency. The following levels were obtained from the estimation: hexanoylcarnitine (C6)- 0.67 μmol/L (normal range 0–0.23 μmol/L); adipylcarnitine (C6DC)- 0.52 μmol/L (normal range 0.01–0.33 μmol/L); octanylcarnitine (C8) I-1.2 μmol/L (normal range 0.01–0.39 μmol/L); decanoylcarnitine (C10)-1.71 μmol/L (normal range 0–0.5 μmol/L); dodecanoylcarnitine (C12)-0.63 μmol/L (normal range 0.02–0.42 μmol/L); tetradecanoylcarnitine (C14)- 0.56 μmol/L (normal range 0.03–0.41 μmol/L) and tetradecanoylcarnitine (C14)- 0.59 μmol/L (normal range 0.01–0.28 μmol/L). Profiling of urine organic acids showed increased excretion of 2-hydroxyglutarate (2HG), adipate, arabitol, and 3-hydroxy butyrate. Muscle biopsy was carried out and histopathological analysis of transversely cut skeletal muscle tissue showed mild variation in fiber diameter and multiple fine vacuoles in hematoxylin and eosin–stained material. Modified Gomori trichrome stain showed vacuolated fibers with red granular material consistent with ragged red fibers. Oil Red O stain showed vacuolated fibers with Oil Red O–positive material suggesting lipid storage. The patient was started on high carbohydrate diet with restriction on protein, fat and started on riboflavin (200 mg) and carnitine (1.5 g) per day. He was also given symptomatic treatment. He steadily improved and became fully symptom free at 3 months. Figure 2 shows the patient at 3 months of follow-up. The pictures at admission could not be taken as patient’s relatives were unwilling to give permission as the child was very ill.'}
|
Cardiovascular-System
|
CVS
|
[] |
6144612
|
{'Observation': 'This child presented with encephalopathy, fatigue, muscle weakness, ketonuria, and lipid storage in muscles. His tandem mass spectroscopy showed elevated medium-chain acylcarnitine and long-chain acylcarnitine suggestive of MADD. His urine showed elevated excretion of 2HG, adipate, and arabitol.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.', 'Patient and methods': 'Our patient is a 13-year-old boy who was the second child born to non-consanguineous parents. He noticed tiredness and pain in muscles on walking. Patient had about 6 episodes of weakness of all four limbs presenting as difficulty in getting up from sitting posture and falls while walking. He also had vomiting and brown colored urine after exertion. Examination revealed thin built child with a small goiter. Wasting of supraspinatus, infraspinatus, deltoid, and pectoralis muscles was reported with winging of scapula. Power was 4/5 in proximal muscles of upper limbs and 2 to 3/5 in lower limbs. All reflexes were preserved and sensations were normal. Investigations showed severe ketonuria (creatine kinase, 1271 IU/L, lactate dehydrogenase, 2622 IU/L). Liver and renal function tests were normal (aspartate transaminase, 1214 IU/L; alalnine transaminase, 307 IU/L; potential of Hydrogen, 7.4; partial pressure of Carbon Dioxide, 39.9; partial pressure of Oxygen, 77.4; lactate, 2.8 µmol/L). Ultrasonography of abdomen was normal. Estimation of blood levels of free acylcarnitines by tandem mass spectrometry showed significant elevation of short, medium and long-chain acylcarnitines suggestive of multiple acyl-CoA dehydrogenase deficiency. The following levels were obtained from the estimation: hexanoylcarnitine (C6)- 0.67 μmol/L (normal range 0–0.23 μmol/L); adipylcarnitine (C6DC)- 0.52 μmol/L (normal range 0.01–0.33 μmol/L); octanylcarnitine (C8) I-1.2 μmol/L (normal range 0.01–0.39 μmol/L); decanoylcarnitine (C10)-1.71 μmol/L (normal range 0–0.5 μmol/L); dodecanoylcarnitine (C12)-0.63 μmol/L (normal range 0.02–0.42 μmol/L); tetradecanoylcarnitine (C14)- 0.56 μmol/L (normal range 0.03–0.41 μmol/L) and tetradecanoylcarnitine (C14)- 0.59 μmol/L (normal range 0.01–0.28 μmol/L). Profiling of urine organic acids showed increased excretion of 2-hydroxyglutarate (2HG), adipate, arabitol, and 3-hydroxy butyrate. Muscle biopsy was carried out and histopathological analysis of transversely cut skeletal muscle tissue showed mild variation in fiber diameter and multiple fine vacuoles in hematoxylin and eosin–stained material. Modified Gomori trichrome stain showed vacuolated fibers with red granular material consistent with ragged red fibers. Oil Red O stain showed vacuolated fibers with Oil Red O–positive material suggesting lipid storage. The patient was started on high carbohydrate diet with restriction on protein, fat and started on riboflavin (200 mg) and carnitine (1.5 g) per day. He was also given symptomatic treatment. He steadily improved and became fully symptom free at 3 months. Figure 2 shows the patient at 3 months of follow-up. The pictures at admission could not be taken as patient’s relatives were unwilling to give permission as the child was very ill.'}
|
{'Observation': 'This child presented with encephalopathy, fatigue, muscle weakness, ketonuria, and lipid storage in muscles. His tandem mass spectroscopy showed elevated medium-chain acylcarnitine and long-chain acylcarnitine suggestive of MADD. His urine showed elevated excretion of 2HG, adipate, and arabitol.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.', 'Patient and methods': 'Our patient is a 13-year-old boy who was the second child born to non-consanguineous parents. He noticed tiredness and pain in muscles on walking. Patient had about 6 episodes of weakness of all four limbs presenting as difficulty in getting up from sitting posture and falls while walking. He also had vomiting and brown colored urine after exertion. Examination revealed thin built child with a small goiter. Wasting of supraspinatus, infraspinatus, deltoid, and pectoralis muscles was reported with winging of scapula. Power was 4/5 in proximal muscles of upper limbs and 2 to 3/5 in lower limbs. All reflexes were preserved and sensations were normal. Investigations showed severe ketonuria (creatine kinase, 1271 IU/L, lactate dehydrogenase, 2622 IU/L). Liver and renal function tests were normal (aspartate transaminase, 1214 IU/L; alalnine transaminase, 307 IU/L; potential of Hydrogen, 7.4; partial pressure of Carbon Dioxide, 39.9; partial pressure of Oxygen, 77.4; lactate, 2.8 µmol/L). Ultrasonography of abdomen was normal. Estimation of blood levels of free acylcarnitines by tandem mass spectrometry showed significant elevation of short, medium and long-chain acylcarnitines suggestive of multiple acyl-CoA dehydrogenase deficiency. The following levels were obtained from the estimation: hexanoylcarnitine (C6)- 0.67 μmol/L (normal range 0–0.23 μmol/L); adipylcarnitine (C6DC)- 0.52 μmol/L (normal range 0.01–0.33 μmol/L); octanylcarnitine (C8) I-1.2 μmol/L (normal range 0.01–0.39 μmol/L); decanoylcarnitine (C10)-1.71 μmol/L (normal range 0–0.5 μmol/L); dodecanoylcarnitine (C12)-0.63 μmol/L (normal range 0.02–0.42 μmol/L); tetradecanoylcarnitine (C14)- 0.56 μmol/L (normal range 0.03–0.41 μmol/L) and tetradecanoylcarnitine (C14)- 0.59 μmol/L (normal range 0.01–0.28 μmol/L). Profiling of urine organic acids showed increased excretion of 2-hydroxyglutarate (2HG), adipate, arabitol, and 3-hydroxy butyrate. Muscle biopsy was carried out and histopathological analysis of transversely cut skeletal muscle tissue showed mild variation in fiber diameter and multiple fine vacuoles in hematoxylin and eosin–stained material. Modified Gomori trichrome stain showed vacuolated fibers with red granular material consistent with ragged red fibers. Oil Red O stain showed vacuolated fibers with Oil Red O–positive material suggesting lipid storage. The patient was started on high carbohydrate diet with restriction on protein, fat and started on riboflavin (200 mg) and carnitine (1.5 g) per day. He was also given symptomatic treatment. He steadily improved and became fully symptom free at 3 months. Figure 2 shows the patient at 3 months of follow-up. The pictures at admission could not be taken as patient’s relatives were unwilling to give permission as the child was very ill.'}
|
Endocrinology
|
ENDO
|
[
"thin built child with a small goiter"
] |
6144612
|
{'Observation': 'This child presented with encephalopathy, fatigue, muscle weakness, ketonuria, and lipid storage in muscles. His tandem mass spectroscopy showed elevated medium-chain acylcarnitine and long-chain acylcarnitine suggestive of MADD. His urine showed elevated excretion of 2HG, adipate, and arabitol.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.', 'Patient and methods': 'Our patient is a 13-year-old boy who was the second child born to non-consanguineous parents. He noticed tiredness and pain in muscles on walking. Patient had about 6 episodes of weakness of all four limbs presenting as difficulty in getting up from sitting posture and falls while walking. He also had vomiting and brown colored urine after exertion. Examination revealed thin built child with a small goiter. Wasting of supraspinatus, infraspinatus, deltoid, and pectoralis muscles was reported with winging of scapula. Power was 4/5 in proximal muscles of upper limbs and 2 to 3/5 in lower limbs. All reflexes were preserved and sensations were normal. Investigations showed severe ketonuria (creatine kinase, 1271 IU/L, lactate dehydrogenase, 2622 IU/L). Liver and renal function tests were normal (aspartate transaminase, 1214 IU/L; alalnine transaminase, 307 IU/L; potential of Hydrogen, 7.4; partial pressure of Carbon Dioxide, 39.9; partial pressure of Oxygen, 77.4; lactate, 2.8 µmol/L). Ultrasonography of abdomen was normal. Estimation of blood levels of free acylcarnitines by tandem mass spectrometry showed significant elevation of short, medium and long-chain acylcarnitines suggestive of multiple acyl-CoA dehydrogenase deficiency. The following levels were obtained from the estimation: hexanoylcarnitine (C6)- 0.67 μmol/L (normal range 0–0.23 μmol/L); adipylcarnitine (C6DC)- 0.52 μmol/L (normal range 0.01–0.33 μmol/L); octanylcarnitine (C8) I-1.2 μmol/L (normal range 0.01–0.39 μmol/L); decanoylcarnitine (C10)-1.71 μmol/L (normal range 0–0.5 μmol/L); dodecanoylcarnitine (C12)-0.63 μmol/L (normal range 0.02–0.42 μmol/L); tetradecanoylcarnitine (C14)- 0.56 μmol/L (normal range 0.03–0.41 μmol/L) and tetradecanoylcarnitine (C14)- 0.59 μmol/L (normal range 0.01–0.28 μmol/L). Profiling of urine organic acids showed increased excretion of 2-hydroxyglutarate (2HG), adipate, arabitol, and 3-hydroxy butyrate. Muscle biopsy was carried out and histopathological analysis of transversely cut skeletal muscle tissue showed mild variation in fiber diameter and multiple fine vacuoles in hematoxylin and eosin–stained material. Modified Gomori trichrome stain showed vacuolated fibers with red granular material consistent with ragged red fibers. Oil Red O stain showed vacuolated fibers with Oil Red O–positive material suggesting lipid storage. The patient was started on high carbohydrate diet with restriction on protein, fat and started on riboflavin (200 mg) and carnitine (1.5 g) per day. He was also given symptomatic treatment. He steadily improved and became fully symptom free at 3 months. Figure 2 shows the patient at 3 months of follow-up. The pictures at admission could not be taken as patient’s relatives were unwilling to give permission as the child was very ill.'}
|
{'Observation': 'This child presented with encephalopathy, fatigue, muscle weakness, ketonuria, and lipid storage in muscles. His tandem mass spectroscopy showed elevated medium-chain acylcarnitine and long-chain acylcarnitine suggestive of MADD. His urine showed elevated excretion of 2HG, adipate, and arabitol.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.', 'Patient and methods': 'Our patient is a 13-year-old boy who was the second child born to non-consanguineous parents. He noticed tiredness and pain in muscles on walking. Patient had about 6 episodes of weakness of all four limbs presenting as difficulty in getting up from sitting posture and falls while walking. He also had vomiting and brown colored urine after exertion. Examination revealed thin built child with a small goiter. Wasting of supraspinatus, infraspinatus, deltoid, and pectoralis muscles was reported with winging of scapula. Power was 4/5 in proximal muscles of upper limbs and 2 to 3/5 in lower limbs. All reflexes were preserved and sensations were normal. Investigations showed severe ketonuria (creatine kinase, 1271 IU/L, lactate dehydrogenase, 2622 IU/L). Liver and renal function tests were normal (aspartate transaminase, 1214 IU/L; alalnine transaminase, 307 IU/L; potential of Hydrogen, 7.4; partial pressure of Carbon Dioxide, 39.9; partial pressure of Oxygen, 77.4; lactate, 2.8 µmol/L). Ultrasonography of abdomen was normal. Estimation of blood levels of free acylcarnitines by tandem mass spectrometry showed significant elevation of short, medium and long-chain acylcarnitines suggestive of multiple acyl-CoA dehydrogenase deficiency. The following levels were obtained from the estimation: hexanoylcarnitine (C6)- 0.67 μmol/L (normal range 0–0.23 μmol/L); adipylcarnitine (C6DC)- 0.52 μmol/L (normal range 0.01–0.33 μmol/L); octanylcarnitine (C8) I-1.2 μmol/L (normal range 0.01–0.39 μmol/L); decanoylcarnitine (C10)-1.71 μmol/L (normal range 0–0.5 μmol/L); dodecanoylcarnitine (C12)-0.63 μmol/L (normal range 0.02–0.42 μmol/L); tetradecanoylcarnitine (C14)- 0.56 μmol/L (normal range 0.03–0.41 μmol/L) and tetradecanoylcarnitine (C14)- 0.59 μmol/L (normal range 0.01–0.28 μmol/L). Profiling of urine organic acids showed increased excretion of 2-hydroxyglutarate (2HG), adipate, arabitol, and 3-hydroxy butyrate. Muscle biopsy was carried out and histopathological analysis of transversely cut skeletal muscle tissue showed mild variation in fiber diameter and multiple fine vacuoles in hematoxylin and eosin–stained material. Modified Gomori trichrome stain showed vacuolated fibers with red granular material consistent with ragged red fibers. Oil Red O stain showed vacuolated fibers with Oil Red O–positive material suggesting lipid storage. The patient was started on high carbohydrate diet with restriction on protein, fat and started on riboflavin (200 mg) and carnitine (1.5 g) per day. He was also given symptomatic treatment. He steadily improved and became fully symptom free at 3 months. Figure 2 shows the patient at 3 months of follow-up. The pictures at admission could not be taken as patient’s relatives were unwilling to give permission as the child was very ill.'}
|
Genitourinary-System
|
GU
|
[
"brown colored urine after exertion"
] |
6144612
|
{'Observation': 'This child presented with encephalopathy, fatigue, muscle weakness, ketonuria, and lipid storage in muscles. His tandem mass spectroscopy showed elevated medium-chain acylcarnitine and long-chain acylcarnitine suggestive of MADD. His urine showed elevated excretion of 2HG, adipate, and arabitol.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.', 'Patient and methods': 'Our patient is a 13-year-old boy who was the second child born to non-consanguineous parents. He noticed tiredness and pain in muscles on walking. Patient had about 6 episodes of weakness of all four limbs presenting as difficulty in getting up from sitting posture and falls while walking. He also had vomiting and brown colored urine after exertion. Examination revealed thin built child with a small goiter. Wasting of supraspinatus, infraspinatus, deltoid, and pectoralis muscles was reported with winging of scapula. Power was 4/5 in proximal muscles of upper limbs and 2 to 3/5 in lower limbs. All reflexes were preserved and sensations were normal. Investigations showed severe ketonuria (creatine kinase, 1271 IU/L, lactate dehydrogenase, 2622 IU/L). Liver and renal function tests were normal (aspartate transaminase, 1214 IU/L; alalnine transaminase, 307 IU/L; potential of Hydrogen, 7.4; partial pressure of Carbon Dioxide, 39.9; partial pressure of Oxygen, 77.4; lactate, 2.8 µmol/L). Ultrasonography of abdomen was normal. Estimation of blood levels of free acylcarnitines by tandem mass spectrometry showed significant elevation of short, medium and long-chain acylcarnitines suggestive of multiple acyl-CoA dehydrogenase deficiency. The following levels were obtained from the estimation: hexanoylcarnitine (C6)- 0.67 μmol/L (normal range 0–0.23 μmol/L); adipylcarnitine (C6DC)- 0.52 μmol/L (normal range 0.01–0.33 μmol/L); octanylcarnitine (C8) I-1.2 μmol/L (normal range 0.01–0.39 μmol/L); decanoylcarnitine (C10)-1.71 μmol/L (normal range 0–0.5 μmol/L); dodecanoylcarnitine (C12)-0.63 μmol/L (normal range 0.02–0.42 μmol/L); tetradecanoylcarnitine (C14)- 0.56 μmol/L (normal range 0.03–0.41 μmol/L) and tetradecanoylcarnitine (C14)- 0.59 μmol/L (normal range 0.01–0.28 μmol/L). Profiling of urine organic acids showed increased excretion of 2-hydroxyglutarate (2HG), adipate, arabitol, and 3-hydroxy butyrate. Muscle biopsy was carried out and histopathological analysis of transversely cut skeletal muscle tissue showed mild variation in fiber diameter and multiple fine vacuoles in hematoxylin and eosin–stained material. Modified Gomori trichrome stain showed vacuolated fibers with red granular material consistent with ragged red fibers. Oil Red O stain showed vacuolated fibers with Oil Red O–positive material suggesting lipid storage. The patient was started on high carbohydrate diet with restriction on protein, fat and started on riboflavin (200 mg) and carnitine (1.5 g) per day. He was also given symptomatic treatment. He steadily improved and became fully symptom free at 3 months. Figure 2 shows the patient at 3 months of follow-up. The pictures at admission could not be taken as patient’s relatives were unwilling to give permission as the child was very ill.'}
|
{'Observation': 'This child presented with encephalopathy, fatigue, muscle weakness, ketonuria, and lipid storage in muscles. His tandem mass spectroscopy showed elevated medium-chain acylcarnitine and long-chain acylcarnitine suggestive of MADD. His urine showed elevated excretion of 2HG, adipate, and arabitol.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.', 'Patient and methods': 'Our patient is a 13-year-old boy who was the second child born to non-consanguineous parents. He noticed tiredness and pain in muscles on walking. Patient had about 6 episodes of weakness of all four limbs presenting as difficulty in getting up from sitting posture and falls while walking. He also had vomiting and brown colored urine after exertion. Examination revealed thin built child with a small goiter. Wasting of supraspinatus, infraspinatus, deltoid, and pectoralis muscles was reported with winging of scapula. Power was 4/5 in proximal muscles of upper limbs and 2 to 3/5 in lower limbs. All reflexes were preserved and sensations were normal. Investigations showed severe ketonuria (creatine kinase, 1271 IU/L, lactate dehydrogenase, 2622 IU/L). Liver and renal function tests were normal (aspartate transaminase, 1214 IU/L; alalnine transaminase, 307 IU/L; potential of Hydrogen, 7.4; partial pressure of Carbon Dioxide, 39.9; partial pressure of Oxygen, 77.4; lactate, 2.8 µmol/L). Ultrasonography of abdomen was normal. Estimation of blood levels of free acylcarnitines by tandem mass spectrometry showed significant elevation of short, medium and long-chain acylcarnitines suggestive of multiple acyl-CoA dehydrogenase deficiency. The following levels were obtained from the estimation: hexanoylcarnitine (C6)- 0.67 μmol/L (normal range 0–0.23 μmol/L); adipylcarnitine (C6DC)- 0.52 μmol/L (normal range 0.01–0.33 μmol/L); octanylcarnitine (C8) I-1.2 μmol/L (normal range 0.01–0.39 μmol/L); decanoylcarnitine (C10)-1.71 μmol/L (normal range 0–0.5 μmol/L); dodecanoylcarnitine (C12)-0.63 μmol/L (normal range 0.02–0.42 μmol/L); tetradecanoylcarnitine (C14)- 0.56 μmol/L (normal range 0.03–0.41 μmol/L) and tetradecanoylcarnitine (C14)- 0.59 μmol/L (normal range 0.01–0.28 μmol/L). Profiling of urine organic acids showed increased excretion of 2-hydroxyglutarate (2HG), adipate, arabitol, and 3-hydroxy butyrate. Muscle biopsy was carried out and histopathological analysis of transversely cut skeletal muscle tissue showed mild variation in fiber diameter and multiple fine vacuoles in hematoxylin and eosin–stained material. Modified Gomori trichrome stain showed vacuolated fibers with red granular material consistent with ragged red fibers. Oil Red O stain showed vacuolated fibers with Oil Red O–positive material suggesting lipid storage. The patient was started on high carbohydrate diet with restriction on protein, fat and started on riboflavin (200 mg) and carnitine (1.5 g) per day. He was also given symptomatic treatment. He steadily improved and became fully symptom free at 3 months. Figure 2 shows the patient at 3 months of follow-up. The pictures at admission could not be taken as patient’s relatives were unwilling to give permission as the child was very ill.'}
|
Respiratory-System
|
RESP
|
[] |
6144612
|
{'Observation': 'This child presented with encephalopathy, fatigue, muscle weakness, ketonuria, and lipid storage in muscles. His tandem mass spectroscopy showed elevated medium-chain acylcarnitine and long-chain acylcarnitine suggestive of MADD. His urine showed elevated excretion of 2HG, adipate, and arabitol.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.', 'Patient and methods': 'Our patient is a 13-year-old boy who was the second child born to non-consanguineous parents. He noticed tiredness and pain in muscles on walking. Patient had about 6 episodes of weakness of all four limbs presenting as difficulty in getting up from sitting posture and falls while walking. He also had vomiting and brown colored urine after exertion. Examination revealed thin built child with a small goiter. Wasting of supraspinatus, infraspinatus, deltoid, and pectoralis muscles was reported with winging of scapula. Power was 4/5 in proximal muscles of upper limbs and 2 to 3/5 in lower limbs. All reflexes were preserved and sensations were normal. Investigations showed severe ketonuria (creatine kinase, 1271 IU/L, lactate dehydrogenase, 2622 IU/L). Liver and renal function tests were normal (aspartate transaminase, 1214 IU/L; alalnine transaminase, 307 IU/L; potential of Hydrogen, 7.4; partial pressure of Carbon Dioxide, 39.9; partial pressure of Oxygen, 77.4; lactate, 2.8 µmol/L). Ultrasonography of abdomen was normal. Estimation of blood levels of free acylcarnitines by tandem mass spectrometry showed significant elevation of short, medium and long-chain acylcarnitines suggestive of multiple acyl-CoA dehydrogenase deficiency. The following levels were obtained from the estimation: hexanoylcarnitine (C6)- 0.67 μmol/L (normal range 0–0.23 μmol/L); adipylcarnitine (C6DC)- 0.52 μmol/L (normal range 0.01–0.33 μmol/L); octanylcarnitine (C8) I-1.2 μmol/L (normal range 0.01–0.39 μmol/L); decanoylcarnitine (C10)-1.71 μmol/L (normal range 0–0.5 μmol/L); dodecanoylcarnitine (C12)-0.63 μmol/L (normal range 0.02–0.42 μmol/L); tetradecanoylcarnitine (C14)- 0.56 μmol/L (normal range 0.03–0.41 μmol/L) and tetradecanoylcarnitine (C14)- 0.59 μmol/L (normal range 0.01–0.28 μmol/L). Profiling of urine organic acids showed increased excretion of 2-hydroxyglutarate (2HG), adipate, arabitol, and 3-hydroxy butyrate. Muscle biopsy was carried out and histopathological analysis of transversely cut skeletal muscle tissue showed mild variation in fiber diameter and multiple fine vacuoles in hematoxylin and eosin–stained material. Modified Gomori trichrome stain showed vacuolated fibers with red granular material consistent with ragged red fibers. Oil Red O stain showed vacuolated fibers with Oil Red O–positive material suggesting lipid storage. The patient was started on high carbohydrate diet with restriction on protein, fat and started on riboflavin (200 mg) and carnitine (1.5 g) per day. He was also given symptomatic treatment. He steadily improved and became fully symptom free at 3 months. Figure 2 shows the patient at 3 months of follow-up. The pictures at admission could not be taken as patient’s relatives were unwilling to give permission as the child was very ill.'}
|
{'Observation': 'This child presented with encephalopathy, fatigue, muscle weakness, ketonuria, and lipid storage in muscles. His tandem mass spectroscopy showed elevated medium-chain acylcarnitine and long-chain acylcarnitine suggestive of MADD. His urine showed elevated excretion of 2HG, adipate, and arabitol.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.', 'Patient and methods': 'Our patient is a 13-year-old boy who was the second child born to non-consanguineous parents. He noticed tiredness and pain in muscles on walking. Patient had about 6 episodes of weakness of all four limbs presenting as difficulty in getting up from sitting posture and falls while walking. He also had vomiting and brown colored urine after exertion. Examination revealed thin built child with a small goiter. Wasting of supraspinatus, infraspinatus, deltoid, and pectoralis muscles was reported with winging of scapula. Power was 4/5 in proximal muscles of upper limbs and 2 to 3/5 in lower limbs. All reflexes were preserved and sensations were normal. Investigations showed severe ketonuria (creatine kinase, 1271 IU/L, lactate dehydrogenase, 2622 IU/L). Liver and renal function tests were normal (aspartate transaminase, 1214 IU/L; alalnine transaminase, 307 IU/L; potential of Hydrogen, 7.4; partial pressure of Carbon Dioxide, 39.9; partial pressure of Oxygen, 77.4; lactate, 2.8 µmol/L). Ultrasonography of abdomen was normal. Estimation of blood levels of free acylcarnitines by tandem mass spectrometry showed significant elevation of short, medium and long-chain acylcarnitines suggestive of multiple acyl-CoA dehydrogenase deficiency. The following levels were obtained from the estimation: hexanoylcarnitine (C6)- 0.67 μmol/L (normal range 0–0.23 μmol/L); adipylcarnitine (C6DC)- 0.52 μmol/L (normal range 0.01–0.33 μmol/L); octanylcarnitine (C8) I-1.2 μmol/L (normal range 0.01–0.39 μmol/L); decanoylcarnitine (C10)-1.71 μmol/L (normal range 0–0.5 μmol/L); dodecanoylcarnitine (C12)-0.63 μmol/L (normal range 0.02–0.42 μmol/L); tetradecanoylcarnitine (C14)- 0.56 μmol/L (normal range 0.03–0.41 μmol/L) and tetradecanoylcarnitine (C14)- 0.59 μmol/L (normal range 0.01–0.28 μmol/L). Profiling of urine organic acids showed increased excretion of 2-hydroxyglutarate (2HG), adipate, arabitol, and 3-hydroxy butyrate. Muscle biopsy was carried out and histopathological analysis of transversely cut skeletal muscle tissue showed mild variation in fiber diameter and multiple fine vacuoles in hematoxylin and eosin–stained material. Modified Gomori trichrome stain showed vacuolated fibers with red granular material consistent with ragged red fibers. Oil Red O stain showed vacuolated fibers with Oil Red O–positive material suggesting lipid storage. The patient was started on high carbohydrate diet with restriction on protein, fat and started on riboflavin (200 mg) and carnitine (1.5 g) per day. He was also given symptomatic treatment. He steadily improved and became fully symptom free at 3 months. Figure 2 shows the patient at 3 months of follow-up. The pictures at admission could not be taken as patient’s relatives were unwilling to give permission as the child was very ill.'}
|
Musculoskeletal-System
|
MSK
|
[
"muscle weakness",
"lipid storage in muscles",
"tiredness and pain in muscles on walking",
"6 episodes of weakness of all four limbs presenting as difficulty in getting up from sitting posture and falls while walking",
"brown colored urine after exertion",
"Wasting of supraspinatus, infraspinatus, deltoid, and pectoralis muscles was reported with winging of scapula. Power was 4/5 in proximal muscles of upper limbs and 2 to 3/5 in lower limbs",
"creatine kinase, 1271 IU / L",
"Muscle biopsy was carried out and histopathological analysis of transversely cut skeletal muscle tissue showed mild variation in fiber diameter and multiple fine vacuoles in hematoxylin and eosin – stained material. Modified Gomori trichrome stain showed vacuolated fibers with red granular material consistent with ragged red fibers. Oil Red O stain showed vacuolated fibers with Oil Red O – positive material suggesting lipid storage"
] |
6144612
|
{'Observation': 'This child presented with encephalopathy, fatigue, muscle weakness, ketonuria, and lipid storage in muscles. His tandem mass spectroscopy showed elevated medium-chain acylcarnitine and long-chain acylcarnitine suggestive of MADD. His urine showed elevated excretion of 2HG, adipate, and arabitol.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.', 'Patient and methods': 'Our patient is a 13-year-old boy who was the second child born to non-consanguineous parents. He noticed tiredness and pain in muscles on walking. Patient had about 6 episodes of weakness of all four limbs presenting as difficulty in getting up from sitting posture and falls while walking. He also had vomiting and brown colored urine after exertion. Examination revealed thin built child with a small goiter. Wasting of supraspinatus, infraspinatus, deltoid, and pectoralis muscles was reported with winging of scapula. Power was 4/5 in proximal muscles of upper limbs and 2 to 3/5 in lower limbs. All reflexes were preserved and sensations were normal. Investigations showed severe ketonuria (creatine kinase, 1271 IU/L, lactate dehydrogenase, 2622 IU/L). Liver and renal function tests were normal (aspartate transaminase, 1214 IU/L; alalnine transaminase, 307 IU/L; potential of Hydrogen, 7.4; partial pressure of Carbon Dioxide, 39.9; partial pressure of Oxygen, 77.4; lactate, 2.8 µmol/L). Ultrasonography of abdomen was normal. Estimation of blood levels of free acylcarnitines by tandem mass spectrometry showed significant elevation of short, medium and long-chain acylcarnitines suggestive of multiple acyl-CoA dehydrogenase deficiency. The following levels were obtained from the estimation: hexanoylcarnitine (C6)- 0.67 μmol/L (normal range 0–0.23 μmol/L); adipylcarnitine (C6DC)- 0.52 μmol/L (normal range 0.01–0.33 μmol/L); octanylcarnitine (C8) I-1.2 μmol/L (normal range 0.01–0.39 μmol/L); decanoylcarnitine (C10)-1.71 μmol/L (normal range 0–0.5 μmol/L); dodecanoylcarnitine (C12)-0.63 μmol/L (normal range 0.02–0.42 μmol/L); tetradecanoylcarnitine (C14)- 0.56 μmol/L (normal range 0.03–0.41 μmol/L) and tetradecanoylcarnitine (C14)- 0.59 μmol/L (normal range 0.01–0.28 μmol/L). Profiling of urine organic acids showed increased excretion of 2-hydroxyglutarate (2HG), adipate, arabitol, and 3-hydroxy butyrate. Muscle biopsy was carried out and histopathological analysis of transversely cut skeletal muscle tissue showed mild variation in fiber diameter and multiple fine vacuoles in hematoxylin and eosin–stained material. Modified Gomori trichrome stain showed vacuolated fibers with red granular material consistent with ragged red fibers. Oil Red O stain showed vacuolated fibers with Oil Red O–positive material suggesting lipid storage. The patient was started on high carbohydrate diet with restriction on protein, fat and started on riboflavin (200 mg) and carnitine (1.5 g) per day. He was also given symptomatic treatment. He steadily improved and became fully symptom free at 3 months. Figure 2 shows the patient at 3 months of follow-up. The pictures at admission could not be taken as patient’s relatives were unwilling to give permission as the child was very ill.'}
|
{'Observation': 'This child presented with encephalopathy, fatigue, muscle weakness, ketonuria, and lipid storage in muscles. His tandem mass spectroscopy showed elevated medium-chain acylcarnitine and long-chain acylcarnitine suggestive of MADD. His urine showed elevated excretion of 2HG, adipate, and arabitol.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.', 'Patient and methods': 'Our patient is a 13-year-old boy who was the second child born to non-consanguineous parents. He noticed tiredness and pain in muscles on walking. Patient had about 6 episodes of weakness of all four limbs presenting as difficulty in getting up from sitting posture and falls while walking. He also had vomiting and brown colored urine after exertion. Examination revealed thin built child with a small goiter. Wasting of supraspinatus, infraspinatus, deltoid, and pectoralis muscles was reported with winging of scapula. Power was 4/5 in proximal muscles of upper limbs and 2 to 3/5 in lower limbs. All reflexes were preserved and sensations were normal. Investigations showed severe ketonuria (creatine kinase, 1271 IU/L, lactate dehydrogenase, 2622 IU/L). Liver and renal function tests were normal (aspartate transaminase, 1214 IU/L; alalnine transaminase, 307 IU/L; potential of Hydrogen, 7.4; partial pressure of Carbon Dioxide, 39.9; partial pressure of Oxygen, 77.4; lactate, 2.8 µmol/L). Ultrasonography of abdomen was normal. Estimation of blood levels of free acylcarnitines by tandem mass spectrometry showed significant elevation of short, medium and long-chain acylcarnitines suggestive of multiple acyl-CoA dehydrogenase deficiency. The following levels were obtained from the estimation: hexanoylcarnitine (C6)- 0.67 μmol/L (normal range 0–0.23 μmol/L); adipylcarnitine (C6DC)- 0.52 μmol/L (normal range 0.01–0.33 μmol/L); octanylcarnitine (C8) I-1.2 μmol/L (normal range 0.01–0.39 μmol/L); decanoylcarnitine (C10)-1.71 μmol/L (normal range 0–0.5 μmol/L); dodecanoylcarnitine (C12)-0.63 μmol/L (normal range 0.02–0.42 μmol/L); tetradecanoylcarnitine (C14)- 0.56 μmol/L (normal range 0.03–0.41 μmol/L) and tetradecanoylcarnitine (C14)- 0.59 μmol/L (normal range 0.01–0.28 μmol/L). Profiling of urine organic acids showed increased excretion of 2-hydroxyglutarate (2HG), adipate, arabitol, and 3-hydroxy butyrate. Muscle biopsy was carried out and histopathological analysis of transversely cut skeletal muscle tissue showed mild variation in fiber diameter and multiple fine vacuoles in hematoxylin and eosin–stained material. Modified Gomori trichrome stain showed vacuolated fibers with red granular material consistent with ragged red fibers. Oil Red O stain showed vacuolated fibers with Oil Red O–positive material suggesting lipid storage. The patient was started on high carbohydrate diet with restriction on protein, fat and started on riboflavin (200 mg) and carnitine (1.5 g) per day. He was also given symptomatic treatment. He steadily improved and became fully symptom free at 3 months. Figure 2 shows the patient at 3 months of follow-up. The pictures at admission could not be taken as patient’s relatives were unwilling to give permission as the child was very ill.'}
|
Eyes-Ears-Nose-Throat
|
EENT
|
[] |
6144612
|
{'Observation': 'This child presented with encephalopathy, fatigue, muscle weakness, ketonuria, and lipid storage in muscles. His tandem mass spectroscopy showed elevated medium-chain acylcarnitine and long-chain acylcarnitine suggestive of MADD. His urine showed elevated excretion of 2HG, adipate, and arabitol.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.', 'Patient and methods': 'Our patient is a 13-year-old boy who was the second child born to non-consanguineous parents. He noticed tiredness and pain in muscles on walking. Patient had about 6 episodes of weakness of all four limbs presenting as difficulty in getting up from sitting posture and falls while walking. He also had vomiting and brown colored urine after exertion. Examination revealed thin built child with a small goiter. Wasting of supraspinatus, infraspinatus, deltoid, and pectoralis muscles was reported with winging of scapula. Power was 4/5 in proximal muscles of upper limbs and 2 to 3/5 in lower limbs. All reflexes were preserved and sensations were normal. Investigations showed severe ketonuria (creatine kinase, 1271 IU/L, lactate dehydrogenase, 2622 IU/L). Liver and renal function tests were normal (aspartate transaminase, 1214 IU/L; alalnine transaminase, 307 IU/L; potential of Hydrogen, 7.4; partial pressure of Carbon Dioxide, 39.9; partial pressure of Oxygen, 77.4; lactate, 2.8 µmol/L). Ultrasonography of abdomen was normal. Estimation of blood levels of free acylcarnitines by tandem mass spectrometry showed significant elevation of short, medium and long-chain acylcarnitines suggestive of multiple acyl-CoA dehydrogenase deficiency. The following levels were obtained from the estimation: hexanoylcarnitine (C6)- 0.67 μmol/L (normal range 0–0.23 μmol/L); adipylcarnitine (C6DC)- 0.52 μmol/L (normal range 0.01–0.33 μmol/L); octanylcarnitine (C8) I-1.2 μmol/L (normal range 0.01–0.39 μmol/L); decanoylcarnitine (C10)-1.71 μmol/L (normal range 0–0.5 μmol/L); dodecanoylcarnitine (C12)-0.63 μmol/L (normal range 0.02–0.42 μmol/L); tetradecanoylcarnitine (C14)- 0.56 μmol/L (normal range 0.03–0.41 μmol/L) and tetradecanoylcarnitine (C14)- 0.59 μmol/L (normal range 0.01–0.28 μmol/L). Profiling of urine organic acids showed increased excretion of 2-hydroxyglutarate (2HG), adipate, arabitol, and 3-hydroxy butyrate. Muscle biopsy was carried out and histopathological analysis of transversely cut skeletal muscle tissue showed mild variation in fiber diameter and multiple fine vacuoles in hematoxylin and eosin–stained material. Modified Gomori trichrome stain showed vacuolated fibers with red granular material consistent with ragged red fibers. Oil Red O stain showed vacuolated fibers with Oil Red O–positive material suggesting lipid storage. The patient was started on high carbohydrate diet with restriction on protein, fat and started on riboflavin (200 mg) and carnitine (1.5 g) per day. He was also given symptomatic treatment. He steadily improved and became fully symptom free at 3 months. Figure 2 shows the patient at 3 months of follow-up. The pictures at admission could not be taken as patient’s relatives were unwilling to give permission as the child was very ill.'}
|
{'Observation': 'This child presented with encephalopathy, fatigue, muscle weakness, ketonuria, and lipid storage in muscles. His tandem mass spectroscopy showed elevated medium-chain acylcarnitine and long-chain acylcarnitine suggestive of MADD. His urine showed elevated excretion of 2HG, adipate, and arabitol.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.', 'Patient and methods': 'Our patient is a 13-year-old boy who was the second child born to non-consanguineous parents. He noticed tiredness and pain in muscles on walking. Patient had about 6 episodes of weakness of all four limbs presenting as difficulty in getting up from sitting posture and falls while walking. He also had vomiting and brown colored urine after exertion. Examination revealed thin built child with a small goiter. Wasting of supraspinatus, infraspinatus, deltoid, and pectoralis muscles was reported with winging of scapula. Power was 4/5 in proximal muscles of upper limbs and 2 to 3/5 in lower limbs. All reflexes were preserved and sensations were normal. Investigations showed severe ketonuria (creatine kinase, 1271 IU/L, lactate dehydrogenase, 2622 IU/L). Liver and renal function tests were normal (aspartate transaminase, 1214 IU/L; alalnine transaminase, 307 IU/L; potential of Hydrogen, 7.4; partial pressure of Carbon Dioxide, 39.9; partial pressure of Oxygen, 77.4; lactate, 2.8 µmol/L). Ultrasonography of abdomen was normal. Estimation of blood levels of free acylcarnitines by tandem mass spectrometry showed significant elevation of short, medium and long-chain acylcarnitines suggestive of multiple acyl-CoA dehydrogenase deficiency. The following levels were obtained from the estimation: hexanoylcarnitine (C6)- 0.67 μmol/L (normal range 0–0.23 μmol/L); adipylcarnitine (C6DC)- 0.52 μmol/L (normal range 0.01–0.33 μmol/L); octanylcarnitine (C8) I-1.2 μmol/L (normal range 0.01–0.39 μmol/L); decanoylcarnitine (C10)-1.71 μmol/L (normal range 0–0.5 μmol/L); dodecanoylcarnitine (C12)-0.63 μmol/L (normal range 0.02–0.42 μmol/L); tetradecanoylcarnitine (C14)- 0.56 μmol/L (normal range 0.03–0.41 μmol/L) and tetradecanoylcarnitine (C14)- 0.59 μmol/L (normal range 0.01–0.28 μmol/L). Profiling of urine organic acids showed increased excretion of 2-hydroxyglutarate (2HG), adipate, arabitol, and 3-hydroxy butyrate. Muscle biopsy was carried out and histopathological analysis of transversely cut skeletal muscle tissue showed mild variation in fiber diameter and multiple fine vacuoles in hematoxylin and eosin–stained material. Modified Gomori trichrome stain showed vacuolated fibers with red granular material consistent with ragged red fibers. Oil Red O stain showed vacuolated fibers with Oil Red O–positive material suggesting lipid storage. The patient was started on high carbohydrate diet with restriction on protein, fat and started on riboflavin (200 mg) and carnitine (1.5 g) per day. He was also given symptomatic treatment. He steadily improved and became fully symptom free at 3 months. Figure 2 shows the patient at 3 months of follow-up. The pictures at admission could not be taken as patient’s relatives were unwilling to give permission as the child was very ill.'}
|
Dermatology
|
DERM
|
[] |
6144612
|
{'Observation': 'This child presented with encephalopathy, fatigue, muscle weakness, ketonuria, and lipid storage in muscles. His tandem mass spectroscopy showed elevated medium-chain acylcarnitine and long-chain acylcarnitine suggestive of MADD. His urine showed elevated excretion of 2HG, adipate, and arabitol.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.', 'Patient and methods': 'Our patient is a 13-year-old boy who was the second child born to non-consanguineous parents. He noticed tiredness and pain in muscles on walking. Patient had about 6 episodes of weakness of all four limbs presenting as difficulty in getting up from sitting posture and falls while walking. He also had vomiting and brown colored urine after exertion. Examination revealed thin built child with a small goiter. Wasting of supraspinatus, infraspinatus, deltoid, and pectoralis muscles was reported with winging of scapula. Power was 4/5 in proximal muscles of upper limbs and 2 to 3/5 in lower limbs. All reflexes were preserved and sensations were normal. Investigations showed severe ketonuria (creatine kinase, 1271 IU/L, lactate dehydrogenase, 2622 IU/L). Liver and renal function tests were normal (aspartate transaminase, 1214 IU/L; alalnine transaminase, 307 IU/L; potential of Hydrogen, 7.4; partial pressure of Carbon Dioxide, 39.9; partial pressure of Oxygen, 77.4; lactate, 2.8 µmol/L). Ultrasonography of abdomen was normal. Estimation of blood levels of free acylcarnitines by tandem mass spectrometry showed significant elevation of short, medium and long-chain acylcarnitines suggestive of multiple acyl-CoA dehydrogenase deficiency. The following levels were obtained from the estimation: hexanoylcarnitine (C6)- 0.67 μmol/L (normal range 0–0.23 μmol/L); adipylcarnitine (C6DC)- 0.52 μmol/L (normal range 0.01–0.33 μmol/L); octanylcarnitine (C8) I-1.2 μmol/L (normal range 0.01–0.39 μmol/L); decanoylcarnitine (C10)-1.71 μmol/L (normal range 0–0.5 μmol/L); dodecanoylcarnitine (C12)-0.63 μmol/L (normal range 0.02–0.42 μmol/L); tetradecanoylcarnitine (C14)- 0.56 μmol/L (normal range 0.03–0.41 μmol/L) and tetradecanoylcarnitine (C14)- 0.59 μmol/L (normal range 0.01–0.28 μmol/L). Profiling of urine organic acids showed increased excretion of 2-hydroxyglutarate (2HG), adipate, arabitol, and 3-hydroxy butyrate. Muscle biopsy was carried out and histopathological analysis of transversely cut skeletal muscle tissue showed mild variation in fiber diameter and multiple fine vacuoles in hematoxylin and eosin–stained material. Modified Gomori trichrome stain showed vacuolated fibers with red granular material consistent with ragged red fibers. Oil Red O stain showed vacuolated fibers with Oil Red O–positive material suggesting lipid storage. The patient was started on high carbohydrate diet with restriction on protein, fat and started on riboflavin (200 mg) and carnitine (1.5 g) per day. He was also given symptomatic treatment. He steadily improved and became fully symptom free at 3 months. Figure 2 shows the patient at 3 months of follow-up. The pictures at admission could not be taken as patient’s relatives were unwilling to give permission as the child was very ill.'}
|
{'Observation': 'This child presented with encephalopathy, fatigue, muscle weakness, ketonuria, and lipid storage in muscles. His tandem mass spectroscopy showed elevated medium-chain acylcarnitine and long-chain acylcarnitine suggestive of MADD. His urine showed elevated excretion of 2HG, adipate, and arabitol.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.', 'Patient and methods': 'Our patient is a 13-year-old boy who was the second child born to non-consanguineous parents. He noticed tiredness and pain in muscles on walking. Patient had about 6 episodes of weakness of all four limbs presenting as difficulty in getting up from sitting posture and falls while walking. He also had vomiting and brown colored urine after exertion. Examination revealed thin built child with a small goiter. Wasting of supraspinatus, infraspinatus, deltoid, and pectoralis muscles was reported with winging of scapula. Power was 4/5 in proximal muscles of upper limbs and 2 to 3/5 in lower limbs. All reflexes were preserved and sensations were normal. Investigations showed severe ketonuria (creatine kinase, 1271 IU/L, lactate dehydrogenase, 2622 IU/L). Liver and renal function tests were normal (aspartate transaminase, 1214 IU/L; alalnine transaminase, 307 IU/L; potential of Hydrogen, 7.4; partial pressure of Carbon Dioxide, 39.9; partial pressure of Oxygen, 77.4; lactate, 2.8 µmol/L). Ultrasonography of abdomen was normal. Estimation of blood levels of free acylcarnitines by tandem mass spectrometry showed significant elevation of short, medium and long-chain acylcarnitines suggestive of multiple acyl-CoA dehydrogenase deficiency. The following levels were obtained from the estimation: hexanoylcarnitine (C6)- 0.67 μmol/L (normal range 0–0.23 μmol/L); adipylcarnitine (C6DC)- 0.52 μmol/L (normal range 0.01–0.33 μmol/L); octanylcarnitine (C8) I-1.2 μmol/L (normal range 0.01–0.39 μmol/L); decanoylcarnitine (C10)-1.71 μmol/L (normal range 0–0.5 μmol/L); dodecanoylcarnitine (C12)-0.63 μmol/L (normal range 0.02–0.42 μmol/L); tetradecanoylcarnitine (C14)- 0.56 μmol/L (normal range 0.03–0.41 μmol/L) and tetradecanoylcarnitine (C14)- 0.59 μmol/L (normal range 0.01–0.28 μmol/L). Profiling of urine organic acids showed increased excretion of 2-hydroxyglutarate (2HG), adipate, arabitol, and 3-hydroxy butyrate. Muscle biopsy was carried out and histopathological analysis of transversely cut skeletal muscle tissue showed mild variation in fiber diameter and multiple fine vacuoles in hematoxylin and eosin–stained material. Modified Gomori trichrome stain showed vacuolated fibers with red granular material consistent with ragged red fibers. Oil Red O stain showed vacuolated fibers with Oil Red O–positive material suggesting lipid storage. The patient was started on high carbohydrate diet with restriction on protein, fat and started on riboflavin (200 mg) and carnitine (1.5 g) per day. He was also given symptomatic treatment. He steadily improved and became fully symptom free at 3 months. Figure 2 shows the patient at 3 months of follow-up. The pictures at admission could not be taken as patient’s relatives were unwilling to give permission as the child was very ill.'}
|
Pregnancy
|
Pregnancy
|
[] |
6144612
|
{'Observation': 'This child presented with encephalopathy, fatigue, muscle weakness, ketonuria, and lipid storage in muscles. His tandem mass spectroscopy showed elevated medium-chain acylcarnitine and long-chain acylcarnitine suggestive of MADD. His urine showed elevated excretion of 2HG, adipate, and arabitol.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.', 'Patient and methods': 'Our patient is a 13-year-old boy who was the second child born to non-consanguineous parents. He noticed tiredness and pain in muscles on walking. Patient had about 6 episodes of weakness of all four limbs presenting as difficulty in getting up from sitting posture and falls while walking. He also had vomiting and brown colored urine after exertion. Examination revealed thin built child with a small goiter. Wasting of supraspinatus, infraspinatus, deltoid, and pectoralis muscles was reported with winging of scapula. Power was 4/5 in proximal muscles of upper limbs and 2 to 3/5 in lower limbs. All reflexes were preserved and sensations were normal. Investigations showed severe ketonuria (creatine kinase, 1271 IU/L, lactate dehydrogenase, 2622 IU/L). Liver and renal function tests were normal (aspartate transaminase, 1214 IU/L; alalnine transaminase, 307 IU/L; potential of Hydrogen, 7.4; partial pressure of Carbon Dioxide, 39.9; partial pressure of Oxygen, 77.4; lactate, 2.8 µmol/L). Ultrasonography of abdomen was normal. Estimation of blood levels of free acylcarnitines by tandem mass spectrometry showed significant elevation of short, medium and long-chain acylcarnitines suggestive of multiple acyl-CoA dehydrogenase deficiency. The following levels were obtained from the estimation: hexanoylcarnitine (C6)- 0.67 μmol/L (normal range 0–0.23 μmol/L); adipylcarnitine (C6DC)- 0.52 μmol/L (normal range 0.01–0.33 μmol/L); octanylcarnitine (C8) I-1.2 μmol/L (normal range 0.01–0.39 μmol/L); decanoylcarnitine (C10)-1.71 μmol/L (normal range 0–0.5 μmol/L); dodecanoylcarnitine (C12)-0.63 μmol/L (normal range 0.02–0.42 μmol/L); tetradecanoylcarnitine (C14)- 0.56 μmol/L (normal range 0.03–0.41 μmol/L) and tetradecanoylcarnitine (C14)- 0.59 μmol/L (normal range 0.01–0.28 μmol/L). Profiling of urine organic acids showed increased excretion of 2-hydroxyglutarate (2HG), adipate, arabitol, and 3-hydroxy butyrate. Muscle biopsy was carried out and histopathological analysis of transversely cut skeletal muscle tissue showed mild variation in fiber diameter and multiple fine vacuoles in hematoxylin and eosin–stained material. Modified Gomori trichrome stain showed vacuolated fibers with red granular material consistent with ragged red fibers. Oil Red O stain showed vacuolated fibers with Oil Red O–positive material suggesting lipid storage. The patient was started on high carbohydrate diet with restriction on protein, fat and started on riboflavin (200 mg) and carnitine (1.5 g) per day. He was also given symptomatic treatment. He steadily improved and became fully symptom free at 3 months. Figure 2 shows the patient at 3 months of follow-up. The pictures at admission could not be taken as patient’s relatives were unwilling to give permission as the child was very ill.'}
|
{'Observation': 'This child presented with encephalopathy, fatigue, muscle weakness, ketonuria, and lipid storage in muscles. His tandem mass spectroscopy showed elevated medium-chain acylcarnitine and long-chain acylcarnitine suggestive of MADD. His urine showed elevated excretion of 2HG, adipate, and arabitol.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.', 'Patient and methods': 'Our patient is a 13-year-old boy who was the second child born to non-consanguineous parents. He noticed tiredness and pain in muscles on walking. Patient had about 6 episodes of weakness of all four limbs presenting as difficulty in getting up from sitting posture and falls while walking. He also had vomiting and brown colored urine after exertion. Examination revealed thin built child with a small goiter. Wasting of supraspinatus, infraspinatus, deltoid, and pectoralis muscles was reported with winging of scapula. Power was 4/5 in proximal muscles of upper limbs and 2 to 3/5 in lower limbs. All reflexes were preserved and sensations were normal. Investigations showed severe ketonuria (creatine kinase, 1271 IU/L, lactate dehydrogenase, 2622 IU/L). Liver and renal function tests were normal (aspartate transaminase, 1214 IU/L; alalnine transaminase, 307 IU/L; potential of Hydrogen, 7.4; partial pressure of Carbon Dioxide, 39.9; partial pressure of Oxygen, 77.4; lactate, 2.8 µmol/L). Ultrasonography of abdomen was normal. Estimation of blood levels of free acylcarnitines by tandem mass spectrometry showed significant elevation of short, medium and long-chain acylcarnitines suggestive of multiple acyl-CoA dehydrogenase deficiency. The following levels were obtained from the estimation: hexanoylcarnitine (C6)- 0.67 μmol/L (normal range 0–0.23 μmol/L); adipylcarnitine (C6DC)- 0.52 μmol/L (normal range 0.01–0.33 μmol/L); octanylcarnitine (C8) I-1.2 μmol/L (normal range 0.01–0.39 μmol/L); decanoylcarnitine (C10)-1.71 μmol/L (normal range 0–0.5 μmol/L); dodecanoylcarnitine (C12)-0.63 μmol/L (normal range 0.02–0.42 μmol/L); tetradecanoylcarnitine (C14)- 0.56 μmol/L (normal range 0.03–0.41 μmol/L) and tetradecanoylcarnitine (C14)- 0.59 μmol/L (normal range 0.01–0.28 μmol/L). Profiling of urine organic acids showed increased excretion of 2-hydroxyglutarate (2HG), adipate, arabitol, and 3-hydroxy butyrate. Muscle biopsy was carried out and histopathological analysis of transversely cut skeletal muscle tissue showed mild variation in fiber diameter and multiple fine vacuoles in hematoxylin and eosin–stained material. Modified Gomori trichrome stain showed vacuolated fibers with red granular material consistent with ragged red fibers. Oil Red O stain showed vacuolated fibers with Oil Red O–positive material suggesting lipid storage. The patient was started on high carbohydrate diet with restriction on protein, fat and started on riboflavin (200 mg) and carnitine (1.5 g) per day. He was also given symptomatic treatment. He steadily improved and became fully symptom free at 3 months. Figure 2 shows the patient at 3 months of follow-up. The pictures at admission could not be taken as patient’s relatives were unwilling to give permission as the child was very ill.'}
|
Lymphatic-System
|
LYMPH
|
[] |
6144612
|
{'Observation': 'This child presented with encephalopathy, fatigue, muscle weakness, ketonuria, and lipid storage in muscles. His tandem mass spectroscopy showed elevated medium-chain acylcarnitine and long-chain acylcarnitine suggestive of MADD. His urine showed elevated excretion of 2HG, adipate, and arabitol.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.', 'Patient and methods': 'Our patient is a 13-year-old boy who was the second child born to non-consanguineous parents. He noticed tiredness and pain in muscles on walking. Patient had about 6 episodes of weakness of all four limbs presenting as difficulty in getting up from sitting posture and falls while walking. He also had vomiting and brown colored urine after exertion. Examination revealed thin built child with a small goiter. Wasting of supraspinatus, infraspinatus, deltoid, and pectoralis muscles was reported with winging of scapula. Power was 4/5 in proximal muscles of upper limbs and 2 to 3/5 in lower limbs. All reflexes were preserved and sensations were normal. Investigations showed severe ketonuria (creatine kinase, 1271 IU/L, lactate dehydrogenase, 2622 IU/L). Liver and renal function tests were normal (aspartate transaminase, 1214 IU/L; alalnine transaminase, 307 IU/L; potential of Hydrogen, 7.4; partial pressure of Carbon Dioxide, 39.9; partial pressure of Oxygen, 77.4; lactate, 2.8 µmol/L). Ultrasonography of abdomen was normal. Estimation of blood levels of free acylcarnitines by tandem mass spectrometry showed significant elevation of short, medium and long-chain acylcarnitines suggestive of multiple acyl-CoA dehydrogenase deficiency. The following levels were obtained from the estimation: hexanoylcarnitine (C6)- 0.67 μmol/L (normal range 0–0.23 μmol/L); adipylcarnitine (C6DC)- 0.52 μmol/L (normal range 0.01–0.33 μmol/L); octanylcarnitine (C8) I-1.2 μmol/L (normal range 0.01–0.39 μmol/L); decanoylcarnitine (C10)-1.71 μmol/L (normal range 0–0.5 μmol/L); dodecanoylcarnitine (C12)-0.63 μmol/L (normal range 0.02–0.42 μmol/L); tetradecanoylcarnitine (C14)- 0.56 μmol/L (normal range 0.03–0.41 μmol/L) and tetradecanoylcarnitine (C14)- 0.59 μmol/L (normal range 0.01–0.28 μmol/L). Profiling of urine organic acids showed increased excretion of 2-hydroxyglutarate (2HG), adipate, arabitol, and 3-hydroxy butyrate. Muscle biopsy was carried out and histopathological analysis of transversely cut skeletal muscle tissue showed mild variation in fiber diameter and multiple fine vacuoles in hematoxylin and eosin–stained material. Modified Gomori trichrome stain showed vacuolated fibers with red granular material consistent with ragged red fibers. Oil Red O stain showed vacuolated fibers with Oil Red O–positive material suggesting lipid storage. The patient was started on high carbohydrate diet with restriction on protein, fat and started on riboflavin (200 mg) and carnitine (1.5 g) per day. He was also given symptomatic treatment. He steadily improved and became fully symptom free at 3 months. Figure 2 shows the patient at 3 months of follow-up. The pictures at admission could not be taken as patient’s relatives were unwilling to give permission as the child was very ill.'}
|
{'Observation': 'This child presented with encephalopathy, fatigue, muscle weakness, ketonuria, and lipid storage in muscles. His tandem mass spectroscopy showed elevated medium-chain acylcarnitine and long-chain acylcarnitine suggestive of MADD. His urine showed elevated excretion of 2HG, adipate, and arabitol.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.', 'Patient and methods': 'Our patient is a 13-year-old boy who was the second child born to non-consanguineous parents. He noticed tiredness and pain in muscles on walking. Patient had about 6 episodes of weakness of all four limbs presenting as difficulty in getting up from sitting posture and falls while walking. He also had vomiting and brown colored urine after exertion. Examination revealed thin built child with a small goiter. Wasting of supraspinatus, infraspinatus, deltoid, and pectoralis muscles was reported with winging of scapula. Power was 4/5 in proximal muscles of upper limbs and 2 to 3/5 in lower limbs. All reflexes were preserved and sensations were normal. Investigations showed severe ketonuria (creatine kinase, 1271 IU/L, lactate dehydrogenase, 2622 IU/L). Liver and renal function tests were normal (aspartate transaminase, 1214 IU/L; alalnine transaminase, 307 IU/L; potential of Hydrogen, 7.4; partial pressure of Carbon Dioxide, 39.9; partial pressure of Oxygen, 77.4; lactate, 2.8 µmol/L). Ultrasonography of abdomen was normal. Estimation of blood levels of free acylcarnitines by tandem mass spectrometry showed significant elevation of short, medium and long-chain acylcarnitines suggestive of multiple acyl-CoA dehydrogenase deficiency. The following levels were obtained from the estimation: hexanoylcarnitine (C6)- 0.67 μmol/L (normal range 0–0.23 μmol/L); adipylcarnitine (C6DC)- 0.52 μmol/L (normal range 0.01–0.33 μmol/L); octanylcarnitine (C8) I-1.2 μmol/L (normal range 0.01–0.39 μmol/L); decanoylcarnitine (C10)-1.71 μmol/L (normal range 0–0.5 μmol/L); dodecanoylcarnitine (C12)-0.63 μmol/L (normal range 0.02–0.42 μmol/L); tetradecanoylcarnitine (C14)- 0.56 μmol/L (normal range 0.03–0.41 μmol/L) and tetradecanoylcarnitine (C14)- 0.59 μmol/L (normal range 0.01–0.28 μmol/L). Profiling of urine organic acids showed increased excretion of 2-hydroxyglutarate (2HG), adipate, arabitol, and 3-hydroxy butyrate. Muscle biopsy was carried out and histopathological analysis of transversely cut skeletal muscle tissue showed mild variation in fiber diameter and multiple fine vacuoles in hematoxylin and eosin–stained material. Modified Gomori trichrome stain showed vacuolated fibers with red granular material consistent with ragged red fibers. Oil Red O stain showed vacuolated fibers with Oil Red O–positive material suggesting lipid storage. The patient was started on high carbohydrate diet with restriction on protein, fat and started on riboflavin (200 mg) and carnitine (1.5 g) per day. He was also given symptomatic treatment. He steadily improved and became fully symptom free at 3 months. Figure 2 shows the patient at 3 months of follow-up. The pictures at admission could not be taken as patient’s relatives were unwilling to give permission as the child was very ill.'}
|
Age-at-Presentation
|
Age (at case presentation)
|
[
"13 - year - old"
] |
6144612
|
{'Observation': 'This child presented with encephalopathy, fatigue, muscle weakness, ketonuria, and lipid storage in muscles. His tandem mass spectroscopy showed elevated medium-chain acylcarnitine and long-chain acylcarnitine suggestive of MADD. His urine showed elevated excretion of 2HG, adipate, and arabitol.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.', 'Patient and methods': 'Our patient is a 13-year-old boy who was the second child born to non-consanguineous parents. He noticed tiredness and pain in muscles on walking. Patient had about 6 episodes of weakness of all four limbs presenting as difficulty in getting up from sitting posture and falls while walking. He also had vomiting and brown colored urine after exertion. Examination revealed thin built child with a small goiter. Wasting of supraspinatus, infraspinatus, deltoid, and pectoralis muscles was reported with winging of scapula. Power was 4/5 in proximal muscles of upper limbs and 2 to 3/5 in lower limbs. All reflexes were preserved and sensations were normal. Investigations showed severe ketonuria (creatine kinase, 1271 IU/L, lactate dehydrogenase, 2622 IU/L). Liver and renal function tests were normal (aspartate transaminase, 1214 IU/L; alalnine transaminase, 307 IU/L; potential of Hydrogen, 7.4; partial pressure of Carbon Dioxide, 39.9; partial pressure of Oxygen, 77.4; lactate, 2.8 µmol/L). Ultrasonography of abdomen was normal. Estimation of blood levels of free acylcarnitines by tandem mass spectrometry showed significant elevation of short, medium and long-chain acylcarnitines suggestive of multiple acyl-CoA dehydrogenase deficiency. The following levels were obtained from the estimation: hexanoylcarnitine (C6)- 0.67 μmol/L (normal range 0–0.23 μmol/L); adipylcarnitine (C6DC)- 0.52 μmol/L (normal range 0.01–0.33 μmol/L); octanylcarnitine (C8) I-1.2 μmol/L (normal range 0.01–0.39 μmol/L); decanoylcarnitine (C10)-1.71 μmol/L (normal range 0–0.5 μmol/L); dodecanoylcarnitine (C12)-0.63 μmol/L (normal range 0.02–0.42 μmol/L); tetradecanoylcarnitine (C14)- 0.56 μmol/L (normal range 0.03–0.41 μmol/L) and tetradecanoylcarnitine (C14)- 0.59 μmol/L (normal range 0.01–0.28 μmol/L). Profiling of urine organic acids showed increased excretion of 2-hydroxyglutarate (2HG), adipate, arabitol, and 3-hydroxy butyrate. Muscle biopsy was carried out and histopathological analysis of transversely cut skeletal muscle tissue showed mild variation in fiber diameter and multiple fine vacuoles in hematoxylin and eosin–stained material. Modified Gomori trichrome stain showed vacuolated fibers with red granular material consistent with ragged red fibers. Oil Red O stain showed vacuolated fibers with Oil Red O–positive material suggesting lipid storage. The patient was started on high carbohydrate diet with restriction on protein, fat and started on riboflavin (200 mg) and carnitine (1.5 g) per day. He was also given symptomatic treatment. He steadily improved and became fully symptom free at 3 months. Figure 2 shows the patient at 3 months of follow-up. The pictures at admission could not be taken as patient’s relatives were unwilling to give permission as the child was very ill.'}
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{'Observation': 'This child presented with encephalopathy, fatigue, muscle weakness, ketonuria, and lipid storage in muscles. His tandem mass spectroscopy showed elevated medium-chain acylcarnitine and long-chain acylcarnitine suggestive of MADD. His urine showed elevated excretion of 2HG, adipate, and arabitol.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.', 'Patient and methods': 'Our patient is a 13-year-old boy who was the second child born to non-consanguineous parents. He noticed tiredness and pain in muscles on walking. Patient had about 6 episodes of weakness of all four limbs presenting as difficulty in getting up from sitting posture and falls while walking. He also had vomiting and brown colored urine after exertion. Examination revealed thin built child with a small goiter. Wasting of supraspinatus, infraspinatus, deltoid, and pectoralis muscles was reported with winging of scapula. Power was 4/5 in proximal muscles of upper limbs and 2 to 3/5 in lower limbs. All reflexes were preserved and sensations were normal. Investigations showed severe ketonuria (creatine kinase, 1271 IU/L, lactate dehydrogenase, 2622 IU/L). Liver and renal function tests were normal (aspartate transaminase, 1214 IU/L; alalnine transaminase, 307 IU/L; potential of Hydrogen, 7.4; partial pressure of Carbon Dioxide, 39.9; partial pressure of Oxygen, 77.4; lactate, 2.8 µmol/L). Ultrasonography of abdomen was normal. Estimation of blood levels of free acylcarnitines by tandem mass spectrometry showed significant elevation of short, medium and long-chain acylcarnitines suggestive of multiple acyl-CoA dehydrogenase deficiency. The following levels were obtained from the estimation: hexanoylcarnitine (C6)- 0.67 μmol/L (normal range 0–0.23 μmol/L); adipylcarnitine (C6DC)- 0.52 μmol/L (normal range 0.01–0.33 μmol/L); octanylcarnitine (C8) I-1.2 μmol/L (normal range 0.01–0.39 μmol/L); decanoylcarnitine (C10)-1.71 μmol/L (normal range 0–0.5 μmol/L); dodecanoylcarnitine (C12)-0.63 μmol/L (normal range 0.02–0.42 μmol/L); tetradecanoylcarnitine (C14)- 0.56 μmol/L (normal range 0.03–0.41 μmol/L) and tetradecanoylcarnitine (C14)- 0.59 μmol/L (normal range 0.01–0.28 μmol/L). Profiling of urine organic acids showed increased excretion of 2-hydroxyglutarate (2HG), adipate, arabitol, and 3-hydroxy butyrate. Muscle biopsy was carried out and histopathological analysis of transversely cut skeletal muscle tissue showed mild variation in fiber diameter and multiple fine vacuoles in hematoxylin and eosin–stained material. Modified Gomori trichrome stain showed vacuolated fibers with red granular material consistent with ragged red fibers. Oil Red O stain showed vacuolated fibers with Oil Red O–positive material suggesting lipid storage. The patient was started on high carbohydrate diet with restriction on protein, fat and started on riboflavin (200 mg) and carnitine (1.5 g) per day. He was also given symptomatic treatment. He steadily improved and became fully symptom free at 3 months. Figure 2 shows the patient at 3 months of follow-up. The pictures at admission could not be taken as patient’s relatives were unwilling to give permission as the child was very ill.'}
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Age-of-Onset
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Age (of onset)
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[] |
6144612
|
{'Observation': 'This child presented with encephalopathy, fatigue, muscle weakness, ketonuria, and lipid storage in muscles. His tandem mass spectroscopy showed elevated medium-chain acylcarnitine and long-chain acylcarnitine suggestive of MADD. His urine showed elevated excretion of 2HG, adipate, and arabitol.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.', 'Patient and methods': 'Our patient is a 13-year-old boy who was the second child born to non-consanguineous parents. He noticed tiredness and pain in muscles on walking. Patient had about 6 episodes of weakness of all four limbs presenting as difficulty in getting up from sitting posture and falls while walking. He also had vomiting and brown colored urine after exertion. Examination revealed thin built child with a small goiter. Wasting of supraspinatus, infraspinatus, deltoid, and pectoralis muscles was reported with winging of scapula. Power was 4/5 in proximal muscles of upper limbs and 2 to 3/5 in lower limbs. All reflexes were preserved and sensations were normal. Investigations showed severe ketonuria (creatine kinase, 1271 IU/L, lactate dehydrogenase, 2622 IU/L). Liver and renal function tests were normal (aspartate transaminase, 1214 IU/L; alalnine transaminase, 307 IU/L; potential of Hydrogen, 7.4; partial pressure of Carbon Dioxide, 39.9; partial pressure of Oxygen, 77.4; lactate, 2.8 µmol/L). Ultrasonography of abdomen was normal. Estimation of blood levels of free acylcarnitines by tandem mass spectrometry showed significant elevation of short, medium and long-chain acylcarnitines suggestive of multiple acyl-CoA dehydrogenase deficiency. The following levels were obtained from the estimation: hexanoylcarnitine (C6)- 0.67 μmol/L (normal range 0–0.23 μmol/L); adipylcarnitine (C6DC)- 0.52 μmol/L (normal range 0.01–0.33 μmol/L); octanylcarnitine (C8) I-1.2 μmol/L (normal range 0.01–0.39 μmol/L); decanoylcarnitine (C10)-1.71 μmol/L (normal range 0–0.5 μmol/L); dodecanoylcarnitine (C12)-0.63 μmol/L (normal range 0.02–0.42 μmol/L); tetradecanoylcarnitine (C14)- 0.56 μmol/L (normal range 0.03–0.41 μmol/L) and tetradecanoylcarnitine (C14)- 0.59 μmol/L (normal range 0.01–0.28 μmol/L). Profiling of urine organic acids showed increased excretion of 2-hydroxyglutarate (2HG), adipate, arabitol, and 3-hydroxy butyrate. Muscle biopsy was carried out and histopathological analysis of transversely cut skeletal muscle tissue showed mild variation in fiber diameter and multiple fine vacuoles in hematoxylin and eosin–stained material. Modified Gomori trichrome stain showed vacuolated fibers with red granular material consistent with ragged red fibers. Oil Red O stain showed vacuolated fibers with Oil Red O–positive material suggesting lipid storage. The patient was started on high carbohydrate diet with restriction on protein, fat and started on riboflavin (200 mg) and carnitine (1.5 g) per day. He was also given symptomatic treatment. He steadily improved and became fully symptom free at 3 months. Figure 2 shows the patient at 3 months of follow-up. The pictures at admission could not be taken as patient’s relatives were unwilling to give permission as the child was very ill.'}
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{'Observation': 'This child presented with encephalopathy, fatigue, muscle weakness, ketonuria, and lipid storage in muscles. His tandem mass spectroscopy showed elevated medium-chain acylcarnitine and long-chain acylcarnitine suggestive of MADD. His urine showed elevated excretion of 2HG, adipate, and arabitol.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.', 'Patient and methods': 'Our patient is a 13-year-old boy who was the second child born to non-consanguineous parents. He noticed tiredness and pain in muscles on walking. Patient had about 6 episodes of weakness of all four limbs presenting as difficulty in getting up from sitting posture and falls while walking. He also had vomiting and brown colored urine after exertion. Examination revealed thin built child with a small goiter. Wasting of supraspinatus, infraspinatus, deltoid, and pectoralis muscles was reported with winging of scapula. Power was 4/5 in proximal muscles of upper limbs and 2 to 3/5 in lower limbs. All reflexes were preserved and sensations were normal. Investigations showed severe ketonuria (creatine kinase, 1271 IU/L, lactate dehydrogenase, 2622 IU/L). Liver and renal function tests were normal (aspartate transaminase, 1214 IU/L; alalnine transaminase, 307 IU/L; potential of Hydrogen, 7.4; partial pressure of Carbon Dioxide, 39.9; partial pressure of Oxygen, 77.4; lactate, 2.8 µmol/L). Ultrasonography of abdomen was normal. Estimation of blood levels of free acylcarnitines by tandem mass spectrometry showed significant elevation of short, medium and long-chain acylcarnitines suggestive of multiple acyl-CoA dehydrogenase deficiency. The following levels were obtained from the estimation: hexanoylcarnitine (C6)- 0.67 μmol/L (normal range 0–0.23 μmol/L); adipylcarnitine (C6DC)- 0.52 μmol/L (normal range 0.01–0.33 μmol/L); octanylcarnitine (C8) I-1.2 μmol/L (normal range 0.01–0.39 μmol/L); decanoylcarnitine (C10)-1.71 μmol/L (normal range 0–0.5 μmol/L); dodecanoylcarnitine (C12)-0.63 μmol/L (normal range 0.02–0.42 μmol/L); tetradecanoylcarnitine (C14)- 0.56 μmol/L (normal range 0.03–0.41 μmol/L) and tetradecanoylcarnitine (C14)- 0.59 μmol/L (normal range 0.01–0.28 μmol/L). Profiling of urine organic acids showed increased excretion of 2-hydroxyglutarate (2HG), adipate, arabitol, and 3-hydroxy butyrate. Muscle biopsy was carried out and histopathological analysis of transversely cut skeletal muscle tissue showed mild variation in fiber diameter and multiple fine vacuoles in hematoxylin and eosin–stained material. Modified Gomori trichrome stain showed vacuolated fibers with red granular material consistent with ragged red fibers. Oil Red O stain showed vacuolated fibers with Oil Red O–positive material suggesting lipid storage. The patient was started on high carbohydrate diet with restriction on protein, fat and started on riboflavin (200 mg) and carnitine (1.5 g) per day. He was also given symptomatic treatment. He steadily improved and became fully symptom free at 3 months. Figure 2 shows the patient at 3 months of follow-up. The pictures at admission could not be taken as patient’s relatives were unwilling to give permission as the child was very ill.'}
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Confirmed-Diagnosis-IEM
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Confirmed_Diagnosis(IEM)
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[] |
6144612
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{'Observation': 'This child presented with encephalopathy, fatigue, muscle weakness, ketonuria, and lipid storage in muscles. His tandem mass spectroscopy showed elevated medium-chain acylcarnitine and long-chain acylcarnitine suggestive of MADD. His urine showed elevated excretion of 2HG, adipate, and arabitol.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.', 'Patient and methods': 'Our patient is a 13-year-old boy who was the second child born to non-consanguineous parents. He noticed tiredness and pain in muscles on walking. Patient had about 6 episodes of weakness of all four limbs presenting as difficulty in getting up from sitting posture and falls while walking. He also had vomiting and brown colored urine after exertion. Examination revealed thin built child with a small goiter. Wasting of supraspinatus, infraspinatus, deltoid, and pectoralis muscles was reported with winging of scapula. Power was 4/5 in proximal muscles of upper limbs and 2 to 3/5 in lower limbs. All reflexes were preserved and sensations were normal. Investigations showed severe ketonuria (creatine kinase, 1271 IU/L, lactate dehydrogenase, 2622 IU/L). Liver and renal function tests were normal (aspartate transaminase, 1214 IU/L; alalnine transaminase, 307 IU/L; potential of Hydrogen, 7.4; partial pressure of Carbon Dioxide, 39.9; partial pressure of Oxygen, 77.4; lactate, 2.8 µmol/L). Ultrasonography of abdomen was normal. Estimation of blood levels of free acylcarnitines by tandem mass spectrometry showed significant elevation of short, medium and long-chain acylcarnitines suggestive of multiple acyl-CoA dehydrogenase deficiency. The following levels were obtained from the estimation: hexanoylcarnitine (C6)- 0.67 μmol/L (normal range 0–0.23 μmol/L); adipylcarnitine (C6DC)- 0.52 μmol/L (normal range 0.01–0.33 μmol/L); octanylcarnitine (C8) I-1.2 μmol/L (normal range 0.01–0.39 μmol/L); decanoylcarnitine (C10)-1.71 μmol/L (normal range 0–0.5 μmol/L); dodecanoylcarnitine (C12)-0.63 μmol/L (normal range 0.02–0.42 μmol/L); tetradecanoylcarnitine (C14)- 0.56 μmol/L (normal range 0.03–0.41 μmol/L) and tetradecanoylcarnitine (C14)- 0.59 μmol/L (normal range 0.01–0.28 μmol/L). Profiling of urine organic acids showed increased excretion of 2-hydroxyglutarate (2HG), adipate, arabitol, and 3-hydroxy butyrate. Muscle biopsy was carried out and histopathological analysis of transversely cut skeletal muscle tissue showed mild variation in fiber diameter and multiple fine vacuoles in hematoxylin and eosin–stained material. Modified Gomori trichrome stain showed vacuolated fibers with red granular material consistent with ragged red fibers. Oil Red O stain showed vacuolated fibers with Oil Red O–positive material suggesting lipid storage. The patient was started on high carbohydrate diet with restriction on protein, fat and started on riboflavin (200 mg) and carnitine (1.5 g) per day. He was also given symptomatic treatment. He steadily improved and became fully symptom free at 3 months. Figure 2 shows the patient at 3 months of follow-up. The pictures at admission could not be taken as patient’s relatives were unwilling to give permission as the child was very ill.'}
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{'Observation': 'This child presented with encephalopathy, fatigue, muscle weakness, ketonuria, and lipid storage in muscles. His tandem mass spectroscopy showed elevated medium-chain acylcarnitine and long-chain acylcarnitine suggestive of MADD. His urine showed elevated excretion of 2HG, adipate, and arabitol.', 'Declaration of patient consent': 'The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.', 'Patient and methods': 'Our patient is a 13-year-old boy who was the second child born to non-consanguineous parents. He noticed tiredness and pain in muscles on walking. Patient had about 6 episodes of weakness of all four limbs presenting as difficulty in getting up from sitting posture and falls while walking. He also had vomiting and brown colored urine after exertion. Examination revealed thin built child with a small goiter. Wasting of supraspinatus, infraspinatus, deltoid, and pectoralis muscles was reported with winging of scapula. Power was 4/5 in proximal muscles of upper limbs and 2 to 3/5 in lower limbs. All reflexes were preserved and sensations were normal. Investigations showed severe ketonuria (creatine kinase, 1271 IU/L, lactate dehydrogenase, 2622 IU/L). Liver and renal function tests were normal (aspartate transaminase, 1214 IU/L; alalnine transaminase, 307 IU/L; potential of Hydrogen, 7.4; partial pressure of Carbon Dioxide, 39.9; partial pressure of Oxygen, 77.4; lactate, 2.8 µmol/L). Ultrasonography of abdomen was normal. Estimation of blood levels of free acylcarnitines by tandem mass spectrometry showed significant elevation of short, medium and long-chain acylcarnitines suggestive of multiple acyl-CoA dehydrogenase deficiency. The following levels were obtained from the estimation: hexanoylcarnitine (C6)- 0.67 μmol/L (normal range 0–0.23 μmol/L); adipylcarnitine (C6DC)- 0.52 μmol/L (normal range 0.01–0.33 μmol/L); octanylcarnitine (C8) I-1.2 μmol/L (normal range 0.01–0.39 μmol/L); decanoylcarnitine (C10)-1.71 μmol/L (normal range 0–0.5 μmol/L); dodecanoylcarnitine (C12)-0.63 μmol/L (normal range 0.02–0.42 μmol/L); tetradecanoylcarnitine (C14)- 0.56 μmol/L (normal range 0.03–0.41 μmol/L) and tetradecanoylcarnitine (C14)- 0.59 μmol/L (normal range 0.01–0.28 μmol/L). Profiling of urine organic acids showed increased excretion of 2-hydroxyglutarate (2HG), adipate, arabitol, and 3-hydroxy butyrate. Muscle biopsy was carried out and histopathological analysis of transversely cut skeletal muscle tissue showed mild variation in fiber diameter and multiple fine vacuoles in hematoxylin and eosin–stained material. Modified Gomori trichrome stain showed vacuolated fibers with red granular material consistent with ragged red fibers. Oil Red O stain showed vacuolated fibers with Oil Red O–positive material suggesting lipid storage. The patient was started on high carbohydrate diet with restriction on protein, fat and started on riboflavin (200 mg) and carnitine (1.5 g) per day. He was also given symptomatic treatment. He steadily improved and became fully symptom free at 3 months. Figure 2 shows the patient at 3 months of follow-up. The pictures at admission could not be taken as patient’s relatives were unwilling to give permission as the child was very ill.'}
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IEM-Treatment
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IEM_Treatment
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[
". The patient was started on high carbohydrate diet with restriction on protein , fat and started on riboflavin ( 200 mg ) and carnitine ( 1.5 g ) per day ."
] |
6224624
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{'Testing Results': 'Figures 1 a to d represent the continuous HR and BP recordings of twin 1 ( Figure 1 a and b) and twin 2 ( Figure 1 c and d) during the HUT over the 10-second transition from a supine horizontal position to a 70° upright tilt. As seen in Figure 1 a, the HR of twin 1 exhibited a compensatory increase to a maximum of 110 beats/min at 6.9 minutes into the HUT and remained at this level until she was returned to a horizontal and/or supine position. This was a change of 52 beats/min. In Figure 1 b, a systolic BP (SBP) decline of 29.8 mm Hg can be seen at 0.3 minutes into the HUT. The BP of twin 1 recovered quickly to pre-HUT levels and remained stable thereafter throughout the 10-minute HUT. Conversely, for twin 2, HR increased by 45 to 120 beats/min and a 30-mm Hg SBP drop occurred when transitioned from a supine position to a 70° HUT ( Figure 1 c and d). In addition, the HR and SBP remained at these levels throughout the HUT until the twin returned to the supine position. Thus, both twins exhibited orthostatic tachycardia during HUT that was maintained until returning to the supine horizontal body position, which indicated a greater than average response compared with normative data. Figure 1 Head up-tilt (HUT) of twins 1 and 2 for continuous heart rate (a,c) and blood pressure recordings (b,d). For the TST, the baseline (pre-TST) for twin 1 and twin 2 are shown in Figure 2 a and 2 c, respectively, whereas postwarming period results for each twin are found in Figure 2 b and 2 d, respectively. By referencing the temperature scale shown between Figure 2 a and 2 b and Figure 2 c and 2 d, the images clearly demonstrate both twins with cold hands and feet before warming ( Figure 2 a and 2 c). Conversely, in post-TST images, both twins displayed symmetric warming of their hands but their feet remained slightly cooler compared with other body regions ( Figure 2 b and 2 d). Figure 2 Thermoregulatory sweat test baseline and warmed (post) test twin 1 (a,b) and twin 2 (c,d), respectively. A temperature-color gauge is centered between each baseline and the warmed figure with values shown in degrees Fahrenheit. Postwarming images of twin 1 ( Figure 3 a) and twin 2 ( Figure 3 b) are shown with patchy regions of anhidrosis (in yellow) compared with the purple areas of sweat indicator powder, which demonstrated the regions where sweating occurred. Twin 1 had 53% anhidrosis but preserved sweating on the upper trunk, left abdomen, both hands, and medial legs, whereas twin 2 exhibited 50% anhidrosis and residual sweating of the upper trunk, bilateral hands, and medial legs. Figure 3 Diaphoresis patterns of twin 1 (a) and twin 2 (b) at the completion of the thermoregulatory sweat test (TST). QSWEAT results of twin 1 are shown with sweat rates of the forearm (25−50th percentile) ( Figure 4 a); proximal ( Figure 4 b) and distal leg sweat rates were each <10th percentile (abnormal for sex and age) ( Figure 4 c), and the foot was between the 10th to 25th percentile ( Figure 4 d). In addition, these abnormalities were categorized as a “latency of the sweat response” of the forearm, distal leg, and foot, as well as a “lack of recovery” of the proximal leg. Results for twin 2 showed a similar sweat response latency of the proximal leg ( Figure 5 b). Otherwise, twin 2 exhibited normal sweat volumes and rates for her age as seen for the forearm (10th−25th percentile) ( Figure 5 a), proximal leg (25th percentile) ( Figure 5 b), distal leg (25th percentile) ( Figure 5 c), and foot (50−80th percentile) ( Figure 5 d). Figure 4 Quantitative sweat rate (nanoliters per minute) of twin 1 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d). Figure 5 Quantitative sweat rate (nanoliters per minute) of twin 2 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d).', 'Case 1': 'Monozygotic female adolescent twins, aged 16 years old, were originally diagnosed in infancy with NC and found to have a 57-kb deletion of the CTNS gene, the most frequent cause of NC in Western populations. They were on cysteamine bitartrate (cystagon-immediate release) since diagnosis. Each was currently prescribed Procysbi (cysteamine-delayed release) 675 mg every 12 hours. In addition, each twin was prescribed cysteamine hydrochloride (0.44%) eye drops due to cystine crystal accumulation in the lens and cornea. Both twins were transplanted 6 years previously with kidneys from a single deceased donor source. Since that time, both twins experienced several episodes of transplant rejection, whereas twin 1 also developed Epstein-Barr virus positive posttransplant proliferative disorder. Table 1 includes clinical and medication data on the patients at the time of autonomic testing. As shown in Table 1, twin 2 exhibited a diastolic blood pressure (DBP) that exceeded the threshold for sex and height and had DBP readings 20% higher than those of twin 1. Table 1 Characteristics and medications of female monozygotic twins with nephropathic cystinosis Characteristics Twin 1 Twin 2 Age (yrs) 16 Race W Ethnicity H Wt. (kg) 43.6 46.0 Ht. (cm) 152.3 154.8 BMI percentile (for age and sex) (kg/m 2 ) 25th 40th Resting BP (mm Hg) 118/70 123/84 Measured GFR (ml/min per 1.73 m 2 ) 59.3 70.0 CKD stage 3a 2 Tacrolimus level (ng/ml) 5.5 4.5 Medications, Dose, Frequency Procysbi (cysteamine DR) 675 mg q 12 h Cysteamine HCL (0.44%) 1 gtt. OU q h while awake Amlodipine 10 mg/d Cardura 4 mg/d — Lisinopril 10 mg/d Drisdol 50,000 IU/ q 14 d — Cellcept 500 mg BID Tacrolimus 3 mg BID 2 mg BID Synthroid 137 μg/d 125 μg/d Mg oxide 400 mg BID Bactrim 400-80 40 mg 3×/wk BID, twice a day; BMI, body mass index; BP, blood pressure; CKD, chronic kidney disease; DR, delayed release; GFR, glomerular filtration rate by plasma clearance of iohexol; gtt, drops; H, Hispanic; HCL, hydrochloride; Ht., height; IU, international units; Mg, magnesium; OU, both eyes; q, every; W, white; Wt., weight. Laboratory findings (biochemical characteristics) for both twins are shown in Table 2 . Creatinine, blood urea nitrogen, and cystatin C levels were consistent with the CKD stage of each twin. Both patients also had blood drawn for measurement of their leukocyte cystine levels, which were obtained at the time of their regular laboratory tests. Those results were 1.65 and 1.90 nmol 1/2 cystine per milligram per protein for twins 1 and 2, respectively. Because the twins exhibited leukocyte cystine levels >1 nmol 1/2 cystine per milligram per protein, it indicated they had not achieved an optimal degree of substrate depletion for cystinosis patients on cysteamine therapy. This was due to incomplete adherence with their cysteamine bitartrate therapy. Table 3 lists a summary on cystinosis. Table 2 Laboratory results Results Conventional units (SI Units) Twin # Cr BUN Cystatin C Alb Phos Na K Glucose 1 1.08 (95.47) 15 (5.35) (1.25) 4.5 (45) 3.7 (1.20) 136 (136 ) 4.0 (4.0) 98 (5.44) 2 0.81 (71.60) 13 (4.64) (1.09) 4.9 (49) 3.8 (1.23) 137 (137) 4.2 (4.2) 94 (5.22) Normal reference range 0.25−1.14 mg/dl 5.0−18.0 mg/dl 0.5−1.3 mg/l (1−17 yr) 3.6−4.7 g/dl 3.0−4.8 mg/dl 134−146 mEq/l 3.7−5.7 mEq/l 60−110 mg/dl SI units normal Reference Range 22.1−100.78 mmol/l 1.78−6.43 mmol/l 0.50−1.30 mg/l 36.0−47.0 g/l 0.97−1.55 mmol/l 134−146 mmol/l 3.7−5.7 mmol/l 3.33−6.11 mmol/l Alb, albumin; BUN, blood urea nitrogen; Cr, creatinine; K, potassium; Na, sodium; Phos, phosphorus (inorganic); SI, Standard international. Table 3 Teaching points (i) Cystinosis results from a functional defect in the lysosomal-membrane exporter protein, cystinosin (CTNS), thereby resulting in failure of cystine efflux from cell lysosomes. When untreated, cystine crystals result and are deposited throughout the body, including in the cornea, retina, and most organs. (ii) Nephropathic cystinosis (NC) is often diagnosed in infancy due to the development of severe renal Fanconi syndrome with failure to thrive. Chronic electrolyte replacement is essential. (iii) Cystine accumulation is measured in leukocytes with a cystine level < 1 nmol 1/2 cystine per milligram cell protein categorized as being consistent with optimal cystine depletion. (iv) Cysteamine bitartrate is the only Food and Drug Administration−approved therapy for cystinosis and is available in immediate and delayed release formulations. (v) In NC, the 57-kb deletion has been associated with transient receptor potential vanilloid 1 (TRPV1) gene functional impairment. (vi) Long-term extra renal manifestations of NC are frequently observed and include cognitive impairment and/or delays, altered skin and/or heat sensations, abnormal temperature regulation, heat intolerance, reduced sweating, and myopathy, the latter of which may eventually contribute to respiratory failure, all suggestive of autonomic nervous system dysfunction pertinent to thermoregulation. Both twins frequently described issues with heat intolerance and photophobia secondary to corneal cystine crystal deposition, but they demonstrated consistently normal clinical neurological examination findings. We decided to complete further testing of the twins to evaluate heat intolerance and possible associated autonomic dysfunction as opposed to what may simply be avoidance of light exposure on sunny days.', 'Clinical Testing': 'During the period before testing, a directly measured glomerular filtration rate was completed on each twin using a plasma clearance of iohexol procedure. 14 The twins then underwent 3 clinical procedures at the Center for Autonomic Medicine in Pediatrics at Ann & Robert H. Lurie Children’s Hospital of Chicago (Chicago, IL). Those procedures included the head-up tilt (HUT) test to assess baroreceptor function, a thermoregulatory sweat test (TST) to measure sudomotor function, and the quantitative sweat response test (QSWEAT), which is a sudomotor axon reflex test in which responses of the local axon reflex of sweat glands to iontophoresed acetylcholine are quantitated. 15 The use of the TST and QSWEAT procedures on patients are considered to be the gold standard for clinical evaluation, because they demonstrated a 90% sensitivity for detection of small fiber neuropathy. 16 The HUT determines whether orthostatic (in)tolerance can be demonstrated and evaluates the inter-relationship of breathing, heart rate (HR), and BP while the patient transitions from a supine to an upright position and then returns to the supine position. Simply stated, a patient lays on a tilt table in a supine horizontal position for 10 to 20 minutes while baseline measurements are taken. Then, a HUT to 70° is done with measurements collected thereafter for 10 minutes. Following this, a tilt-down to a supine horizontal position occurs and is sustained for 2 minutes of additional measurements. During the TST, the core body temperature is increased slowly to 1 ° C higher than at prewarming (baseline) or a patient reaches a core temperature of 38 ° C (whichever is greater). To prepare for the procedure, sweat-indicator powder is applied to the patient’s anterior surface while lying supine on a bed. The patient is then rolled into the chamber, and it is sealed shut, while continuous surveillance and collection of all physiological measurements of the patient, chamber, and temperatures occurs. The ambient temperature is slowly increased with an average ramp rate of 5.0 °C/hour and with a relative humidity range of 35% to 45%. Finally, for the QSWEAT, the patient is placed in a supine horizontal position. Once situated, 4 quarter-sized capsules of acetylcholine are topically applied on the forearm, proximal and distal leg, and foot. An imperceivable 2-mA current is delivered over a 5-minute period, followed by a 5-minute recovery, which results in an accurate quantitation of sweat produced in small areas of the skin.'}
|
{'Testing Results': 'Figures 1 a to d represent the continuous HR and BP recordings of twin 1 ( Figure 1 a and b) and twin 2 ( Figure 1 c and d) during the HUT over the 10-second transition from a supine horizontal position to a 70° upright tilt. As seen in Figure 1 a, the HR of twin 1 exhibited a compensatory increase to a maximum of 110 beats/min at 6.9 minutes into the HUT and remained at this level until she was returned to a horizontal and/or supine position. This was a change of 52 beats/min. In Figure 1 b, a systolic BP (SBP) decline of 29.8 mm Hg can be seen at 0.3 minutes into the HUT. The BP of twin 1 recovered quickly to pre-HUT levels and remained stable thereafter throughout the 10-minute HUT. Conversely, for twin 2, HR increased by 45 to 120 beats/min and a 30-mm Hg SBP drop occurred when transitioned from a supine position to a 70° HUT ( Figure 1 c and d). In addition, the HR and SBP remained at these levels throughout the HUT until the twin returned to the supine position. Thus, both twins exhibited orthostatic tachycardia during HUT that was maintained until returning to the supine horizontal body position, which indicated a greater than average response compared with normative data. Figure 1 Head up-tilt (HUT) of twins 1 and 2 for continuous heart rate (a,c) and blood pressure recordings (b,d). For the TST, the baseline (pre-TST) for twin 1 and twin 2 are shown in Figure 2 a and 2 c, respectively, whereas postwarming period results for each twin are found in Figure 2 b and 2 d, respectively. By referencing the temperature scale shown between Figure 2 a and 2 b and Figure 2 c and 2 d, the images clearly demonstrate both twins with cold hands and feet before warming ( Figure 2 a and 2 c). Conversely, in post-TST images, both twins displayed symmetric warming of their hands but their feet remained slightly cooler compared with other body regions ( Figure 2 b and 2 d). Figure 2 Thermoregulatory sweat test baseline and warmed (post) test twin 1 (a,b) and twin 2 (c,d), respectively. A temperature-color gauge is centered between each baseline and the warmed figure with values shown in degrees Fahrenheit. Postwarming images of twin 1 ( Figure 3 a) and twin 2 ( Figure 3 b) are shown with patchy regions of anhidrosis (in yellow) compared with the purple areas of sweat indicator powder, which demonstrated the regions where sweating occurred. Twin 1 had 53% anhidrosis but preserved sweating on the upper trunk, left abdomen, both hands, and medial legs, whereas twin 2 exhibited 50% anhidrosis and residual sweating of the upper trunk, bilateral hands, and medial legs. Figure 3 Diaphoresis patterns of twin 1 (a) and twin 2 (b) at the completion of the thermoregulatory sweat test (TST). QSWEAT results of twin 1 are shown with sweat rates of the forearm (25−50th percentile) ( Figure 4 a); proximal ( Figure 4 b) and distal leg sweat rates were each <10th percentile (abnormal for sex and age) ( Figure 4 c), and the foot was between the 10th to 25th percentile ( Figure 4 d). In addition, these abnormalities were categorized as a “latency of the sweat response” of the forearm, distal leg, and foot, as well as a “lack of recovery” of the proximal leg. Results for twin 2 showed a similar sweat response latency of the proximal leg ( Figure 5 b). Otherwise, twin 2 exhibited normal sweat volumes and rates for her age as seen for the forearm (10th−25th percentile) ( Figure 5 a), proximal leg (25th percentile) ( Figure 5 b), distal leg (25th percentile) ( Figure 5 c), and foot (50−80th percentile) ( Figure 5 d). Figure 4 Quantitative sweat rate (nanoliters per minute) of twin 1 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d). Figure 5 Quantitative sweat rate (nanoliters per minute) of twin 2 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d).', 'Case 1': 'Monozygotic female adolescent twins, aged 16 years old, were originally diagnosed in infancy with NC and found to have a 57-kb deletion of the CTNS gene, the most frequent cause of NC in Western populations. They were on cysteamine bitartrate (cystagon-immediate release) since diagnosis. Each was currently prescribed Procysbi (cysteamine-delayed release) 675 mg every 12 hours. In addition, each twin was prescribed cysteamine hydrochloride (0.44%) eye drops due to cystine crystal accumulation in the lens and cornea. Both twins were transplanted 6 years previously with kidneys from a single deceased donor source. Since that time, both twins experienced several episodes of transplant rejection, whereas twin 1 also developed Epstein-Barr virus positive posttransplant proliferative disorder. Table 1 includes clinical and medication data on the patients at the time of autonomic testing. As shown in Table 1, twin 2 exhibited a diastolic blood pressure (DBP) that exceeded the threshold for sex and height and had DBP readings 20% higher than those of twin 1. Table 1 Characteristics and medications of female monozygotic twins with nephropathic cystinosis Characteristics Twin 1 Twin 2 Age (yrs) 16 Race W Ethnicity H Wt. (kg) 43.6 46.0 Ht. (cm) 152.3 154.8 BMI percentile (for age and sex) (kg/m 2 ) 25th 40th Resting BP (mm Hg) 118/70 123/84 Measured GFR (ml/min per 1.73 m 2 ) 59.3 70.0 CKD stage 3a 2 Tacrolimus level (ng/ml) 5.5 4.5 Medications, Dose, Frequency Procysbi (cysteamine DR) 675 mg q 12 h Cysteamine HCL (0.44%) 1 gtt. OU q h while awake Amlodipine 10 mg/d Cardura 4 mg/d — Lisinopril 10 mg/d Drisdol 50,000 IU/ q 14 d — Cellcept 500 mg BID Tacrolimus 3 mg BID 2 mg BID Synthroid 137 μg/d 125 μg/d Mg oxide 400 mg BID Bactrim 400-80 40 mg 3×/wk BID, twice a day; BMI, body mass index; BP, blood pressure; CKD, chronic kidney disease; DR, delayed release; GFR, glomerular filtration rate by plasma clearance of iohexol; gtt, drops; H, Hispanic; HCL, hydrochloride; Ht., height; IU, international units; Mg, magnesium; OU, both eyes; q, every; W, white; Wt., weight. Laboratory findings (biochemical characteristics) for both twins are shown in Table 2 . Creatinine, blood urea nitrogen, and cystatin C levels were consistent with the CKD stage of each twin. Both patients also had blood drawn for measurement of their leukocyte cystine levels, which were obtained at the time of their regular laboratory tests. Those results were 1.65 and 1.90 nmol 1/2 cystine per milligram per protein for twins 1 and 2, respectively. Because the twins exhibited leukocyte cystine levels >1 nmol 1/2 cystine per milligram per protein, it indicated they had not achieved an optimal degree of substrate depletion for cystinosis patients on cysteamine therapy. This was due to incomplete adherence with their cysteamine bitartrate therapy. Table 3 lists a summary on cystinosis. Table 2 Laboratory results Results Conventional units (SI Units) Twin # Cr BUN Cystatin C Alb Phos Na K Glucose 1 1.08 (95.47) 15 (5.35) (1.25) 4.5 (45) 3.7 (1.20) 136 (136 ) 4.0 (4.0) 98 (5.44) 2 0.81 (71.60) 13 (4.64) (1.09) 4.9 (49) 3.8 (1.23) 137 (137) 4.2 (4.2) 94 (5.22) Normal reference range 0.25−1.14 mg/dl 5.0−18.0 mg/dl 0.5−1.3 mg/l (1−17 yr) 3.6−4.7 g/dl 3.0−4.8 mg/dl 134−146 mEq/l 3.7−5.7 mEq/l 60−110 mg/dl SI units normal Reference Range 22.1−100.78 mmol/l 1.78−6.43 mmol/l 0.50−1.30 mg/l 36.0−47.0 g/l 0.97−1.55 mmol/l 134−146 mmol/l 3.7−5.7 mmol/l 3.33−6.11 mmol/l Alb, albumin; BUN, blood urea nitrogen; Cr, creatinine; K, potassium; Na, sodium; Phos, phosphorus (inorganic); SI, Standard international. Table 3 Teaching points (i) Cystinosis results from a functional defect in the lysosomal-membrane exporter protein, cystinosin (CTNS), thereby resulting in failure of cystine efflux from cell lysosomes. When untreated, cystine crystals result and are deposited throughout the body, including in the cornea, retina, and most organs. (ii) Nephropathic cystinosis (NC) is often diagnosed in infancy due to the development of severe renal Fanconi syndrome with failure to thrive. Chronic electrolyte replacement is essential. (iii) Cystine accumulation is measured in leukocytes with a cystine level < 1 nmol 1/2 cystine per milligram cell protein categorized as being consistent with optimal cystine depletion. (iv) Cysteamine bitartrate is the only Food and Drug Administration−approved therapy for cystinosis and is available in immediate and delayed release formulations. (v) In NC, the 57-kb deletion has been associated with transient receptor potential vanilloid 1 (TRPV1) gene functional impairment. (vi) Long-term extra renal manifestations of NC are frequently observed and include cognitive impairment and/or delays, altered skin and/or heat sensations, abnormal temperature regulation, heat intolerance, reduced sweating, and myopathy, the latter of which may eventually contribute to respiratory failure, all suggestive of autonomic nervous system dysfunction pertinent to thermoregulation. Both twins frequently described issues with heat intolerance and photophobia secondary to corneal cystine crystal deposition, but they demonstrated consistently normal clinical neurological examination findings. We decided to complete further testing of the twins to evaluate heat intolerance and possible associated autonomic dysfunction as opposed to what may simply be avoidance of light exposure on sunny days.', 'Clinical Testing': 'During the period before testing, a directly measured glomerular filtration rate was completed on each twin using a plasma clearance of iohexol procedure. 14 The twins then underwent 3 clinical procedures at the Center for Autonomic Medicine in Pediatrics at Ann & Robert H. Lurie Children’s Hospital of Chicago (Chicago, IL). Those procedures included the head-up tilt (HUT) test to assess baroreceptor function, a thermoregulatory sweat test (TST) to measure sudomotor function, and the quantitative sweat response test (QSWEAT), which is a sudomotor axon reflex test in which responses of the local axon reflex of sweat glands to iontophoresed acetylcholine are quantitated. 15 The use of the TST and QSWEAT procedures on patients are considered to be the gold standard for clinical evaluation, because they demonstrated a 90% sensitivity for detection of small fiber neuropathy. 16 The HUT determines whether orthostatic (in)tolerance can be demonstrated and evaluates the inter-relationship of breathing, heart rate (HR), and BP while the patient transitions from a supine to an upright position and then returns to the supine position. Simply stated, a patient lays on a tilt table in a supine horizontal position for 10 to 20 minutes while baseline measurements are taken. Then, a HUT to 70° is done with measurements collected thereafter for 10 minutes. Following this, a tilt-down to a supine horizontal position occurs and is sustained for 2 minutes of additional measurements. During the TST, the core body temperature is increased slowly to 1 ° C higher than at prewarming (baseline) or a patient reaches a core temperature of 38 ° C (whichever is greater). To prepare for the procedure, sweat-indicator powder is applied to the patient’s anterior surface while lying supine on a bed. The patient is then rolled into the chamber, and it is sealed shut, while continuous surveillance and collection of all physiological measurements of the patient, chamber, and temperatures occurs. The ambient temperature is slowly increased with an average ramp rate of 5.0 °C/hour and with a relative humidity range of 35% to 45%. Finally, for the QSWEAT, the patient is placed in a supine horizontal position. Once situated, 4 quarter-sized capsules of acetylcholine are topically applied on the forearm, proximal and distal leg, and foot. An imperceivable 2-mA current is delivered over a 5-minute period, followed by a 5-minute recovery, which results in an accurate quantitation of sweat produced in small areas of the skin.'}
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Vitals-and-Hematology
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Vitals_Hema
|
[
"HR of twin 1 exhibited a compensatory increase to a maximum of 110 beats / min",
"HR increased by 45 to 120 beats / min",
"twin 2 exhibited a diastolic blood pressure ( DBP ) that exceeded the threshold for sex and height and had DBP readings 20 % higher than those of twin 1",
"Wt. ( kg ) 43.6 46.0 Ht. ( cm ) 152.3 154.8 BMI percentile ( for age and sex ) ( kg / m 2 ) 25th 40th Resting BP ( mm Hg ) 118/70 123/84"
] |
6224624
|
{'Testing Results': 'Figures 1 a to d represent the continuous HR and BP recordings of twin 1 ( Figure 1 a and b) and twin 2 ( Figure 1 c and d) during the HUT over the 10-second transition from a supine horizontal position to a 70° upright tilt. As seen in Figure 1 a, the HR of twin 1 exhibited a compensatory increase to a maximum of 110 beats/min at 6.9 minutes into the HUT and remained at this level until she was returned to a horizontal and/or supine position. This was a change of 52 beats/min. In Figure 1 b, a systolic BP (SBP) decline of 29.8 mm Hg can be seen at 0.3 minutes into the HUT. The BP of twin 1 recovered quickly to pre-HUT levels and remained stable thereafter throughout the 10-minute HUT. Conversely, for twin 2, HR increased by 45 to 120 beats/min and a 30-mm Hg SBP drop occurred when transitioned from a supine position to a 70° HUT ( Figure 1 c and d). In addition, the HR and SBP remained at these levels throughout the HUT until the twin returned to the supine position. Thus, both twins exhibited orthostatic tachycardia during HUT that was maintained until returning to the supine horizontal body position, which indicated a greater than average response compared with normative data. Figure 1 Head up-tilt (HUT) of twins 1 and 2 for continuous heart rate (a,c) and blood pressure recordings (b,d). For the TST, the baseline (pre-TST) for twin 1 and twin 2 are shown in Figure 2 a and 2 c, respectively, whereas postwarming period results for each twin are found in Figure 2 b and 2 d, respectively. By referencing the temperature scale shown between Figure 2 a and 2 b and Figure 2 c and 2 d, the images clearly demonstrate both twins with cold hands and feet before warming ( Figure 2 a and 2 c). Conversely, in post-TST images, both twins displayed symmetric warming of their hands but their feet remained slightly cooler compared with other body regions ( Figure 2 b and 2 d). Figure 2 Thermoregulatory sweat test baseline and warmed (post) test twin 1 (a,b) and twin 2 (c,d), respectively. A temperature-color gauge is centered between each baseline and the warmed figure with values shown in degrees Fahrenheit. Postwarming images of twin 1 ( Figure 3 a) and twin 2 ( Figure 3 b) are shown with patchy regions of anhidrosis (in yellow) compared with the purple areas of sweat indicator powder, which demonstrated the regions where sweating occurred. Twin 1 had 53% anhidrosis but preserved sweating on the upper trunk, left abdomen, both hands, and medial legs, whereas twin 2 exhibited 50% anhidrosis and residual sweating of the upper trunk, bilateral hands, and medial legs. Figure 3 Diaphoresis patterns of twin 1 (a) and twin 2 (b) at the completion of the thermoregulatory sweat test (TST). QSWEAT results of twin 1 are shown with sweat rates of the forearm (25−50th percentile) ( Figure 4 a); proximal ( Figure 4 b) and distal leg sweat rates were each <10th percentile (abnormal for sex and age) ( Figure 4 c), and the foot was between the 10th to 25th percentile ( Figure 4 d). In addition, these abnormalities were categorized as a “latency of the sweat response” of the forearm, distal leg, and foot, as well as a “lack of recovery” of the proximal leg. Results for twin 2 showed a similar sweat response latency of the proximal leg ( Figure 5 b). Otherwise, twin 2 exhibited normal sweat volumes and rates for her age as seen for the forearm (10th−25th percentile) ( Figure 5 a), proximal leg (25th percentile) ( Figure 5 b), distal leg (25th percentile) ( Figure 5 c), and foot (50−80th percentile) ( Figure 5 d). Figure 4 Quantitative sweat rate (nanoliters per minute) of twin 1 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d). Figure 5 Quantitative sweat rate (nanoliters per minute) of twin 2 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d).', 'Case 1': 'Monozygotic female adolescent twins, aged 16 years old, were originally diagnosed in infancy with NC and found to have a 57-kb deletion of the CTNS gene, the most frequent cause of NC in Western populations. They were on cysteamine bitartrate (cystagon-immediate release) since diagnosis. Each was currently prescribed Procysbi (cysteamine-delayed release) 675 mg every 12 hours. In addition, each twin was prescribed cysteamine hydrochloride (0.44%) eye drops due to cystine crystal accumulation in the lens and cornea. Both twins were transplanted 6 years previously with kidneys from a single deceased donor source. Since that time, both twins experienced several episodes of transplant rejection, whereas twin 1 also developed Epstein-Barr virus positive posttransplant proliferative disorder. Table 1 includes clinical and medication data on the patients at the time of autonomic testing. As shown in Table 1, twin 2 exhibited a diastolic blood pressure (DBP) that exceeded the threshold for sex and height and had DBP readings 20% higher than those of twin 1. Table 1 Characteristics and medications of female monozygotic twins with nephropathic cystinosis Characteristics Twin 1 Twin 2 Age (yrs) 16 Race W Ethnicity H Wt. (kg) 43.6 46.0 Ht. (cm) 152.3 154.8 BMI percentile (for age and sex) (kg/m 2 ) 25th 40th Resting BP (mm Hg) 118/70 123/84 Measured GFR (ml/min per 1.73 m 2 ) 59.3 70.0 CKD stage 3a 2 Tacrolimus level (ng/ml) 5.5 4.5 Medications, Dose, Frequency Procysbi (cysteamine DR) 675 mg q 12 h Cysteamine HCL (0.44%) 1 gtt. OU q h while awake Amlodipine 10 mg/d Cardura 4 mg/d — Lisinopril 10 mg/d Drisdol 50,000 IU/ q 14 d — Cellcept 500 mg BID Tacrolimus 3 mg BID 2 mg BID Synthroid 137 μg/d 125 μg/d Mg oxide 400 mg BID Bactrim 400-80 40 mg 3×/wk BID, twice a day; BMI, body mass index; BP, blood pressure; CKD, chronic kidney disease; DR, delayed release; GFR, glomerular filtration rate by plasma clearance of iohexol; gtt, drops; H, Hispanic; HCL, hydrochloride; Ht., height; IU, international units; Mg, magnesium; OU, both eyes; q, every; W, white; Wt., weight. Laboratory findings (biochemical characteristics) for both twins are shown in Table 2 . Creatinine, blood urea nitrogen, and cystatin C levels were consistent with the CKD stage of each twin. Both patients also had blood drawn for measurement of their leukocyte cystine levels, which were obtained at the time of their regular laboratory tests. Those results were 1.65 and 1.90 nmol 1/2 cystine per milligram per protein for twins 1 and 2, respectively. Because the twins exhibited leukocyte cystine levels >1 nmol 1/2 cystine per milligram per protein, it indicated they had not achieved an optimal degree of substrate depletion for cystinosis patients on cysteamine therapy. This was due to incomplete adherence with their cysteamine bitartrate therapy. Table 3 lists a summary on cystinosis. Table 2 Laboratory results Results Conventional units (SI Units) Twin # Cr BUN Cystatin C Alb Phos Na K Glucose 1 1.08 (95.47) 15 (5.35) (1.25) 4.5 (45) 3.7 (1.20) 136 (136 ) 4.0 (4.0) 98 (5.44) 2 0.81 (71.60) 13 (4.64) (1.09) 4.9 (49) 3.8 (1.23) 137 (137) 4.2 (4.2) 94 (5.22) Normal reference range 0.25−1.14 mg/dl 5.0−18.0 mg/dl 0.5−1.3 mg/l (1−17 yr) 3.6−4.7 g/dl 3.0−4.8 mg/dl 134−146 mEq/l 3.7−5.7 mEq/l 60−110 mg/dl SI units normal Reference Range 22.1−100.78 mmol/l 1.78−6.43 mmol/l 0.50−1.30 mg/l 36.0−47.0 g/l 0.97−1.55 mmol/l 134−146 mmol/l 3.7−5.7 mmol/l 3.33−6.11 mmol/l Alb, albumin; BUN, blood urea nitrogen; Cr, creatinine; K, potassium; Na, sodium; Phos, phosphorus (inorganic); SI, Standard international. Table 3 Teaching points (i) Cystinosis results from a functional defect in the lysosomal-membrane exporter protein, cystinosin (CTNS), thereby resulting in failure of cystine efflux from cell lysosomes. When untreated, cystine crystals result and are deposited throughout the body, including in the cornea, retina, and most organs. (ii) Nephropathic cystinosis (NC) is often diagnosed in infancy due to the development of severe renal Fanconi syndrome with failure to thrive. Chronic electrolyte replacement is essential. (iii) Cystine accumulation is measured in leukocytes with a cystine level < 1 nmol 1/2 cystine per milligram cell protein categorized as being consistent with optimal cystine depletion. (iv) Cysteamine bitartrate is the only Food and Drug Administration−approved therapy for cystinosis and is available in immediate and delayed release formulations. (v) In NC, the 57-kb deletion has been associated with transient receptor potential vanilloid 1 (TRPV1) gene functional impairment. (vi) Long-term extra renal manifestations of NC are frequently observed and include cognitive impairment and/or delays, altered skin and/or heat sensations, abnormal temperature regulation, heat intolerance, reduced sweating, and myopathy, the latter of which may eventually contribute to respiratory failure, all suggestive of autonomic nervous system dysfunction pertinent to thermoregulation. Both twins frequently described issues with heat intolerance and photophobia secondary to corneal cystine crystal deposition, but they demonstrated consistently normal clinical neurological examination findings. We decided to complete further testing of the twins to evaluate heat intolerance and possible associated autonomic dysfunction as opposed to what may simply be avoidance of light exposure on sunny days.', 'Clinical Testing': 'During the period before testing, a directly measured glomerular filtration rate was completed on each twin using a plasma clearance of iohexol procedure. 14 The twins then underwent 3 clinical procedures at the Center for Autonomic Medicine in Pediatrics at Ann & Robert H. Lurie Children’s Hospital of Chicago (Chicago, IL). Those procedures included the head-up tilt (HUT) test to assess baroreceptor function, a thermoregulatory sweat test (TST) to measure sudomotor function, and the quantitative sweat response test (QSWEAT), which is a sudomotor axon reflex test in which responses of the local axon reflex of sweat glands to iontophoresed acetylcholine are quantitated. 15 The use of the TST and QSWEAT procedures on patients are considered to be the gold standard for clinical evaluation, because they demonstrated a 90% sensitivity for detection of small fiber neuropathy. 16 The HUT determines whether orthostatic (in)tolerance can be demonstrated and evaluates the inter-relationship of breathing, heart rate (HR), and BP while the patient transitions from a supine to an upright position and then returns to the supine position. Simply stated, a patient lays on a tilt table in a supine horizontal position for 10 to 20 minutes while baseline measurements are taken. Then, a HUT to 70° is done with measurements collected thereafter for 10 minutes. Following this, a tilt-down to a supine horizontal position occurs and is sustained for 2 minutes of additional measurements. During the TST, the core body temperature is increased slowly to 1 ° C higher than at prewarming (baseline) or a patient reaches a core temperature of 38 ° C (whichever is greater). To prepare for the procedure, sweat-indicator powder is applied to the patient’s anterior surface while lying supine on a bed. The patient is then rolled into the chamber, and it is sealed shut, while continuous surveillance and collection of all physiological measurements of the patient, chamber, and temperatures occurs. The ambient temperature is slowly increased with an average ramp rate of 5.0 °C/hour and with a relative humidity range of 35% to 45%. Finally, for the QSWEAT, the patient is placed in a supine horizontal position. Once situated, 4 quarter-sized capsules of acetylcholine are topically applied on the forearm, proximal and distal leg, and foot. An imperceivable 2-mA current is delivered over a 5-minute period, followed by a 5-minute recovery, which results in an accurate quantitation of sweat produced in small areas of the skin.'}
|
{'Testing Results': 'Figures 1 a to d represent the continuous HR and BP recordings of twin 1 ( Figure 1 a and b) and twin 2 ( Figure 1 c and d) during the HUT over the 10-second transition from a supine horizontal position to a 70° upright tilt. As seen in Figure 1 a, the HR of twin 1 exhibited a compensatory increase to a maximum of 110 beats/min at 6.9 minutes into the HUT and remained at this level until she was returned to a horizontal and/or supine position. This was a change of 52 beats/min. In Figure 1 b, a systolic BP (SBP) decline of 29.8 mm Hg can be seen at 0.3 minutes into the HUT. The BP of twin 1 recovered quickly to pre-HUT levels and remained stable thereafter throughout the 10-minute HUT. Conversely, for twin 2, HR increased by 45 to 120 beats/min and a 30-mm Hg SBP drop occurred when transitioned from a supine position to a 70° HUT ( Figure 1 c and d). In addition, the HR and SBP remained at these levels throughout the HUT until the twin returned to the supine position. Thus, both twins exhibited orthostatic tachycardia during HUT that was maintained until returning to the supine horizontal body position, which indicated a greater than average response compared with normative data. Figure 1 Head up-tilt (HUT) of twins 1 and 2 for continuous heart rate (a,c) and blood pressure recordings (b,d). For the TST, the baseline (pre-TST) for twin 1 and twin 2 are shown in Figure 2 a and 2 c, respectively, whereas postwarming period results for each twin are found in Figure 2 b and 2 d, respectively. By referencing the temperature scale shown between Figure 2 a and 2 b and Figure 2 c and 2 d, the images clearly demonstrate both twins with cold hands and feet before warming ( Figure 2 a and 2 c). Conversely, in post-TST images, both twins displayed symmetric warming of their hands but their feet remained slightly cooler compared with other body regions ( Figure 2 b and 2 d). Figure 2 Thermoregulatory sweat test baseline and warmed (post) test twin 1 (a,b) and twin 2 (c,d), respectively. A temperature-color gauge is centered between each baseline and the warmed figure with values shown in degrees Fahrenheit. Postwarming images of twin 1 ( Figure 3 a) and twin 2 ( Figure 3 b) are shown with patchy regions of anhidrosis (in yellow) compared with the purple areas of sweat indicator powder, which demonstrated the regions where sweating occurred. Twin 1 had 53% anhidrosis but preserved sweating on the upper trunk, left abdomen, both hands, and medial legs, whereas twin 2 exhibited 50% anhidrosis and residual sweating of the upper trunk, bilateral hands, and medial legs. Figure 3 Diaphoresis patterns of twin 1 (a) and twin 2 (b) at the completion of the thermoregulatory sweat test (TST). QSWEAT results of twin 1 are shown with sweat rates of the forearm (25−50th percentile) ( Figure 4 a); proximal ( Figure 4 b) and distal leg sweat rates were each <10th percentile (abnormal for sex and age) ( Figure 4 c), and the foot was between the 10th to 25th percentile ( Figure 4 d). In addition, these abnormalities were categorized as a “latency of the sweat response” of the forearm, distal leg, and foot, as well as a “lack of recovery” of the proximal leg. Results for twin 2 showed a similar sweat response latency of the proximal leg ( Figure 5 b). Otherwise, twin 2 exhibited normal sweat volumes and rates for her age as seen for the forearm (10th−25th percentile) ( Figure 5 a), proximal leg (25th percentile) ( Figure 5 b), distal leg (25th percentile) ( Figure 5 c), and foot (50−80th percentile) ( Figure 5 d). Figure 4 Quantitative sweat rate (nanoliters per minute) of twin 1 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d). Figure 5 Quantitative sweat rate (nanoliters per minute) of twin 2 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d).', 'Case 1': 'Monozygotic female adolescent twins, aged 16 years old, were originally diagnosed in infancy with NC and found to have a 57-kb deletion of the CTNS gene, the most frequent cause of NC in Western populations. They were on cysteamine bitartrate (cystagon-immediate release) since diagnosis. Each was currently prescribed Procysbi (cysteamine-delayed release) 675 mg every 12 hours. In addition, each twin was prescribed cysteamine hydrochloride (0.44%) eye drops due to cystine crystal accumulation in the lens and cornea. Both twins were transplanted 6 years previously with kidneys from a single deceased donor source. Since that time, both twins experienced several episodes of transplant rejection, whereas twin 1 also developed Epstein-Barr virus positive posttransplant proliferative disorder. Table 1 includes clinical and medication data on the patients at the time of autonomic testing. As shown in Table 1, twin 2 exhibited a diastolic blood pressure (DBP) that exceeded the threshold for sex and height and had DBP readings 20% higher than those of twin 1. Table 1 Characteristics and medications of female monozygotic twins with nephropathic cystinosis Characteristics Twin 1 Twin 2 Age (yrs) 16 Race W Ethnicity H Wt. (kg) 43.6 46.0 Ht. (cm) 152.3 154.8 BMI percentile (for age and sex) (kg/m 2 ) 25th 40th Resting BP (mm Hg) 118/70 123/84 Measured GFR (ml/min per 1.73 m 2 ) 59.3 70.0 CKD stage 3a 2 Tacrolimus level (ng/ml) 5.5 4.5 Medications, Dose, Frequency Procysbi (cysteamine DR) 675 mg q 12 h Cysteamine HCL (0.44%) 1 gtt. OU q h while awake Amlodipine 10 mg/d Cardura 4 mg/d — Lisinopril 10 mg/d Drisdol 50,000 IU/ q 14 d — Cellcept 500 mg BID Tacrolimus 3 mg BID 2 mg BID Synthroid 137 μg/d 125 μg/d Mg oxide 400 mg BID Bactrim 400-80 40 mg 3×/wk BID, twice a day; BMI, body mass index; BP, blood pressure; CKD, chronic kidney disease; DR, delayed release; GFR, glomerular filtration rate by plasma clearance of iohexol; gtt, drops; H, Hispanic; HCL, hydrochloride; Ht., height; IU, international units; Mg, magnesium; OU, both eyes; q, every; W, white; Wt., weight. Laboratory findings (biochemical characteristics) for both twins are shown in Table 2 . Creatinine, blood urea nitrogen, and cystatin C levels were consistent with the CKD stage of each twin. Both patients also had blood drawn for measurement of their leukocyte cystine levels, which were obtained at the time of their regular laboratory tests. Those results were 1.65 and 1.90 nmol 1/2 cystine per milligram per protein for twins 1 and 2, respectively. Because the twins exhibited leukocyte cystine levels >1 nmol 1/2 cystine per milligram per protein, it indicated they had not achieved an optimal degree of substrate depletion for cystinosis patients on cysteamine therapy. This was due to incomplete adherence with their cysteamine bitartrate therapy. Table 3 lists a summary on cystinosis. Table 2 Laboratory results Results Conventional units (SI Units) Twin # Cr BUN Cystatin C Alb Phos Na K Glucose 1 1.08 (95.47) 15 (5.35) (1.25) 4.5 (45) 3.7 (1.20) 136 (136 ) 4.0 (4.0) 98 (5.44) 2 0.81 (71.60) 13 (4.64) (1.09) 4.9 (49) 3.8 (1.23) 137 (137) 4.2 (4.2) 94 (5.22) Normal reference range 0.25−1.14 mg/dl 5.0−18.0 mg/dl 0.5−1.3 mg/l (1−17 yr) 3.6−4.7 g/dl 3.0−4.8 mg/dl 134−146 mEq/l 3.7−5.7 mEq/l 60−110 mg/dl SI units normal Reference Range 22.1−100.78 mmol/l 1.78−6.43 mmol/l 0.50−1.30 mg/l 36.0−47.0 g/l 0.97−1.55 mmol/l 134−146 mmol/l 3.7−5.7 mmol/l 3.33−6.11 mmol/l Alb, albumin; BUN, blood urea nitrogen; Cr, creatinine; K, potassium; Na, sodium; Phos, phosphorus (inorganic); SI, Standard international. Table 3 Teaching points (i) Cystinosis results from a functional defect in the lysosomal-membrane exporter protein, cystinosin (CTNS), thereby resulting in failure of cystine efflux from cell lysosomes. When untreated, cystine crystals result and are deposited throughout the body, including in the cornea, retina, and most organs. (ii) Nephropathic cystinosis (NC) is often diagnosed in infancy due to the development of severe renal Fanconi syndrome with failure to thrive. Chronic electrolyte replacement is essential. (iii) Cystine accumulation is measured in leukocytes with a cystine level < 1 nmol 1/2 cystine per milligram cell protein categorized as being consistent with optimal cystine depletion. (iv) Cysteamine bitartrate is the only Food and Drug Administration−approved therapy for cystinosis and is available in immediate and delayed release formulations. (v) In NC, the 57-kb deletion has been associated with transient receptor potential vanilloid 1 (TRPV1) gene functional impairment. (vi) Long-term extra renal manifestations of NC are frequently observed and include cognitive impairment and/or delays, altered skin and/or heat sensations, abnormal temperature regulation, heat intolerance, reduced sweating, and myopathy, the latter of which may eventually contribute to respiratory failure, all suggestive of autonomic nervous system dysfunction pertinent to thermoregulation. Both twins frequently described issues with heat intolerance and photophobia secondary to corneal cystine crystal deposition, but they demonstrated consistently normal clinical neurological examination findings. We decided to complete further testing of the twins to evaluate heat intolerance and possible associated autonomic dysfunction as opposed to what may simply be avoidance of light exposure on sunny days.', 'Clinical Testing': 'During the period before testing, a directly measured glomerular filtration rate was completed on each twin using a plasma clearance of iohexol procedure. 14 The twins then underwent 3 clinical procedures at the Center for Autonomic Medicine in Pediatrics at Ann & Robert H. Lurie Children’s Hospital of Chicago (Chicago, IL). Those procedures included the head-up tilt (HUT) test to assess baroreceptor function, a thermoregulatory sweat test (TST) to measure sudomotor function, and the quantitative sweat response test (QSWEAT), which is a sudomotor axon reflex test in which responses of the local axon reflex of sweat glands to iontophoresed acetylcholine are quantitated. 15 The use of the TST and QSWEAT procedures on patients are considered to be the gold standard for clinical evaluation, because they demonstrated a 90% sensitivity for detection of small fiber neuropathy. 16 The HUT determines whether orthostatic (in)tolerance can be demonstrated and evaluates the inter-relationship of breathing, heart rate (HR), and BP while the patient transitions from a supine to an upright position and then returns to the supine position. Simply stated, a patient lays on a tilt table in a supine horizontal position for 10 to 20 minutes while baseline measurements are taken. Then, a HUT to 70° is done with measurements collected thereafter for 10 minutes. Following this, a tilt-down to a supine horizontal position occurs and is sustained for 2 minutes of additional measurements. During the TST, the core body temperature is increased slowly to 1 ° C higher than at prewarming (baseline) or a patient reaches a core temperature of 38 ° C (whichever is greater). To prepare for the procedure, sweat-indicator powder is applied to the patient’s anterior surface while lying supine on a bed. The patient is then rolled into the chamber, and it is sealed shut, while continuous surveillance and collection of all physiological measurements of the patient, chamber, and temperatures occurs. The ambient temperature is slowly increased with an average ramp rate of 5.0 °C/hour and with a relative humidity range of 35% to 45%. Finally, for the QSWEAT, the patient is placed in a supine horizontal position. Once situated, 4 quarter-sized capsules of acetylcholine are topically applied on the forearm, proximal and distal leg, and foot. An imperceivable 2-mA current is delivered over a 5-minute period, followed by a 5-minute recovery, which results in an accurate quantitation of sweat produced in small areas of the skin.'}
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Gastrointestinal-System
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GI
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[] |
6224624
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{'Testing Results': 'Figures 1 a to d represent the continuous HR and BP recordings of twin 1 ( Figure 1 a and b) and twin 2 ( Figure 1 c and d) during the HUT over the 10-second transition from a supine horizontal position to a 70° upright tilt. As seen in Figure 1 a, the HR of twin 1 exhibited a compensatory increase to a maximum of 110 beats/min at 6.9 minutes into the HUT and remained at this level until she was returned to a horizontal and/or supine position. This was a change of 52 beats/min. In Figure 1 b, a systolic BP (SBP) decline of 29.8 mm Hg can be seen at 0.3 minutes into the HUT. The BP of twin 1 recovered quickly to pre-HUT levels and remained stable thereafter throughout the 10-minute HUT. Conversely, for twin 2, HR increased by 45 to 120 beats/min and a 30-mm Hg SBP drop occurred when transitioned from a supine position to a 70° HUT ( Figure 1 c and d). In addition, the HR and SBP remained at these levels throughout the HUT until the twin returned to the supine position. Thus, both twins exhibited orthostatic tachycardia during HUT that was maintained until returning to the supine horizontal body position, which indicated a greater than average response compared with normative data. Figure 1 Head up-tilt (HUT) of twins 1 and 2 for continuous heart rate (a,c) and blood pressure recordings (b,d). For the TST, the baseline (pre-TST) for twin 1 and twin 2 are shown in Figure 2 a and 2 c, respectively, whereas postwarming period results for each twin are found in Figure 2 b and 2 d, respectively. By referencing the temperature scale shown between Figure 2 a and 2 b and Figure 2 c and 2 d, the images clearly demonstrate both twins with cold hands and feet before warming ( Figure 2 a and 2 c). Conversely, in post-TST images, both twins displayed symmetric warming of their hands but their feet remained slightly cooler compared with other body regions ( Figure 2 b and 2 d). Figure 2 Thermoregulatory sweat test baseline and warmed (post) test twin 1 (a,b) and twin 2 (c,d), respectively. A temperature-color gauge is centered between each baseline and the warmed figure with values shown in degrees Fahrenheit. Postwarming images of twin 1 ( Figure 3 a) and twin 2 ( Figure 3 b) are shown with patchy regions of anhidrosis (in yellow) compared with the purple areas of sweat indicator powder, which demonstrated the regions where sweating occurred. Twin 1 had 53% anhidrosis but preserved sweating on the upper trunk, left abdomen, both hands, and medial legs, whereas twin 2 exhibited 50% anhidrosis and residual sweating of the upper trunk, bilateral hands, and medial legs. Figure 3 Diaphoresis patterns of twin 1 (a) and twin 2 (b) at the completion of the thermoregulatory sweat test (TST). QSWEAT results of twin 1 are shown with sweat rates of the forearm (25−50th percentile) ( Figure 4 a); proximal ( Figure 4 b) and distal leg sweat rates were each <10th percentile (abnormal for sex and age) ( Figure 4 c), and the foot was between the 10th to 25th percentile ( Figure 4 d). In addition, these abnormalities were categorized as a “latency of the sweat response” of the forearm, distal leg, and foot, as well as a “lack of recovery” of the proximal leg. Results for twin 2 showed a similar sweat response latency of the proximal leg ( Figure 5 b). Otherwise, twin 2 exhibited normal sweat volumes and rates for her age as seen for the forearm (10th−25th percentile) ( Figure 5 a), proximal leg (25th percentile) ( Figure 5 b), distal leg (25th percentile) ( Figure 5 c), and foot (50−80th percentile) ( Figure 5 d). Figure 4 Quantitative sweat rate (nanoliters per minute) of twin 1 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d). Figure 5 Quantitative sweat rate (nanoliters per minute) of twin 2 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d).', 'Case 1': 'Monozygotic female adolescent twins, aged 16 years old, were originally diagnosed in infancy with NC and found to have a 57-kb deletion of the CTNS gene, the most frequent cause of NC in Western populations. They were on cysteamine bitartrate (cystagon-immediate release) since diagnosis. Each was currently prescribed Procysbi (cysteamine-delayed release) 675 mg every 12 hours. In addition, each twin was prescribed cysteamine hydrochloride (0.44%) eye drops due to cystine crystal accumulation in the lens and cornea. Both twins were transplanted 6 years previously with kidneys from a single deceased donor source. Since that time, both twins experienced several episodes of transplant rejection, whereas twin 1 also developed Epstein-Barr virus positive posttransplant proliferative disorder. Table 1 includes clinical and medication data on the patients at the time of autonomic testing. As shown in Table 1, twin 2 exhibited a diastolic blood pressure (DBP) that exceeded the threshold for sex and height and had DBP readings 20% higher than those of twin 1. Table 1 Characteristics and medications of female monozygotic twins with nephropathic cystinosis Characteristics Twin 1 Twin 2 Age (yrs) 16 Race W Ethnicity H Wt. (kg) 43.6 46.0 Ht. (cm) 152.3 154.8 BMI percentile (for age and sex) (kg/m 2 ) 25th 40th Resting BP (mm Hg) 118/70 123/84 Measured GFR (ml/min per 1.73 m 2 ) 59.3 70.0 CKD stage 3a 2 Tacrolimus level (ng/ml) 5.5 4.5 Medications, Dose, Frequency Procysbi (cysteamine DR) 675 mg q 12 h Cysteamine HCL (0.44%) 1 gtt. OU q h while awake Amlodipine 10 mg/d Cardura 4 mg/d — Lisinopril 10 mg/d Drisdol 50,000 IU/ q 14 d — Cellcept 500 mg BID Tacrolimus 3 mg BID 2 mg BID Synthroid 137 μg/d 125 μg/d Mg oxide 400 mg BID Bactrim 400-80 40 mg 3×/wk BID, twice a day; BMI, body mass index; BP, blood pressure; CKD, chronic kidney disease; DR, delayed release; GFR, glomerular filtration rate by plasma clearance of iohexol; gtt, drops; H, Hispanic; HCL, hydrochloride; Ht., height; IU, international units; Mg, magnesium; OU, both eyes; q, every; W, white; Wt., weight. Laboratory findings (biochemical characteristics) for both twins are shown in Table 2 . Creatinine, blood urea nitrogen, and cystatin C levels were consistent with the CKD stage of each twin. Both patients also had blood drawn for measurement of their leukocyte cystine levels, which were obtained at the time of their regular laboratory tests. Those results were 1.65 and 1.90 nmol 1/2 cystine per milligram per protein for twins 1 and 2, respectively. Because the twins exhibited leukocyte cystine levels >1 nmol 1/2 cystine per milligram per protein, it indicated they had not achieved an optimal degree of substrate depletion for cystinosis patients on cysteamine therapy. This was due to incomplete adherence with their cysteamine bitartrate therapy. Table 3 lists a summary on cystinosis. Table 2 Laboratory results Results Conventional units (SI Units) Twin # Cr BUN Cystatin C Alb Phos Na K Glucose 1 1.08 (95.47) 15 (5.35) (1.25) 4.5 (45) 3.7 (1.20) 136 (136 ) 4.0 (4.0) 98 (5.44) 2 0.81 (71.60) 13 (4.64) (1.09) 4.9 (49) 3.8 (1.23) 137 (137) 4.2 (4.2) 94 (5.22) Normal reference range 0.25−1.14 mg/dl 5.0−18.0 mg/dl 0.5−1.3 mg/l (1−17 yr) 3.6−4.7 g/dl 3.0−4.8 mg/dl 134−146 mEq/l 3.7−5.7 mEq/l 60−110 mg/dl SI units normal Reference Range 22.1−100.78 mmol/l 1.78−6.43 mmol/l 0.50−1.30 mg/l 36.0−47.0 g/l 0.97−1.55 mmol/l 134−146 mmol/l 3.7−5.7 mmol/l 3.33−6.11 mmol/l Alb, albumin; BUN, blood urea nitrogen; Cr, creatinine; K, potassium; Na, sodium; Phos, phosphorus (inorganic); SI, Standard international. Table 3 Teaching points (i) Cystinosis results from a functional defect in the lysosomal-membrane exporter protein, cystinosin (CTNS), thereby resulting in failure of cystine efflux from cell lysosomes. When untreated, cystine crystals result and are deposited throughout the body, including in the cornea, retina, and most organs. (ii) Nephropathic cystinosis (NC) is often diagnosed in infancy due to the development of severe renal Fanconi syndrome with failure to thrive. Chronic electrolyte replacement is essential. (iii) Cystine accumulation is measured in leukocytes with a cystine level < 1 nmol 1/2 cystine per milligram cell protein categorized as being consistent with optimal cystine depletion. (iv) Cysteamine bitartrate is the only Food and Drug Administration−approved therapy for cystinosis and is available in immediate and delayed release formulations. (v) In NC, the 57-kb deletion has been associated with transient receptor potential vanilloid 1 (TRPV1) gene functional impairment. (vi) Long-term extra renal manifestations of NC are frequently observed and include cognitive impairment and/or delays, altered skin and/or heat sensations, abnormal temperature regulation, heat intolerance, reduced sweating, and myopathy, the latter of which may eventually contribute to respiratory failure, all suggestive of autonomic nervous system dysfunction pertinent to thermoregulation. Both twins frequently described issues with heat intolerance and photophobia secondary to corneal cystine crystal deposition, but they demonstrated consistently normal clinical neurological examination findings. We decided to complete further testing of the twins to evaluate heat intolerance and possible associated autonomic dysfunction as opposed to what may simply be avoidance of light exposure on sunny days.', 'Clinical Testing': 'During the period before testing, a directly measured glomerular filtration rate was completed on each twin using a plasma clearance of iohexol procedure. 14 The twins then underwent 3 clinical procedures at the Center for Autonomic Medicine in Pediatrics at Ann & Robert H. Lurie Children’s Hospital of Chicago (Chicago, IL). Those procedures included the head-up tilt (HUT) test to assess baroreceptor function, a thermoregulatory sweat test (TST) to measure sudomotor function, and the quantitative sweat response test (QSWEAT), which is a sudomotor axon reflex test in which responses of the local axon reflex of sweat glands to iontophoresed acetylcholine are quantitated. 15 The use of the TST and QSWEAT procedures on patients are considered to be the gold standard for clinical evaluation, because they demonstrated a 90% sensitivity for detection of small fiber neuropathy. 16 The HUT determines whether orthostatic (in)tolerance can be demonstrated and evaluates the inter-relationship of breathing, heart rate (HR), and BP while the patient transitions from a supine to an upright position and then returns to the supine position. Simply stated, a patient lays on a tilt table in a supine horizontal position for 10 to 20 minutes while baseline measurements are taken. Then, a HUT to 70° is done with measurements collected thereafter for 10 minutes. Following this, a tilt-down to a supine horizontal position occurs and is sustained for 2 minutes of additional measurements. During the TST, the core body temperature is increased slowly to 1 ° C higher than at prewarming (baseline) or a patient reaches a core temperature of 38 ° C (whichever is greater). To prepare for the procedure, sweat-indicator powder is applied to the patient’s anterior surface while lying supine on a bed. The patient is then rolled into the chamber, and it is sealed shut, while continuous surveillance and collection of all physiological measurements of the patient, chamber, and temperatures occurs. The ambient temperature is slowly increased with an average ramp rate of 5.0 °C/hour and with a relative humidity range of 35% to 45%. Finally, for the QSWEAT, the patient is placed in a supine horizontal position. Once situated, 4 quarter-sized capsules of acetylcholine are topically applied on the forearm, proximal and distal leg, and foot. An imperceivable 2-mA current is delivered over a 5-minute period, followed by a 5-minute recovery, which results in an accurate quantitation of sweat produced in small areas of the skin.'}
|
{'Testing Results': 'Figures 1 a to d represent the continuous HR and BP recordings of twin 1 ( Figure 1 a and b) and twin 2 ( Figure 1 c and d) during the HUT over the 10-second transition from a supine horizontal position to a 70° upright tilt. As seen in Figure 1 a, the HR of twin 1 exhibited a compensatory increase to a maximum of 110 beats/min at 6.9 minutes into the HUT and remained at this level until she was returned to a horizontal and/or supine position. This was a change of 52 beats/min. In Figure 1 b, a systolic BP (SBP) decline of 29.8 mm Hg can be seen at 0.3 minutes into the HUT. The BP of twin 1 recovered quickly to pre-HUT levels and remained stable thereafter throughout the 10-minute HUT. Conversely, for twin 2, HR increased by 45 to 120 beats/min and a 30-mm Hg SBP drop occurred when transitioned from a supine position to a 70° HUT ( Figure 1 c and d). In addition, the HR and SBP remained at these levels throughout the HUT until the twin returned to the supine position. Thus, both twins exhibited orthostatic tachycardia during HUT that was maintained until returning to the supine horizontal body position, which indicated a greater than average response compared with normative data. Figure 1 Head up-tilt (HUT) of twins 1 and 2 for continuous heart rate (a,c) and blood pressure recordings (b,d). For the TST, the baseline (pre-TST) for twin 1 and twin 2 are shown in Figure 2 a and 2 c, respectively, whereas postwarming period results for each twin are found in Figure 2 b and 2 d, respectively. By referencing the temperature scale shown between Figure 2 a and 2 b and Figure 2 c and 2 d, the images clearly demonstrate both twins with cold hands and feet before warming ( Figure 2 a and 2 c). Conversely, in post-TST images, both twins displayed symmetric warming of their hands but their feet remained slightly cooler compared with other body regions ( Figure 2 b and 2 d). Figure 2 Thermoregulatory sweat test baseline and warmed (post) test twin 1 (a,b) and twin 2 (c,d), respectively. A temperature-color gauge is centered between each baseline and the warmed figure with values shown in degrees Fahrenheit. Postwarming images of twin 1 ( Figure 3 a) and twin 2 ( Figure 3 b) are shown with patchy regions of anhidrosis (in yellow) compared with the purple areas of sweat indicator powder, which demonstrated the regions where sweating occurred. Twin 1 had 53% anhidrosis but preserved sweating on the upper trunk, left abdomen, both hands, and medial legs, whereas twin 2 exhibited 50% anhidrosis and residual sweating of the upper trunk, bilateral hands, and medial legs. Figure 3 Diaphoresis patterns of twin 1 (a) and twin 2 (b) at the completion of the thermoregulatory sweat test (TST). QSWEAT results of twin 1 are shown with sweat rates of the forearm (25−50th percentile) ( Figure 4 a); proximal ( Figure 4 b) and distal leg sweat rates were each <10th percentile (abnormal for sex and age) ( Figure 4 c), and the foot was between the 10th to 25th percentile ( Figure 4 d). In addition, these abnormalities were categorized as a “latency of the sweat response” of the forearm, distal leg, and foot, as well as a “lack of recovery” of the proximal leg. Results for twin 2 showed a similar sweat response latency of the proximal leg ( Figure 5 b). Otherwise, twin 2 exhibited normal sweat volumes and rates for her age as seen for the forearm (10th−25th percentile) ( Figure 5 a), proximal leg (25th percentile) ( Figure 5 b), distal leg (25th percentile) ( Figure 5 c), and foot (50−80th percentile) ( Figure 5 d). Figure 4 Quantitative sweat rate (nanoliters per minute) of twin 1 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d). Figure 5 Quantitative sweat rate (nanoliters per minute) of twin 2 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d).', 'Case 1': 'Monozygotic female adolescent twins, aged 16 years old, were originally diagnosed in infancy with NC and found to have a 57-kb deletion of the CTNS gene, the most frequent cause of NC in Western populations. They were on cysteamine bitartrate (cystagon-immediate release) since diagnosis. Each was currently prescribed Procysbi (cysteamine-delayed release) 675 mg every 12 hours. In addition, each twin was prescribed cysteamine hydrochloride (0.44%) eye drops due to cystine crystal accumulation in the lens and cornea. Both twins were transplanted 6 years previously with kidneys from a single deceased donor source. Since that time, both twins experienced several episodes of transplant rejection, whereas twin 1 also developed Epstein-Barr virus positive posttransplant proliferative disorder. Table 1 includes clinical and medication data on the patients at the time of autonomic testing. As shown in Table 1, twin 2 exhibited a diastolic blood pressure (DBP) that exceeded the threshold for sex and height and had DBP readings 20% higher than those of twin 1. Table 1 Characteristics and medications of female monozygotic twins with nephropathic cystinosis Characteristics Twin 1 Twin 2 Age (yrs) 16 Race W Ethnicity H Wt. (kg) 43.6 46.0 Ht. (cm) 152.3 154.8 BMI percentile (for age and sex) (kg/m 2 ) 25th 40th Resting BP (mm Hg) 118/70 123/84 Measured GFR (ml/min per 1.73 m 2 ) 59.3 70.0 CKD stage 3a 2 Tacrolimus level (ng/ml) 5.5 4.5 Medications, Dose, Frequency Procysbi (cysteamine DR) 675 mg q 12 h Cysteamine HCL (0.44%) 1 gtt. OU q h while awake Amlodipine 10 mg/d Cardura 4 mg/d — Lisinopril 10 mg/d Drisdol 50,000 IU/ q 14 d — Cellcept 500 mg BID Tacrolimus 3 mg BID 2 mg BID Synthroid 137 μg/d 125 μg/d Mg oxide 400 mg BID Bactrim 400-80 40 mg 3×/wk BID, twice a day; BMI, body mass index; BP, blood pressure; CKD, chronic kidney disease; DR, delayed release; GFR, glomerular filtration rate by plasma clearance of iohexol; gtt, drops; H, Hispanic; HCL, hydrochloride; Ht., height; IU, international units; Mg, magnesium; OU, both eyes; q, every; W, white; Wt., weight. Laboratory findings (biochemical characteristics) for both twins are shown in Table 2 . Creatinine, blood urea nitrogen, and cystatin C levels were consistent with the CKD stage of each twin. Both patients also had blood drawn for measurement of their leukocyte cystine levels, which were obtained at the time of their regular laboratory tests. Those results were 1.65 and 1.90 nmol 1/2 cystine per milligram per protein for twins 1 and 2, respectively. Because the twins exhibited leukocyte cystine levels >1 nmol 1/2 cystine per milligram per protein, it indicated they had not achieved an optimal degree of substrate depletion for cystinosis patients on cysteamine therapy. This was due to incomplete adherence with their cysteamine bitartrate therapy. Table 3 lists a summary on cystinosis. Table 2 Laboratory results Results Conventional units (SI Units) Twin # Cr BUN Cystatin C Alb Phos Na K Glucose 1 1.08 (95.47) 15 (5.35) (1.25) 4.5 (45) 3.7 (1.20) 136 (136 ) 4.0 (4.0) 98 (5.44) 2 0.81 (71.60) 13 (4.64) (1.09) 4.9 (49) 3.8 (1.23) 137 (137) 4.2 (4.2) 94 (5.22) Normal reference range 0.25−1.14 mg/dl 5.0−18.0 mg/dl 0.5−1.3 mg/l (1−17 yr) 3.6−4.7 g/dl 3.0−4.8 mg/dl 134−146 mEq/l 3.7−5.7 mEq/l 60−110 mg/dl SI units normal Reference Range 22.1−100.78 mmol/l 1.78−6.43 mmol/l 0.50−1.30 mg/l 36.0−47.0 g/l 0.97−1.55 mmol/l 134−146 mmol/l 3.7−5.7 mmol/l 3.33−6.11 mmol/l Alb, albumin; BUN, blood urea nitrogen; Cr, creatinine; K, potassium; Na, sodium; Phos, phosphorus (inorganic); SI, Standard international. Table 3 Teaching points (i) Cystinosis results from a functional defect in the lysosomal-membrane exporter protein, cystinosin (CTNS), thereby resulting in failure of cystine efflux from cell lysosomes. When untreated, cystine crystals result and are deposited throughout the body, including in the cornea, retina, and most organs. (ii) Nephropathic cystinosis (NC) is often diagnosed in infancy due to the development of severe renal Fanconi syndrome with failure to thrive. Chronic electrolyte replacement is essential. (iii) Cystine accumulation is measured in leukocytes with a cystine level < 1 nmol 1/2 cystine per milligram cell protein categorized as being consistent with optimal cystine depletion. (iv) Cysteamine bitartrate is the only Food and Drug Administration−approved therapy for cystinosis and is available in immediate and delayed release formulations. (v) In NC, the 57-kb deletion has been associated with transient receptor potential vanilloid 1 (TRPV1) gene functional impairment. (vi) Long-term extra renal manifestations of NC are frequently observed and include cognitive impairment and/or delays, altered skin and/or heat sensations, abnormal temperature regulation, heat intolerance, reduced sweating, and myopathy, the latter of which may eventually contribute to respiratory failure, all suggestive of autonomic nervous system dysfunction pertinent to thermoregulation. Both twins frequently described issues with heat intolerance and photophobia secondary to corneal cystine crystal deposition, but they demonstrated consistently normal clinical neurological examination findings. We decided to complete further testing of the twins to evaluate heat intolerance and possible associated autonomic dysfunction as opposed to what may simply be avoidance of light exposure on sunny days.', 'Clinical Testing': 'During the period before testing, a directly measured glomerular filtration rate was completed on each twin using a plasma clearance of iohexol procedure. 14 The twins then underwent 3 clinical procedures at the Center for Autonomic Medicine in Pediatrics at Ann & Robert H. Lurie Children’s Hospital of Chicago (Chicago, IL). Those procedures included the head-up tilt (HUT) test to assess baroreceptor function, a thermoregulatory sweat test (TST) to measure sudomotor function, and the quantitative sweat response test (QSWEAT), which is a sudomotor axon reflex test in which responses of the local axon reflex of sweat glands to iontophoresed acetylcholine are quantitated. 15 The use of the TST and QSWEAT procedures on patients are considered to be the gold standard for clinical evaluation, because they demonstrated a 90% sensitivity for detection of small fiber neuropathy. 16 The HUT determines whether orthostatic (in)tolerance can be demonstrated and evaluates the inter-relationship of breathing, heart rate (HR), and BP while the patient transitions from a supine to an upright position and then returns to the supine position. Simply stated, a patient lays on a tilt table in a supine horizontal position for 10 to 20 minutes while baseline measurements are taken. Then, a HUT to 70° is done with measurements collected thereafter for 10 minutes. Following this, a tilt-down to a supine horizontal position occurs and is sustained for 2 minutes of additional measurements. During the TST, the core body temperature is increased slowly to 1 ° C higher than at prewarming (baseline) or a patient reaches a core temperature of 38 ° C (whichever is greater). To prepare for the procedure, sweat-indicator powder is applied to the patient’s anterior surface while lying supine on a bed. The patient is then rolled into the chamber, and it is sealed shut, while continuous surveillance and collection of all physiological measurements of the patient, chamber, and temperatures occurs. The ambient temperature is slowly increased with an average ramp rate of 5.0 °C/hour and with a relative humidity range of 35% to 45%. Finally, for the QSWEAT, the patient is placed in a supine horizontal position. Once situated, 4 quarter-sized capsules of acetylcholine are topically applied on the forearm, proximal and distal leg, and foot. An imperceivable 2-mA current is delivered over a 5-minute period, followed by a 5-minute recovery, which results in an accurate quantitation of sweat produced in small areas of the skin.'}
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Patient-History
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History
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[
"Monozygotic female adolescent twins, aged 16 years old, were originally diagnosed in infancy with NC and found to have a 57 - kb deletion of the CTNS gene, the most frequent cause of NC in Western populations.",
"Both twins were transplanted 6 years previously with kidneys from a single deceased donor source. Since that time, both twins experienced several episodes of transplant rejection, whereas twin 1 also developed Epstein - Barr virus positive posttransplant proliferative disorder"
] |
6224624
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{'Testing Results': 'Figures 1 a to d represent the continuous HR and BP recordings of twin 1 ( Figure 1 a and b) and twin 2 ( Figure 1 c and d) during the HUT over the 10-second transition from a supine horizontal position to a 70° upright tilt. As seen in Figure 1 a, the HR of twin 1 exhibited a compensatory increase to a maximum of 110 beats/min at 6.9 minutes into the HUT and remained at this level until she was returned to a horizontal and/or supine position. This was a change of 52 beats/min. In Figure 1 b, a systolic BP (SBP) decline of 29.8 mm Hg can be seen at 0.3 minutes into the HUT. The BP of twin 1 recovered quickly to pre-HUT levels and remained stable thereafter throughout the 10-minute HUT. Conversely, for twin 2, HR increased by 45 to 120 beats/min and a 30-mm Hg SBP drop occurred when transitioned from a supine position to a 70° HUT ( Figure 1 c and d). In addition, the HR and SBP remained at these levels throughout the HUT until the twin returned to the supine position. Thus, both twins exhibited orthostatic tachycardia during HUT that was maintained until returning to the supine horizontal body position, which indicated a greater than average response compared with normative data. Figure 1 Head up-tilt (HUT) of twins 1 and 2 for continuous heart rate (a,c) and blood pressure recordings (b,d). For the TST, the baseline (pre-TST) for twin 1 and twin 2 are shown in Figure 2 a and 2 c, respectively, whereas postwarming period results for each twin are found in Figure 2 b and 2 d, respectively. By referencing the temperature scale shown between Figure 2 a and 2 b and Figure 2 c and 2 d, the images clearly demonstrate both twins with cold hands and feet before warming ( Figure 2 a and 2 c). Conversely, in post-TST images, both twins displayed symmetric warming of their hands but their feet remained slightly cooler compared with other body regions ( Figure 2 b and 2 d). Figure 2 Thermoregulatory sweat test baseline and warmed (post) test twin 1 (a,b) and twin 2 (c,d), respectively. A temperature-color gauge is centered between each baseline and the warmed figure with values shown in degrees Fahrenheit. Postwarming images of twin 1 ( Figure 3 a) and twin 2 ( Figure 3 b) are shown with patchy regions of anhidrosis (in yellow) compared with the purple areas of sweat indicator powder, which demonstrated the regions where sweating occurred. Twin 1 had 53% anhidrosis but preserved sweating on the upper trunk, left abdomen, both hands, and medial legs, whereas twin 2 exhibited 50% anhidrosis and residual sweating of the upper trunk, bilateral hands, and medial legs. Figure 3 Diaphoresis patterns of twin 1 (a) and twin 2 (b) at the completion of the thermoregulatory sweat test (TST). QSWEAT results of twin 1 are shown with sweat rates of the forearm (25−50th percentile) ( Figure 4 a); proximal ( Figure 4 b) and distal leg sweat rates were each <10th percentile (abnormal for sex and age) ( Figure 4 c), and the foot was between the 10th to 25th percentile ( Figure 4 d). In addition, these abnormalities were categorized as a “latency of the sweat response” of the forearm, distal leg, and foot, as well as a “lack of recovery” of the proximal leg. Results for twin 2 showed a similar sweat response latency of the proximal leg ( Figure 5 b). Otherwise, twin 2 exhibited normal sweat volumes and rates for her age as seen for the forearm (10th−25th percentile) ( Figure 5 a), proximal leg (25th percentile) ( Figure 5 b), distal leg (25th percentile) ( Figure 5 c), and foot (50−80th percentile) ( Figure 5 d). Figure 4 Quantitative sweat rate (nanoliters per minute) of twin 1 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d). Figure 5 Quantitative sweat rate (nanoliters per minute) of twin 2 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d).', 'Case 1': 'Monozygotic female adolescent twins, aged 16 years old, were originally diagnosed in infancy with NC and found to have a 57-kb deletion of the CTNS gene, the most frequent cause of NC in Western populations. They were on cysteamine bitartrate (cystagon-immediate release) since diagnosis. Each was currently prescribed Procysbi (cysteamine-delayed release) 675 mg every 12 hours. In addition, each twin was prescribed cysteamine hydrochloride (0.44%) eye drops due to cystine crystal accumulation in the lens and cornea. Both twins were transplanted 6 years previously with kidneys from a single deceased donor source. Since that time, both twins experienced several episodes of transplant rejection, whereas twin 1 also developed Epstein-Barr virus positive posttransplant proliferative disorder. Table 1 includes clinical and medication data on the patients at the time of autonomic testing. As shown in Table 1, twin 2 exhibited a diastolic blood pressure (DBP) that exceeded the threshold for sex and height and had DBP readings 20% higher than those of twin 1. Table 1 Characteristics and medications of female monozygotic twins with nephropathic cystinosis Characteristics Twin 1 Twin 2 Age (yrs) 16 Race W Ethnicity H Wt. (kg) 43.6 46.0 Ht. (cm) 152.3 154.8 BMI percentile (for age and sex) (kg/m 2 ) 25th 40th Resting BP (mm Hg) 118/70 123/84 Measured GFR (ml/min per 1.73 m 2 ) 59.3 70.0 CKD stage 3a 2 Tacrolimus level (ng/ml) 5.5 4.5 Medications, Dose, Frequency Procysbi (cysteamine DR) 675 mg q 12 h Cysteamine HCL (0.44%) 1 gtt. OU q h while awake Amlodipine 10 mg/d Cardura 4 mg/d — Lisinopril 10 mg/d Drisdol 50,000 IU/ q 14 d — Cellcept 500 mg BID Tacrolimus 3 mg BID 2 mg BID Synthroid 137 μg/d 125 μg/d Mg oxide 400 mg BID Bactrim 400-80 40 mg 3×/wk BID, twice a day; BMI, body mass index; BP, blood pressure; CKD, chronic kidney disease; DR, delayed release; GFR, glomerular filtration rate by plasma clearance of iohexol; gtt, drops; H, Hispanic; HCL, hydrochloride; Ht., height; IU, international units; Mg, magnesium; OU, both eyes; q, every; W, white; Wt., weight. Laboratory findings (biochemical characteristics) for both twins are shown in Table 2 . Creatinine, blood urea nitrogen, and cystatin C levels were consistent with the CKD stage of each twin. Both patients also had blood drawn for measurement of their leukocyte cystine levels, which were obtained at the time of their regular laboratory tests. Those results were 1.65 and 1.90 nmol 1/2 cystine per milligram per protein for twins 1 and 2, respectively. Because the twins exhibited leukocyte cystine levels >1 nmol 1/2 cystine per milligram per protein, it indicated they had not achieved an optimal degree of substrate depletion for cystinosis patients on cysteamine therapy. This was due to incomplete adherence with their cysteamine bitartrate therapy. Table 3 lists a summary on cystinosis. Table 2 Laboratory results Results Conventional units (SI Units) Twin # Cr BUN Cystatin C Alb Phos Na K Glucose 1 1.08 (95.47) 15 (5.35) (1.25) 4.5 (45) 3.7 (1.20) 136 (136 ) 4.0 (4.0) 98 (5.44) 2 0.81 (71.60) 13 (4.64) (1.09) 4.9 (49) 3.8 (1.23) 137 (137) 4.2 (4.2) 94 (5.22) Normal reference range 0.25−1.14 mg/dl 5.0−18.0 mg/dl 0.5−1.3 mg/l (1−17 yr) 3.6−4.7 g/dl 3.0−4.8 mg/dl 134−146 mEq/l 3.7−5.7 mEq/l 60−110 mg/dl SI units normal Reference Range 22.1−100.78 mmol/l 1.78−6.43 mmol/l 0.50−1.30 mg/l 36.0−47.0 g/l 0.97−1.55 mmol/l 134−146 mmol/l 3.7−5.7 mmol/l 3.33−6.11 mmol/l Alb, albumin; BUN, blood urea nitrogen; Cr, creatinine; K, potassium; Na, sodium; Phos, phosphorus (inorganic); SI, Standard international. Table 3 Teaching points (i) Cystinosis results from a functional defect in the lysosomal-membrane exporter protein, cystinosin (CTNS), thereby resulting in failure of cystine efflux from cell lysosomes. When untreated, cystine crystals result and are deposited throughout the body, including in the cornea, retina, and most organs. (ii) Nephropathic cystinosis (NC) is often diagnosed in infancy due to the development of severe renal Fanconi syndrome with failure to thrive. Chronic electrolyte replacement is essential. (iii) Cystine accumulation is measured in leukocytes with a cystine level < 1 nmol 1/2 cystine per milligram cell protein categorized as being consistent with optimal cystine depletion. (iv) Cysteamine bitartrate is the only Food and Drug Administration−approved therapy for cystinosis and is available in immediate and delayed release formulations. (v) In NC, the 57-kb deletion has been associated with transient receptor potential vanilloid 1 (TRPV1) gene functional impairment. (vi) Long-term extra renal manifestations of NC are frequently observed and include cognitive impairment and/or delays, altered skin and/or heat sensations, abnormal temperature regulation, heat intolerance, reduced sweating, and myopathy, the latter of which may eventually contribute to respiratory failure, all suggestive of autonomic nervous system dysfunction pertinent to thermoregulation. Both twins frequently described issues with heat intolerance and photophobia secondary to corneal cystine crystal deposition, but they demonstrated consistently normal clinical neurological examination findings. We decided to complete further testing of the twins to evaluate heat intolerance and possible associated autonomic dysfunction as opposed to what may simply be avoidance of light exposure on sunny days.', 'Clinical Testing': 'During the period before testing, a directly measured glomerular filtration rate was completed on each twin using a plasma clearance of iohexol procedure. 14 The twins then underwent 3 clinical procedures at the Center for Autonomic Medicine in Pediatrics at Ann & Robert H. Lurie Children’s Hospital of Chicago (Chicago, IL). Those procedures included the head-up tilt (HUT) test to assess baroreceptor function, a thermoregulatory sweat test (TST) to measure sudomotor function, and the quantitative sweat response test (QSWEAT), which is a sudomotor axon reflex test in which responses of the local axon reflex of sweat glands to iontophoresed acetylcholine are quantitated. 15 The use of the TST and QSWEAT procedures on patients are considered to be the gold standard for clinical evaluation, because they demonstrated a 90% sensitivity for detection of small fiber neuropathy. 16 The HUT determines whether orthostatic (in)tolerance can be demonstrated and evaluates the inter-relationship of breathing, heart rate (HR), and BP while the patient transitions from a supine to an upright position and then returns to the supine position. Simply stated, a patient lays on a tilt table in a supine horizontal position for 10 to 20 minutes while baseline measurements are taken. Then, a HUT to 70° is done with measurements collected thereafter for 10 minutes. Following this, a tilt-down to a supine horizontal position occurs and is sustained for 2 minutes of additional measurements. During the TST, the core body temperature is increased slowly to 1 ° C higher than at prewarming (baseline) or a patient reaches a core temperature of 38 ° C (whichever is greater). To prepare for the procedure, sweat-indicator powder is applied to the patient’s anterior surface while lying supine on a bed. The patient is then rolled into the chamber, and it is sealed shut, while continuous surveillance and collection of all physiological measurements of the patient, chamber, and temperatures occurs. The ambient temperature is slowly increased with an average ramp rate of 5.0 °C/hour and with a relative humidity range of 35% to 45%. Finally, for the QSWEAT, the patient is placed in a supine horizontal position. Once situated, 4 quarter-sized capsules of acetylcholine are topically applied on the forearm, proximal and distal leg, and foot. An imperceivable 2-mA current is delivered over a 5-minute period, followed by a 5-minute recovery, which results in an accurate quantitation of sweat produced in small areas of the skin.'}
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{'Testing Results': 'Figures 1 a to d represent the continuous HR and BP recordings of twin 1 ( Figure 1 a and b) and twin 2 ( Figure 1 c and d) during the HUT over the 10-second transition from a supine horizontal position to a 70° upright tilt. As seen in Figure 1 a, the HR of twin 1 exhibited a compensatory increase to a maximum of 110 beats/min at 6.9 minutes into the HUT and remained at this level until she was returned to a horizontal and/or supine position. This was a change of 52 beats/min. In Figure 1 b, a systolic BP (SBP) decline of 29.8 mm Hg can be seen at 0.3 minutes into the HUT. The BP of twin 1 recovered quickly to pre-HUT levels and remained stable thereafter throughout the 10-minute HUT. Conversely, for twin 2, HR increased by 45 to 120 beats/min and a 30-mm Hg SBP drop occurred when transitioned from a supine position to a 70° HUT ( Figure 1 c and d). In addition, the HR and SBP remained at these levels throughout the HUT until the twin returned to the supine position. Thus, both twins exhibited orthostatic tachycardia during HUT that was maintained until returning to the supine horizontal body position, which indicated a greater than average response compared with normative data. Figure 1 Head up-tilt (HUT) of twins 1 and 2 for continuous heart rate (a,c) and blood pressure recordings (b,d). For the TST, the baseline (pre-TST) for twin 1 and twin 2 are shown in Figure 2 a and 2 c, respectively, whereas postwarming period results for each twin are found in Figure 2 b and 2 d, respectively. By referencing the temperature scale shown between Figure 2 a and 2 b and Figure 2 c and 2 d, the images clearly demonstrate both twins with cold hands and feet before warming ( Figure 2 a and 2 c). Conversely, in post-TST images, both twins displayed symmetric warming of their hands but their feet remained slightly cooler compared with other body regions ( Figure 2 b and 2 d). Figure 2 Thermoregulatory sweat test baseline and warmed (post) test twin 1 (a,b) and twin 2 (c,d), respectively. A temperature-color gauge is centered between each baseline and the warmed figure with values shown in degrees Fahrenheit. Postwarming images of twin 1 ( Figure 3 a) and twin 2 ( Figure 3 b) are shown with patchy regions of anhidrosis (in yellow) compared with the purple areas of sweat indicator powder, which demonstrated the regions where sweating occurred. Twin 1 had 53% anhidrosis but preserved sweating on the upper trunk, left abdomen, both hands, and medial legs, whereas twin 2 exhibited 50% anhidrosis and residual sweating of the upper trunk, bilateral hands, and medial legs. Figure 3 Diaphoresis patterns of twin 1 (a) and twin 2 (b) at the completion of the thermoregulatory sweat test (TST). QSWEAT results of twin 1 are shown with sweat rates of the forearm (25−50th percentile) ( Figure 4 a); proximal ( Figure 4 b) and distal leg sweat rates were each <10th percentile (abnormal for sex and age) ( Figure 4 c), and the foot was between the 10th to 25th percentile ( Figure 4 d). In addition, these abnormalities were categorized as a “latency of the sweat response” of the forearm, distal leg, and foot, as well as a “lack of recovery” of the proximal leg. Results for twin 2 showed a similar sweat response latency of the proximal leg ( Figure 5 b). Otherwise, twin 2 exhibited normal sweat volumes and rates for her age as seen for the forearm (10th−25th percentile) ( Figure 5 a), proximal leg (25th percentile) ( Figure 5 b), distal leg (25th percentile) ( Figure 5 c), and foot (50−80th percentile) ( Figure 5 d). Figure 4 Quantitative sweat rate (nanoliters per minute) of twin 1 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d). Figure 5 Quantitative sweat rate (nanoliters per minute) of twin 2 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d).', 'Case 1': 'Monozygotic female adolescent twins, aged 16 years old, were originally diagnosed in infancy with NC and found to have a 57-kb deletion of the CTNS gene, the most frequent cause of NC in Western populations. They were on cysteamine bitartrate (cystagon-immediate release) since diagnosis. Each was currently prescribed Procysbi (cysteamine-delayed release) 675 mg every 12 hours. In addition, each twin was prescribed cysteamine hydrochloride (0.44%) eye drops due to cystine crystal accumulation in the lens and cornea. Both twins were transplanted 6 years previously with kidneys from a single deceased donor source. Since that time, both twins experienced several episodes of transplant rejection, whereas twin 1 also developed Epstein-Barr virus positive posttransplant proliferative disorder. Table 1 includes clinical and medication data on the patients at the time of autonomic testing. As shown in Table 1, twin 2 exhibited a diastolic blood pressure (DBP) that exceeded the threshold for sex and height and had DBP readings 20% higher than those of twin 1. Table 1 Characteristics and medications of female monozygotic twins with nephropathic cystinosis Characteristics Twin 1 Twin 2 Age (yrs) 16 Race W Ethnicity H Wt. (kg) 43.6 46.0 Ht. (cm) 152.3 154.8 BMI percentile (for age and sex) (kg/m 2 ) 25th 40th Resting BP (mm Hg) 118/70 123/84 Measured GFR (ml/min per 1.73 m 2 ) 59.3 70.0 CKD stage 3a 2 Tacrolimus level (ng/ml) 5.5 4.5 Medications, Dose, Frequency Procysbi (cysteamine DR) 675 mg q 12 h Cysteamine HCL (0.44%) 1 gtt. OU q h while awake Amlodipine 10 mg/d Cardura 4 mg/d — Lisinopril 10 mg/d Drisdol 50,000 IU/ q 14 d — Cellcept 500 mg BID Tacrolimus 3 mg BID 2 mg BID Synthroid 137 μg/d 125 μg/d Mg oxide 400 mg BID Bactrim 400-80 40 mg 3×/wk BID, twice a day; BMI, body mass index; BP, blood pressure; CKD, chronic kidney disease; DR, delayed release; GFR, glomerular filtration rate by plasma clearance of iohexol; gtt, drops; H, Hispanic; HCL, hydrochloride; Ht., height; IU, international units; Mg, magnesium; OU, both eyes; q, every; W, white; Wt., weight. Laboratory findings (biochemical characteristics) for both twins are shown in Table 2 . Creatinine, blood urea nitrogen, and cystatin C levels were consistent with the CKD stage of each twin. Both patients also had blood drawn for measurement of their leukocyte cystine levels, which were obtained at the time of their regular laboratory tests. Those results were 1.65 and 1.90 nmol 1/2 cystine per milligram per protein for twins 1 and 2, respectively. Because the twins exhibited leukocyte cystine levels >1 nmol 1/2 cystine per milligram per protein, it indicated they had not achieved an optimal degree of substrate depletion for cystinosis patients on cysteamine therapy. This was due to incomplete adherence with their cysteamine bitartrate therapy. Table 3 lists a summary on cystinosis. Table 2 Laboratory results Results Conventional units (SI Units) Twin # Cr BUN Cystatin C Alb Phos Na K Glucose 1 1.08 (95.47) 15 (5.35) (1.25) 4.5 (45) 3.7 (1.20) 136 (136 ) 4.0 (4.0) 98 (5.44) 2 0.81 (71.60) 13 (4.64) (1.09) 4.9 (49) 3.8 (1.23) 137 (137) 4.2 (4.2) 94 (5.22) Normal reference range 0.25−1.14 mg/dl 5.0−18.0 mg/dl 0.5−1.3 mg/l (1−17 yr) 3.6−4.7 g/dl 3.0−4.8 mg/dl 134−146 mEq/l 3.7−5.7 mEq/l 60−110 mg/dl SI units normal Reference Range 22.1−100.78 mmol/l 1.78−6.43 mmol/l 0.50−1.30 mg/l 36.0−47.0 g/l 0.97−1.55 mmol/l 134−146 mmol/l 3.7−5.7 mmol/l 3.33−6.11 mmol/l Alb, albumin; BUN, blood urea nitrogen; Cr, creatinine; K, potassium; Na, sodium; Phos, phosphorus (inorganic); SI, Standard international. Table 3 Teaching points (i) Cystinosis results from a functional defect in the lysosomal-membrane exporter protein, cystinosin (CTNS), thereby resulting in failure of cystine efflux from cell lysosomes. When untreated, cystine crystals result and are deposited throughout the body, including in the cornea, retina, and most organs. (ii) Nephropathic cystinosis (NC) is often diagnosed in infancy due to the development of severe renal Fanconi syndrome with failure to thrive. Chronic electrolyte replacement is essential. (iii) Cystine accumulation is measured in leukocytes with a cystine level < 1 nmol 1/2 cystine per milligram cell protein categorized as being consistent with optimal cystine depletion. (iv) Cysteamine bitartrate is the only Food and Drug Administration−approved therapy for cystinosis and is available in immediate and delayed release formulations. (v) In NC, the 57-kb deletion has been associated with transient receptor potential vanilloid 1 (TRPV1) gene functional impairment. (vi) Long-term extra renal manifestations of NC are frequently observed and include cognitive impairment and/or delays, altered skin and/or heat sensations, abnormal temperature regulation, heat intolerance, reduced sweating, and myopathy, the latter of which may eventually contribute to respiratory failure, all suggestive of autonomic nervous system dysfunction pertinent to thermoregulation. Both twins frequently described issues with heat intolerance and photophobia secondary to corneal cystine crystal deposition, but they demonstrated consistently normal clinical neurological examination findings. We decided to complete further testing of the twins to evaluate heat intolerance and possible associated autonomic dysfunction as opposed to what may simply be avoidance of light exposure on sunny days.', 'Clinical Testing': 'During the period before testing, a directly measured glomerular filtration rate was completed on each twin using a plasma clearance of iohexol procedure. 14 The twins then underwent 3 clinical procedures at the Center for Autonomic Medicine in Pediatrics at Ann & Robert H. Lurie Children’s Hospital of Chicago (Chicago, IL). Those procedures included the head-up tilt (HUT) test to assess baroreceptor function, a thermoregulatory sweat test (TST) to measure sudomotor function, and the quantitative sweat response test (QSWEAT), which is a sudomotor axon reflex test in which responses of the local axon reflex of sweat glands to iontophoresed acetylcholine are quantitated. 15 The use of the TST and QSWEAT procedures on patients are considered to be the gold standard for clinical evaluation, because they demonstrated a 90% sensitivity for detection of small fiber neuropathy. 16 The HUT determines whether orthostatic (in)tolerance can be demonstrated and evaluates the inter-relationship of breathing, heart rate (HR), and BP while the patient transitions from a supine to an upright position and then returns to the supine position. Simply stated, a patient lays on a tilt table in a supine horizontal position for 10 to 20 minutes while baseline measurements are taken. Then, a HUT to 70° is done with measurements collected thereafter for 10 minutes. Following this, a tilt-down to a supine horizontal position occurs and is sustained for 2 minutes of additional measurements. During the TST, the core body temperature is increased slowly to 1 ° C higher than at prewarming (baseline) or a patient reaches a core temperature of 38 ° C (whichever is greater). To prepare for the procedure, sweat-indicator powder is applied to the patient’s anterior surface while lying supine on a bed. The patient is then rolled into the chamber, and it is sealed shut, while continuous surveillance and collection of all physiological measurements of the patient, chamber, and temperatures occurs. The ambient temperature is slowly increased with an average ramp rate of 5.0 °C/hour and with a relative humidity range of 35% to 45%. Finally, for the QSWEAT, the patient is placed in a supine horizontal position. Once situated, 4 quarter-sized capsules of acetylcholine are topically applied on the forearm, proximal and distal leg, and foot. An imperceivable 2-mA current is delivered over a 5-minute period, followed by a 5-minute recovery, which results in an accurate quantitation of sweat produced in small areas of the skin.'}
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Neurology
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Neuro
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6224624
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{'Testing Results': 'Figures 1 a to d represent the continuous HR and BP recordings of twin 1 ( Figure 1 a and b) and twin 2 ( Figure 1 c and d) during the HUT over the 10-second transition from a supine horizontal position to a 70° upright tilt. As seen in Figure 1 a, the HR of twin 1 exhibited a compensatory increase to a maximum of 110 beats/min at 6.9 minutes into the HUT and remained at this level until she was returned to a horizontal and/or supine position. This was a change of 52 beats/min. In Figure 1 b, a systolic BP (SBP) decline of 29.8 mm Hg can be seen at 0.3 minutes into the HUT. The BP of twin 1 recovered quickly to pre-HUT levels and remained stable thereafter throughout the 10-minute HUT. Conversely, for twin 2, HR increased by 45 to 120 beats/min and a 30-mm Hg SBP drop occurred when transitioned from a supine position to a 70° HUT ( Figure 1 c and d). In addition, the HR and SBP remained at these levels throughout the HUT until the twin returned to the supine position. Thus, both twins exhibited orthostatic tachycardia during HUT that was maintained until returning to the supine horizontal body position, which indicated a greater than average response compared with normative data. Figure 1 Head up-tilt (HUT) of twins 1 and 2 for continuous heart rate (a,c) and blood pressure recordings (b,d). For the TST, the baseline (pre-TST) for twin 1 and twin 2 are shown in Figure 2 a and 2 c, respectively, whereas postwarming period results for each twin are found in Figure 2 b and 2 d, respectively. By referencing the temperature scale shown between Figure 2 a and 2 b and Figure 2 c and 2 d, the images clearly demonstrate both twins with cold hands and feet before warming ( Figure 2 a and 2 c). Conversely, in post-TST images, both twins displayed symmetric warming of their hands but their feet remained slightly cooler compared with other body regions ( Figure 2 b and 2 d). Figure 2 Thermoregulatory sweat test baseline and warmed (post) test twin 1 (a,b) and twin 2 (c,d), respectively. A temperature-color gauge is centered between each baseline and the warmed figure with values shown in degrees Fahrenheit. Postwarming images of twin 1 ( Figure 3 a) and twin 2 ( Figure 3 b) are shown with patchy regions of anhidrosis (in yellow) compared with the purple areas of sweat indicator powder, which demonstrated the regions where sweating occurred. Twin 1 had 53% anhidrosis but preserved sweating on the upper trunk, left abdomen, both hands, and medial legs, whereas twin 2 exhibited 50% anhidrosis and residual sweating of the upper trunk, bilateral hands, and medial legs. Figure 3 Diaphoresis patterns of twin 1 (a) and twin 2 (b) at the completion of the thermoregulatory sweat test (TST). QSWEAT results of twin 1 are shown with sweat rates of the forearm (25−50th percentile) ( Figure 4 a); proximal ( Figure 4 b) and distal leg sweat rates were each <10th percentile (abnormal for sex and age) ( Figure 4 c), and the foot was between the 10th to 25th percentile ( Figure 4 d). In addition, these abnormalities were categorized as a “latency of the sweat response” of the forearm, distal leg, and foot, as well as a “lack of recovery” of the proximal leg. Results for twin 2 showed a similar sweat response latency of the proximal leg ( Figure 5 b). Otherwise, twin 2 exhibited normal sweat volumes and rates for her age as seen for the forearm (10th−25th percentile) ( Figure 5 a), proximal leg (25th percentile) ( Figure 5 b), distal leg (25th percentile) ( Figure 5 c), and foot (50−80th percentile) ( Figure 5 d). Figure 4 Quantitative sweat rate (nanoliters per minute) of twin 1 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d). Figure 5 Quantitative sweat rate (nanoliters per minute) of twin 2 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d).', 'Case 1': 'Monozygotic female adolescent twins, aged 16 years old, were originally diagnosed in infancy with NC and found to have a 57-kb deletion of the CTNS gene, the most frequent cause of NC in Western populations. They were on cysteamine bitartrate (cystagon-immediate release) since diagnosis. Each was currently prescribed Procysbi (cysteamine-delayed release) 675 mg every 12 hours. In addition, each twin was prescribed cysteamine hydrochloride (0.44%) eye drops due to cystine crystal accumulation in the lens and cornea. Both twins were transplanted 6 years previously with kidneys from a single deceased donor source. Since that time, both twins experienced several episodes of transplant rejection, whereas twin 1 also developed Epstein-Barr virus positive posttransplant proliferative disorder. Table 1 includes clinical and medication data on the patients at the time of autonomic testing. As shown in Table 1, twin 2 exhibited a diastolic blood pressure (DBP) that exceeded the threshold for sex and height and had DBP readings 20% higher than those of twin 1. Table 1 Characteristics and medications of female monozygotic twins with nephropathic cystinosis Characteristics Twin 1 Twin 2 Age (yrs) 16 Race W Ethnicity H Wt. (kg) 43.6 46.0 Ht. (cm) 152.3 154.8 BMI percentile (for age and sex) (kg/m 2 ) 25th 40th Resting BP (mm Hg) 118/70 123/84 Measured GFR (ml/min per 1.73 m 2 ) 59.3 70.0 CKD stage 3a 2 Tacrolimus level (ng/ml) 5.5 4.5 Medications, Dose, Frequency Procysbi (cysteamine DR) 675 mg q 12 h Cysteamine HCL (0.44%) 1 gtt. OU q h while awake Amlodipine 10 mg/d Cardura 4 mg/d — Lisinopril 10 mg/d Drisdol 50,000 IU/ q 14 d — Cellcept 500 mg BID Tacrolimus 3 mg BID 2 mg BID Synthroid 137 μg/d 125 μg/d Mg oxide 400 mg BID Bactrim 400-80 40 mg 3×/wk BID, twice a day; BMI, body mass index; BP, blood pressure; CKD, chronic kidney disease; DR, delayed release; GFR, glomerular filtration rate by plasma clearance of iohexol; gtt, drops; H, Hispanic; HCL, hydrochloride; Ht., height; IU, international units; Mg, magnesium; OU, both eyes; q, every; W, white; Wt., weight. Laboratory findings (biochemical characteristics) for both twins are shown in Table 2 . Creatinine, blood urea nitrogen, and cystatin C levels were consistent with the CKD stage of each twin. Both patients also had blood drawn for measurement of their leukocyte cystine levels, which were obtained at the time of their regular laboratory tests. Those results were 1.65 and 1.90 nmol 1/2 cystine per milligram per protein for twins 1 and 2, respectively. Because the twins exhibited leukocyte cystine levels >1 nmol 1/2 cystine per milligram per protein, it indicated they had not achieved an optimal degree of substrate depletion for cystinosis patients on cysteamine therapy. This was due to incomplete adherence with their cysteamine bitartrate therapy. Table 3 lists a summary on cystinosis. Table 2 Laboratory results Results Conventional units (SI Units) Twin # Cr BUN Cystatin C Alb Phos Na K Glucose 1 1.08 (95.47) 15 (5.35) (1.25) 4.5 (45) 3.7 (1.20) 136 (136 ) 4.0 (4.0) 98 (5.44) 2 0.81 (71.60) 13 (4.64) (1.09) 4.9 (49) 3.8 (1.23) 137 (137) 4.2 (4.2) 94 (5.22) Normal reference range 0.25−1.14 mg/dl 5.0−18.0 mg/dl 0.5−1.3 mg/l (1−17 yr) 3.6−4.7 g/dl 3.0−4.8 mg/dl 134−146 mEq/l 3.7−5.7 mEq/l 60−110 mg/dl SI units normal Reference Range 22.1−100.78 mmol/l 1.78−6.43 mmol/l 0.50−1.30 mg/l 36.0−47.0 g/l 0.97−1.55 mmol/l 134−146 mmol/l 3.7−5.7 mmol/l 3.33−6.11 mmol/l Alb, albumin; BUN, blood urea nitrogen; Cr, creatinine; K, potassium; Na, sodium; Phos, phosphorus (inorganic); SI, Standard international. Table 3 Teaching points (i) Cystinosis results from a functional defect in the lysosomal-membrane exporter protein, cystinosin (CTNS), thereby resulting in failure of cystine efflux from cell lysosomes. When untreated, cystine crystals result and are deposited throughout the body, including in the cornea, retina, and most organs. (ii) Nephropathic cystinosis (NC) is often diagnosed in infancy due to the development of severe renal Fanconi syndrome with failure to thrive. Chronic electrolyte replacement is essential. (iii) Cystine accumulation is measured in leukocytes with a cystine level < 1 nmol 1/2 cystine per milligram cell protein categorized as being consistent with optimal cystine depletion. (iv) Cysteamine bitartrate is the only Food and Drug Administration−approved therapy for cystinosis and is available in immediate and delayed release formulations. (v) In NC, the 57-kb deletion has been associated with transient receptor potential vanilloid 1 (TRPV1) gene functional impairment. (vi) Long-term extra renal manifestations of NC are frequently observed and include cognitive impairment and/or delays, altered skin and/or heat sensations, abnormal temperature regulation, heat intolerance, reduced sweating, and myopathy, the latter of which may eventually contribute to respiratory failure, all suggestive of autonomic nervous system dysfunction pertinent to thermoregulation. Both twins frequently described issues with heat intolerance and photophobia secondary to corneal cystine crystal deposition, but they demonstrated consistently normal clinical neurological examination findings. We decided to complete further testing of the twins to evaluate heat intolerance and possible associated autonomic dysfunction as opposed to what may simply be avoidance of light exposure on sunny days.', 'Clinical Testing': 'During the period before testing, a directly measured glomerular filtration rate was completed on each twin using a plasma clearance of iohexol procedure. 14 The twins then underwent 3 clinical procedures at the Center for Autonomic Medicine in Pediatrics at Ann & Robert H. Lurie Children’s Hospital of Chicago (Chicago, IL). Those procedures included the head-up tilt (HUT) test to assess baroreceptor function, a thermoregulatory sweat test (TST) to measure sudomotor function, and the quantitative sweat response test (QSWEAT), which is a sudomotor axon reflex test in which responses of the local axon reflex of sweat glands to iontophoresed acetylcholine are quantitated. 15 The use of the TST and QSWEAT procedures on patients are considered to be the gold standard for clinical evaluation, because they demonstrated a 90% sensitivity for detection of small fiber neuropathy. 16 The HUT determines whether orthostatic (in)tolerance can be demonstrated and evaluates the inter-relationship of breathing, heart rate (HR), and BP while the patient transitions from a supine to an upright position and then returns to the supine position. Simply stated, a patient lays on a tilt table in a supine horizontal position for 10 to 20 minutes while baseline measurements are taken. Then, a HUT to 70° is done with measurements collected thereafter for 10 minutes. Following this, a tilt-down to a supine horizontal position occurs and is sustained for 2 minutes of additional measurements. During the TST, the core body temperature is increased slowly to 1 ° C higher than at prewarming (baseline) or a patient reaches a core temperature of 38 ° C (whichever is greater). To prepare for the procedure, sweat-indicator powder is applied to the patient’s anterior surface while lying supine on a bed. The patient is then rolled into the chamber, and it is sealed shut, while continuous surveillance and collection of all physiological measurements of the patient, chamber, and temperatures occurs. The ambient temperature is slowly increased with an average ramp rate of 5.0 °C/hour and with a relative humidity range of 35% to 45%. Finally, for the QSWEAT, the patient is placed in a supine horizontal position. Once situated, 4 quarter-sized capsules of acetylcholine are topically applied on the forearm, proximal and distal leg, and foot. An imperceivable 2-mA current is delivered over a 5-minute period, followed by a 5-minute recovery, which results in an accurate quantitation of sweat produced in small areas of the skin.'}
|
{'Testing Results': 'Figures 1 a to d represent the continuous HR and BP recordings of twin 1 ( Figure 1 a and b) and twin 2 ( Figure 1 c and d) during the HUT over the 10-second transition from a supine horizontal position to a 70° upright tilt. As seen in Figure 1 a, the HR of twin 1 exhibited a compensatory increase to a maximum of 110 beats/min at 6.9 minutes into the HUT and remained at this level until she was returned to a horizontal and/or supine position. This was a change of 52 beats/min. In Figure 1 b, a systolic BP (SBP) decline of 29.8 mm Hg can be seen at 0.3 minutes into the HUT. The BP of twin 1 recovered quickly to pre-HUT levels and remained stable thereafter throughout the 10-minute HUT. Conversely, for twin 2, HR increased by 45 to 120 beats/min and a 30-mm Hg SBP drop occurred when transitioned from a supine position to a 70° HUT ( Figure 1 c and d). In addition, the HR and SBP remained at these levels throughout the HUT until the twin returned to the supine position. Thus, both twins exhibited orthostatic tachycardia during HUT that was maintained until returning to the supine horizontal body position, which indicated a greater than average response compared with normative data. Figure 1 Head up-tilt (HUT) of twins 1 and 2 for continuous heart rate (a,c) and blood pressure recordings (b,d). For the TST, the baseline (pre-TST) for twin 1 and twin 2 are shown in Figure 2 a and 2 c, respectively, whereas postwarming period results for each twin are found in Figure 2 b and 2 d, respectively. By referencing the temperature scale shown between Figure 2 a and 2 b and Figure 2 c and 2 d, the images clearly demonstrate both twins with cold hands and feet before warming ( Figure 2 a and 2 c). Conversely, in post-TST images, both twins displayed symmetric warming of their hands but their feet remained slightly cooler compared with other body regions ( Figure 2 b and 2 d). Figure 2 Thermoregulatory sweat test baseline and warmed (post) test twin 1 (a,b) and twin 2 (c,d), respectively. A temperature-color gauge is centered between each baseline and the warmed figure with values shown in degrees Fahrenheit. Postwarming images of twin 1 ( Figure 3 a) and twin 2 ( Figure 3 b) are shown with patchy regions of anhidrosis (in yellow) compared with the purple areas of sweat indicator powder, which demonstrated the regions where sweating occurred. Twin 1 had 53% anhidrosis but preserved sweating on the upper trunk, left abdomen, both hands, and medial legs, whereas twin 2 exhibited 50% anhidrosis and residual sweating of the upper trunk, bilateral hands, and medial legs. Figure 3 Diaphoresis patterns of twin 1 (a) and twin 2 (b) at the completion of the thermoregulatory sweat test (TST). QSWEAT results of twin 1 are shown with sweat rates of the forearm (25−50th percentile) ( Figure 4 a); proximal ( Figure 4 b) and distal leg sweat rates were each <10th percentile (abnormal for sex and age) ( Figure 4 c), and the foot was between the 10th to 25th percentile ( Figure 4 d). In addition, these abnormalities were categorized as a “latency of the sweat response” of the forearm, distal leg, and foot, as well as a “lack of recovery” of the proximal leg. Results for twin 2 showed a similar sweat response latency of the proximal leg ( Figure 5 b). Otherwise, twin 2 exhibited normal sweat volumes and rates for her age as seen for the forearm (10th−25th percentile) ( Figure 5 a), proximal leg (25th percentile) ( Figure 5 b), distal leg (25th percentile) ( Figure 5 c), and foot (50−80th percentile) ( Figure 5 d). Figure 4 Quantitative sweat rate (nanoliters per minute) of twin 1 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d). Figure 5 Quantitative sweat rate (nanoliters per minute) of twin 2 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d).', 'Case 1': 'Monozygotic female adolescent twins, aged 16 years old, were originally diagnosed in infancy with NC and found to have a 57-kb deletion of the CTNS gene, the most frequent cause of NC in Western populations. They were on cysteamine bitartrate (cystagon-immediate release) since diagnosis. Each was currently prescribed Procysbi (cysteamine-delayed release) 675 mg every 12 hours. In addition, each twin was prescribed cysteamine hydrochloride (0.44%) eye drops due to cystine crystal accumulation in the lens and cornea. Both twins were transplanted 6 years previously with kidneys from a single deceased donor source. Since that time, both twins experienced several episodes of transplant rejection, whereas twin 1 also developed Epstein-Barr virus positive posttransplant proliferative disorder. Table 1 includes clinical and medication data on the patients at the time of autonomic testing. As shown in Table 1, twin 2 exhibited a diastolic blood pressure (DBP) that exceeded the threshold for sex and height and had DBP readings 20% higher than those of twin 1. Table 1 Characteristics and medications of female monozygotic twins with nephropathic cystinosis Characteristics Twin 1 Twin 2 Age (yrs) 16 Race W Ethnicity H Wt. (kg) 43.6 46.0 Ht. (cm) 152.3 154.8 BMI percentile (for age and sex) (kg/m 2 ) 25th 40th Resting BP (mm Hg) 118/70 123/84 Measured GFR (ml/min per 1.73 m 2 ) 59.3 70.0 CKD stage 3a 2 Tacrolimus level (ng/ml) 5.5 4.5 Medications, Dose, Frequency Procysbi (cysteamine DR) 675 mg q 12 h Cysteamine HCL (0.44%) 1 gtt. OU q h while awake Amlodipine 10 mg/d Cardura 4 mg/d — Lisinopril 10 mg/d Drisdol 50,000 IU/ q 14 d — Cellcept 500 mg BID Tacrolimus 3 mg BID 2 mg BID Synthroid 137 μg/d 125 μg/d Mg oxide 400 mg BID Bactrim 400-80 40 mg 3×/wk BID, twice a day; BMI, body mass index; BP, blood pressure; CKD, chronic kidney disease; DR, delayed release; GFR, glomerular filtration rate by plasma clearance of iohexol; gtt, drops; H, Hispanic; HCL, hydrochloride; Ht., height; IU, international units; Mg, magnesium; OU, both eyes; q, every; W, white; Wt., weight. Laboratory findings (biochemical characteristics) for both twins are shown in Table 2 . Creatinine, blood urea nitrogen, and cystatin C levels were consistent with the CKD stage of each twin. Both patients also had blood drawn for measurement of their leukocyte cystine levels, which were obtained at the time of their regular laboratory tests. Those results were 1.65 and 1.90 nmol 1/2 cystine per milligram per protein for twins 1 and 2, respectively. Because the twins exhibited leukocyte cystine levels >1 nmol 1/2 cystine per milligram per protein, it indicated they had not achieved an optimal degree of substrate depletion for cystinosis patients on cysteamine therapy. This was due to incomplete adherence with their cysteamine bitartrate therapy. Table 3 lists a summary on cystinosis. Table 2 Laboratory results Results Conventional units (SI Units) Twin # Cr BUN Cystatin C Alb Phos Na K Glucose 1 1.08 (95.47) 15 (5.35) (1.25) 4.5 (45) 3.7 (1.20) 136 (136 ) 4.0 (4.0) 98 (5.44) 2 0.81 (71.60) 13 (4.64) (1.09) 4.9 (49) 3.8 (1.23) 137 (137) 4.2 (4.2) 94 (5.22) Normal reference range 0.25−1.14 mg/dl 5.0−18.0 mg/dl 0.5−1.3 mg/l (1−17 yr) 3.6−4.7 g/dl 3.0−4.8 mg/dl 134−146 mEq/l 3.7−5.7 mEq/l 60−110 mg/dl SI units normal Reference Range 22.1−100.78 mmol/l 1.78−6.43 mmol/l 0.50−1.30 mg/l 36.0−47.0 g/l 0.97−1.55 mmol/l 134−146 mmol/l 3.7−5.7 mmol/l 3.33−6.11 mmol/l Alb, albumin; BUN, blood urea nitrogen; Cr, creatinine; K, potassium; Na, sodium; Phos, phosphorus (inorganic); SI, Standard international. Table 3 Teaching points (i) Cystinosis results from a functional defect in the lysosomal-membrane exporter protein, cystinosin (CTNS), thereby resulting in failure of cystine efflux from cell lysosomes. When untreated, cystine crystals result and are deposited throughout the body, including in the cornea, retina, and most organs. (ii) Nephropathic cystinosis (NC) is often diagnosed in infancy due to the development of severe renal Fanconi syndrome with failure to thrive. Chronic electrolyte replacement is essential. (iii) Cystine accumulation is measured in leukocytes with a cystine level < 1 nmol 1/2 cystine per milligram cell protein categorized as being consistent with optimal cystine depletion. (iv) Cysteamine bitartrate is the only Food and Drug Administration−approved therapy for cystinosis and is available in immediate and delayed release formulations. (v) In NC, the 57-kb deletion has been associated with transient receptor potential vanilloid 1 (TRPV1) gene functional impairment. (vi) Long-term extra renal manifestations of NC are frequently observed and include cognitive impairment and/or delays, altered skin and/or heat sensations, abnormal temperature regulation, heat intolerance, reduced sweating, and myopathy, the latter of which may eventually contribute to respiratory failure, all suggestive of autonomic nervous system dysfunction pertinent to thermoregulation. Both twins frequently described issues with heat intolerance and photophobia secondary to corneal cystine crystal deposition, but they demonstrated consistently normal clinical neurological examination findings. We decided to complete further testing of the twins to evaluate heat intolerance and possible associated autonomic dysfunction as opposed to what may simply be avoidance of light exposure on sunny days.', 'Clinical Testing': 'During the period before testing, a directly measured glomerular filtration rate was completed on each twin using a plasma clearance of iohexol procedure. 14 The twins then underwent 3 clinical procedures at the Center for Autonomic Medicine in Pediatrics at Ann & Robert H. Lurie Children’s Hospital of Chicago (Chicago, IL). Those procedures included the head-up tilt (HUT) test to assess baroreceptor function, a thermoregulatory sweat test (TST) to measure sudomotor function, and the quantitative sweat response test (QSWEAT), which is a sudomotor axon reflex test in which responses of the local axon reflex of sweat glands to iontophoresed acetylcholine are quantitated. 15 The use of the TST and QSWEAT procedures on patients are considered to be the gold standard for clinical evaluation, because they demonstrated a 90% sensitivity for detection of small fiber neuropathy. 16 The HUT determines whether orthostatic (in)tolerance can be demonstrated and evaluates the inter-relationship of breathing, heart rate (HR), and BP while the patient transitions from a supine to an upright position and then returns to the supine position. Simply stated, a patient lays on a tilt table in a supine horizontal position for 10 to 20 minutes while baseline measurements are taken. Then, a HUT to 70° is done with measurements collected thereafter for 10 minutes. Following this, a tilt-down to a supine horizontal position occurs and is sustained for 2 minutes of additional measurements. During the TST, the core body temperature is increased slowly to 1 ° C higher than at prewarming (baseline) or a patient reaches a core temperature of 38 ° C (whichever is greater). To prepare for the procedure, sweat-indicator powder is applied to the patient’s anterior surface while lying supine on a bed. The patient is then rolled into the chamber, and it is sealed shut, while continuous surveillance and collection of all physiological measurements of the patient, chamber, and temperatures occurs. The ambient temperature is slowly increased with an average ramp rate of 5.0 °C/hour and with a relative humidity range of 35% to 45%. Finally, for the QSWEAT, the patient is placed in a supine horizontal position. Once situated, 4 quarter-sized capsules of acetylcholine are topically applied on the forearm, proximal and distal leg, and foot. An imperceivable 2-mA current is delivered over a 5-minute period, followed by a 5-minute recovery, which results in an accurate quantitation of sweat produced in small areas of the skin.'}
|
Laboratory-and-Imaging
|
Lab_Image
|
[
"Measured GFR ( ml / min per 1.73 m 2 ) 59.3 70.0",
"Tacrolimus level ( ng / ml ) 5.5 4.5",
"Creatinine, blood urea nitrogen, and cystatin C levels were consistent with the CKD stage of each twin. Both patients also had blood drawn for measurement of their leukocyte cystine levels, which were obtained at the time of their regular laboratory tests. Those results were 1.65 and 1.90 nmol 1/2 cystine per milligram per protein for twins 1 and 2, respectively",
"Cr BUN Cystatin C Alb Phos Na K Glucose 1 1.08 ( 95.47 ) 15 ( 5.35 ) ( 1.25 ) 4.5 ( 45 ) 3.7 ( 1.20 ) 136 ( 136 ) 4.0 ( 4.0 ) 98 ( 5.44 ) 2 0.81 ( 71.60 ) 13 ( 4.64 ) ( 1.09 ) 4.9 ( 49 ) 3.8 ( 1.23 ) 137 ( 137 ) 4.2 ( 4.2 ) 94 ( 5.22 ) Normal reference range 0.25−1.14 mg / dl 5.0−18.0 mg / dl 0.5−1.3 mg / l ( 1−17 yr ) 3.6−4.7 g / dl 3.0−4.8 mg / dl 134−146 mEq / l 3.7−5.7 mEq / l 60−110 mg / dl SI units normal Reference Range 22.1−100.78 mmol / l 1.78−6.43 mmol / l 0.50−1.30 mg / l 36.0−47.0 g / l 0.97−1.55 mmol / l 134−146 mmol / l 3.7−5.7 mmol / l 3.33−6.11 mmol / l"
] |
6224624
|
{'Testing Results': 'Figures 1 a to d represent the continuous HR and BP recordings of twin 1 ( Figure 1 a and b) and twin 2 ( Figure 1 c and d) during the HUT over the 10-second transition from a supine horizontal position to a 70° upright tilt. As seen in Figure 1 a, the HR of twin 1 exhibited a compensatory increase to a maximum of 110 beats/min at 6.9 minutes into the HUT and remained at this level until she was returned to a horizontal and/or supine position. This was a change of 52 beats/min. In Figure 1 b, a systolic BP (SBP) decline of 29.8 mm Hg can be seen at 0.3 minutes into the HUT. The BP of twin 1 recovered quickly to pre-HUT levels and remained stable thereafter throughout the 10-minute HUT. Conversely, for twin 2, HR increased by 45 to 120 beats/min and a 30-mm Hg SBP drop occurred when transitioned from a supine position to a 70° HUT ( Figure 1 c and d). In addition, the HR and SBP remained at these levels throughout the HUT until the twin returned to the supine position. Thus, both twins exhibited orthostatic tachycardia during HUT that was maintained until returning to the supine horizontal body position, which indicated a greater than average response compared with normative data. Figure 1 Head up-tilt (HUT) of twins 1 and 2 for continuous heart rate (a,c) and blood pressure recordings (b,d). For the TST, the baseline (pre-TST) for twin 1 and twin 2 are shown in Figure 2 a and 2 c, respectively, whereas postwarming period results for each twin are found in Figure 2 b and 2 d, respectively. By referencing the temperature scale shown between Figure 2 a and 2 b and Figure 2 c and 2 d, the images clearly demonstrate both twins with cold hands and feet before warming ( Figure 2 a and 2 c). Conversely, in post-TST images, both twins displayed symmetric warming of their hands but their feet remained slightly cooler compared with other body regions ( Figure 2 b and 2 d). Figure 2 Thermoregulatory sweat test baseline and warmed (post) test twin 1 (a,b) and twin 2 (c,d), respectively. A temperature-color gauge is centered between each baseline and the warmed figure with values shown in degrees Fahrenheit. Postwarming images of twin 1 ( Figure 3 a) and twin 2 ( Figure 3 b) are shown with patchy regions of anhidrosis (in yellow) compared with the purple areas of sweat indicator powder, which demonstrated the regions where sweating occurred. Twin 1 had 53% anhidrosis but preserved sweating on the upper trunk, left abdomen, both hands, and medial legs, whereas twin 2 exhibited 50% anhidrosis and residual sweating of the upper trunk, bilateral hands, and medial legs. Figure 3 Diaphoresis patterns of twin 1 (a) and twin 2 (b) at the completion of the thermoregulatory sweat test (TST). QSWEAT results of twin 1 are shown with sweat rates of the forearm (25−50th percentile) ( Figure 4 a); proximal ( Figure 4 b) and distal leg sweat rates were each <10th percentile (abnormal for sex and age) ( Figure 4 c), and the foot was between the 10th to 25th percentile ( Figure 4 d). In addition, these abnormalities were categorized as a “latency of the sweat response” of the forearm, distal leg, and foot, as well as a “lack of recovery” of the proximal leg. Results for twin 2 showed a similar sweat response latency of the proximal leg ( Figure 5 b). Otherwise, twin 2 exhibited normal sweat volumes and rates for her age as seen for the forearm (10th−25th percentile) ( Figure 5 a), proximal leg (25th percentile) ( Figure 5 b), distal leg (25th percentile) ( Figure 5 c), and foot (50−80th percentile) ( Figure 5 d). Figure 4 Quantitative sweat rate (nanoliters per minute) of twin 1 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d). Figure 5 Quantitative sweat rate (nanoliters per minute) of twin 2 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d).', 'Case 1': 'Monozygotic female adolescent twins, aged 16 years old, were originally diagnosed in infancy with NC and found to have a 57-kb deletion of the CTNS gene, the most frequent cause of NC in Western populations. They were on cysteamine bitartrate (cystagon-immediate release) since diagnosis. Each was currently prescribed Procysbi (cysteamine-delayed release) 675 mg every 12 hours. In addition, each twin was prescribed cysteamine hydrochloride (0.44%) eye drops due to cystine crystal accumulation in the lens and cornea. Both twins were transplanted 6 years previously with kidneys from a single deceased donor source. Since that time, both twins experienced several episodes of transplant rejection, whereas twin 1 also developed Epstein-Barr virus positive posttransplant proliferative disorder. Table 1 includes clinical and medication data on the patients at the time of autonomic testing. As shown in Table 1, twin 2 exhibited a diastolic blood pressure (DBP) that exceeded the threshold for sex and height and had DBP readings 20% higher than those of twin 1. Table 1 Characteristics and medications of female monozygotic twins with nephropathic cystinosis Characteristics Twin 1 Twin 2 Age (yrs) 16 Race W Ethnicity H Wt. (kg) 43.6 46.0 Ht. (cm) 152.3 154.8 BMI percentile (for age and sex) (kg/m 2 ) 25th 40th Resting BP (mm Hg) 118/70 123/84 Measured GFR (ml/min per 1.73 m 2 ) 59.3 70.0 CKD stage 3a 2 Tacrolimus level (ng/ml) 5.5 4.5 Medications, Dose, Frequency Procysbi (cysteamine DR) 675 mg q 12 h Cysteamine HCL (0.44%) 1 gtt. OU q h while awake Amlodipine 10 mg/d Cardura 4 mg/d — Lisinopril 10 mg/d Drisdol 50,000 IU/ q 14 d — Cellcept 500 mg BID Tacrolimus 3 mg BID 2 mg BID Synthroid 137 μg/d 125 μg/d Mg oxide 400 mg BID Bactrim 400-80 40 mg 3×/wk BID, twice a day; BMI, body mass index; BP, blood pressure; CKD, chronic kidney disease; DR, delayed release; GFR, glomerular filtration rate by plasma clearance of iohexol; gtt, drops; H, Hispanic; HCL, hydrochloride; Ht., height; IU, international units; Mg, magnesium; OU, both eyes; q, every; W, white; Wt., weight. Laboratory findings (biochemical characteristics) for both twins are shown in Table 2 . Creatinine, blood urea nitrogen, and cystatin C levels were consistent with the CKD stage of each twin. Both patients also had blood drawn for measurement of their leukocyte cystine levels, which were obtained at the time of their regular laboratory tests. Those results were 1.65 and 1.90 nmol 1/2 cystine per milligram per protein for twins 1 and 2, respectively. Because the twins exhibited leukocyte cystine levels >1 nmol 1/2 cystine per milligram per protein, it indicated they had not achieved an optimal degree of substrate depletion for cystinosis patients on cysteamine therapy. This was due to incomplete adherence with their cysteamine bitartrate therapy. Table 3 lists a summary on cystinosis. Table 2 Laboratory results Results Conventional units (SI Units) Twin # Cr BUN Cystatin C Alb Phos Na K Glucose 1 1.08 (95.47) 15 (5.35) (1.25) 4.5 (45) 3.7 (1.20) 136 (136 ) 4.0 (4.0) 98 (5.44) 2 0.81 (71.60) 13 (4.64) (1.09) 4.9 (49) 3.8 (1.23) 137 (137) 4.2 (4.2) 94 (5.22) Normal reference range 0.25−1.14 mg/dl 5.0−18.0 mg/dl 0.5−1.3 mg/l (1−17 yr) 3.6−4.7 g/dl 3.0−4.8 mg/dl 134−146 mEq/l 3.7−5.7 mEq/l 60−110 mg/dl SI units normal Reference Range 22.1−100.78 mmol/l 1.78−6.43 mmol/l 0.50−1.30 mg/l 36.0−47.0 g/l 0.97−1.55 mmol/l 134−146 mmol/l 3.7−5.7 mmol/l 3.33−6.11 mmol/l Alb, albumin; BUN, blood urea nitrogen; Cr, creatinine; K, potassium; Na, sodium; Phos, phosphorus (inorganic); SI, Standard international. Table 3 Teaching points (i) Cystinosis results from a functional defect in the lysosomal-membrane exporter protein, cystinosin (CTNS), thereby resulting in failure of cystine efflux from cell lysosomes. When untreated, cystine crystals result and are deposited throughout the body, including in the cornea, retina, and most organs. (ii) Nephropathic cystinosis (NC) is often diagnosed in infancy due to the development of severe renal Fanconi syndrome with failure to thrive. Chronic electrolyte replacement is essential. (iii) Cystine accumulation is measured in leukocytes with a cystine level < 1 nmol 1/2 cystine per milligram cell protein categorized as being consistent with optimal cystine depletion. (iv) Cysteamine bitartrate is the only Food and Drug Administration−approved therapy for cystinosis and is available in immediate and delayed release formulations. (v) In NC, the 57-kb deletion has been associated with transient receptor potential vanilloid 1 (TRPV1) gene functional impairment. (vi) Long-term extra renal manifestations of NC are frequently observed and include cognitive impairment and/or delays, altered skin and/or heat sensations, abnormal temperature regulation, heat intolerance, reduced sweating, and myopathy, the latter of which may eventually contribute to respiratory failure, all suggestive of autonomic nervous system dysfunction pertinent to thermoregulation. Both twins frequently described issues with heat intolerance and photophobia secondary to corneal cystine crystal deposition, but they demonstrated consistently normal clinical neurological examination findings. We decided to complete further testing of the twins to evaluate heat intolerance and possible associated autonomic dysfunction as opposed to what may simply be avoidance of light exposure on sunny days.', 'Clinical Testing': 'During the period before testing, a directly measured glomerular filtration rate was completed on each twin using a plasma clearance of iohexol procedure. 14 The twins then underwent 3 clinical procedures at the Center for Autonomic Medicine in Pediatrics at Ann & Robert H. Lurie Children’s Hospital of Chicago (Chicago, IL). Those procedures included the head-up tilt (HUT) test to assess baroreceptor function, a thermoregulatory sweat test (TST) to measure sudomotor function, and the quantitative sweat response test (QSWEAT), which is a sudomotor axon reflex test in which responses of the local axon reflex of sweat glands to iontophoresed acetylcholine are quantitated. 15 The use of the TST and QSWEAT procedures on patients are considered to be the gold standard for clinical evaluation, because they demonstrated a 90% sensitivity for detection of small fiber neuropathy. 16 The HUT determines whether orthostatic (in)tolerance can be demonstrated and evaluates the inter-relationship of breathing, heart rate (HR), and BP while the patient transitions from a supine to an upright position and then returns to the supine position. Simply stated, a patient lays on a tilt table in a supine horizontal position for 10 to 20 minutes while baseline measurements are taken. Then, a HUT to 70° is done with measurements collected thereafter for 10 minutes. Following this, a tilt-down to a supine horizontal position occurs and is sustained for 2 minutes of additional measurements. During the TST, the core body temperature is increased slowly to 1 ° C higher than at prewarming (baseline) or a patient reaches a core temperature of 38 ° C (whichever is greater). To prepare for the procedure, sweat-indicator powder is applied to the patient’s anterior surface while lying supine on a bed. The patient is then rolled into the chamber, and it is sealed shut, while continuous surveillance and collection of all physiological measurements of the patient, chamber, and temperatures occurs. The ambient temperature is slowly increased with an average ramp rate of 5.0 °C/hour and with a relative humidity range of 35% to 45%. Finally, for the QSWEAT, the patient is placed in a supine horizontal position. Once situated, 4 quarter-sized capsules of acetylcholine are topically applied on the forearm, proximal and distal leg, and foot. An imperceivable 2-mA current is delivered over a 5-minute period, followed by a 5-minute recovery, which results in an accurate quantitation of sweat produced in small areas of the skin.'}
|
{'Testing Results': 'Figures 1 a to d represent the continuous HR and BP recordings of twin 1 ( Figure 1 a and b) and twin 2 ( Figure 1 c and d) during the HUT over the 10-second transition from a supine horizontal position to a 70° upright tilt. As seen in Figure 1 a, the HR of twin 1 exhibited a compensatory increase to a maximum of 110 beats/min at 6.9 minutes into the HUT and remained at this level until she was returned to a horizontal and/or supine position. This was a change of 52 beats/min. In Figure 1 b, a systolic BP (SBP) decline of 29.8 mm Hg can be seen at 0.3 minutes into the HUT. The BP of twin 1 recovered quickly to pre-HUT levels and remained stable thereafter throughout the 10-minute HUT. Conversely, for twin 2, HR increased by 45 to 120 beats/min and a 30-mm Hg SBP drop occurred when transitioned from a supine position to a 70° HUT ( Figure 1 c and d). In addition, the HR and SBP remained at these levels throughout the HUT until the twin returned to the supine position. Thus, both twins exhibited orthostatic tachycardia during HUT that was maintained until returning to the supine horizontal body position, which indicated a greater than average response compared with normative data. Figure 1 Head up-tilt (HUT) of twins 1 and 2 for continuous heart rate (a,c) and blood pressure recordings (b,d). For the TST, the baseline (pre-TST) for twin 1 and twin 2 are shown in Figure 2 a and 2 c, respectively, whereas postwarming period results for each twin are found in Figure 2 b and 2 d, respectively. By referencing the temperature scale shown between Figure 2 a and 2 b and Figure 2 c and 2 d, the images clearly demonstrate both twins with cold hands and feet before warming ( Figure 2 a and 2 c). Conversely, in post-TST images, both twins displayed symmetric warming of their hands but their feet remained slightly cooler compared with other body regions ( Figure 2 b and 2 d). Figure 2 Thermoregulatory sweat test baseline and warmed (post) test twin 1 (a,b) and twin 2 (c,d), respectively. A temperature-color gauge is centered between each baseline and the warmed figure with values shown in degrees Fahrenheit. Postwarming images of twin 1 ( Figure 3 a) and twin 2 ( Figure 3 b) are shown with patchy regions of anhidrosis (in yellow) compared with the purple areas of sweat indicator powder, which demonstrated the regions where sweating occurred. Twin 1 had 53% anhidrosis but preserved sweating on the upper trunk, left abdomen, both hands, and medial legs, whereas twin 2 exhibited 50% anhidrosis and residual sweating of the upper trunk, bilateral hands, and medial legs. Figure 3 Diaphoresis patterns of twin 1 (a) and twin 2 (b) at the completion of the thermoregulatory sweat test (TST). QSWEAT results of twin 1 are shown with sweat rates of the forearm (25−50th percentile) ( Figure 4 a); proximal ( Figure 4 b) and distal leg sweat rates were each <10th percentile (abnormal for sex and age) ( Figure 4 c), and the foot was between the 10th to 25th percentile ( Figure 4 d). In addition, these abnormalities were categorized as a “latency of the sweat response” of the forearm, distal leg, and foot, as well as a “lack of recovery” of the proximal leg. Results for twin 2 showed a similar sweat response latency of the proximal leg ( Figure 5 b). Otherwise, twin 2 exhibited normal sweat volumes and rates for her age as seen for the forearm (10th−25th percentile) ( Figure 5 a), proximal leg (25th percentile) ( Figure 5 b), distal leg (25th percentile) ( Figure 5 c), and foot (50−80th percentile) ( Figure 5 d). Figure 4 Quantitative sweat rate (nanoliters per minute) of twin 1 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d). Figure 5 Quantitative sweat rate (nanoliters per minute) of twin 2 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d).', 'Case 1': 'Monozygotic female adolescent twins, aged 16 years old, were originally diagnosed in infancy with NC and found to have a 57-kb deletion of the CTNS gene, the most frequent cause of NC in Western populations. They were on cysteamine bitartrate (cystagon-immediate release) since diagnosis. Each was currently prescribed Procysbi (cysteamine-delayed release) 675 mg every 12 hours. In addition, each twin was prescribed cysteamine hydrochloride (0.44%) eye drops due to cystine crystal accumulation in the lens and cornea. Both twins were transplanted 6 years previously with kidneys from a single deceased donor source. Since that time, both twins experienced several episodes of transplant rejection, whereas twin 1 also developed Epstein-Barr virus positive posttransplant proliferative disorder. Table 1 includes clinical and medication data on the patients at the time of autonomic testing. As shown in Table 1, twin 2 exhibited a diastolic blood pressure (DBP) that exceeded the threshold for sex and height and had DBP readings 20% higher than those of twin 1. Table 1 Characteristics and medications of female monozygotic twins with nephropathic cystinosis Characteristics Twin 1 Twin 2 Age (yrs) 16 Race W Ethnicity H Wt. (kg) 43.6 46.0 Ht. (cm) 152.3 154.8 BMI percentile (for age and sex) (kg/m 2 ) 25th 40th Resting BP (mm Hg) 118/70 123/84 Measured GFR (ml/min per 1.73 m 2 ) 59.3 70.0 CKD stage 3a 2 Tacrolimus level (ng/ml) 5.5 4.5 Medications, Dose, Frequency Procysbi (cysteamine DR) 675 mg q 12 h Cysteamine HCL (0.44%) 1 gtt. OU q h while awake Amlodipine 10 mg/d Cardura 4 mg/d — Lisinopril 10 mg/d Drisdol 50,000 IU/ q 14 d — Cellcept 500 mg BID Tacrolimus 3 mg BID 2 mg BID Synthroid 137 μg/d 125 μg/d Mg oxide 400 mg BID Bactrim 400-80 40 mg 3×/wk BID, twice a day; BMI, body mass index; BP, blood pressure; CKD, chronic kidney disease; DR, delayed release; GFR, glomerular filtration rate by plasma clearance of iohexol; gtt, drops; H, Hispanic; HCL, hydrochloride; Ht., height; IU, international units; Mg, magnesium; OU, both eyes; q, every; W, white; Wt., weight. Laboratory findings (biochemical characteristics) for both twins are shown in Table 2 . Creatinine, blood urea nitrogen, and cystatin C levels were consistent with the CKD stage of each twin. Both patients also had blood drawn for measurement of their leukocyte cystine levels, which were obtained at the time of their regular laboratory tests. Those results were 1.65 and 1.90 nmol 1/2 cystine per milligram per protein for twins 1 and 2, respectively. Because the twins exhibited leukocyte cystine levels >1 nmol 1/2 cystine per milligram per protein, it indicated they had not achieved an optimal degree of substrate depletion for cystinosis patients on cysteamine therapy. This was due to incomplete adherence with their cysteamine bitartrate therapy. Table 3 lists a summary on cystinosis. Table 2 Laboratory results Results Conventional units (SI Units) Twin # Cr BUN Cystatin C Alb Phos Na K Glucose 1 1.08 (95.47) 15 (5.35) (1.25) 4.5 (45) 3.7 (1.20) 136 (136 ) 4.0 (4.0) 98 (5.44) 2 0.81 (71.60) 13 (4.64) (1.09) 4.9 (49) 3.8 (1.23) 137 (137) 4.2 (4.2) 94 (5.22) Normal reference range 0.25−1.14 mg/dl 5.0−18.0 mg/dl 0.5−1.3 mg/l (1−17 yr) 3.6−4.7 g/dl 3.0−4.8 mg/dl 134−146 mEq/l 3.7−5.7 mEq/l 60−110 mg/dl SI units normal Reference Range 22.1−100.78 mmol/l 1.78−6.43 mmol/l 0.50−1.30 mg/l 36.0−47.0 g/l 0.97−1.55 mmol/l 134−146 mmol/l 3.7−5.7 mmol/l 3.33−6.11 mmol/l Alb, albumin; BUN, blood urea nitrogen; Cr, creatinine; K, potassium; Na, sodium; Phos, phosphorus (inorganic); SI, Standard international. Table 3 Teaching points (i) Cystinosis results from a functional defect in the lysosomal-membrane exporter protein, cystinosin (CTNS), thereby resulting in failure of cystine efflux from cell lysosomes. When untreated, cystine crystals result and are deposited throughout the body, including in the cornea, retina, and most organs. (ii) Nephropathic cystinosis (NC) is often diagnosed in infancy due to the development of severe renal Fanconi syndrome with failure to thrive. Chronic electrolyte replacement is essential. (iii) Cystine accumulation is measured in leukocytes with a cystine level < 1 nmol 1/2 cystine per milligram cell protein categorized as being consistent with optimal cystine depletion. (iv) Cysteamine bitartrate is the only Food and Drug Administration−approved therapy for cystinosis and is available in immediate and delayed release formulations. (v) In NC, the 57-kb deletion has been associated with transient receptor potential vanilloid 1 (TRPV1) gene functional impairment. (vi) Long-term extra renal manifestations of NC are frequently observed and include cognitive impairment and/or delays, altered skin and/or heat sensations, abnormal temperature regulation, heat intolerance, reduced sweating, and myopathy, the latter of which may eventually contribute to respiratory failure, all suggestive of autonomic nervous system dysfunction pertinent to thermoregulation. Both twins frequently described issues with heat intolerance and photophobia secondary to corneal cystine crystal deposition, but they demonstrated consistently normal clinical neurological examination findings. We decided to complete further testing of the twins to evaluate heat intolerance and possible associated autonomic dysfunction as opposed to what may simply be avoidance of light exposure on sunny days.', 'Clinical Testing': 'During the period before testing, a directly measured glomerular filtration rate was completed on each twin using a plasma clearance of iohexol procedure. 14 The twins then underwent 3 clinical procedures at the Center for Autonomic Medicine in Pediatrics at Ann & Robert H. Lurie Children’s Hospital of Chicago (Chicago, IL). Those procedures included the head-up tilt (HUT) test to assess baroreceptor function, a thermoregulatory sweat test (TST) to measure sudomotor function, and the quantitative sweat response test (QSWEAT), which is a sudomotor axon reflex test in which responses of the local axon reflex of sweat glands to iontophoresed acetylcholine are quantitated. 15 The use of the TST and QSWEAT procedures on patients are considered to be the gold standard for clinical evaluation, because they demonstrated a 90% sensitivity for detection of small fiber neuropathy. 16 The HUT determines whether orthostatic (in)tolerance can be demonstrated and evaluates the inter-relationship of breathing, heart rate (HR), and BP while the patient transitions from a supine to an upright position and then returns to the supine position. Simply stated, a patient lays on a tilt table in a supine horizontal position for 10 to 20 minutes while baseline measurements are taken. Then, a HUT to 70° is done with measurements collected thereafter for 10 minutes. Following this, a tilt-down to a supine horizontal position occurs and is sustained for 2 minutes of additional measurements. During the TST, the core body temperature is increased slowly to 1 ° C higher than at prewarming (baseline) or a patient reaches a core temperature of 38 ° C (whichever is greater). To prepare for the procedure, sweat-indicator powder is applied to the patient’s anterior surface while lying supine on a bed. The patient is then rolled into the chamber, and it is sealed shut, while continuous surveillance and collection of all physiological measurements of the patient, chamber, and temperatures occurs. The ambient temperature is slowly increased with an average ramp rate of 5.0 °C/hour and with a relative humidity range of 35% to 45%. Finally, for the QSWEAT, the patient is placed in a supine horizontal position. Once situated, 4 quarter-sized capsules of acetylcholine are topically applied on the forearm, proximal and distal leg, and foot. An imperceivable 2-mA current is delivered over a 5-minute period, followed by a 5-minute recovery, which results in an accurate quantitation of sweat produced in small areas of the skin.'}
|
Cardiovascular-System
|
CVS
|
[
"HR of twin 1 exhibited a compensatory increase to a maximum of 110 beats / min at 6.9 minutes into the HUT and remained at this level until she was returned to a horizontal and/or supine position. This was a change of 52 beats / min. In Figure 1 b, a systolic BP ( SBP ) decline of 29.8 mm Hg can be seen at 0.3 minutes into the HUT. The BP of twin 1 recovered quickly to pre - HUT levels and remained stable thereafter throughout the 10 - minute HUT. Conversely, for twin 2, HR increased by 45 to 120 beats / min and a 30 - mm Hg SBP drop occurred when transitioned from a supine position to a 70 ° HUT ( Figure 1 c and d ). In addition, the HR and SBP remained at these levels throughout the HUT until the twin returned to the supine position. Thus, both twins exhibited orthostatic tachycardia during HUT that was maintained until returning to the supine horizontal body position, which indicated a greater than average response compared with normative data",
"cold hands and feet before warming",
"symmetric warming of their hands but their feet remained slightly cooler",
"twin 2 exhibited a diastolic blood pressure ( DBP ) that exceeded the threshold for sex and height and had DBP readings 20 % higher than those of twin 1.",
"heat intolerance"
] |
6224624
|
{'Testing Results': 'Figures 1 a to d represent the continuous HR and BP recordings of twin 1 ( Figure 1 a and b) and twin 2 ( Figure 1 c and d) during the HUT over the 10-second transition from a supine horizontal position to a 70° upright tilt. As seen in Figure 1 a, the HR of twin 1 exhibited a compensatory increase to a maximum of 110 beats/min at 6.9 minutes into the HUT and remained at this level until she was returned to a horizontal and/or supine position. This was a change of 52 beats/min. In Figure 1 b, a systolic BP (SBP) decline of 29.8 mm Hg can be seen at 0.3 minutes into the HUT. The BP of twin 1 recovered quickly to pre-HUT levels and remained stable thereafter throughout the 10-minute HUT. Conversely, for twin 2, HR increased by 45 to 120 beats/min and a 30-mm Hg SBP drop occurred when transitioned from a supine position to a 70° HUT ( Figure 1 c and d). In addition, the HR and SBP remained at these levels throughout the HUT until the twin returned to the supine position. Thus, both twins exhibited orthostatic tachycardia during HUT that was maintained until returning to the supine horizontal body position, which indicated a greater than average response compared with normative data. Figure 1 Head up-tilt (HUT) of twins 1 and 2 for continuous heart rate (a,c) and blood pressure recordings (b,d). For the TST, the baseline (pre-TST) for twin 1 and twin 2 are shown in Figure 2 a and 2 c, respectively, whereas postwarming period results for each twin are found in Figure 2 b and 2 d, respectively. By referencing the temperature scale shown between Figure 2 a and 2 b and Figure 2 c and 2 d, the images clearly demonstrate both twins with cold hands and feet before warming ( Figure 2 a and 2 c). Conversely, in post-TST images, both twins displayed symmetric warming of their hands but their feet remained slightly cooler compared with other body regions ( Figure 2 b and 2 d). Figure 2 Thermoregulatory sweat test baseline and warmed (post) test twin 1 (a,b) and twin 2 (c,d), respectively. A temperature-color gauge is centered between each baseline and the warmed figure with values shown in degrees Fahrenheit. Postwarming images of twin 1 ( Figure 3 a) and twin 2 ( Figure 3 b) are shown with patchy regions of anhidrosis (in yellow) compared with the purple areas of sweat indicator powder, which demonstrated the regions where sweating occurred. Twin 1 had 53% anhidrosis but preserved sweating on the upper trunk, left abdomen, both hands, and medial legs, whereas twin 2 exhibited 50% anhidrosis and residual sweating of the upper trunk, bilateral hands, and medial legs. Figure 3 Diaphoresis patterns of twin 1 (a) and twin 2 (b) at the completion of the thermoregulatory sweat test (TST). QSWEAT results of twin 1 are shown with sweat rates of the forearm (25−50th percentile) ( Figure 4 a); proximal ( Figure 4 b) and distal leg sweat rates were each <10th percentile (abnormal for sex and age) ( Figure 4 c), and the foot was between the 10th to 25th percentile ( Figure 4 d). In addition, these abnormalities were categorized as a “latency of the sweat response” of the forearm, distal leg, and foot, as well as a “lack of recovery” of the proximal leg. Results for twin 2 showed a similar sweat response latency of the proximal leg ( Figure 5 b). Otherwise, twin 2 exhibited normal sweat volumes and rates for her age as seen for the forearm (10th−25th percentile) ( Figure 5 a), proximal leg (25th percentile) ( Figure 5 b), distal leg (25th percentile) ( Figure 5 c), and foot (50−80th percentile) ( Figure 5 d). Figure 4 Quantitative sweat rate (nanoliters per minute) of twin 1 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d). Figure 5 Quantitative sweat rate (nanoliters per minute) of twin 2 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d).', 'Case 1': 'Monozygotic female adolescent twins, aged 16 years old, were originally diagnosed in infancy with NC and found to have a 57-kb deletion of the CTNS gene, the most frequent cause of NC in Western populations. They were on cysteamine bitartrate (cystagon-immediate release) since diagnosis. Each was currently prescribed Procysbi (cysteamine-delayed release) 675 mg every 12 hours. In addition, each twin was prescribed cysteamine hydrochloride (0.44%) eye drops due to cystine crystal accumulation in the lens and cornea. Both twins were transplanted 6 years previously with kidneys from a single deceased donor source. Since that time, both twins experienced several episodes of transplant rejection, whereas twin 1 also developed Epstein-Barr virus positive posttransplant proliferative disorder. Table 1 includes clinical and medication data on the patients at the time of autonomic testing. As shown in Table 1, twin 2 exhibited a diastolic blood pressure (DBP) that exceeded the threshold for sex and height and had DBP readings 20% higher than those of twin 1. Table 1 Characteristics and medications of female monozygotic twins with nephropathic cystinosis Characteristics Twin 1 Twin 2 Age (yrs) 16 Race W Ethnicity H Wt. (kg) 43.6 46.0 Ht. (cm) 152.3 154.8 BMI percentile (for age and sex) (kg/m 2 ) 25th 40th Resting BP (mm Hg) 118/70 123/84 Measured GFR (ml/min per 1.73 m 2 ) 59.3 70.0 CKD stage 3a 2 Tacrolimus level (ng/ml) 5.5 4.5 Medications, Dose, Frequency Procysbi (cysteamine DR) 675 mg q 12 h Cysteamine HCL (0.44%) 1 gtt. OU q h while awake Amlodipine 10 mg/d Cardura 4 mg/d — Lisinopril 10 mg/d Drisdol 50,000 IU/ q 14 d — Cellcept 500 mg BID Tacrolimus 3 mg BID 2 mg BID Synthroid 137 μg/d 125 μg/d Mg oxide 400 mg BID Bactrim 400-80 40 mg 3×/wk BID, twice a day; BMI, body mass index; BP, blood pressure; CKD, chronic kidney disease; DR, delayed release; GFR, glomerular filtration rate by plasma clearance of iohexol; gtt, drops; H, Hispanic; HCL, hydrochloride; Ht., height; IU, international units; Mg, magnesium; OU, both eyes; q, every; W, white; Wt., weight. Laboratory findings (biochemical characteristics) for both twins are shown in Table 2 . Creatinine, blood urea nitrogen, and cystatin C levels were consistent with the CKD stage of each twin. Both patients also had blood drawn for measurement of their leukocyte cystine levels, which were obtained at the time of their regular laboratory tests. Those results were 1.65 and 1.90 nmol 1/2 cystine per milligram per protein for twins 1 and 2, respectively. Because the twins exhibited leukocyte cystine levels >1 nmol 1/2 cystine per milligram per protein, it indicated they had not achieved an optimal degree of substrate depletion for cystinosis patients on cysteamine therapy. This was due to incomplete adherence with their cysteamine bitartrate therapy. Table 3 lists a summary on cystinosis. Table 2 Laboratory results Results Conventional units (SI Units) Twin # Cr BUN Cystatin C Alb Phos Na K Glucose 1 1.08 (95.47) 15 (5.35) (1.25) 4.5 (45) 3.7 (1.20) 136 (136 ) 4.0 (4.0) 98 (5.44) 2 0.81 (71.60) 13 (4.64) (1.09) 4.9 (49) 3.8 (1.23) 137 (137) 4.2 (4.2) 94 (5.22) Normal reference range 0.25−1.14 mg/dl 5.0−18.0 mg/dl 0.5−1.3 mg/l (1−17 yr) 3.6−4.7 g/dl 3.0−4.8 mg/dl 134−146 mEq/l 3.7−5.7 mEq/l 60−110 mg/dl SI units normal Reference Range 22.1−100.78 mmol/l 1.78−6.43 mmol/l 0.50−1.30 mg/l 36.0−47.0 g/l 0.97−1.55 mmol/l 134−146 mmol/l 3.7−5.7 mmol/l 3.33−6.11 mmol/l Alb, albumin; BUN, blood urea nitrogen; Cr, creatinine; K, potassium; Na, sodium; Phos, phosphorus (inorganic); SI, Standard international. Table 3 Teaching points (i) Cystinosis results from a functional defect in the lysosomal-membrane exporter protein, cystinosin (CTNS), thereby resulting in failure of cystine efflux from cell lysosomes. When untreated, cystine crystals result and are deposited throughout the body, including in the cornea, retina, and most organs. (ii) Nephropathic cystinosis (NC) is often diagnosed in infancy due to the development of severe renal Fanconi syndrome with failure to thrive. Chronic electrolyte replacement is essential. (iii) Cystine accumulation is measured in leukocytes with a cystine level < 1 nmol 1/2 cystine per milligram cell protein categorized as being consistent with optimal cystine depletion. (iv) Cysteamine bitartrate is the only Food and Drug Administration−approved therapy for cystinosis and is available in immediate and delayed release formulations. (v) In NC, the 57-kb deletion has been associated with transient receptor potential vanilloid 1 (TRPV1) gene functional impairment. (vi) Long-term extra renal manifestations of NC are frequently observed and include cognitive impairment and/or delays, altered skin and/or heat sensations, abnormal temperature regulation, heat intolerance, reduced sweating, and myopathy, the latter of which may eventually contribute to respiratory failure, all suggestive of autonomic nervous system dysfunction pertinent to thermoregulation. Both twins frequently described issues with heat intolerance and photophobia secondary to corneal cystine crystal deposition, but they demonstrated consistently normal clinical neurological examination findings. We decided to complete further testing of the twins to evaluate heat intolerance and possible associated autonomic dysfunction as opposed to what may simply be avoidance of light exposure on sunny days.', 'Clinical Testing': 'During the period before testing, a directly measured glomerular filtration rate was completed on each twin using a plasma clearance of iohexol procedure. 14 The twins then underwent 3 clinical procedures at the Center for Autonomic Medicine in Pediatrics at Ann & Robert H. Lurie Children’s Hospital of Chicago (Chicago, IL). Those procedures included the head-up tilt (HUT) test to assess baroreceptor function, a thermoregulatory sweat test (TST) to measure sudomotor function, and the quantitative sweat response test (QSWEAT), which is a sudomotor axon reflex test in which responses of the local axon reflex of sweat glands to iontophoresed acetylcholine are quantitated. 15 The use of the TST and QSWEAT procedures on patients are considered to be the gold standard for clinical evaluation, because they demonstrated a 90% sensitivity for detection of small fiber neuropathy. 16 The HUT determines whether orthostatic (in)tolerance can be demonstrated and evaluates the inter-relationship of breathing, heart rate (HR), and BP while the patient transitions from a supine to an upright position and then returns to the supine position. Simply stated, a patient lays on a tilt table in a supine horizontal position for 10 to 20 minutes while baseline measurements are taken. Then, a HUT to 70° is done with measurements collected thereafter for 10 minutes. Following this, a tilt-down to a supine horizontal position occurs and is sustained for 2 minutes of additional measurements. During the TST, the core body temperature is increased slowly to 1 ° C higher than at prewarming (baseline) or a patient reaches a core temperature of 38 ° C (whichever is greater). To prepare for the procedure, sweat-indicator powder is applied to the patient’s anterior surface while lying supine on a bed. The patient is then rolled into the chamber, and it is sealed shut, while continuous surveillance and collection of all physiological measurements of the patient, chamber, and temperatures occurs. The ambient temperature is slowly increased with an average ramp rate of 5.0 °C/hour and with a relative humidity range of 35% to 45%. Finally, for the QSWEAT, the patient is placed in a supine horizontal position. Once situated, 4 quarter-sized capsules of acetylcholine are topically applied on the forearm, proximal and distal leg, and foot. An imperceivable 2-mA current is delivered over a 5-minute period, followed by a 5-minute recovery, which results in an accurate quantitation of sweat produced in small areas of the skin.'}
|
{'Testing Results': 'Figures 1 a to d represent the continuous HR and BP recordings of twin 1 ( Figure 1 a and b) and twin 2 ( Figure 1 c and d) during the HUT over the 10-second transition from a supine horizontal position to a 70° upright tilt. As seen in Figure 1 a, the HR of twin 1 exhibited a compensatory increase to a maximum of 110 beats/min at 6.9 minutes into the HUT and remained at this level until she was returned to a horizontal and/or supine position. This was a change of 52 beats/min. In Figure 1 b, a systolic BP (SBP) decline of 29.8 mm Hg can be seen at 0.3 minutes into the HUT. The BP of twin 1 recovered quickly to pre-HUT levels and remained stable thereafter throughout the 10-minute HUT. Conversely, for twin 2, HR increased by 45 to 120 beats/min and a 30-mm Hg SBP drop occurred when transitioned from a supine position to a 70° HUT ( Figure 1 c and d). In addition, the HR and SBP remained at these levels throughout the HUT until the twin returned to the supine position. Thus, both twins exhibited orthostatic tachycardia during HUT that was maintained until returning to the supine horizontal body position, which indicated a greater than average response compared with normative data. Figure 1 Head up-tilt (HUT) of twins 1 and 2 for continuous heart rate (a,c) and blood pressure recordings (b,d). For the TST, the baseline (pre-TST) for twin 1 and twin 2 are shown in Figure 2 a and 2 c, respectively, whereas postwarming period results for each twin are found in Figure 2 b and 2 d, respectively. By referencing the temperature scale shown between Figure 2 a and 2 b and Figure 2 c and 2 d, the images clearly demonstrate both twins with cold hands and feet before warming ( Figure 2 a and 2 c). Conversely, in post-TST images, both twins displayed symmetric warming of their hands but their feet remained slightly cooler compared with other body regions ( Figure 2 b and 2 d). Figure 2 Thermoregulatory sweat test baseline and warmed (post) test twin 1 (a,b) and twin 2 (c,d), respectively. A temperature-color gauge is centered between each baseline and the warmed figure with values shown in degrees Fahrenheit. Postwarming images of twin 1 ( Figure 3 a) and twin 2 ( Figure 3 b) are shown with patchy regions of anhidrosis (in yellow) compared with the purple areas of sweat indicator powder, which demonstrated the regions where sweating occurred. Twin 1 had 53% anhidrosis but preserved sweating on the upper trunk, left abdomen, both hands, and medial legs, whereas twin 2 exhibited 50% anhidrosis and residual sweating of the upper trunk, bilateral hands, and medial legs. Figure 3 Diaphoresis patterns of twin 1 (a) and twin 2 (b) at the completion of the thermoregulatory sweat test (TST). QSWEAT results of twin 1 are shown with sweat rates of the forearm (25−50th percentile) ( Figure 4 a); proximal ( Figure 4 b) and distal leg sweat rates were each <10th percentile (abnormal for sex and age) ( Figure 4 c), and the foot was between the 10th to 25th percentile ( Figure 4 d). In addition, these abnormalities were categorized as a “latency of the sweat response” of the forearm, distal leg, and foot, as well as a “lack of recovery” of the proximal leg. Results for twin 2 showed a similar sweat response latency of the proximal leg ( Figure 5 b). Otherwise, twin 2 exhibited normal sweat volumes and rates for her age as seen for the forearm (10th−25th percentile) ( Figure 5 a), proximal leg (25th percentile) ( Figure 5 b), distal leg (25th percentile) ( Figure 5 c), and foot (50−80th percentile) ( Figure 5 d). Figure 4 Quantitative sweat rate (nanoliters per minute) of twin 1 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d). Figure 5 Quantitative sweat rate (nanoliters per minute) of twin 2 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d).', 'Case 1': 'Monozygotic female adolescent twins, aged 16 years old, were originally diagnosed in infancy with NC and found to have a 57-kb deletion of the CTNS gene, the most frequent cause of NC in Western populations. They were on cysteamine bitartrate (cystagon-immediate release) since diagnosis. Each was currently prescribed Procysbi (cysteamine-delayed release) 675 mg every 12 hours. In addition, each twin was prescribed cysteamine hydrochloride (0.44%) eye drops due to cystine crystal accumulation in the lens and cornea. Both twins were transplanted 6 years previously with kidneys from a single deceased donor source. Since that time, both twins experienced several episodes of transplant rejection, whereas twin 1 also developed Epstein-Barr virus positive posttransplant proliferative disorder. Table 1 includes clinical and medication data on the patients at the time of autonomic testing. As shown in Table 1, twin 2 exhibited a diastolic blood pressure (DBP) that exceeded the threshold for sex and height and had DBP readings 20% higher than those of twin 1. Table 1 Characteristics and medications of female monozygotic twins with nephropathic cystinosis Characteristics Twin 1 Twin 2 Age (yrs) 16 Race W Ethnicity H Wt. (kg) 43.6 46.0 Ht. (cm) 152.3 154.8 BMI percentile (for age and sex) (kg/m 2 ) 25th 40th Resting BP (mm Hg) 118/70 123/84 Measured GFR (ml/min per 1.73 m 2 ) 59.3 70.0 CKD stage 3a 2 Tacrolimus level (ng/ml) 5.5 4.5 Medications, Dose, Frequency Procysbi (cysteamine DR) 675 mg q 12 h Cysteamine HCL (0.44%) 1 gtt. OU q h while awake Amlodipine 10 mg/d Cardura 4 mg/d — Lisinopril 10 mg/d Drisdol 50,000 IU/ q 14 d — Cellcept 500 mg BID Tacrolimus 3 mg BID 2 mg BID Synthroid 137 μg/d 125 μg/d Mg oxide 400 mg BID Bactrim 400-80 40 mg 3×/wk BID, twice a day; BMI, body mass index; BP, blood pressure; CKD, chronic kidney disease; DR, delayed release; GFR, glomerular filtration rate by plasma clearance of iohexol; gtt, drops; H, Hispanic; HCL, hydrochloride; Ht., height; IU, international units; Mg, magnesium; OU, both eyes; q, every; W, white; Wt., weight. Laboratory findings (biochemical characteristics) for both twins are shown in Table 2 . Creatinine, blood urea nitrogen, and cystatin C levels were consistent with the CKD stage of each twin. Both patients also had blood drawn for measurement of their leukocyte cystine levels, which were obtained at the time of their regular laboratory tests. Those results were 1.65 and 1.90 nmol 1/2 cystine per milligram per protein for twins 1 and 2, respectively. Because the twins exhibited leukocyte cystine levels >1 nmol 1/2 cystine per milligram per protein, it indicated they had not achieved an optimal degree of substrate depletion for cystinosis patients on cysteamine therapy. This was due to incomplete adherence with their cysteamine bitartrate therapy. Table 3 lists a summary on cystinosis. Table 2 Laboratory results Results Conventional units (SI Units) Twin # Cr BUN Cystatin C Alb Phos Na K Glucose 1 1.08 (95.47) 15 (5.35) (1.25) 4.5 (45) 3.7 (1.20) 136 (136 ) 4.0 (4.0) 98 (5.44) 2 0.81 (71.60) 13 (4.64) (1.09) 4.9 (49) 3.8 (1.23) 137 (137) 4.2 (4.2) 94 (5.22) Normal reference range 0.25−1.14 mg/dl 5.0−18.0 mg/dl 0.5−1.3 mg/l (1−17 yr) 3.6−4.7 g/dl 3.0−4.8 mg/dl 134−146 mEq/l 3.7−5.7 mEq/l 60−110 mg/dl SI units normal Reference Range 22.1−100.78 mmol/l 1.78−6.43 mmol/l 0.50−1.30 mg/l 36.0−47.0 g/l 0.97−1.55 mmol/l 134−146 mmol/l 3.7−5.7 mmol/l 3.33−6.11 mmol/l Alb, albumin; BUN, blood urea nitrogen; Cr, creatinine; K, potassium; Na, sodium; Phos, phosphorus (inorganic); SI, Standard international. Table 3 Teaching points (i) Cystinosis results from a functional defect in the lysosomal-membrane exporter protein, cystinosin (CTNS), thereby resulting in failure of cystine efflux from cell lysosomes. When untreated, cystine crystals result and are deposited throughout the body, including in the cornea, retina, and most organs. (ii) Nephropathic cystinosis (NC) is often diagnosed in infancy due to the development of severe renal Fanconi syndrome with failure to thrive. Chronic electrolyte replacement is essential. (iii) Cystine accumulation is measured in leukocytes with a cystine level < 1 nmol 1/2 cystine per milligram cell protein categorized as being consistent with optimal cystine depletion. (iv) Cysteamine bitartrate is the only Food and Drug Administration−approved therapy for cystinosis and is available in immediate and delayed release formulations. (v) In NC, the 57-kb deletion has been associated with transient receptor potential vanilloid 1 (TRPV1) gene functional impairment. (vi) Long-term extra renal manifestations of NC are frequently observed and include cognitive impairment and/or delays, altered skin and/or heat sensations, abnormal temperature regulation, heat intolerance, reduced sweating, and myopathy, the latter of which may eventually contribute to respiratory failure, all suggestive of autonomic nervous system dysfunction pertinent to thermoregulation. Both twins frequently described issues with heat intolerance and photophobia secondary to corneal cystine crystal deposition, but they demonstrated consistently normal clinical neurological examination findings. We decided to complete further testing of the twins to evaluate heat intolerance and possible associated autonomic dysfunction as opposed to what may simply be avoidance of light exposure on sunny days.', 'Clinical Testing': 'During the period before testing, a directly measured glomerular filtration rate was completed on each twin using a plasma clearance of iohexol procedure. 14 The twins then underwent 3 clinical procedures at the Center for Autonomic Medicine in Pediatrics at Ann & Robert H. Lurie Children’s Hospital of Chicago (Chicago, IL). Those procedures included the head-up tilt (HUT) test to assess baroreceptor function, a thermoregulatory sweat test (TST) to measure sudomotor function, and the quantitative sweat response test (QSWEAT), which is a sudomotor axon reflex test in which responses of the local axon reflex of sweat glands to iontophoresed acetylcholine are quantitated. 15 The use of the TST and QSWEAT procedures on patients are considered to be the gold standard for clinical evaluation, because they demonstrated a 90% sensitivity for detection of small fiber neuropathy. 16 The HUT determines whether orthostatic (in)tolerance can be demonstrated and evaluates the inter-relationship of breathing, heart rate (HR), and BP while the patient transitions from a supine to an upright position and then returns to the supine position. Simply stated, a patient lays on a tilt table in a supine horizontal position for 10 to 20 minutes while baseline measurements are taken. Then, a HUT to 70° is done with measurements collected thereafter for 10 minutes. Following this, a tilt-down to a supine horizontal position occurs and is sustained for 2 minutes of additional measurements. During the TST, the core body temperature is increased slowly to 1 ° C higher than at prewarming (baseline) or a patient reaches a core temperature of 38 ° C (whichever is greater). To prepare for the procedure, sweat-indicator powder is applied to the patient’s anterior surface while lying supine on a bed. The patient is then rolled into the chamber, and it is sealed shut, while continuous surveillance and collection of all physiological measurements of the patient, chamber, and temperatures occurs. The ambient temperature is slowly increased with an average ramp rate of 5.0 °C/hour and with a relative humidity range of 35% to 45%. Finally, for the QSWEAT, the patient is placed in a supine horizontal position. Once situated, 4 quarter-sized capsules of acetylcholine are topically applied on the forearm, proximal and distal leg, and foot. An imperceivable 2-mA current is delivered over a 5-minute period, followed by a 5-minute recovery, which results in an accurate quantitation of sweat produced in small areas of the skin.'}
|
Endocrinology
|
ENDO
|
[] |
6224624
|
{'Testing Results': 'Figures 1 a to d represent the continuous HR and BP recordings of twin 1 ( Figure 1 a and b) and twin 2 ( Figure 1 c and d) during the HUT over the 10-second transition from a supine horizontal position to a 70° upright tilt. As seen in Figure 1 a, the HR of twin 1 exhibited a compensatory increase to a maximum of 110 beats/min at 6.9 minutes into the HUT and remained at this level until she was returned to a horizontal and/or supine position. This was a change of 52 beats/min. In Figure 1 b, a systolic BP (SBP) decline of 29.8 mm Hg can be seen at 0.3 minutes into the HUT. The BP of twin 1 recovered quickly to pre-HUT levels and remained stable thereafter throughout the 10-minute HUT. Conversely, for twin 2, HR increased by 45 to 120 beats/min and a 30-mm Hg SBP drop occurred when transitioned from a supine position to a 70° HUT ( Figure 1 c and d). In addition, the HR and SBP remained at these levels throughout the HUT until the twin returned to the supine position. Thus, both twins exhibited orthostatic tachycardia during HUT that was maintained until returning to the supine horizontal body position, which indicated a greater than average response compared with normative data. Figure 1 Head up-tilt (HUT) of twins 1 and 2 for continuous heart rate (a,c) and blood pressure recordings (b,d). For the TST, the baseline (pre-TST) for twin 1 and twin 2 are shown in Figure 2 a and 2 c, respectively, whereas postwarming period results for each twin are found in Figure 2 b and 2 d, respectively. By referencing the temperature scale shown between Figure 2 a and 2 b and Figure 2 c and 2 d, the images clearly demonstrate both twins with cold hands and feet before warming ( Figure 2 a and 2 c). Conversely, in post-TST images, both twins displayed symmetric warming of their hands but their feet remained slightly cooler compared with other body regions ( Figure 2 b and 2 d). Figure 2 Thermoregulatory sweat test baseline and warmed (post) test twin 1 (a,b) and twin 2 (c,d), respectively. A temperature-color gauge is centered between each baseline and the warmed figure with values shown in degrees Fahrenheit. Postwarming images of twin 1 ( Figure 3 a) and twin 2 ( Figure 3 b) are shown with patchy regions of anhidrosis (in yellow) compared with the purple areas of sweat indicator powder, which demonstrated the regions where sweating occurred. Twin 1 had 53% anhidrosis but preserved sweating on the upper trunk, left abdomen, both hands, and medial legs, whereas twin 2 exhibited 50% anhidrosis and residual sweating of the upper trunk, bilateral hands, and medial legs. Figure 3 Diaphoresis patterns of twin 1 (a) and twin 2 (b) at the completion of the thermoregulatory sweat test (TST). QSWEAT results of twin 1 are shown with sweat rates of the forearm (25−50th percentile) ( Figure 4 a); proximal ( Figure 4 b) and distal leg sweat rates were each <10th percentile (abnormal for sex and age) ( Figure 4 c), and the foot was between the 10th to 25th percentile ( Figure 4 d). In addition, these abnormalities were categorized as a “latency of the sweat response” of the forearm, distal leg, and foot, as well as a “lack of recovery” of the proximal leg. Results for twin 2 showed a similar sweat response latency of the proximal leg ( Figure 5 b). Otherwise, twin 2 exhibited normal sweat volumes and rates for her age as seen for the forearm (10th−25th percentile) ( Figure 5 a), proximal leg (25th percentile) ( Figure 5 b), distal leg (25th percentile) ( Figure 5 c), and foot (50−80th percentile) ( Figure 5 d). Figure 4 Quantitative sweat rate (nanoliters per minute) of twin 1 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d). Figure 5 Quantitative sweat rate (nanoliters per minute) of twin 2 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d).', 'Case 1': 'Monozygotic female adolescent twins, aged 16 years old, were originally diagnosed in infancy with NC and found to have a 57-kb deletion of the CTNS gene, the most frequent cause of NC in Western populations. They were on cysteamine bitartrate (cystagon-immediate release) since diagnosis. Each was currently prescribed Procysbi (cysteamine-delayed release) 675 mg every 12 hours. In addition, each twin was prescribed cysteamine hydrochloride (0.44%) eye drops due to cystine crystal accumulation in the lens and cornea. Both twins were transplanted 6 years previously with kidneys from a single deceased donor source. Since that time, both twins experienced several episodes of transplant rejection, whereas twin 1 also developed Epstein-Barr virus positive posttransplant proliferative disorder. Table 1 includes clinical and medication data on the patients at the time of autonomic testing. As shown in Table 1, twin 2 exhibited a diastolic blood pressure (DBP) that exceeded the threshold for sex and height and had DBP readings 20% higher than those of twin 1. Table 1 Characteristics and medications of female monozygotic twins with nephropathic cystinosis Characteristics Twin 1 Twin 2 Age (yrs) 16 Race W Ethnicity H Wt. (kg) 43.6 46.0 Ht. (cm) 152.3 154.8 BMI percentile (for age and sex) (kg/m 2 ) 25th 40th Resting BP (mm Hg) 118/70 123/84 Measured GFR (ml/min per 1.73 m 2 ) 59.3 70.0 CKD stage 3a 2 Tacrolimus level (ng/ml) 5.5 4.5 Medications, Dose, Frequency Procysbi (cysteamine DR) 675 mg q 12 h Cysteamine HCL (0.44%) 1 gtt. OU q h while awake Amlodipine 10 mg/d Cardura 4 mg/d — Lisinopril 10 mg/d Drisdol 50,000 IU/ q 14 d — Cellcept 500 mg BID Tacrolimus 3 mg BID 2 mg BID Synthroid 137 μg/d 125 μg/d Mg oxide 400 mg BID Bactrim 400-80 40 mg 3×/wk BID, twice a day; BMI, body mass index; BP, blood pressure; CKD, chronic kidney disease; DR, delayed release; GFR, glomerular filtration rate by plasma clearance of iohexol; gtt, drops; H, Hispanic; HCL, hydrochloride; Ht., height; IU, international units; Mg, magnesium; OU, both eyes; q, every; W, white; Wt., weight. Laboratory findings (biochemical characteristics) for both twins are shown in Table 2 . Creatinine, blood urea nitrogen, and cystatin C levels were consistent with the CKD stage of each twin. Both patients also had blood drawn for measurement of their leukocyte cystine levels, which were obtained at the time of their regular laboratory tests. Those results were 1.65 and 1.90 nmol 1/2 cystine per milligram per protein for twins 1 and 2, respectively. Because the twins exhibited leukocyte cystine levels >1 nmol 1/2 cystine per milligram per protein, it indicated they had not achieved an optimal degree of substrate depletion for cystinosis patients on cysteamine therapy. This was due to incomplete adherence with their cysteamine bitartrate therapy. Table 3 lists a summary on cystinosis. Table 2 Laboratory results Results Conventional units (SI Units) Twin # Cr BUN Cystatin C Alb Phos Na K Glucose 1 1.08 (95.47) 15 (5.35) (1.25) 4.5 (45) 3.7 (1.20) 136 (136 ) 4.0 (4.0) 98 (5.44) 2 0.81 (71.60) 13 (4.64) (1.09) 4.9 (49) 3.8 (1.23) 137 (137) 4.2 (4.2) 94 (5.22) Normal reference range 0.25−1.14 mg/dl 5.0−18.0 mg/dl 0.5−1.3 mg/l (1−17 yr) 3.6−4.7 g/dl 3.0−4.8 mg/dl 134−146 mEq/l 3.7−5.7 mEq/l 60−110 mg/dl SI units normal Reference Range 22.1−100.78 mmol/l 1.78−6.43 mmol/l 0.50−1.30 mg/l 36.0−47.0 g/l 0.97−1.55 mmol/l 134−146 mmol/l 3.7−5.7 mmol/l 3.33−6.11 mmol/l Alb, albumin; BUN, blood urea nitrogen; Cr, creatinine; K, potassium; Na, sodium; Phos, phosphorus (inorganic); SI, Standard international. Table 3 Teaching points (i) Cystinosis results from a functional defect in the lysosomal-membrane exporter protein, cystinosin (CTNS), thereby resulting in failure of cystine efflux from cell lysosomes. When untreated, cystine crystals result and are deposited throughout the body, including in the cornea, retina, and most organs. (ii) Nephropathic cystinosis (NC) is often diagnosed in infancy due to the development of severe renal Fanconi syndrome with failure to thrive. Chronic electrolyte replacement is essential. (iii) Cystine accumulation is measured in leukocytes with a cystine level < 1 nmol 1/2 cystine per milligram cell protein categorized as being consistent with optimal cystine depletion. (iv) Cysteamine bitartrate is the only Food and Drug Administration−approved therapy for cystinosis and is available in immediate and delayed release formulations. (v) In NC, the 57-kb deletion has been associated with transient receptor potential vanilloid 1 (TRPV1) gene functional impairment. (vi) Long-term extra renal manifestations of NC are frequently observed and include cognitive impairment and/or delays, altered skin and/or heat sensations, abnormal temperature regulation, heat intolerance, reduced sweating, and myopathy, the latter of which may eventually contribute to respiratory failure, all suggestive of autonomic nervous system dysfunction pertinent to thermoregulation. Both twins frequently described issues with heat intolerance and photophobia secondary to corneal cystine crystal deposition, but they demonstrated consistently normal clinical neurological examination findings. We decided to complete further testing of the twins to evaluate heat intolerance and possible associated autonomic dysfunction as opposed to what may simply be avoidance of light exposure on sunny days.', 'Clinical Testing': 'During the period before testing, a directly measured glomerular filtration rate was completed on each twin using a plasma clearance of iohexol procedure. 14 The twins then underwent 3 clinical procedures at the Center for Autonomic Medicine in Pediatrics at Ann & Robert H. Lurie Children’s Hospital of Chicago (Chicago, IL). Those procedures included the head-up tilt (HUT) test to assess baroreceptor function, a thermoregulatory sweat test (TST) to measure sudomotor function, and the quantitative sweat response test (QSWEAT), which is a sudomotor axon reflex test in which responses of the local axon reflex of sweat glands to iontophoresed acetylcholine are quantitated. 15 The use of the TST and QSWEAT procedures on patients are considered to be the gold standard for clinical evaluation, because they demonstrated a 90% sensitivity for detection of small fiber neuropathy. 16 The HUT determines whether orthostatic (in)tolerance can be demonstrated and evaluates the inter-relationship of breathing, heart rate (HR), and BP while the patient transitions from a supine to an upright position and then returns to the supine position. Simply stated, a patient lays on a tilt table in a supine horizontal position for 10 to 20 minutes while baseline measurements are taken. Then, a HUT to 70° is done with measurements collected thereafter for 10 minutes. Following this, a tilt-down to a supine horizontal position occurs and is sustained for 2 minutes of additional measurements. During the TST, the core body temperature is increased slowly to 1 ° C higher than at prewarming (baseline) or a patient reaches a core temperature of 38 ° C (whichever is greater). To prepare for the procedure, sweat-indicator powder is applied to the patient’s anterior surface while lying supine on a bed. The patient is then rolled into the chamber, and it is sealed shut, while continuous surveillance and collection of all physiological measurements of the patient, chamber, and temperatures occurs. The ambient temperature is slowly increased with an average ramp rate of 5.0 °C/hour and with a relative humidity range of 35% to 45%. Finally, for the QSWEAT, the patient is placed in a supine horizontal position. Once situated, 4 quarter-sized capsules of acetylcholine are topically applied on the forearm, proximal and distal leg, and foot. An imperceivable 2-mA current is delivered over a 5-minute period, followed by a 5-minute recovery, which results in an accurate quantitation of sweat produced in small areas of the skin.'}
|
{'Testing Results': 'Figures 1 a to d represent the continuous HR and BP recordings of twin 1 ( Figure 1 a and b) and twin 2 ( Figure 1 c and d) during the HUT over the 10-second transition from a supine horizontal position to a 70° upright tilt. As seen in Figure 1 a, the HR of twin 1 exhibited a compensatory increase to a maximum of 110 beats/min at 6.9 minutes into the HUT and remained at this level until she was returned to a horizontal and/or supine position. This was a change of 52 beats/min. In Figure 1 b, a systolic BP (SBP) decline of 29.8 mm Hg can be seen at 0.3 minutes into the HUT. The BP of twin 1 recovered quickly to pre-HUT levels and remained stable thereafter throughout the 10-minute HUT. Conversely, for twin 2, HR increased by 45 to 120 beats/min and a 30-mm Hg SBP drop occurred when transitioned from a supine position to a 70° HUT ( Figure 1 c and d). In addition, the HR and SBP remained at these levels throughout the HUT until the twin returned to the supine position. Thus, both twins exhibited orthostatic tachycardia during HUT that was maintained until returning to the supine horizontal body position, which indicated a greater than average response compared with normative data. Figure 1 Head up-tilt (HUT) of twins 1 and 2 for continuous heart rate (a,c) and blood pressure recordings (b,d). For the TST, the baseline (pre-TST) for twin 1 and twin 2 are shown in Figure 2 a and 2 c, respectively, whereas postwarming period results for each twin are found in Figure 2 b and 2 d, respectively. By referencing the temperature scale shown between Figure 2 a and 2 b and Figure 2 c and 2 d, the images clearly demonstrate both twins with cold hands and feet before warming ( Figure 2 a and 2 c). Conversely, in post-TST images, both twins displayed symmetric warming of their hands but their feet remained slightly cooler compared with other body regions ( Figure 2 b and 2 d). Figure 2 Thermoregulatory sweat test baseline and warmed (post) test twin 1 (a,b) and twin 2 (c,d), respectively. A temperature-color gauge is centered between each baseline and the warmed figure with values shown in degrees Fahrenheit. Postwarming images of twin 1 ( Figure 3 a) and twin 2 ( Figure 3 b) are shown with patchy regions of anhidrosis (in yellow) compared with the purple areas of sweat indicator powder, which demonstrated the regions where sweating occurred. Twin 1 had 53% anhidrosis but preserved sweating on the upper trunk, left abdomen, both hands, and medial legs, whereas twin 2 exhibited 50% anhidrosis and residual sweating of the upper trunk, bilateral hands, and medial legs. Figure 3 Diaphoresis patterns of twin 1 (a) and twin 2 (b) at the completion of the thermoregulatory sweat test (TST). QSWEAT results of twin 1 are shown with sweat rates of the forearm (25−50th percentile) ( Figure 4 a); proximal ( Figure 4 b) and distal leg sweat rates were each <10th percentile (abnormal for sex and age) ( Figure 4 c), and the foot was between the 10th to 25th percentile ( Figure 4 d). In addition, these abnormalities were categorized as a “latency of the sweat response” of the forearm, distal leg, and foot, as well as a “lack of recovery” of the proximal leg. Results for twin 2 showed a similar sweat response latency of the proximal leg ( Figure 5 b). Otherwise, twin 2 exhibited normal sweat volumes and rates for her age as seen for the forearm (10th−25th percentile) ( Figure 5 a), proximal leg (25th percentile) ( Figure 5 b), distal leg (25th percentile) ( Figure 5 c), and foot (50−80th percentile) ( Figure 5 d). Figure 4 Quantitative sweat rate (nanoliters per minute) of twin 1 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d). Figure 5 Quantitative sweat rate (nanoliters per minute) of twin 2 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d).', 'Case 1': 'Monozygotic female adolescent twins, aged 16 years old, were originally diagnosed in infancy with NC and found to have a 57-kb deletion of the CTNS gene, the most frequent cause of NC in Western populations. They were on cysteamine bitartrate (cystagon-immediate release) since diagnosis. Each was currently prescribed Procysbi (cysteamine-delayed release) 675 mg every 12 hours. In addition, each twin was prescribed cysteamine hydrochloride (0.44%) eye drops due to cystine crystal accumulation in the lens and cornea. Both twins were transplanted 6 years previously with kidneys from a single deceased donor source. Since that time, both twins experienced several episodes of transplant rejection, whereas twin 1 also developed Epstein-Barr virus positive posttransplant proliferative disorder. Table 1 includes clinical and medication data on the patients at the time of autonomic testing. As shown in Table 1, twin 2 exhibited a diastolic blood pressure (DBP) that exceeded the threshold for sex and height and had DBP readings 20% higher than those of twin 1. Table 1 Characteristics and medications of female monozygotic twins with nephropathic cystinosis Characteristics Twin 1 Twin 2 Age (yrs) 16 Race W Ethnicity H Wt. (kg) 43.6 46.0 Ht. (cm) 152.3 154.8 BMI percentile (for age and sex) (kg/m 2 ) 25th 40th Resting BP (mm Hg) 118/70 123/84 Measured GFR (ml/min per 1.73 m 2 ) 59.3 70.0 CKD stage 3a 2 Tacrolimus level (ng/ml) 5.5 4.5 Medications, Dose, Frequency Procysbi (cysteamine DR) 675 mg q 12 h Cysteamine HCL (0.44%) 1 gtt. OU q h while awake Amlodipine 10 mg/d Cardura 4 mg/d — Lisinopril 10 mg/d Drisdol 50,000 IU/ q 14 d — Cellcept 500 mg BID Tacrolimus 3 mg BID 2 mg BID Synthroid 137 μg/d 125 μg/d Mg oxide 400 mg BID Bactrim 400-80 40 mg 3×/wk BID, twice a day; BMI, body mass index; BP, blood pressure; CKD, chronic kidney disease; DR, delayed release; GFR, glomerular filtration rate by plasma clearance of iohexol; gtt, drops; H, Hispanic; HCL, hydrochloride; Ht., height; IU, international units; Mg, magnesium; OU, both eyes; q, every; W, white; Wt., weight. Laboratory findings (biochemical characteristics) for both twins are shown in Table 2 . Creatinine, blood urea nitrogen, and cystatin C levels were consistent with the CKD stage of each twin. Both patients also had blood drawn for measurement of their leukocyte cystine levels, which were obtained at the time of their regular laboratory tests. Those results were 1.65 and 1.90 nmol 1/2 cystine per milligram per protein for twins 1 and 2, respectively. Because the twins exhibited leukocyte cystine levels >1 nmol 1/2 cystine per milligram per protein, it indicated they had not achieved an optimal degree of substrate depletion for cystinosis patients on cysteamine therapy. This was due to incomplete adherence with their cysteamine bitartrate therapy. Table 3 lists a summary on cystinosis. Table 2 Laboratory results Results Conventional units (SI Units) Twin # Cr BUN Cystatin C Alb Phos Na K Glucose 1 1.08 (95.47) 15 (5.35) (1.25) 4.5 (45) 3.7 (1.20) 136 (136 ) 4.0 (4.0) 98 (5.44) 2 0.81 (71.60) 13 (4.64) (1.09) 4.9 (49) 3.8 (1.23) 137 (137) 4.2 (4.2) 94 (5.22) Normal reference range 0.25−1.14 mg/dl 5.0−18.0 mg/dl 0.5−1.3 mg/l (1−17 yr) 3.6−4.7 g/dl 3.0−4.8 mg/dl 134−146 mEq/l 3.7−5.7 mEq/l 60−110 mg/dl SI units normal Reference Range 22.1−100.78 mmol/l 1.78−6.43 mmol/l 0.50−1.30 mg/l 36.0−47.0 g/l 0.97−1.55 mmol/l 134−146 mmol/l 3.7−5.7 mmol/l 3.33−6.11 mmol/l Alb, albumin; BUN, blood urea nitrogen; Cr, creatinine; K, potassium; Na, sodium; Phos, phosphorus (inorganic); SI, Standard international. Table 3 Teaching points (i) Cystinosis results from a functional defect in the lysosomal-membrane exporter protein, cystinosin (CTNS), thereby resulting in failure of cystine efflux from cell lysosomes. When untreated, cystine crystals result and are deposited throughout the body, including in the cornea, retina, and most organs. (ii) Nephropathic cystinosis (NC) is often diagnosed in infancy due to the development of severe renal Fanconi syndrome with failure to thrive. Chronic electrolyte replacement is essential. (iii) Cystine accumulation is measured in leukocytes with a cystine level < 1 nmol 1/2 cystine per milligram cell protein categorized as being consistent with optimal cystine depletion. (iv) Cysteamine bitartrate is the only Food and Drug Administration−approved therapy for cystinosis and is available in immediate and delayed release formulations. (v) In NC, the 57-kb deletion has been associated with transient receptor potential vanilloid 1 (TRPV1) gene functional impairment. (vi) Long-term extra renal manifestations of NC are frequently observed and include cognitive impairment and/or delays, altered skin and/or heat sensations, abnormal temperature regulation, heat intolerance, reduced sweating, and myopathy, the latter of which may eventually contribute to respiratory failure, all suggestive of autonomic nervous system dysfunction pertinent to thermoregulation. Both twins frequently described issues with heat intolerance and photophobia secondary to corneal cystine crystal deposition, but they demonstrated consistently normal clinical neurological examination findings. We decided to complete further testing of the twins to evaluate heat intolerance and possible associated autonomic dysfunction as opposed to what may simply be avoidance of light exposure on sunny days.', 'Clinical Testing': 'During the period before testing, a directly measured glomerular filtration rate was completed on each twin using a plasma clearance of iohexol procedure. 14 The twins then underwent 3 clinical procedures at the Center for Autonomic Medicine in Pediatrics at Ann & Robert H. Lurie Children’s Hospital of Chicago (Chicago, IL). Those procedures included the head-up tilt (HUT) test to assess baroreceptor function, a thermoregulatory sweat test (TST) to measure sudomotor function, and the quantitative sweat response test (QSWEAT), which is a sudomotor axon reflex test in which responses of the local axon reflex of sweat glands to iontophoresed acetylcholine are quantitated. 15 The use of the TST and QSWEAT procedures on patients are considered to be the gold standard for clinical evaluation, because they demonstrated a 90% sensitivity for detection of small fiber neuropathy. 16 The HUT determines whether orthostatic (in)tolerance can be demonstrated and evaluates the inter-relationship of breathing, heart rate (HR), and BP while the patient transitions from a supine to an upright position and then returns to the supine position. Simply stated, a patient lays on a tilt table in a supine horizontal position for 10 to 20 minutes while baseline measurements are taken. Then, a HUT to 70° is done with measurements collected thereafter for 10 minutes. Following this, a tilt-down to a supine horizontal position occurs and is sustained for 2 minutes of additional measurements. During the TST, the core body temperature is increased slowly to 1 ° C higher than at prewarming (baseline) or a patient reaches a core temperature of 38 ° C (whichever is greater). To prepare for the procedure, sweat-indicator powder is applied to the patient’s anterior surface while lying supine on a bed. The patient is then rolled into the chamber, and it is sealed shut, while continuous surveillance and collection of all physiological measurements of the patient, chamber, and temperatures occurs. The ambient temperature is slowly increased with an average ramp rate of 5.0 °C/hour and with a relative humidity range of 35% to 45%. Finally, for the QSWEAT, the patient is placed in a supine horizontal position. Once situated, 4 quarter-sized capsules of acetylcholine are topically applied on the forearm, proximal and distal leg, and foot. An imperceivable 2-mA current is delivered over a 5-minute period, followed by a 5-minute recovery, which results in an accurate quantitation of sweat produced in small areas of the skin.'}
|
Genitourinary-System
|
GU
|
[] |
6224624
|
{'Testing Results': 'Figures 1 a to d represent the continuous HR and BP recordings of twin 1 ( Figure 1 a and b) and twin 2 ( Figure 1 c and d) during the HUT over the 10-second transition from a supine horizontal position to a 70° upright tilt. As seen in Figure 1 a, the HR of twin 1 exhibited a compensatory increase to a maximum of 110 beats/min at 6.9 minutes into the HUT and remained at this level until she was returned to a horizontal and/or supine position. This was a change of 52 beats/min. In Figure 1 b, a systolic BP (SBP) decline of 29.8 mm Hg can be seen at 0.3 minutes into the HUT. The BP of twin 1 recovered quickly to pre-HUT levels and remained stable thereafter throughout the 10-minute HUT. Conversely, for twin 2, HR increased by 45 to 120 beats/min and a 30-mm Hg SBP drop occurred when transitioned from a supine position to a 70° HUT ( Figure 1 c and d). In addition, the HR and SBP remained at these levels throughout the HUT until the twin returned to the supine position. Thus, both twins exhibited orthostatic tachycardia during HUT that was maintained until returning to the supine horizontal body position, which indicated a greater than average response compared with normative data. Figure 1 Head up-tilt (HUT) of twins 1 and 2 for continuous heart rate (a,c) and blood pressure recordings (b,d). For the TST, the baseline (pre-TST) for twin 1 and twin 2 are shown in Figure 2 a and 2 c, respectively, whereas postwarming period results for each twin are found in Figure 2 b and 2 d, respectively. By referencing the temperature scale shown between Figure 2 a and 2 b and Figure 2 c and 2 d, the images clearly demonstrate both twins with cold hands and feet before warming ( Figure 2 a and 2 c). Conversely, in post-TST images, both twins displayed symmetric warming of their hands but their feet remained slightly cooler compared with other body regions ( Figure 2 b and 2 d). Figure 2 Thermoregulatory sweat test baseline and warmed (post) test twin 1 (a,b) and twin 2 (c,d), respectively. A temperature-color gauge is centered between each baseline and the warmed figure with values shown in degrees Fahrenheit. Postwarming images of twin 1 ( Figure 3 a) and twin 2 ( Figure 3 b) are shown with patchy regions of anhidrosis (in yellow) compared with the purple areas of sweat indicator powder, which demonstrated the regions where sweating occurred. Twin 1 had 53% anhidrosis but preserved sweating on the upper trunk, left abdomen, both hands, and medial legs, whereas twin 2 exhibited 50% anhidrosis and residual sweating of the upper trunk, bilateral hands, and medial legs. Figure 3 Diaphoresis patterns of twin 1 (a) and twin 2 (b) at the completion of the thermoregulatory sweat test (TST). QSWEAT results of twin 1 are shown with sweat rates of the forearm (25−50th percentile) ( Figure 4 a); proximal ( Figure 4 b) and distal leg sweat rates were each <10th percentile (abnormal for sex and age) ( Figure 4 c), and the foot was between the 10th to 25th percentile ( Figure 4 d). In addition, these abnormalities were categorized as a “latency of the sweat response” of the forearm, distal leg, and foot, as well as a “lack of recovery” of the proximal leg. Results for twin 2 showed a similar sweat response latency of the proximal leg ( Figure 5 b). Otherwise, twin 2 exhibited normal sweat volumes and rates for her age as seen for the forearm (10th−25th percentile) ( Figure 5 a), proximal leg (25th percentile) ( Figure 5 b), distal leg (25th percentile) ( Figure 5 c), and foot (50−80th percentile) ( Figure 5 d). Figure 4 Quantitative sweat rate (nanoliters per minute) of twin 1 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d). Figure 5 Quantitative sweat rate (nanoliters per minute) of twin 2 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d).', 'Case 1': 'Monozygotic female adolescent twins, aged 16 years old, were originally diagnosed in infancy with NC and found to have a 57-kb deletion of the CTNS gene, the most frequent cause of NC in Western populations. They were on cysteamine bitartrate (cystagon-immediate release) since diagnosis. Each was currently prescribed Procysbi (cysteamine-delayed release) 675 mg every 12 hours. In addition, each twin was prescribed cysteamine hydrochloride (0.44%) eye drops due to cystine crystal accumulation in the lens and cornea. Both twins were transplanted 6 years previously with kidneys from a single deceased donor source. Since that time, both twins experienced several episodes of transplant rejection, whereas twin 1 also developed Epstein-Barr virus positive posttransplant proliferative disorder. Table 1 includes clinical and medication data on the patients at the time of autonomic testing. As shown in Table 1, twin 2 exhibited a diastolic blood pressure (DBP) that exceeded the threshold for sex and height and had DBP readings 20% higher than those of twin 1. Table 1 Characteristics and medications of female monozygotic twins with nephropathic cystinosis Characteristics Twin 1 Twin 2 Age (yrs) 16 Race W Ethnicity H Wt. (kg) 43.6 46.0 Ht. (cm) 152.3 154.8 BMI percentile (for age and sex) (kg/m 2 ) 25th 40th Resting BP (mm Hg) 118/70 123/84 Measured GFR (ml/min per 1.73 m 2 ) 59.3 70.0 CKD stage 3a 2 Tacrolimus level (ng/ml) 5.5 4.5 Medications, Dose, Frequency Procysbi (cysteamine DR) 675 mg q 12 h Cysteamine HCL (0.44%) 1 gtt. OU q h while awake Amlodipine 10 mg/d Cardura 4 mg/d — Lisinopril 10 mg/d Drisdol 50,000 IU/ q 14 d — Cellcept 500 mg BID Tacrolimus 3 mg BID 2 mg BID Synthroid 137 μg/d 125 μg/d Mg oxide 400 mg BID Bactrim 400-80 40 mg 3×/wk BID, twice a day; BMI, body mass index; BP, blood pressure; CKD, chronic kidney disease; DR, delayed release; GFR, glomerular filtration rate by plasma clearance of iohexol; gtt, drops; H, Hispanic; HCL, hydrochloride; Ht., height; IU, international units; Mg, magnesium; OU, both eyes; q, every; W, white; Wt., weight. Laboratory findings (biochemical characteristics) for both twins are shown in Table 2 . Creatinine, blood urea nitrogen, and cystatin C levels were consistent with the CKD stage of each twin. Both patients also had blood drawn for measurement of their leukocyte cystine levels, which were obtained at the time of their regular laboratory tests. Those results were 1.65 and 1.90 nmol 1/2 cystine per milligram per protein for twins 1 and 2, respectively. Because the twins exhibited leukocyte cystine levels >1 nmol 1/2 cystine per milligram per protein, it indicated they had not achieved an optimal degree of substrate depletion for cystinosis patients on cysteamine therapy. This was due to incomplete adherence with their cysteamine bitartrate therapy. Table 3 lists a summary on cystinosis. Table 2 Laboratory results Results Conventional units (SI Units) Twin # Cr BUN Cystatin C Alb Phos Na K Glucose 1 1.08 (95.47) 15 (5.35) (1.25) 4.5 (45) 3.7 (1.20) 136 (136 ) 4.0 (4.0) 98 (5.44) 2 0.81 (71.60) 13 (4.64) (1.09) 4.9 (49) 3.8 (1.23) 137 (137) 4.2 (4.2) 94 (5.22) Normal reference range 0.25−1.14 mg/dl 5.0−18.0 mg/dl 0.5−1.3 mg/l (1−17 yr) 3.6−4.7 g/dl 3.0−4.8 mg/dl 134−146 mEq/l 3.7−5.7 mEq/l 60−110 mg/dl SI units normal Reference Range 22.1−100.78 mmol/l 1.78−6.43 mmol/l 0.50−1.30 mg/l 36.0−47.0 g/l 0.97−1.55 mmol/l 134−146 mmol/l 3.7−5.7 mmol/l 3.33−6.11 mmol/l Alb, albumin; BUN, blood urea nitrogen; Cr, creatinine; K, potassium; Na, sodium; Phos, phosphorus (inorganic); SI, Standard international. Table 3 Teaching points (i) Cystinosis results from a functional defect in the lysosomal-membrane exporter protein, cystinosin (CTNS), thereby resulting in failure of cystine efflux from cell lysosomes. When untreated, cystine crystals result and are deposited throughout the body, including in the cornea, retina, and most organs. (ii) Nephropathic cystinosis (NC) is often diagnosed in infancy due to the development of severe renal Fanconi syndrome with failure to thrive. Chronic electrolyte replacement is essential. (iii) Cystine accumulation is measured in leukocytes with a cystine level < 1 nmol 1/2 cystine per milligram cell protein categorized as being consistent with optimal cystine depletion. (iv) Cysteamine bitartrate is the only Food and Drug Administration−approved therapy for cystinosis and is available in immediate and delayed release formulations. (v) In NC, the 57-kb deletion has been associated with transient receptor potential vanilloid 1 (TRPV1) gene functional impairment. (vi) Long-term extra renal manifestations of NC are frequently observed and include cognitive impairment and/or delays, altered skin and/or heat sensations, abnormal temperature regulation, heat intolerance, reduced sweating, and myopathy, the latter of which may eventually contribute to respiratory failure, all suggestive of autonomic nervous system dysfunction pertinent to thermoregulation. Both twins frequently described issues with heat intolerance and photophobia secondary to corneal cystine crystal deposition, but they demonstrated consistently normal clinical neurological examination findings. We decided to complete further testing of the twins to evaluate heat intolerance and possible associated autonomic dysfunction as opposed to what may simply be avoidance of light exposure on sunny days.', 'Clinical Testing': 'During the period before testing, a directly measured glomerular filtration rate was completed on each twin using a plasma clearance of iohexol procedure. 14 The twins then underwent 3 clinical procedures at the Center for Autonomic Medicine in Pediatrics at Ann & Robert H. Lurie Children’s Hospital of Chicago (Chicago, IL). Those procedures included the head-up tilt (HUT) test to assess baroreceptor function, a thermoregulatory sweat test (TST) to measure sudomotor function, and the quantitative sweat response test (QSWEAT), which is a sudomotor axon reflex test in which responses of the local axon reflex of sweat glands to iontophoresed acetylcholine are quantitated. 15 The use of the TST and QSWEAT procedures on patients are considered to be the gold standard for clinical evaluation, because they demonstrated a 90% sensitivity for detection of small fiber neuropathy. 16 The HUT determines whether orthostatic (in)tolerance can be demonstrated and evaluates the inter-relationship of breathing, heart rate (HR), and BP while the patient transitions from a supine to an upright position and then returns to the supine position. Simply stated, a patient lays on a tilt table in a supine horizontal position for 10 to 20 minutes while baseline measurements are taken. Then, a HUT to 70° is done with measurements collected thereafter for 10 minutes. Following this, a tilt-down to a supine horizontal position occurs and is sustained for 2 minutes of additional measurements. During the TST, the core body temperature is increased slowly to 1 ° C higher than at prewarming (baseline) or a patient reaches a core temperature of 38 ° C (whichever is greater). To prepare for the procedure, sweat-indicator powder is applied to the patient’s anterior surface while lying supine on a bed. The patient is then rolled into the chamber, and it is sealed shut, while continuous surveillance and collection of all physiological measurements of the patient, chamber, and temperatures occurs. The ambient temperature is slowly increased with an average ramp rate of 5.0 °C/hour and with a relative humidity range of 35% to 45%. Finally, for the QSWEAT, the patient is placed in a supine horizontal position. Once situated, 4 quarter-sized capsules of acetylcholine are topically applied on the forearm, proximal and distal leg, and foot. An imperceivable 2-mA current is delivered over a 5-minute period, followed by a 5-minute recovery, which results in an accurate quantitation of sweat produced in small areas of the skin.'}
|
{'Testing Results': 'Figures 1 a to d represent the continuous HR and BP recordings of twin 1 ( Figure 1 a and b) and twin 2 ( Figure 1 c and d) during the HUT over the 10-second transition from a supine horizontal position to a 70° upright tilt. As seen in Figure 1 a, the HR of twin 1 exhibited a compensatory increase to a maximum of 110 beats/min at 6.9 minutes into the HUT and remained at this level until she was returned to a horizontal and/or supine position. This was a change of 52 beats/min. In Figure 1 b, a systolic BP (SBP) decline of 29.8 mm Hg can be seen at 0.3 minutes into the HUT. The BP of twin 1 recovered quickly to pre-HUT levels and remained stable thereafter throughout the 10-minute HUT. Conversely, for twin 2, HR increased by 45 to 120 beats/min and a 30-mm Hg SBP drop occurred when transitioned from a supine position to a 70° HUT ( Figure 1 c and d). In addition, the HR and SBP remained at these levels throughout the HUT until the twin returned to the supine position. Thus, both twins exhibited orthostatic tachycardia during HUT that was maintained until returning to the supine horizontal body position, which indicated a greater than average response compared with normative data. Figure 1 Head up-tilt (HUT) of twins 1 and 2 for continuous heart rate (a,c) and blood pressure recordings (b,d). For the TST, the baseline (pre-TST) for twin 1 and twin 2 are shown in Figure 2 a and 2 c, respectively, whereas postwarming period results for each twin are found in Figure 2 b and 2 d, respectively. By referencing the temperature scale shown between Figure 2 a and 2 b and Figure 2 c and 2 d, the images clearly demonstrate both twins with cold hands and feet before warming ( Figure 2 a and 2 c). Conversely, in post-TST images, both twins displayed symmetric warming of their hands but their feet remained slightly cooler compared with other body regions ( Figure 2 b and 2 d). Figure 2 Thermoregulatory sweat test baseline and warmed (post) test twin 1 (a,b) and twin 2 (c,d), respectively. A temperature-color gauge is centered between each baseline and the warmed figure with values shown in degrees Fahrenheit. Postwarming images of twin 1 ( Figure 3 a) and twin 2 ( Figure 3 b) are shown with patchy regions of anhidrosis (in yellow) compared with the purple areas of sweat indicator powder, which demonstrated the regions where sweating occurred. Twin 1 had 53% anhidrosis but preserved sweating on the upper trunk, left abdomen, both hands, and medial legs, whereas twin 2 exhibited 50% anhidrosis and residual sweating of the upper trunk, bilateral hands, and medial legs. Figure 3 Diaphoresis patterns of twin 1 (a) and twin 2 (b) at the completion of the thermoregulatory sweat test (TST). QSWEAT results of twin 1 are shown with sweat rates of the forearm (25−50th percentile) ( Figure 4 a); proximal ( Figure 4 b) and distal leg sweat rates were each <10th percentile (abnormal for sex and age) ( Figure 4 c), and the foot was between the 10th to 25th percentile ( Figure 4 d). In addition, these abnormalities were categorized as a “latency of the sweat response” of the forearm, distal leg, and foot, as well as a “lack of recovery” of the proximal leg. Results for twin 2 showed a similar sweat response latency of the proximal leg ( Figure 5 b). Otherwise, twin 2 exhibited normal sweat volumes and rates for her age as seen for the forearm (10th−25th percentile) ( Figure 5 a), proximal leg (25th percentile) ( Figure 5 b), distal leg (25th percentile) ( Figure 5 c), and foot (50−80th percentile) ( Figure 5 d). Figure 4 Quantitative sweat rate (nanoliters per minute) of twin 1 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d). Figure 5 Quantitative sweat rate (nanoliters per minute) of twin 2 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d).', 'Case 1': 'Monozygotic female adolescent twins, aged 16 years old, were originally diagnosed in infancy with NC and found to have a 57-kb deletion of the CTNS gene, the most frequent cause of NC in Western populations. They were on cysteamine bitartrate (cystagon-immediate release) since diagnosis. Each was currently prescribed Procysbi (cysteamine-delayed release) 675 mg every 12 hours. In addition, each twin was prescribed cysteamine hydrochloride (0.44%) eye drops due to cystine crystal accumulation in the lens and cornea. Both twins were transplanted 6 years previously with kidneys from a single deceased donor source. Since that time, both twins experienced several episodes of transplant rejection, whereas twin 1 also developed Epstein-Barr virus positive posttransplant proliferative disorder. Table 1 includes clinical and medication data on the patients at the time of autonomic testing. As shown in Table 1, twin 2 exhibited a diastolic blood pressure (DBP) that exceeded the threshold for sex and height and had DBP readings 20% higher than those of twin 1. Table 1 Characteristics and medications of female monozygotic twins with nephropathic cystinosis Characteristics Twin 1 Twin 2 Age (yrs) 16 Race W Ethnicity H Wt. (kg) 43.6 46.0 Ht. (cm) 152.3 154.8 BMI percentile (for age and sex) (kg/m 2 ) 25th 40th Resting BP (mm Hg) 118/70 123/84 Measured GFR (ml/min per 1.73 m 2 ) 59.3 70.0 CKD stage 3a 2 Tacrolimus level (ng/ml) 5.5 4.5 Medications, Dose, Frequency Procysbi (cysteamine DR) 675 mg q 12 h Cysteamine HCL (0.44%) 1 gtt. OU q h while awake Amlodipine 10 mg/d Cardura 4 mg/d — Lisinopril 10 mg/d Drisdol 50,000 IU/ q 14 d — Cellcept 500 mg BID Tacrolimus 3 mg BID 2 mg BID Synthroid 137 μg/d 125 μg/d Mg oxide 400 mg BID Bactrim 400-80 40 mg 3×/wk BID, twice a day; BMI, body mass index; BP, blood pressure; CKD, chronic kidney disease; DR, delayed release; GFR, glomerular filtration rate by plasma clearance of iohexol; gtt, drops; H, Hispanic; HCL, hydrochloride; Ht., height; IU, international units; Mg, magnesium; OU, both eyes; q, every; W, white; Wt., weight. Laboratory findings (biochemical characteristics) for both twins are shown in Table 2 . Creatinine, blood urea nitrogen, and cystatin C levels were consistent with the CKD stage of each twin. Both patients also had blood drawn for measurement of their leukocyte cystine levels, which were obtained at the time of their regular laboratory tests. Those results were 1.65 and 1.90 nmol 1/2 cystine per milligram per protein for twins 1 and 2, respectively. Because the twins exhibited leukocyte cystine levels >1 nmol 1/2 cystine per milligram per protein, it indicated they had not achieved an optimal degree of substrate depletion for cystinosis patients on cysteamine therapy. This was due to incomplete adherence with their cysteamine bitartrate therapy. Table 3 lists a summary on cystinosis. Table 2 Laboratory results Results Conventional units (SI Units) Twin # Cr BUN Cystatin C Alb Phos Na K Glucose 1 1.08 (95.47) 15 (5.35) (1.25) 4.5 (45) 3.7 (1.20) 136 (136 ) 4.0 (4.0) 98 (5.44) 2 0.81 (71.60) 13 (4.64) (1.09) 4.9 (49) 3.8 (1.23) 137 (137) 4.2 (4.2) 94 (5.22) Normal reference range 0.25−1.14 mg/dl 5.0−18.0 mg/dl 0.5−1.3 mg/l (1−17 yr) 3.6−4.7 g/dl 3.0−4.8 mg/dl 134−146 mEq/l 3.7−5.7 mEq/l 60−110 mg/dl SI units normal Reference Range 22.1−100.78 mmol/l 1.78−6.43 mmol/l 0.50−1.30 mg/l 36.0−47.0 g/l 0.97−1.55 mmol/l 134−146 mmol/l 3.7−5.7 mmol/l 3.33−6.11 mmol/l Alb, albumin; BUN, blood urea nitrogen; Cr, creatinine; K, potassium; Na, sodium; Phos, phosphorus (inorganic); SI, Standard international. Table 3 Teaching points (i) Cystinosis results from a functional defect in the lysosomal-membrane exporter protein, cystinosin (CTNS), thereby resulting in failure of cystine efflux from cell lysosomes. When untreated, cystine crystals result and are deposited throughout the body, including in the cornea, retina, and most organs. (ii) Nephropathic cystinosis (NC) is often diagnosed in infancy due to the development of severe renal Fanconi syndrome with failure to thrive. Chronic electrolyte replacement is essential. (iii) Cystine accumulation is measured in leukocytes with a cystine level < 1 nmol 1/2 cystine per milligram cell protein categorized as being consistent with optimal cystine depletion. (iv) Cysteamine bitartrate is the only Food and Drug Administration−approved therapy for cystinosis and is available in immediate and delayed release formulations. (v) In NC, the 57-kb deletion has been associated with transient receptor potential vanilloid 1 (TRPV1) gene functional impairment. (vi) Long-term extra renal manifestations of NC are frequently observed and include cognitive impairment and/or delays, altered skin and/or heat sensations, abnormal temperature regulation, heat intolerance, reduced sweating, and myopathy, the latter of which may eventually contribute to respiratory failure, all suggestive of autonomic nervous system dysfunction pertinent to thermoregulation. Both twins frequently described issues with heat intolerance and photophobia secondary to corneal cystine crystal deposition, but they demonstrated consistently normal clinical neurological examination findings. We decided to complete further testing of the twins to evaluate heat intolerance and possible associated autonomic dysfunction as opposed to what may simply be avoidance of light exposure on sunny days.', 'Clinical Testing': 'During the period before testing, a directly measured glomerular filtration rate was completed on each twin using a plasma clearance of iohexol procedure. 14 The twins then underwent 3 clinical procedures at the Center for Autonomic Medicine in Pediatrics at Ann & Robert H. Lurie Children’s Hospital of Chicago (Chicago, IL). Those procedures included the head-up tilt (HUT) test to assess baroreceptor function, a thermoregulatory sweat test (TST) to measure sudomotor function, and the quantitative sweat response test (QSWEAT), which is a sudomotor axon reflex test in which responses of the local axon reflex of sweat glands to iontophoresed acetylcholine are quantitated. 15 The use of the TST and QSWEAT procedures on patients are considered to be the gold standard for clinical evaluation, because they demonstrated a 90% sensitivity for detection of small fiber neuropathy. 16 The HUT determines whether orthostatic (in)tolerance can be demonstrated and evaluates the inter-relationship of breathing, heart rate (HR), and BP while the patient transitions from a supine to an upright position and then returns to the supine position. Simply stated, a patient lays on a tilt table in a supine horizontal position for 10 to 20 minutes while baseline measurements are taken. Then, a HUT to 70° is done with measurements collected thereafter for 10 minutes. Following this, a tilt-down to a supine horizontal position occurs and is sustained for 2 minutes of additional measurements. During the TST, the core body temperature is increased slowly to 1 ° C higher than at prewarming (baseline) or a patient reaches a core temperature of 38 ° C (whichever is greater). To prepare for the procedure, sweat-indicator powder is applied to the patient’s anterior surface while lying supine on a bed. The patient is then rolled into the chamber, and it is sealed shut, while continuous surveillance and collection of all physiological measurements of the patient, chamber, and temperatures occurs. The ambient temperature is slowly increased with an average ramp rate of 5.0 °C/hour and with a relative humidity range of 35% to 45%. Finally, for the QSWEAT, the patient is placed in a supine horizontal position. Once situated, 4 quarter-sized capsules of acetylcholine are topically applied on the forearm, proximal and distal leg, and foot. An imperceivable 2-mA current is delivered over a 5-minute period, followed by a 5-minute recovery, which results in an accurate quantitation of sweat produced in small areas of the skin.'}
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Respiratory-System
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RESP
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[] |
6224624
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{'Testing Results': 'Figures 1 a to d represent the continuous HR and BP recordings of twin 1 ( Figure 1 a and b) and twin 2 ( Figure 1 c and d) during the HUT over the 10-second transition from a supine horizontal position to a 70° upright tilt. As seen in Figure 1 a, the HR of twin 1 exhibited a compensatory increase to a maximum of 110 beats/min at 6.9 minutes into the HUT and remained at this level until she was returned to a horizontal and/or supine position. This was a change of 52 beats/min. In Figure 1 b, a systolic BP (SBP) decline of 29.8 mm Hg can be seen at 0.3 minutes into the HUT. The BP of twin 1 recovered quickly to pre-HUT levels and remained stable thereafter throughout the 10-minute HUT. Conversely, for twin 2, HR increased by 45 to 120 beats/min and a 30-mm Hg SBP drop occurred when transitioned from a supine position to a 70° HUT ( Figure 1 c and d). In addition, the HR and SBP remained at these levels throughout the HUT until the twin returned to the supine position. Thus, both twins exhibited orthostatic tachycardia during HUT that was maintained until returning to the supine horizontal body position, which indicated a greater than average response compared with normative data. Figure 1 Head up-tilt (HUT) of twins 1 and 2 for continuous heart rate (a,c) and blood pressure recordings (b,d). For the TST, the baseline (pre-TST) for twin 1 and twin 2 are shown in Figure 2 a and 2 c, respectively, whereas postwarming period results for each twin are found in Figure 2 b and 2 d, respectively. By referencing the temperature scale shown between Figure 2 a and 2 b and Figure 2 c and 2 d, the images clearly demonstrate both twins with cold hands and feet before warming ( Figure 2 a and 2 c). Conversely, in post-TST images, both twins displayed symmetric warming of their hands but their feet remained slightly cooler compared with other body regions ( Figure 2 b and 2 d). Figure 2 Thermoregulatory sweat test baseline and warmed (post) test twin 1 (a,b) and twin 2 (c,d), respectively. A temperature-color gauge is centered between each baseline and the warmed figure with values shown in degrees Fahrenheit. Postwarming images of twin 1 ( Figure 3 a) and twin 2 ( Figure 3 b) are shown with patchy regions of anhidrosis (in yellow) compared with the purple areas of sweat indicator powder, which demonstrated the regions where sweating occurred. Twin 1 had 53% anhidrosis but preserved sweating on the upper trunk, left abdomen, both hands, and medial legs, whereas twin 2 exhibited 50% anhidrosis and residual sweating of the upper trunk, bilateral hands, and medial legs. Figure 3 Diaphoresis patterns of twin 1 (a) and twin 2 (b) at the completion of the thermoregulatory sweat test (TST). QSWEAT results of twin 1 are shown with sweat rates of the forearm (25−50th percentile) ( Figure 4 a); proximal ( Figure 4 b) and distal leg sweat rates were each <10th percentile (abnormal for sex and age) ( Figure 4 c), and the foot was between the 10th to 25th percentile ( Figure 4 d). In addition, these abnormalities were categorized as a “latency of the sweat response” of the forearm, distal leg, and foot, as well as a “lack of recovery” of the proximal leg. Results for twin 2 showed a similar sweat response latency of the proximal leg ( Figure 5 b). Otherwise, twin 2 exhibited normal sweat volumes and rates for her age as seen for the forearm (10th−25th percentile) ( Figure 5 a), proximal leg (25th percentile) ( Figure 5 b), distal leg (25th percentile) ( Figure 5 c), and foot (50−80th percentile) ( Figure 5 d). Figure 4 Quantitative sweat rate (nanoliters per minute) of twin 1 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d). Figure 5 Quantitative sweat rate (nanoliters per minute) of twin 2 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d).', 'Case 1': 'Monozygotic female adolescent twins, aged 16 years old, were originally diagnosed in infancy with NC and found to have a 57-kb deletion of the CTNS gene, the most frequent cause of NC in Western populations. They were on cysteamine bitartrate (cystagon-immediate release) since diagnosis. Each was currently prescribed Procysbi (cysteamine-delayed release) 675 mg every 12 hours. In addition, each twin was prescribed cysteamine hydrochloride (0.44%) eye drops due to cystine crystal accumulation in the lens and cornea. Both twins were transplanted 6 years previously with kidneys from a single deceased donor source. Since that time, both twins experienced several episodes of transplant rejection, whereas twin 1 also developed Epstein-Barr virus positive posttransplant proliferative disorder. Table 1 includes clinical and medication data on the patients at the time of autonomic testing. As shown in Table 1, twin 2 exhibited a diastolic blood pressure (DBP) that exceeded the threshold for sex and height and had DBP readings 20% higher than those of twin 1. Table 1 Characteristics and medications of female monozygotic twins with nephropathic cystinosis Characteristics Twin 1 Twin 2 Age (yrs) 16 Race W Ethnicity H Wt. (kg) 43.6 46.0 Ht. (cm) 152.3 154.8 BMI percentile (for age and sex) (kg/m 2 ) 25th 40th Resting BP (mm Hg) 118/70 123/84 Measured GFR (ml/min per 1.73 m 2 ) 59.3 70.0 CKD stage 3a 2 Tacrolimus level (ng/ml) 5.5 4.5 Medications, Dose, Frequency Procysbi (cysteamine DR) 675 mg q 12 h Cysteamine HCL (0.44%) 1 gtt. OU q h while awake Amlodipine 10 mg/d Cardura 4 mg/d — Lisinopril 10 mg/d Drisdol 50,000 IU/ q 14 d — Cellcept 500 mg BID Tacrolimus 3 mg BID 2 mg BID Synthroid 137 μg/d 125 μg/d Mg oxide 400 mg BID Bactrim 400-80 40 mg 3×/wk BID, twice a day; BMI, body mass index; BP, blood pressure; CKD, chronic kidney disease; DR, delayed release; GFR, glomerular filtration rate by plasma clearance of iohexol; gtt, drops; H, Hispanic; HCL, hydrochloride; Ht., height; IU, international units; Mg, magnesium; OU, both eyes; q, every; W, white; Wt., weight. Laboratory findings (biochemical characteristics) for both twins are shown in Table 2 . Creatinine, blood urea nitrogen, and cystatin C levels were consistent with the CKD stage of each twin. Both patients also had blood drawn for measurement of their leukocyte cystine levels, which were obtained at the time of their regular laboratory tests. Those results were 1.65 and 1.90 nmol 1/2 cystine per milligram per protein for twins 1 and 2, respectively. Because the twins exhibited leukocyte cystine levels >1 nmol 1/2 cystine per milligram per protein, it indicated they had not achieved an optimal degree of substrate depletion for cystinosis patients on cysteamine therapy. This was due to incomplete adherence with their cysteamine bitartrate therapy. Table 3 lists a summary on cystinosis. Table 2 Laboratory results Results Conventional units (SI Units) Twin # Cr BUN Cystatin C Alb Phos Na K Glucose 1 1.08 (95.47) 15 (5.35) (1.25) 4.5 (45) 3.7 (1.20) 136 (136 ) 4.0 (4.0) 98 (5.44) 2 0.81 (71.60) 13 (4.64) (1.09) 4.9 (49) 3.8 (1.23) 137 (137) 4.2 (4.2) 94 (5.22) Normal reference range 0.25−1.14 mg/dl 5.0−18.0 mg/dl 0.5−1.3 mg/l (1−17 yr) 3.6−4.7 g/dl 3.0−4.8 mg/dl 134−146 mEq/l 3.7−5.7 mEq/l 60−110 mg/dl SI units normal Reference Range 22.1−100.78 mmol/l 1.78−6.43 mmol/l 0.50−1.30 mg/l 36.0−47.0 g/l 0.97−1.55 mmol/l 134−146 mmol/l 3.7−5.7 mmol/l 3.33−6.11 mmol/l Alb, albumin; BUN, blood urea nitrogen; Cr, creatinine; K, potassium; Na, sodium; Phos, phosphorus (inorganic); SI, Standard international. Table 3 Teaching points (i) Cystinosis results from a functional defect in the lysosomal-membrane exporter protein, cystinosin (CTNS), thereby resulting in failure of cystine efflux from cell lysosomes. When untreated, cystine crystals result and are deposited throughout the body, including in the cornea, retina, and most organs. (ii) Nephropathic cystinosis (NC) is often diagnosed in infancy due to the development of severe renal Fanconi syndrome with failure to thrive. Chronic electrolyte replacement is essential. (iii) Cystine accumulation is measured in leukocytes with a cystine level < 1 nmol 1/2 cystine per milligram cell protein categorized as being consistent with optimal cystine depletion. (iv) Cysteamine bitartrate is the only Food and Drug Administration−approved therapy for cystinosis and is available in immediate and delayed release formulations. (v) In NC, the 57-kb deletion has been associated with transient receptor potential vanilloid 1 (TRPV1) gene functional impairment. (vi) Long-term extra renal manifestations of NC are frequently observed and include cognitive impairment and/or delays, altered skin and/or heat sensations, abnormal temperature regulation, heat intolerance, reduced sweating, and myopathy, the latter of which may eventually contribute to respiratory failure, all suggestive of autonomic nervous system dysfunction pertinent to thermoregulation. Both twins frequently described issues with heat intolerance and photophobia secondary to corneal cystine crystal deposition, but they demonstrated consistently normal clinical neurological examination findings. We decided to complete further testing of the twins to evaluate heat intolerance and possible associated autonomic dysfunction as opposed to what may simply be avoidance of light exposure on sunny days.', 'Clinical Testing': 'During the period before testing, a directly measured glomerular filtration rate was completed on each twin using a plasma clearance of iohexol procedure. 14 The twins then underwent 3 clinical procedures at the Center for Autonomic Medicine in Pediatrics at Ann & Robert H. Lurie Children’s Hospital of Chicago (Chicago, IL). Those procedures included the head-up tilt (HUT) test to assess baroreceptor function, a thermoregulatory sweat test (TST) to measure sudomotor function, and the quantitative sweat response test (QSWEAT), which is a sudomotor axon reflex test in which responses of the local axon reflex of sweat glands to iontophoresed acetylcholine are quantitated. 15 The use of the TST and QSWEAT procedures on patients are considered to be the gold standard for clinical evaluation, because they demonstrated a 90% sensitivity for detection of small fiber neuropathy. 16 The HUT determines whether orthostatic (in)tolerance can be demonstrated and evaluates the inter-relationship of breathing, heart rate (HR), and BP while the patient transitions from a supine to an upright position and then returns to the supine position. Simply stated, a patient lays on a tilt table in a supine horizontal position for 10 to 20 minutes while baseline measurements are taken. Then, a HUT to 70° is done with measurements collected thereafter for 10 minutes. Following this, a tilt-down to a supine horizontal position occurs and is sustained for 2 minutes of additional measurements. During the TST, the core body temperature is increased slowly to 1 ° C higher than at prewarming (baseline) or a patient reaches a core temperature of 38 ° C (whichever is greater). To prepare for the procedure, sweat-indicator powder is applied to the patient’s anterior surface while lying supine on a bed. The patient is then rolled into the chamber, and it is sealed shut, while continuous surveillance and collection of all physiological measurements of the patient, chamber, and temperatures occurs. The ambient temperature is slowly increased with an average ramp rate of 5.0 °C/hour and with a relative humidity range of 35% to 45%. Finally, for the QSWEAT, the patient is placed in a supine horizontal position. Once situated, 4 quarter-sized capsules of acetylcholine are topically applied on the forearm, proximal and distal leg, and foot. An imperceivable 2-mA current is delivered over a 5-minute period, followed by a 5-minute recovery, which results in an accurate quantitation of sweat produced in small areas of the skin.'}
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{'Testing Results': 'Figures 1 a to d represent the continuous HR and BP recordings of twin 1 ( Figure 1 a and b) and twin 2 ( Figure 1 c and d) during the HUT over the 10-second transition from a supine horizontal position to a 70° upright tilt. As seen in Figure 1 a, the HR of twin 1 exhibited a compensatory increase to a maximum of 110 beats/min at 6.9 minutes into the HUT and remained at this level until she was returned to a horizontal and/or supine position. This was a change of 52 beats/min. In Figure 1 b, a systolic BP (SBP) decline of 29.8 mm Hg can be seen at 0.3 minutes into the HUT. The BP of twin 1 recovered quickly to pre-HUT levels and remained stable thereafter throughout the 10-minute HUT. Conversely, for twin 2, HR increased by 45 to 120 beats/min and a 30-mm Hg SBP drop occurred when transitioned from a supine position to a 70° HUT ( Figure 1 c and d). In addition, the HR and SBP remained at these levels throughout the HUT until the twin returned to the supine position. Thus, both twins exhibited orthostatic tachycardia during HUT that was maintained until returning to the supine horizontal body position, which indicated a greater than average response compared with normative data. Figure 1 Head up-tilt (HUT) of twins 1 and 2 for continuous heart rate (a,c) and blood pressure recordings (b,d). For the TST, the baseline (pre-TST) for twin 1 and twin 2 are shown in Figure 2 a and 2 c, respectively, whereas postwarming period results for each twin are found in Figure 2 b and 2 d, respectively. By referencing the temperature scale shown between Figure 2 a and 2 b and Figure 2 c and 2 d, the images clearly demonstrate both twins with cold hands and feet before warming ( Figure 2 a and 2 c). Conversely, in post-TST images, both twins displayed symmetric warming of their hands but their feet remained slightly cooler compared with other body regions ( Figure 2 b and 2 d). Figure 2 Thermoregulatory sweat test baseline and warmed (post) test twin 1 (a,b) and twin 2 (c,d), respectively. A temperature-color gauge is centered between each baseline and the warmed figure with values shown in degrees Fahrenheit. Postwarming images of twin 1 ( Figure 3 a) and twin 2 ( Figure 3 b) are shown with patchy regions of anhidrosis (in yellow) compared with the purple areas of sweat indicator powder, which demonstrated the regions where sweating occurred. Twin 1 had 53% anhidrosis but preserved sweating on the upper trunk, left abdomen, both hands, and medial legs, whereas twin 2 exhibited 50% anhidrosis and residual sweating of the upper trunk, bilateral hands, and medial legs. Figure 3 Diaphoresis patterns of twin 1 (a) and twin 2 (b) at the completion of the thermoregulatory sweat test (TST). QSWEAT results of twin 1 are shown with sweat rates of the forearm (25−50th percentile) ( Figure 4 a); proximal ( Figure 4 b) and distal leg sweat rates were each <10th percentile (abnormal for sex and age) ( Figure 4 c), and the foot was between the 10th to 25th percentile ( Figure 4 d). In addition, these abnormalities were categorized as a “latency of the sweat response” of the forearm, distal leg, and foot, as well as a “lack of recovery” of the proximal leg. Results for twin 2 showed a similar sweat response latency of the proximal leg ( Figure 5 b). Otherwise, twin 2 exhibited normal sweat volumes and rates for her age as seen for the forearm (10th−25th percentile) ( Figure 5 a), proximal leg (25th percentile) ( Figure 5 b), distal leg (25th percentile) ( Figure 5 c), and foot (50−80th percentile) ( Figure 5 d). Figure 4 Quantitative sweat rate (nanoliters per minute) of twin 1 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d). Figure 5 Quantitative sweat rate (nanoliters per minute) of twin 2 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d).', 'Case 1': 'Monozygotic female adolescent twins, aged 16 years old, were originally diagnosed in infancy with NC and found to have a 57-kb deletion of the CTNS gene, the most frequent cause of NC in Western populations. They were on cysteamine bitartrate (cystagon-immediate release) since diagnosis. Each was currently prescribed Procysbi (cysteamine-delayed release) 675 mg every 12 hours. In addition, each twin was prescribed cysteamine hydrochloride (0.44%) eye drops due to cystine crystal accumulation in the lens and cornea. Both twins were transplanted 6 years previously with kidneys from a single deceased donor source. Since that time, both twins experienced several episodes of transplant rejection, whereas twin 1 also developed Epstein-Barr virus positive posttransplant proliferative disorder. Table 1 includes clinical and medication data on the patients at the time of autonomic testing. As shown in Table 1, twin 2 exhibited a diastolic blood pressure (DBP) that exceeded the threshold for sex and height and had DBP readings 20% higher than those of twin 1. Table 1 Characteristics and medications of female monozygotic twins with nephropathic cystinosis Characteristics Twin 1 Twin 2 Age (yrs) 16 Race W Ethnicity H Wt. (kg) 43.6 46.0 Ht. (cm) 152.3 154.8 BMI percentile (for age and sex) (kg/m 2 ) 25th 40th Resting BP (mm Hg) 118/70 123/84 Measured GFR (ml/min per 1.73 m 2 ) 59.3 70.0 CKD stage 3a 2 Tacrolimus level (ng/ml) 5.5 4.5 Medications, Dose, Frequency Procysbi (cysteamine DR) 675 mg q 12 h Cysteamine HCL (0.44%) 1 gtt. OU q h while awake Amlodipine 10 mg/d Cardura 4 mg/d — Lisinopril 10 mg/d Drisdol 50,000 IU/ q 14 d — Cellcept 500 mg BID Tacrolimus 3 mg BID 2 mg BID Synthroid 137 μg/d 125 μg/d Mg oxide 400 mg BID Bactrim 400-80 40 mg 3×/wk BID, twice a day; BMI, body mass index; BP, blood pressure; CKD, chronic kidney disease; DR, delayed release; GFR, glomerular filtration rate by plasma clearance of iohexol; gtt, drops; H, Hispanic; HCL, hydrochloride; Ht., height; IU, international units; Mg, magnesium; OU, both eyes; q, every; W, white; Wt., weight. Laboratory findings (biochemical characteristics) for both twins are shown in Table 2 . Creatinine, blood urea nitrogen, and cystatin C levels were consistent with the CKD stage of each twin. Both patients also had blood drawn for measurement of their leukocyte cystine levels, which were obtained at the time of their regular laboratory tests. Those results were 1.65 and 1.90 nmol 1/2 cystine per milligram per protein for twins 1 and 2, respectively. Because the twins exhibited leukocyte cystine levels >1 nmol 1/2 cystine per milligram per protein, it indicated they had not achieved an optimal degree of substrate depletion for cystinosis patients on cysteamine therapy. This was due to incomplete adherence with their cysteamine bitartrate therapy. Table 3 lists a summary on cystinosis. Table 2 Laboratory results Results Conventional units (SI Units) Twin # Cr BUN Cystatin C Alb Phos Na K Glucose 1 1.08 (95.47) 15 (5.35) (1.25) 4.5 (45) 3.7 (1.20) 136 (136 ) 4.0 (4.0) 98 (5.44) 2 0.81 (71.60) 13 (4.64) (1.09) 4.9 (49) 3.8 (1.23) 137 (137) 4.2 (4.2) 94 (5.22) Normal reference range 0.25−1.14 mg/dl 5.0−18.0 mg/dl 0.5−1.3 mg/l (1−17 yr) 3.6−4.7 g/dl 3.0−4.8 mg/dl 134−146 mEq/l 3.7−5.7 mEq/l 60−110 mg/dl SI units normal Reference Range 22.1−100.78 mmol/l 1.78−6.43 mmol/l 0.50−1.30 mg/l 36.0−47.0 g/l 0.97−1.55 mmol/l 134−146 mmol/l 3.7−5.7 mmol/l 3.33−6.11 mmol/l Alb, albumin; BUN, blood urea nitrogen; Cr, creatinine; K, potassium; Na, sodium; Phos, phosphorus (inorganic); SI, Standard international. Table 3 Teaching points (i) Cystinosis results from a functional defect in the lysosomal-membrane exporter protein, cystinosin (CTNS), thereby resulting in failure of cystine efflux from cell lysosomes. When untreated, cystine crystals result and are deposited throughout the body, including in the cornea, retina, and most organs. (ii) Nephropathic cystinosis (NC) is often diagnosed in infancy due to the development of severe renal Fanconi syndrome with failure to thrive. Chronic electrolyte replacement is essential. (iii) Cystine accumulation is measured in leukocytes with a cystine level < 1 nmol 1/2 cystine per milligram cell protein categorized as being consistent with optimal cystine depletion. (iv) Cysteamine bitartrate is the only Food and Drug Administration−approved therapy for cystinosis and is available in immediate and delayed release formulations. (v) In NC, the 57-kb deletion has been associated with transient receptor potential vanilloid 1 (TRPV1) gene functional impairment. (vi) Long-term extra renal manifestations of NC are frequently observed and include cognitive impairment and/or delays, altered skin and/or heat sensations, abnormal temperature regulation, heat intolerance, reduced sweating, and myopathy, the latter of which may eventually contribute to respiratory failure, all suggestive of autonomic nervous system dysfunction pertinent to thermoregulation. Both twins frequently described issues with heat intolerance and photophobia secondary to corneal cystine crystal deposition, but they demonstrated consistently normal clinical neurological examination findings. We decided to complete further testing of the twins to evaluate heat intolerance and possible associated autonomic dysfunction as opposed to what may simply be avoidance of light exposure on sunny days.', 'Clinical Testing': 'During the period before testing, a directly measured glomerular filtration rate was completed on each twin using a plasma clearance of iohexol procedure. 14 The twins then underwent 3 clinical procedures at the Center for Autonomic Medicine in Pediatrics at Ann & Robert H. Lurie Children’s Hospital of Chicago (Chicago, IL). Those procedures included the head-up tilt (HUT) test to assess baroreceptor function, a thermoregulatory sweat test (TST) to measure sudomotor function, and the quantitative sweat response test (QSWEAT), which is a sudomotor axon reflex test in which responses of the local axon reflex of sweat glands to iontophoresed acetylcholine are quantitated. 15 The use of the TST and QSWEAT procedures on patients are considered to be the gold standard for clinical evaluation, because they demonstrated a 90% sensitivity for detection of small fiber neuropathy. 16 The HUT determines whether orthostatic (in)tolerance can be demonstrated and evaluates the inter-relationship of breathing, heart rate (HR), and BP while the patient transitions from a supine to an upright position and then returns to the supine position. Simply stated, a patient lays on a tilt table in a supine horizontal position for 10 to 20 minutes while baseline measurements are taken. Then, a HUT to 70° is done with measurements collected thereafter for 10 minutes. Following this, a tilt-down to a supine horizontal position occurs and is sustained for 2 minutes of additional measurements. During the TST, the core body temperature is increased slowly to 1 ° C higher than at prewarming (baseline) or a patient reaches a core temperature of 38 ° C (whichever is greater). To prepare for the procedure, sweat-indicator powder is applied to the patient’s anterior surface while lying supine on a bed. The patient is then rolled into the chamber, and it is sealed shut, while continuous surveillance and collection of all physiological measurements of the patient, chamber, and temperatures occurs. The ambient temperature is slowly increased with an average ramp rate of 5.0 °C/hour and with a relative humidity range of 35% to 45%. Finally, for the QSWEAT, the patient is placed in a supine horizontal position. Once situated, 4 quarter-sized capsules of acetylcholine are topically applied on the forearm, proximal and distal leg, and foot. An imperceivable 2-mA current is delivered over a 5-minute period, followed by a 5-minute recovery, which results in an accurate quantitation of sweat produced in small areas of the skin.'}
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Musculoskeletal-System
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MSK
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[] |
6224624
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{'Testing Results': 'Figures 1 a to d represent the continuous HR and BP recordings of twin 1 ( Figure 1 a and b) and twin 2 ( Figure 1 c and d) during the HUT over the 10-second transition from a supine horizontal position to a 70° upright tilt. As seen in Figure 1 a, the HR of twin 1 exhibited a compensatory increase to a maximum of 110 beats/min at 6.9 minutes into the HUT and remained at this level until she was returned to a horizontal and/or supine position. This was a change of 52 beats/min. In Figure 1 b, a systolic BP (SBP) decline of 29.8 mm Hg can be seen at 0.3 minutes into the HUT. The BP of twin 1 recovered quickly to pre-HUT levels and remained stable thereafter throughout the 10-minute HUT. Conversely, for twin 2, HR increased by 45 to 120 beats/min and a 30-mm Hg SBP drop occurred when transitioned from a supine position to a 70° HUT ( Figure 1 c and d). In addition, the HR and SBP remained at these levels throughout the HUT until the twin returned to the supine position. Thus, both twins exhibited orthostatic tachycardia during HUT that was maintained until returning to the supine horizontal body position, which indicated a greater than average response compared with normative data. Figure 1 Head up-tilt (HUT) of twins 1 and 2 for continuous heart rate (a,c) and blood pressure recordings (b,d). For the TST, the baseline (pre-TST) for twin 1 and twin 2 are shown in Figure 2 a and 2 c, respectively, whereas postwarming period results for each twin are found in Figure 2 b and 2 d, respectively. By referencing the temperature scale shown between Figure 2 a and 2 b and Figure 2 c and 2 d, the images clearly demonstrate both twins with cold hands and feet before warming ( Figure 2 a and 2 c). Conversely, in post-TST images, both twins displayed symmetric warming of their hands but their feet remained slightly cooler compared with other body regions ( Figure 2 b and 2 d). Figure 2 Thermoregulatory sweat test baseline and warmed (post) test twin 1 (a,b) and twin 2 (c,d), respectively. A temperature-color gauge is centered between each baseline and the warmed figure with values shown in degrees Fahrenheit. Postwarming images of twin 1 ( Figure 3 a) and twin 2 ( Figure 3 b) are shown with patchy regions of anhidrosis (in yellow) compared with the purple areas of sweat indicator powder, which demonstrated the regions where sweating occurred. Twin 1 had 53% anhidrosis but preserved sweating on the upper trunk, left abdomen, both hands, and medial legs, whereas twin 2 exhibited 50% anhidrosis and residual sweating of the upper trunk, bilateral hands, and medial legs. Figure 3 Diaphoresis patterns of twin 1 (a) and twin 2 (b) at the completion of the thermoregulatory sweat test (TST). QSWEAT results of twin 1 are shown with sweat rates of the forearm (25−50th percentile) ( Figure 4 a); proximal ( Figure 4 b) and distal leg sweat rates were each <10th percentile (abnormal for sex and age) ( Figure 4 c), and the foot was between the 10th to 25th percentile ( Figure 4 d). In addition, these abnormalities were categorized as a “latency of the sweat response” of the forearm, distal leg, and foot, as well as a “lack of recovery” of the proximal leg. Results for twin 2 showed a similar sweat response latency of the proximal leg ( Figure 5 b). Otherwise, twin 2 exhibited normal sweat volumes and rates for her age as seen for the forearm (10th−25th percentile) ( Figure 5 a), proximal leg (25th percentile) ( Figure 5 b), distal leg (25th percentile) ( Figure 5 c), and foot (50−80th percentile) ( Figure 5 d). Figure 4 Quantitative sweat rate (nanoliters per minute) of twin 1 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d). Figure 5 Quantitative sweat rate (nanoliters per minute) of twin 2 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d).', 'Case 1': 'Monozygotic female adolescent twins, aged 16 years old, were originally diagnosed in infancy with NC and found to have a 57-kb deletion of the CTNS gene, the most frequent cause of NC in Western populations. They were on cysteamine bitartrate (cystagon-immediate release) since diagnosis. Each was currently prescribed Procysbi (cysteamine-delayed release) 675 mg every 12 hours. In addition, each twin was prescribed cysteamine hydrochloride (0.44%) eye drops due to cystine crystal accumulation in the lens and cornea. Both twins were transplanted 6 years previously with kidneys from a single deceased donor source. Since that time, both twins experienced several episodes of transplant rejection, whereas twin 1 also developed Epstein-Barr virus positive posttransplant proliferative disorder. Table 1 includes clinical and medication data on the patients at the time of autonomic testing. As shown in Table 1, twin 2 exhibited a diastolic blood pressure (DBP) that exceeded the threshold for sex and height and had DBP readings 20% higher than those of twin 1. Table 1 Characteristics and medications of female monozygotic twins with nephropathic cystinosis Characteristics Twin 1 Twin 2 Age (yrs) 16 Race W Ethnicity H Wt. (kg) 43.6 46.0 Ht. (cm) 152.3 154.8 BMI percentile (for age and sex) (kg/m 2 ) 25th 40th Resting BP (mm Hg) 118/70 123/84 Measured GFR (ml/min per 1.73 m 2 ) 59.3 70.0 CKD stage 3a 2 Tacrolimus level (ng/ml) 5.5 4.5 Medications, Dose, Frequency Procysbi (cysteamine DR) 675 mg q 12 h Cysteamine HCL (0.44%) 1 gtt. OU q h while awake Amlodipine 10 mg/d Cardura 4 mg/d — Lisinopril 10 mg/d Drisdol 50,000 IU/ q 14 d — Cellcept 500 mg BID Tacrolimus 3 mg BID 2 mg BID Synthroid 137 μg/d 125 μg/d Mg oxide 400 mg BID Bactrim 400-80 40 mg 3×/wk BID, twice a day; BMI, body mass index; BP, blood pressure; CKD, chronic kidney disease; DR, delayed release; GFR, glomerular filtration rate by plasma clearance of iohexol; gtt, drops; H, Hispanic; HCL, hydrochloride; Ht., height; IU, international units; Mg, magnesium; OU, both eyes; q, every; W, white; Wt., weight. Laboratory findings (biochemical characteristics) for both twins are shown in Table 2 . Creatinine, blood urea nitrogen, and cystatin C levels were consistent with the CKD stage of each twin. Both patients also had blood drawn for measurement of their leukocyte cystine levels, which were obtained at the time of their regular laboratory tests. Those results were 1.65 and 1.90 nmol 1/2 cystine per milligram per protein for twins 1 and 2, respectively. Because the twins exhibited leukocyte cystine levels >1 nmol 1/2 cystine per milligram per protein, it indicated they had not achieved an optimal degree of substrate depletion for cystinosis patients on cysteamine therapy. This was due to incomplete adherence with their cysteamine bitartrate therapy. Table 3 lists a summary on cystinosis. Table 2 Laboratory results Results Conventional units (SI Units) Twin # Cr BUN Cystatin C Alb Phos Na K Glucose 1 1.08 (95.47) 15 (5.35) (1.25) 4.5 (45) 3.7 (1.20) 136 (136 ) 4.0 (4.0) 98 (5.44) 2 0.81 (71.60) 13 (4.64) (1.09) 4.9 (49) 3.8 (1.23) 137 (137) 4.2 (4.2) 94 (5.22) Normal reference range 0.25−1.14 mg/dl 5.0−18.0 mg/dl 0.5−1.3 mg/l (1−17 yr) 3.6−4.7 g/dl 3.0−4.8 mg/dl 134−146 mEq/l 3.7−5.7 mEq/l 60−110 mg/dl SI units normal Reference Range 22.1−100.78 mmol/l 1.78−6.43 mmol/l 0.50−1.30 mg/l 36.0−47.0 g/l 0.97−1.55 mmol/l 134−146 mmol/l 3.7−5.7 mmol/l 3.33−6.11 mmol/l Alb, albumin; BUN, blood urea nitrogen; Cr, creatinine; K, potassium; Na, sodium; Phos, phosphorus (inorganic); SI, Standard international. Table 3 Teaching points (i) Cystinosis results from a functional defect in the lysosomal-membrane exporter protein, cystinosin (CTNS), thereby resulting in failure of cystine efflux from cell lysosomes. When untreated, cystine crystals result and are deposited throughout the body, including in the cornea, retina, and most organs. (ii) Nephropathic cystinosis (NC) is often diagnosed in infancy due to the development of severe renal Fanconi syndrome with failure to thrive. Chronic electrolyte replacement is essential. (iii) Cystine accumulation is measured in leukocytes with a cystine level < 1 nmol 1/2 cystine per milligram cell protein categorized as being consistent with optimal cystine depletion. (iv) Cysteamine bitartrate is the only Food and Drug Administration−approved therapy for cystinosis and is available in immediate and delayed release formulations. (v) In NC, the 57-kb deletion has been associated with transient receptor potential vanilloid 1 (TRPV1) gene functional impairment. (vi) Long-term extra renal manifestations of NC are frequently observed and include cognitive impairment and/or delays, altered skin and/or heat sensations, abnormal temperature regulation, heat intolerance, reduced sweating, and myopathy, the latter of which may eventually contribute to respiratory failure, all suggestive of autonomic nervous system dysfunction pertinent to thermoregulation. Both twins frequently described issues with heat intolerance and photophobia secondary to corneal cystine crystal deposition, but they demonstrated consistently normal clinical neurological examination findings. We decided to complete further testing of the twins to evaluate heat intolerance and possible associated autonomic dysfunction as opposed to what may simply be avoidance of light exposure on sunny days.', 'Clinical Testing': 'During the period before testing, a directly measured glomerular filtration rate was completed on each twin using a plasma clearance of iohexol procedure. 14 The twins then underwent 3 clinical procedures at the Center for Autonomic Medicine in Pediatrics at Ann & Robert H. Lurie Children’s Hospital of Chicago (Chicago, IL). Those procedures included the head-up tilt (HUT) test to assess baroreceptor function, a thermoregulatory sweat test (TST) to measure sudomotor function, and the quantitative sweat response test (QSWEAT), which is a sudomotor axon reflex test in which responses of the local axon reflex of sweat glands to iontophoresed acetylcholine are quantitated. 15 The use of the TST and QSWEAT procedures on patients are considered to be the gold standard for clinical evaluation, because they demonstrated a 90% sensitivity for detection of small fiber neuropathy. 16 The HUT determines whether orthostatic (in)tolerance can be demonstrated and evaluates the inter-relationship of breathing, heart rate (HR), and BP while the patient transitions from a supine to an upright position and then returns to the supine position. Simply stated, a patient lays on a tilt table in a supine horizontal position for 10 to 20 minutes while baseline measurements are taken. Then, a HUT to 70° is done with measurements collected thereafter for 10 minutes. Following this, a tilt-down to a supine horizontal position occurs and is sustained for 2 minutes of additional measurements. During the TST, the core body temperature is increased slowly to 1 ° C higher than at prewarming (baseline) or a patient reaches a core temperature of 38 ° C (whichever is greater). To prepare for the procedure, sweat-indicator powder is applied to the patient’s anterior surface while lying supine on a bed. The patient is then rolled into the chamber, and it is sealed shut, while continuous surveillance and collection of all physiological measurements of the patient, chamber, and temperatures occurs. The ambient temperature is slowly increased with an average ramp rate of 5.0 °C/hour and with a relative humidity range of 35% to 45%. Finally, for the QSWEAT, the patient is placed in a supine horizontal position. Once situated, 4 quarter-sized capsules of acetylcholine are topically applied on the forearm, proximal and distal leg, and foot. An imperceivable 2-mA current is delivered over a 5-minute period, followed by a 5-minute recovery, which results in an accurate quantitation of sweat produced in small areas of the skin.'}
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{'Testing Results': 'Figures 1 a to d represent the continuous HR and BP recordings of twin 1 ( Figure 1 a and b) and twin 2 ( Figure 1 c and d) during the HUT over the 10-second transition from a supine horizontal position to a 70° upright tilt. As seen in Figure 1 a, the HR of twin 1 exhibited a compensatory increase to a maximum of 110 beats/min at 6.9 minutes into the HUT and remained at this level until she was returned to a horizontal and/or supine position. This was a change of 52 beats/min. In Figure 1 b, a systolic BP (SBP) decline of 29.8 mm Hg can be seen at 0.3 minutes into the HUT. The BP of twin 1 recovered quickly to pre-HUT levels and remained stable thereafter throughout the 10-minute HUT. Conversely, for twin 2, HR increased by 45 to 120 beats/min and a 30-mm Hg SBP drop occurred when transitioned from a supine position to a 70° HUT ( Figure 1 c and d). In addition, the HR and SBP remained at these levels throughout the HUT until the twin returned to the supine position. Thus, both twins exhibited orthostatic tachycardia during HUT that was maintained until returning to the supine horizontal body position, which indicated a greater than average response compared with normative data. Figure 1 Head up-tilt (HUT) of twins 1 and 2 for continuous heart rate (a,c) and blood pressure recordings (b,d). For the TST, the baseline (pre-TST) for twin 1 and twin 2 are shown in Figure 2 a and 2 c, respectively, whereas postwarming period results for each twin are found in Figure 2 b and 2 d, respectively. By referencing the temperature scale shown between Figure 2 a and 2 b and Figure 2 c and 2 d, the images clearly demonstrate both twins with cold hands and feet before warming ( Figure 2 a and 2 c). Conversely, in post-TST images, both twins displayed symmetric warming of their hands but their feet remained slightly cooler compared with other body regions ( Figure 2 b and 2 d). Figure 2 Thermoregulatory sweat test baseline and warmed (post) test twin 1 (a,b) and twin 2 (c,d), respectively. A temperature-color gauge is centered between each baseline and the warmed figure with values shown in degrees Fahrenheit. Postwarming images of twin 1 ( Figure 3 a) and twin 2 ( Figure 3 b) are shown with patchy regions of anhidrosis (in yellow) compared with the purple areas of sweat indicator powder, which demonstrated the regions where sweating occurred. Twin 1 had 53% anhidrosis but preserved sweating on the upper trunk, left abdomen, both hands, and medial legs, whereas twin 2 exhibited 50% anhidrosis and residual sweating of the upper trunk, bilateral hands, and medial legs. Figure 3 Diaphoresis patterns of twin 1 (a) and twin 2 (b) at the completion of the thermoregulatory sweat test (TST). QSWEAT results of twin 1 are shown with sweat rates of the forearm (25−50th percentile) ( Figure 4 a); proximal ( Figure 4 b) and distal leg sweat rates were each <10th percentile (abnormal for sex and age) ( Figure 4 c), and the foot was between the 10th to 25th percentile ( Figure 4 d). In addition, these abnormalities were categorized as a “latency of the sweat response” of the forearm, distal leg, and foot, as well as a “lack of recovery” of the proximal leg. Results for twin 2 showed a similar sweat response latency of the proximal leg ( Figure 5 b). Otherwise, twin 2 exhibited normal sweat volumes and rates for her age as seen for the forearm (10th−25th percentile) ( Figure 5 a), proximal leg (25th percentile) ( Figure 5 b), distal leg (25th percentile) ( Figure 5 c), and foot (50−80th percentile) ( Figure 5 d). Figure 4 Quantitative sweat rate (nanoliters per minute) of twin 1 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d). Figure 5 Quantitative sweat rate (nanoliters per minute) of twin 2 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d).', 'Case 1': 'Monozygotic female adolescent twins, aged 16 years old, were originally diagnosed in infancy with NC and found to have a 57-kb deletion of the CTNS gene, the most frequent cause of NC in Western populations. They were on cysteamine bitartrate (cystagon-immediate release) since diagnosis. Each was currently prescribed Procysbi (cysteamine-delayed release) 675 mg every 12 hours. In addition, each twin was prescribed cysteamine hydrochloride (0.44%) eye drops due to cystine crystal accumulation in the lens and cornea. Both twins were transplanted 6 years previously with kidneys from a single deceased donor source. Since that time, both twins experienced several episodes of transplant rejection, whereas twin 1 also developed Epstein-Barr virus positive posttransplant proliferative disorder. Table 1 includes clinical and medication data on the patients at the time of autonomic testing. As shown in Table 1, twin 2 exhibited a diastolic blood pressure (DBP) that exceeded the threshold for sex and height and had DBP readings 20% higher than those of twin 1. Table 1 Characteristics and medications of female monozygotic twins with nephropathic cystinosis Characteristics Twin 1 Twin 2 Age (yrs) 16 Race W Ethnicity H Wt. (kg) 43.6 46.0 Ht. (cm) 152.3 154.8 BMI percentile (for age and sex) (kg/m 2 ) 25th 40th Resting BP (mm Hg) 118/70 123/84 Measured GFR (ml/min per 1.73 m 2 ) 59.3 70.0 CKD stage 3a 2 Tacrolimus level (ng/ml) 5.5 4.5 Medications, Dose, Frequency Procysbi (cysteamine DR) 675 mg q 12 h Cysteamine HCL (0.44%) 1 gtt. OU q h while awake Amlodipine 10 mg/d Cardura 4 mg/d — Lisinopril 10 mg/d Drisdol 50,000 IU/ q 14 d — Cellcept 500 mg BID Tacrolimus 3 mg BID 2 mg BID Synthroid 137 μg/d 125 μg/d Mg oxide 400 mg BID Bactrim 400-80 40 mg 3×/wk BID, twice a day; BMI, body mass index; BP, blood pressure; CKD, chronic kidney disease; DR, delayed release; GFR, glomerular filtration rate by plasma clearance of iohexol; gtt, drops; H, Hispanic; HCL, hydrochloride; Ht., height; IU, international units; Mg, magnesium; OU, both eyes; q, every; W, white; Wt., weight. Laboratory findings (biochemical characteristics) for both twins are shown in Table 2 . Creatinine, blood urea nitrogen, and cystatin C levels were consistent with the CKD stage of each twin. Both patients also had blood drawn for measurement of their leukocyte cystine levels, which were obtained at the time of their regular laboratory tests. Those results were 1.65 and 1.90 nmol 1/2 cystine per milligram per protein for twins 1 and 2, respectively. Because the twins exhibited leukocyte cystine levels >1 nmol 1/2 cystine per milligram per protein, it indicated they had not achieved an optimal degree of substrate depletion for cystinosis patients on cysteamine therapy. This was due to incomplete adherence with their cysteamine bitartrate therapy. Table 3 lists a summary on cystinosis. Table 2 Laboratory results Results Conventional units (SI Units) Twin # Cr BUN Cystatin C Alb Phos Na K Glucose 1 1.08 (95.47) 15 (5.35) (1.25) 4.5 (45) 3.7 (1.20) 136 (136 ) 4.0 (4.0) 98 (5.44) 2 0.81 (71.60) 13 (4.64) (1.09) 4.9 (49) 3.8 (1.23) 137 (137) 4.2 (4.2) 94 (5.22) Normal reference range 0.25−1.14 mg/dl 5.0−18.0 mg/dl 0.5−1.3 mg/l (1−17 yr) 3.6−4.7 g/dl 3.0−4.8 mg/dl 134−146 mEq/l 3.7−5.7 mEq/l 60−110 mg/dl SI units normal Reference Range 22.1−100.78 mmol/l 1.78−6.43 mmol/l 0.50−1.30 mg/l 36.0−47.0 g/l 0.97−1.55 mmol/l 134−146 mmol/l 3.7−5.7 mmol/l 3.33−6.11 mmol/l Alb, albumin; BUN, blood urea nitrogen; Cr, creatinine; K, potassium; Na, sodium; Phos, phosphorus (inorganic); SI, Standard international. Table 3 Teaching points (i) Cystinosis results from a functional defect in the lysosomal-membrane exporter protein, cystinosin (CTNS), thereby resulting in failure of cystine efflux from cell lysosomes. When untreated, cystine crystals result and are deposited throughout the body, including in the cornea, retina, and most organs. (ii) Nephropathic cystinosis (NC) is often diagnosed in infancy due to the development of severe renal Fanconi syndrome with failure to thrive. Chronic electrolyte replacement is essential. (iii) Cystine accumulation is measured in leukocytes with a cystine level < 1 nmol 1/2 cystine per milligram cell protein categorized as being consistent with optimal cystine depletion. (iv) Cysteamine bitartrate is the only Food and Drug Administration−approved therapy for cystinosis and is available in immediate and delayed release formulations. (v) In NC, the 57-kb deletion has been associated with transient receptor potential vanilloid 1 (TRPV1) gene functional impairment. (vi) Long-term extra renal manifestations of NC are frequently observed and include cognitive impairment and/or delays, altered skin and/or heat sensations, abnormal temperature regulation, heat intolerance, reduced sweating, and myopathy, the latter of which may eventually contribute to respiratory failure, all suggestive of autonomic nervous system dysfunction pertinent to thermoregulation. Both twins frequently described issues with heat intolerance and photophobia secondary to corneal cystine crystal deposition, but they demonstrated consistently normal clinical neurological examination findings. We decided to complete further testing of the twins to evaluate heat intolerance and possible associated autonomic dysfunction as opposed to what may simply be avoidance of light exposure on sunny days.', 'Clinical Testing': 'During the period before testing, a directly measured glomerular filtration rate was completed on each twin using a plasma clearance of iohexol procedure. 14 The twins then underwent 3 clinical procedures at the Center for Autonomic Medicine in Pediatrics at Ann & Robert H. Lurie Children’s Hospital of Chicago (Chicago, IL). Those procedures included the head-up tilt (HUT) test to assess baroreceptor function, a thermoregulatory sweat test (TST) to measure sudomotor function, and the quantitative sweat response test (QSWEAT), which is a sudomotor axon reflex test in which responses of the local axon reflex of sweat glands to iontophoresed acetylcholine are quantitated. 15 The use of the TST and QSWEAT procedures on patients are considered to be the gold standard for clinical evaluation, because they demonstrated a 90% sensitivity for detection of small fiber neuropathy. 16 The HUT determines whether orthostatic (in)tolerance can be demonstrated and evaluates the inter-relationship of breathing, heart rate (HR), and BP while the patient transitions from a supine to an upright position and then returns to the supine position. Simply stated, a patient lays on a tilt table in a supine horizontal position for 10 to 20 minutes while baseline measurements are taken. Then, a HUT to 70° is done with measurements collected thereafter for 10 minutes. Following this, a tilt-down to a supine horizontal position occurs and is sustained for 2 minutes of additional measurements. During the TST, the core body temperature is increased slowly to 1 ° C higher than at prewarming (baseline) or a patient reaches a core temperature of 38 ° C (whichever is greater). To prepare for the procedure, sweat-indicator powder is applied to the patient’s anterior surface while lying supine on a bed. The patient is then rolled into the chamber, and it is sealed shut, while continuous surveillance and collection of all physiological measurements of the patient, chamber, and temperatures occurs. The ambient temperature is slowly increased with an average ramp rate of 5.0 °C/hour and with a relative humidity range of 35% to 45%. Finally, for the QSWEAT, the patient is placed in a supine horizontal position. Once situated, 4 quarter-sized capsules of acetylcholine are topically applied on the forearm, proximal and distal leg, and foot. An imperceivable 2-mA current is delivered over a 5-minute period, followed by a 5-minute recovery, which results in an accurate quantitation of sweat produced in small areas of the skin.'}
|
Eyes-Ears-Nose-Throat
|
EENT
|
[
"cystine crystal accumulation in the lens and cornea",
"photophobia secondary to corneal cystine crystal deposition"
] |
6224624
|
{'Testing Results': 'Figures 1 a to d represent the continuous HR and BP recordings of twin 1 ( Figure 1 a and b) and twin 2 ( Figure 1 c and d) during the HUT over the 10-second transition from a supine horizontal position to a 70° upright tilt. As seen in Figure 1 a, the HR of twin 1 exhibited a compensatory increase to a maximum of 110 beats/min at 6.9 minutes into the HUT and remained at this level until she was returned to a horizontal and/or supine position. This was a change of 52 beats/min. In Figure 1 b, a systolic BP (SBP) decline of 29.8 mm Hg can be seen at 0.3 minutes into the HUT. The BP of twin 1 recovered quickly to pre-HUT levels and remained stable thereafter throughout the 10-minute HUT. Conversely, for twin 2, HR increased by 45 to 120 beats/min and a 30-mm Hg SBP drop occurred when transitioned from a supine position to a 70° HUT ( Figure 1 c and d). In addition, the HR and SBP remained at these levels throughout the HUT until the twin returned to the supine position. Thus, both twins exhibited orthostatic tachycardia during HUT that was maintained until returning to the supine horizontal body position, which indicated a greater than average response compared with normative data. Figure 1 Head up-tilt (HUT) of twins 1 and 2 for continuous heart rate (a,c) and blood pressure recordings (b,d). For the TST, the baseline (pre-TST) for twin 1 and twin 2 are shown in Figure 2 a and 2 c, respectively, whereas postwarming period results for each twin are found in Figure 2 b and 2 d, respectively. By referencing the temperature scale shown between Figure 2 a and 2 b and Figure 2 c and 2 d, the images clearly demonstrate both twins with cold hands and feet before warming ( Figure 2 a and 2 c). Conversely, in post-TST images, both twins displayed symmetric warming of their hands but their feet remained slightly cooler compared with other body regions ( Figure 2 b and 2 d). Figure 2 Thermoregulatory sweat test baseline and warmed (post) test twin 1 (a,b) and twin 2 (c,d), respectively. A temperature-color gauge is centered between each baseline and the warmed figure with values shown in degrees Fahrenheit. Postwarming images of twin 1 ( Figure 3 a) and twin 2 ( Figure 3 b) are shown with patchy regions of anhidrosis (in yellow) compared with the purple areas of sweat indicator powder, which demonstrated the regions where sweating occurred. Twin 1 had 53% anhidrosis but preserved sweating on the upper trunk, left abdomen, both hands, and medial legs, whereas twin 2 exhibited 50% anhidrosis and residual sweating of the upper trunk, bilateral hands, and medial legs. Figure 3 Diaphoresis patterns of twin 1 (a) and twin 2 (b) at the completion of the thermoregulatory sweat test (TST). QSWEAT results of twin 1 are shown with sweat rates of the forearm (25−50th percentile) ( Figure 4 a); proximal ( Figure 4 b) and distal leg sweat rates were each <10th percentile (abnormal for sex and age) ( Figure 4 c), and the foot was between the 10th to 25th percentile ( Figure 4 d). In addition, these abnormalities were categorized as a “latency of the sweat response” of the forearm, distal leg, and foot, as well as a “lack of recovery” of the proximal leg. Results for twin 2 showed a similar sweat response latency of the proximal leg ( Figure 5 b). Otherwise, twin 2 exhibited normal sweat volumes and rates for her age as seen for the forearm (10th−25th percentile) ( Figure 5 a), proximal leg (25th percentile) ( Figure 5 b), distal leg (25th percentile) ( Figure 5 c), and foot (50−80th percentile) ( Figure 5 d). Figure 4 Quantitative sweat rate (nanoliters per minute) of twin 1 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d). Figure 5 Quantitative sweat rate (nanoliters per minute) of twin 2 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d).', 'Case 1': 'Monozygotic female adolescent twins, aged 16 years old, were originally diagnosed in infancy with NC and found to have a 57-kb deletion of the CTNS gene, the most frequent cause of NC in Western populations. They were on cysteamine bitartrate (cystagon-immediate release) since diagnosis. Each was currently prescribed Procysbi (cysteamine-delayed release) 675 mg every 12 hours. In addition, each twin was prescribed cysteamine hydrochloride (0.44%) eye drops due to cystine crystal accumulation in the lens and cornea. Both twins were transplanted 6 years previously with kidneys from a single deceased donor source. Since that time, both twins experienced several episodes of transplant rejection, whereas twin 1 also developed Epstein-Barr virus positive posttransplant proliferative disorder. Table 1 includes clinical and medication data on the patients at the time of autonomic testing. As shown in Table 1, twin 2 exhibited a diastolic blood pressure (DBP) that exceeded the threshold for sex and height and had DBP readings 20% higher than those of twin 1. Table 1 Characteristics and medications of female monozygotic twins with nephropathic cystinosis Characteristics Twin 1 Twin 2 Age (yrs) 16 Race W Ethnicity H Wt. (kg) 43.6 46.0 Ht. (cm) 152.3 154.8 BMI percentile (for age and sex) (kg/m 2 ) 25th 40th Resting BP (mm Hg) 118/70 123/84 Measured GFR (ml/min per 1.73 m 2 ) 59.3 70.0 CKD stage 3a 2 Tacrolimus level (ng/ml) 5.5 4.5 Medications, Dose, Frequency Procysbi (cysteamine DR) 675 mg q 12 h Cysteamine HCL (0.44%) 1 gtt. OU q h while awake Amlodipine 10 mg/d Cardura 4 mg/d — Lisinopril 10 mg/d Drisdol 50,000 IU/ q 14 d — Cellcept 500 mg BID Tacrolimus 3 mg BID 2 mg BID Synthroid 137 μg/d 125 μg/d Mg oxide 400 mg BID Bactrim 400-80 40 mg 3×/wk BID, twice a day; BMI, body mass index; BP, blood pressure; CKD, chronic kidney disease; DR, delayed release; GFR, glomerular filtration rate by plasma clearance of iohexol; gtt, drops; H, Hispanic; HCL, hydrochloride; Ht., height; IU, international units; Mg, magnesium; OU, both eyes; q, every; W, white; Wt., weight. Laboratory findings (biochemical characteristics) for both twins are shown in Table 2 . Creatinine, blood urea nitrogen, and cystatin C levels were consistent with the CKD stage of each twin. Both patients also had blood drawn for measurement of their leukocyte cystine levels, which were obtained at the time of their regular laboratory tests. Those results were 1.65 and 1.90 nmol 1/2 cystine per milligram per protein for twins 1 and 2, respectively. Because the twins exhibited leukocyte cystine levels >1 nmol 1/2 cystine per milligram per protein, it indicated they had not achieved an optimal degree of substrate depletion for cystinosis patients on cysteamine therapy. This was due to incomplete adherence with their cysteamine bitartrate therapy. Table 3 lists a summary on cystinosis. Table 2 Laboratory results Results Conventional units (SI Units) Twin # Cr BUN Cystatin C Alb Phos Na K Glucose 1 1.08 (95.47) 15 (5.35) (1.25) 4.5 (45) 3.7 (1.20) 136 (136 ) 4.0 (4.0) 98 (5.44) 2 0.81 (71.60) 13 (4.64) (1.09) 4.9 (49) 3.8 (1.23) 137 (137) 4.2 (4.2) 94 (5.22) Normal reference range 0.25−1.14 mg/dl 5.0−18.0 mg/dl 0.5−1.3 mg/l (1−17 yr) 3.6−4.7 g/dl 3.0−4.8 mg/dl 134−146 mEq/l 3.7−5.7 mEq/l 60−110 mg/dl SI units normal Reference Range 22.1−100.78 mmol/l 1.78−6.43 mmol/l 0.50−1.30 mg/l 36.0−47.0 g/l 0.97−1.55 mmol/l 134−146 mmol/l 3.7−5.7 mmol/l 3.33−6.11 mmol/l Alb, albumin; BUN, blood urea nitrogen; Cr, creatinine; K, potassium; Na, sodium; Phos, phosphorus (inorganic); SI, Standard international. Table 3 Teaching points (i) Cystinosis results from a functional defect in the lysosomal-membrane exporter protein, cystinosin (CTNS), thereby resulting in failure of cystine efflux from cell lysosomes. When untreated, cystine crystals result and are deposited throughout the body, including in the cornea, retina, and most organs. (ii) Nephropathic cystinosis (NC) is often diagnosed in infancy due to the development of severe renal Fanconi syndrome with failure to thrive. Chronic electrolyte replacement is essential. (iii) Cystine accumulation is measured in leukocytes with a cystine level < 1 nmol 1/2 cystine per milligram cell protein categorized as being consistent with optimal cystine depletion. (iv) Cysteamine bitartrate is the only Food and Drug Administration−approved therapy for cystinosis and is available in immediate and delayed release formulations. (v) In NC, the 57-kb deletion has been associated with transient receptor potential vanilloid 1 (TRPV1) gene functional impairment. (vi) Long-term extra renal manifestations of NC are frequently observed and include cognitive impairment and/or delays, altered skin and/or heat sensations, abnormal temperature regulation, heat intolerance, reduced sweating, and myopathy, the latter of which may eventually contribute to respiratory failure, all suggestive of autonomic nervous system dysfunction pertinent to thermoregulation. Both twins frequently described issues with heat intolerance and photophobia secondary to corneal cystine crystal deposition, but they demonstrated consistently normal clinical neurological examination findings. We decided to complete further testing of the twins to evaluate heat intolerance and possible associated autonomic dysfunction as opposed to what may simply be avoidance of light exposure on sunny days.', 'Clinical Testing': 'During the period before testing, a directly measured glomerular filtration rate was completed on each twin using a plasma clearance of iohexol procedure. 14 The twins then underwent 3 clinical procedures at the Center for Autonomic Medicine in Pediatrics at Ann & Robert H. Lurie Children’s Hospital of Chicago (Chicago, IL). Those procedures included the head-up tilt (HUT) test to assess baroreceptor function, a thermoregulatory sweat test (TST) to measure sudomotor function, and the quantitative sweat response test (QSWEAT), which is a sudomotor axon reflex test in which responses of the local axon reflex of sweat glands to iontophoresed acetylcholine are quantitated. 15 The use of the TST and QSWEAT procedures on patients are considered to be the gold standard for clinical evaluation, because they demonstrated a 90% sensitivity for detection of small fiber neuropathy. 16 The HUT determines whether orthostatic (in)tolerance can be demonstrated and evaluates the inter-relationship of breathing, heart rate (HR), and BP while the patient transitions from a supine to an upright position and then returns to the supine position. Simply stated, a patient lays on a tilt table in a supine horizontal position for 10 to 20 minutes while baseline measurements are taken. Then, a HUT to 70° is done with measurements collected thereafter for 10 minutes. Following this, a tilt-down to a supine horizontal position occurs and is sustained for 2 minutes of additional measurements. During the TST, the core body temperature is increased slowly to 1 ° C higher than at prewarming (baseline) or a patient reaches a core temperature of 38 ° C (whichever is greater). To prepare for the procedure, sweat-indicator powder is applied to the patient’s anterior surface while lying supine on a bed. The patient is then rolled into the chamber, and it is sealed shut, while continuous surveillance and collection of all physiological measurements of the patient, chamber, and temperatures occurs. The ambient temperature is slowly increased with an average ramp rate of 5.0 °C/hour and with a relative humidity range of 35% to 45%. Finally, for the QSWEAT, the patient is placed in a supine horizontal position. Once situated, 4 quarter-sized capsules of acetylcholine are topically applied on the forearm, proximal and distal leg, and foot. An imperceivable 2-mA current is delivered over a 5-minute period, followed by a 5-minute recovery, which results in an accurate quantitation of sweat produced in small areas of the skin.'}
|
{'Testing Results': 'Figures 1 a to d represent the continuous HR and BP recordings of twin 1 ( Figure 1 a and b) and twin 2 ( Figure 1 c and d) during the HUT over the 10-second transition from a supine horizontal position to a 70° upright tilt. As seen in Figure 1 a, the HR of twin 1 exhibited a compensatory increase to a maximum of 110 beats/min at 6.9 minutes into the HUT and remained at this level until she was returned to a horizontal and/or supine position. This was a change of 52 beats/min. In Figure 1 b, a systolic BP (SBP) decline of 29.8 mm Hg can be seen at 0.3 minutes into the HUT. The BP of twin 1 recovered quickly to pre-HUT levels and remained stable thereafter throughout the 10-minute HUT. Conversely, for twin 2, HR increased by 45 to 120 beats/min and a 30-mm Hg SBP drop occurred when transitioned from a supine position to a 70° HUT ( Figure 1 c and d). In addition, the HR and SBP remained at these levels throughout the HUT until the twin returned to the supine position. Thus, both twins exhibited orthostatic tachycardia during HUT that was maintained until returning to the supine horizontal body position, which indicated a greater than average response compared with normative data. Figure 1 Head up-tilt (HUT) of twins 1 and 2 for continuous heart rate (a,c) and blood pressure recordings (b,d). For the TST, the baseline (pre-TST) for twin 1 and twin 2 are shown in Figure 2 a and 2 c, respectively, whereas postwarming period results for each twin are found in Figure 2 b and 2 d, respectively. By referencing the temperature scale shown between Figure 2 a and 2 b and Figure 2 c and 2 d, the images clearly demonstrate both twins with cold hands and feet before warming ( Figure 2 a and 2 c). Conversely, in post-TST images, both twins displayed symmetric warming of their hands but their feet remained slightly cooler compared with other body regions ( Figure 2 b and 2 d). Figure 2 Thermoregulatory sweat test baseline and warmed (post) test twin 1 (a,b) and twin 2 (c,d), respectively. A temperature-color gauge is centered between each baseline and the warmed figure with values shown in degrees Fahrenheit. Postwarming images of twin 1 ( Figure 3 a) and twin 2 ( Figure 3 b) are shown with patchy regions of anhidrosis (in yellow) compared with the purple areas of sweat indicator powder, which demonstrated the regions where sweating occurred. Twin 1 had 53% anhidrosis but preserved sweating on the upper trunk, left abdomen, both hands, and medial legs, whereas twin 2 exhibited 50% anhidrosis and residual sweating of the upper trunk, bilateral hands, and medial legs. Figure 3 Diaphoresis patterns of twin 1 (a) and twin 2 (b) at the completion of the thermoregulatory sweat test (TST). QSWEAT results of twin 1 are shown with sweat rates of the forearm (25−50th percentile) ( Figure 4 a); proximal ( Figure 4 b) and distal leg sweat rates were each <10th percentile (abnormal for sex and age) ( Figure 4 c), and the foot was between the 10th to 25th percentile ( Figure 4 d). In addition, these abnormalities were categorized as a “latency of the sweat response” of the forearm, distal leg, and foot, as well as a “lack of recovery” of the proximal leg. Results for twin 2 showed a similar sweat response latency of the proximal leg ( Figure 5 b). Otherwise, twin 2 exhibited normal sweat volumes and rates for her age as seen for the forearm (10th−25th percentile) ( Figure 5 a), proximal leg (25th percentile) ( Figure 5 b), distal leg (25th percentile) ( Figure 5 c), and foot (50−80th percentile) ( Figure 5 d). Figure 4 Quantitative sweat rate (nanoliters per minute) of twin 1 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d). Figure 5 Quantitative sweat rate (nanoliters per minute) of twin 2 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d).', 'Case 1': 'Monozygotic female adolescent twins, aged 16 years old, were originally diagnosed in infancy with NC and found to have a 57-kb deletion of the CTNS gene, the most frequent cause of NC in Western populations. They were on cysteamine bitartrate (cystagon-immediate release) since diagnosis. Each was currently prescribed Procysbi (cysteamine-delayed release) 675 mg every 12 hours. In addition, each twin was prescribed cysteamine hydrochloride (0.44%) eye drops due to cystine crystal accumulation in the lens and cornea. Both twins were transplanted 6 years previously with kidneys from a single deceased donor source. Since that time, both twins experienced several episodes of transplant rejection, whereas twin 1 also developed Epstein-Barr virus positive posttransplant proliferative disorder. Table 1 includes clinical and medication data on the patients at the time of autonomic testing. As shown in Table 1, twin 2 exhibited a diastolic blood pressure (DBP) that exceeded the threshold for sex and height and had DBP readings 20% higher than those of twin 1. Table 1 Characteristics and medications of female monozygotic twins with nephropathic cystinosis Characteristics Twin 1 Twin 2 Age (yrs) 16 Race W Ethnicity H Wt. (kg) 43.6 46.0 Ht. (cm) 152.3 154.8 BMI percentile (for age and sex) (kg/m 2 ) 25th 40th Resting BP (mm Hg) 118/70 123/84 Measured GFR (ml/min per 1.73 m 2 ) 59.3 70.0 CKD stage 3a 2 Tacrolimus level (ng/ml) 5.5 4.5 Medications, Dose, Frequency Procysbi (cysteamine DR) 675 mg q 12 h Cysteamine HCL (0.44%) 1 gtt. OU q h while awake Amlodipine 10 mg/d Cardura 4 mg/d — Lisinopril 10 mg/d Drisdol 50,000 IU/ q 14 d — Cellcept 500 mg BID Tacrolimus 3 mg BID 2 mg BID Synthroid 137 μg/d 125 μg/d Mg oxide 400 mg BID Bactrim 400-80 40 mg 3×/wk BID, twice a day; BMI, body mass index; BP, blood pressure; CKD, chronic kidney disease; DR, delayed release; GFR, glomerular filtration rate by plasma clearance of iohexol; gtt, drops; H, Hispanic; HCL, hydrochloride; Ht., height; IU, international units; Mg, magnesium; OU, both eyes; q, every; W, white; Wt., weight. Laboratory findings (biochemical characteristics) for both twins are shown in Table 2 . Creatinine, blood urea nitrogen, and cystatin C levels were consistent with the CKD stage of each twin. Both patients also had blood drawn for measurement of their leukocyte cystine levels, which were obtained at the time of their regular laboratory tests. Those results were 1.65 and 1.90 nmol 1/2 cystine per milligram per protein for twins 1 and 2, respectively. Because the twins exhibited leukocyte cystine levels >1 nmol 1/2 cystine per milligram per protein, it indicated they had not achieved an optimal degree of substrate depletion for cystinosis patients on cysteamine therapy. This was due to incomplete adherence with their cysteamine bitartrate therapy. Table 3 lists a summary on cystinosis. Table 2 Laboratory results Results Conventional units (SI Units) Twin # Cr BUN Cystatin C Alb Phos Na K Glucose 1 1.08 (95.47) 15 (5.35) (1.25) 4.5 (45) 3.7 (1.20) 136 (136 ) 4.0 (4.0) 98 (5.44) 2 0.81 (71.60) 13 (4.64) (1.09) 4.9 (49) 3.8 (1.23) 137 (137) 4.2 (4.2) 94 (5.22) Normal reference range 0.25−1.14 mg/dl 5.0−18.0 mg/dl 0.5−1.3 mg/l (1−17 yr) 3.6−4.7 g/dl 3.0−4.8 mg/dl 134−146 mEq/l 3.7−5.7 mEq/l 60−110 mg/dl SI units normal Reference Range 22.1−100.78 mmol/l 1.78−6.43 mmol/l 0.50−1.30 mg/l 36.0−47.0 g/l 0.97−1.55 mmol/l 134−146 mmol/l 3.7−5.7 mmol/l 3.33−6.11 mmol/l Alb, albumin; BUN, blood urea nitrogen; Cr, creatinine; K, potassium; Na, sodium; Phos, phosphorus (inorganic); SI, Standard international. Table 3 Teaching points (i) Cystinosis results from a functional defect in the lysosomal-membrane exporter protein, cystinosin (CTNS), thereby resulting in failure of cystine efflux from cell lysosomes. When untreated, cystine crystals result and are deposited throughout the body, including in the cornea, retina, and most organs. (ii) Nephropathic cystinosis (NC) is often diagnosed in infancy due to the development of severe renal Fanconi syndrome with failure to thrive. Chronic electrolyte replacement is essential. (iii) Cystine accumulation is measured in leukocytes with a cystine level < 1 nmol 1/2 cystine per milligram cell protein categorized as being consistent with optimal cystine depletion. (iv) Cysteamine bitartrate is the only Food and Drug Administration−approved therapy for cystinosis and is available in immediate and delayed release formulations. (v) In NC, the 57-kb deletion has been associated with transient receptor potential vanilloid 1 (TRPV1) gene functional impairment. (vi) Long-term extra renal manifestations of NC are frequently observed and include cognitive impairment and/or delays, altered skin and/or heat sensations, abnormal temperature regulation, heat intolerance, reduced sweating, and myopathy, the latter of which may eventually contribute to respiratory failure, all suggestive of autonomic nervous system dysfunction pertinent to thermoregulation. Both twins frequently described issues with heat intolerance and photophobia secondary to corneal cystine crystal deposition, but they demonstrated consistently normal clinical neurological examination findings. We decided to complete further testing of the twins to evaluate heat intolerance and possible associated autonomic dysfunction as opposed to what may simply be avoidance of light exposure on sunny days.', 'Clinical Testing': 'During the period before testing, a directly measured glomerular filtration rate was completed on each twin using a plasma clearance of iohexol procedure. 14 The twins then underwent 3 clinical procedures at the Center for Autonomic Medicine in Pediatrics at Ann & Robert H. Lurie Children’s Hospital of Chicago (Chicago, IL). Those procedures included the head-up tilt (HUT) test to assess baroreceptor function, a thermoregulatory sweat test (TST) to measure sudomotor function, and the quantitative sweat response test (QSWEAT), which is a sudomotor axon reflex test in which responses of the local axon reflex of sweat glands to iontophoresed acetylcholine are quantitated. 15 The use of the TST and QSWEAT procedures on patients are considered to be the gold standard for clinical evaluation, because they demonstrated a 90% sensitivity for detection of small fiber neuropathy. 16 The HUT determines whether orthostatic (in)tolerance can be demonstrated and evaluates the inter-relationship of breathing, heart rate (HR), and BP while the patient transitions from a supine to an upright position and then returns to the supine position. Simply stated, a patient lays on a tilt table in a supine horizontal position for 10 to 20 minutes while baseline measurements are taken. Then, a HUT to 70° is done with measurements collected thereafter for 10 minutes. Following this, a tilt-down to a supine horizontal position occurs and is sustained for 2 minutes of additional measurements. During the TST, the core body temperature is increased slowly to 1 ° C higher than at prewarming (baseline) or a patient reaches a core temperature of 38 ° C (whichever is greater). To prepare for the procedure, sweat-indicator powder is applied to the patient’s anterior surface while lying supine on a bed. The patient is then rolled into the chamber, and it is sealed shut, while continuous surveillance and collection of all physiological measurements of the patient, chamber, and temperatures occurs. The ambient temperature is slowly increased with an average ramp rate of 5.0 °C/hour and with a relative humidity range of 35% to 45%. Finally, for the QSWEAT, the patient is placed in a supine horizontal position. Once situated, 4 quarter-sized capsules of acetylcholine are topically applied on the forearm, proximal and distal leg, and foot. An imperceivable 2-mA current is delivered over a 5-minute period, followed by a 5-minute recovery, which results in an accurate quantitation of sweat produced in small areas of the skin.'}
|
Dermatology
|
DERM
|
[] |
6224624
|
{'Testing Results': 'Figures 1 a to d represent the continuous HR and BP recordings of twin 1 ( Figure 1 a and b) and twin 2 ( Figure 1 c and d) during the HUT over the 10-second transition from a supine horizontal position to a 70° upright tilt. As seen in Figure 1 a, the HR of twin 1 exhibited a compensatory increase to a maximum of 110 beats/min at 6.9 minutes into the HUT and remained at this level until she was returned to a horizontal and/or supine position. This was a change of 52 beats/min. In Figure 1 b, a systolic BP (SBP) decline of 29.8 mm Hg can be seen at 0.3 minutes into the HUT. The BP of twin 1 recovered quickly to pre-HUT levels and remained stable thereafter throughout the 10-minute HUT. Conversely, for twin 2, HR increased by 45 to 120 beats/min and a 30-mm Hg SBP drop occurred when transitioned from a supine position to a 70° HUT ( Figure 1 c and d). In addition, the HR and SBP remained at these levels throughout the HUT until the twin returned to the supine position. Thus, both twins exhibited orthostatic tachycardia during HUT that was maintained until returning to the supine horizontal body position, which indicated a greater than average response compared with normative data. Figure 1 Head up-tilt (HUT) of twins 1 and 2 for continuous heart rate (a,c) and blood pressure recordings (b,d). For the TST, the baseline (pre-TST) for twin 1 and twin 2 are shown in Figure 2 a and 2 c, respectively, whereas postwarming period results for each twin are found in Figure 2 b and 2 d, respectively. By referencing the temperature scale shown between Figure 2 a and 2 b and Figure 2 c and 2 d, the images clearly demonstrate both twins with cold hands and feet before warming ( Figure 2 a and 2 c). Conversely, in post-TST images, both twins displayed symmetric warming of their hands but their feet remained slightly cooler compared with other body regions ( Figure 2 b and 2 d). Figure 2 Thermoregulatory sweat test baseline and warmed (post) test twin 1 (a,b) and twin 2 (c,d), respectively. A temperature-color gauge is centered between each baseline and the warmed figure with values shown in degrees Fahrenheit. Postwarming images of twin 1 ( Figure 3 a) and twin 2 ( Figure 3 b) are shown with patchy regions of anhidrosis (in yellow) compared with the purple areas of sweat indicator powder, which demonstrated the regions where sweating occurred. Twin 1 had 53% anhidrosis but preserved sweating on the upper trunk, left abdomen, both hands, and medial legs, whereas twin 2 exhibited 50% anhidrosis and residual sweating of the upper trunk, bilateral hands, and medial legs. Figure 3 Diaphoresis patterns of twin 1 (a) and twin 2 (b) at the completion of the thermoregulatory sweat test (TST). QSWEAT results of twin 1 are shown with sweat rates of the forearm (25−50th percentile) ( Figure 4 a); proximal ( Figure 4 b) and distal leg sweat rates were each <10th percentile (abnormal for sex and age) ( Figure 4 c), and the foot was between the 10th to 25th percentile ( Figure 4 d). In addition, these abnormalities were categorized as a “latency of the sweat response” of the forearm, distal leg, and foot, as well as a “lack of recovery” of the proximal leg. Results for twin 2 showed a similar sweat response latency of the proximal leg ( Figure 5 b). Otherwise, twin 2 exhibited normal sweat volumes and rates for her age as seen for the forearm (10th−25th percentile) ( Figure 5 a), proximal leg (25th percentile) ( Figure 5 b), distal leg (25th percentile) ( Figure 5 c), and foot (50−80th percentile) ( Figure 5 d). Figure 4 Quantitative sweat rate (nanoliters per minute) of twin 1 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d). Figure 5 Quantitative sweat rate (nanoliters per minute) of twin 2 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d).', 'Case 1': 'Monozygotic female adolescent twins, aged 16 years old, were originally diagnosed in infancy with NC and found to have a 57-kb deletion of the CTNS gene, the most frequent cause of NC in Western populations. They were on cysteamine bitartrate (cystagon-immediate release) since diagnosis. Each was currently prescribed Procysbi (cysteamine-delayed release) 675 mg every 12 hours. In addition, each twin was prescribed cysteamine hydrochloride (0.44%) eye drops due to cystine crystal accumulation in the lens and cornea. Both twins were transplanted 6 years previously with kidneys from a single deceased donor source. Since that time, both twins experienced several episodes of transplant rejection, whereas twin 1 also developed Epstein-Barr virus positive posttransplant proliferative disorder. Table 1 includes clinical and medication data on the patients at the time of autonomic testing. As shown in Table 1, twin 2 exhibited a diastolic blood pressure (DBP) that exceeded the threshold for sex and height and had DBP readings 20% higher than those of twin 1. Table 1 Characteristics and medications of female monozygotic twins with nephropathic cystinosis Characteristics Twin 1 Twin 2 Age (yrs) 16 Race W Ethnicity H Wt. (kg) 43.6 46.0 Ht. (cm) 152.3 154.8 BMI percentile (for age and sex) (kg/m 2 ) 25th 40th Resting BP (mm Hg) 118/70 123/84 Measured GFR (ml/min per 1.73 m 2 ) 59.3 70.0 CKD stage 3a 2 Tacrolimus level (ng/ml) 5.5 4.5 Medications, Dose, Frequency Procysbi (cysteamine DR) 675 mg q 12 h Cysteamine HCL (0.44%) 1 gtt. OU q h while awake Amlodipine 10 mg/d Cardura 4 mg/d — Lisinopril 10 mg/d Drisdol 50,000 IU/ q 14 d — Cellcept 500 mg BID Tacrolimus 3 mg BID 2 mg BID Synthroid 137 μg/d 125 μg/d Mg oxide 400 mg BID Bactrim 400-80 40 mg 3×/wk BID, twice a day; BMI, body mass index; BP, blood pressure; CKD, chronic kidney disease; DR, delayed release; GFR, glomerular filtration rate by plasma clearance of iohexol; gtt, drops; H, Hispanic; HCL, hydrochloride; Ht., height; IU, international units; Mg, magnesium; OU, both eyes; q, every; W, white; Wt., weight. Laboratory findings (biochemical characteristics) for both twins are shown in Table 2 . Creatinine, blood urea nitrogen, and cystatin C levels were consistent with the CKD stage of each twin. Both patients also had blood drawn for measurement of their leukocyte cystine levels, which were obtained at the time of their regular laboratory tests. Those results were 1.65 and 1.90 nmol 1/2 cystine per milligram per protein for twins 1 and 2, respectively. Because the twins exhibited leukocyte cystine levels >1 nmol 1/2 cystine per milligram per protein, it indicated they had not achieved an optimal degree of substrate depletion for cystinosis patients on cysteamine therapy. This was due to incomplete adherence with their cysteamine bitartrate therapy. Table 3 lists a summary on cystinosis. Table 2 Laboratory results Results Conventional units (SI Units) Twin # Cr BUN Cystatin C Alb Phos Na K Glucose 1 1.08 (95.47) 15 (5.35) (1.25) 4.5 (45) 3.7 (1.20) 136 (136 ) 4.0 (4.0) 98 (5.44) 2 0.81 (71.60) 13 (4.64) (1.09) 4.9 (49) 3.8 (1.23) 137 (137) 4.2 (4.2) 94 (5.22) Normal reference range 0.25−1.14 mg/dl 5.0−18.0 mg/dl 0.5−1.3 mg/l (1−17 yr) 3.6−4.7 g/dl 3.0−4.8 mg/dl 134−146 mEq/l 3.7−5.7 mEq/l 60−110 mg/dl SI units normal Reference Range 22.1−100.78 mmol/l 1.78−6.43 mmol/l 0.50−1.30 mg/l 36.0−47.0 g/l 0.97−1.55 mmol/l 134−146 mmol/l 3.7−5.7 mmol/l 3.33−6.11 mmol/l Alb, albumin; BUN, blood urea nitrogen; Cr, creatinine; K, potassium; Na, sodium; Phos, phosphorus (inorganic); SI, Standard international. Table 3 Teaching points (i) Cystinosis results from a functional defect in the lysosomal-membrane exporter protein, cystinosin (CTNS), thereby resulting in failure of cystine efflux from cell lysosomes. When untreated, cystine crystals result and are deposited throughout the body, including in the cornea, retina, and most organs. (ii) Nephropathic cystinosis (NC) is often diagnosed in infancy due to the development of severe renal Fanconi syndrome with failure to thrive. Chronic electrolyte replacement is essential. (iii) Cystine accumulation is measured in leukocytes with a cystine level < 1 nmol 1/2 cystine per milligram cell protein categorized as being consistent with optimal cystine depletion. (iv) Cysteamine bitartrate is the only Food and Drug Administration−approved therapy for cystinosis and is available in immediate and delayed release formulations. (v) In NC, the 57-kb deletion has been associated with transient receptor potential vanilloid 1 (TRPV1) gene functional impairment. (vi) Long-term extra renal manifestations of NC are frequently observed and include cognitive impairment and/or delays, altered skin and/or heat sensations, abnormal temperature regulation, heat intolerance, reduced sweating, and myopathy, the latter of which may eventually contribute to respiratory failure, all suggestive of autonomic nervous system dysfunction pertinent to thermoregulation. Both twins frequently described issues with heat intolerance and photophobia secondary to corneal cystine crystal deposition, but they demonstrated consistently normal clinical neurological examination findings. We decided to complete further testing of the twins to evaluate heat intolerance and possible associated autonomic dysfunction as opposed to what may simply be avoidance of light exposure on sunny days.', 'Clinical Testing': 'During the period before testing, a directly measured glomerular filtration rate was completed on each twin using a plasma clearance of iohexol procedure. 14 The twins then underwent 3 clinical procedures at the Center for Autonomic Medicine in Pediatrics at Ann & Robert H. Lurie Children’s Hospital of Chicago (Chicago, IL). Those procedures included the head-up tilt (HUT) test to assess baroreceptor function, a thermoregulatory sweat test (TST) to measure sudomotor function, and the quantitative sweat response test (QSWEAT), which is a sudomotor axon reflex test in which responses of the local axon reflex of sweat glands to iontophoresed acetylcholine are quantitated. 15 The use of the TST and QSWEAT procedures on patients are considered to be the gold standard for clinical evaluation, because they demonstrated a 90% sensitivity for detection of small fiber neuropathy. 16 The HUT determines whether orthostatic (in)tolerance can be demonstrated and evaluates the inter-relationship of breathing, heart rate (HR), and BP while the patient transitions from a supine to an upright position and then returns to the supine position. Simply stated, a patient lays on a tilt table in a supine horizontal position for 10 to 20 minutes while baseline measurements are taken. Then, a HUT to 70° is done with measurements collected thereafter for 10 minutes. Following this, a tilt-down to a supine horizontal position occurs and is sustained for 2 minutes of additional measurements. During the TST, the core body temperature is increased slowly to 1 ° C higher than at prewarming (baseline) or a patient reaches a core temperature of 38 ° C (whichever is greater). To prepare for the procedure, sweat-indicator powder is applied to the patient’s anterior surface while lying supine on a bed. The patient is then rolled into the chamber, and it is sealed shut, while continuous surveillance and collection of all physiological measurements of the patient, chamber, and temperatures occurs. The ambient temperature is slowly increased with an average ramp rate of 5.0 °C/hour and with a relative humidity range of 35% to 45%. Finally, for the QSWEAT, the patient is placed in a supine horizontal position. Once situated, 4 quarter-sized capsules of acetylcholine are topically applied on the forearm, proximal and distal leg, and foot. An imperceivable 2-mA current is delivered over a 5-minute period, followed by a 5-minute recovery, which results in an accurate quantitation of sweat produced in small areas of the skin.'}
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{'Testing Results': 'Figures 1 a to d represent the continuous HR and BP recordings of twin 1 ( Figure 1 a and b) and twin 2 ( Figure 1 c and d) during the HUT over the 10-second transition from a supine horizontal position to a 70° upright tilt. As seen in Figure 1 a, the HR of twin 1 exhibited a compensatory increase to a maximum of 110 beats/min at 6.9 minutes into the HUT and remained at this level until she was returned to a horizontal and/or supine position. This was a change of 52 beats/min. In Figure 1 b, a systolic BP (SBP) decline of 29.8 mm Hg can be seen at 0.3 minutes into the HUT. The BP of twin 1 recovered quickly to pre-HUT levels and remained stable thereafter throughout the 10-minute HUT. Conversely, for twin 2, HR increased by 45 to 120 beats/min and a 30-mm Hg SBP drop occurred when transitioned from a supine position to a 70° HUT ( Figure 1 c and d). In addition, the HR and SBP remained at these levels throughout the HUT until the twin returned to the supine position. Thus, both twins exhibited orthostatic tachycardia during HUT that was maintained until returning to the supine horizontal body position, which indicated a greater than average response compared with normative data. Figure 1 Head up-tilt (HUT) of twins 1 and 2 for continuous heart rate (a,c) and blood pressure recordings (b,d). For the TST, the baseline (pre-TST) for twin 1 and twin 2 are shown in Figure 2 a and 2 c, respectively, whereas postwarming period results for each twin are found in Figure 2 b and 2 d, respectively. By referencing the temperature scale shown between Figure 2 a and 2 b and Figure 2 c and 2 d, the images clearly demonstrate both twins with cold hands and feet before warming ( Figure 2 a and 2 c). Conversely, in post-TST images, both twins displayed symmetric warming of their hands but their feet remained slightly cooler compared with other body regions ( Figure 2 b and 2 d). Figure 2 Thermoregulatory sweat test baseline and warmed (post) test twin 1 (a,b) and twin 2 (c,d), respectively. A temperature-color gauge is centered between each baseline and the warmed figure with values shown in degrees Fahrenheit. Postwarming images of twin 1 ( Figure 3 a) and twin 2 ( Figure 3 b) are shown with patchy regions of anhidrosis (in yellow) compared with the purple areas of sweat indicator powder, which demonstrated the regions where sweating occurred. Twin 1 had 53% anhidrosis but preserved sweating on the upper trunk, left abdomen, both hands, and medial legs, whereas twin 2 exhibited 50% anhidrosis and residual sweating of the upper trunk, bilateral hands, and medial legs. Figure 3 Diaphoresis patterns of twin 1 (a) and twin 2 (b) at the completion of the thermoregulatory sweat test (TST). QSWEAT results of twin 1 are shown with sweat rates of the forearm (25−50th percentile) ( Figure 4 a); proximal ( Figure 4 b) and distal leg sweat rates were each <10th percentile (abnormal for sex and age) ( Figure 4 c), and the foot was between the 10th to 25th percentile ( Figure 4 d). In addition, these abnormalities were categorized as a “latency of the sweat response” of the forearm, distal leg, and foot, as well as a “lack of recovery” of the proximal leg. Results for twin 2 showed a similar sweat response latency of the proximal leg ( Figure 5 b). Otherwise, twin 2 exhibited normal sweat volumes and rates for her age as seen for the forearm (10th−25th percentile) ( Figure 5 a), proximal leg (25th percentile) ( Figure 5 b), distal leg (25th percentile) ( Figure 5 c), and foot (50−80th percentile) ( Figure 5 d). Figure 4 Quantitative sweat rate (nanoliters per minute) of twin 1 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d). Figure 5 Quantitative sweat rate (nanoliters per minute) of twin 2 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d).', 'Case 1': 'Monozygotic female adolescent twins, aged 16 years old, were originally diagnosed in infancy with NC and found to have a 57-kb deletion of the CTNS gene, the most frequent cause of NC in Western populations. They were on cysteamine bitartrate (cystagon-immediate release) since diagnosis. Each was currently prescribed Procysbi (cysteamine-delayed release) 675 mg every 12 hours. In addition, each twin was prescribed cysteamine hydrochloride (0.44%) eye drops due to cystine crystal accumulation in the lens and cornea. Both twins were transplanted 6 years previously with kidneys from a single deceased donor source. Since that time, both twins experienced several episodes of transplant rejection, whereas twin 1 also developed Epstein-Barr virus positive posttransplant proliferative disorder. Table 1 includes clinical and medication data on the patients at the time of autonomic testing. As shown in Table 1, twin 2 exhibited a diastolic blood pressure (DBP) that exceeded the threshold for sex and height and had DBP readings 20% higher than those of twin 1. Table 1 Characteristics and medications of female monozygotic twins with nephropathic cystinosis Characteristics Twin 1 Twin 2 Age (yrs) 16 Race W Ethnicity H Wt. (kg) 43.6 46.0 Ht. (cm) 152.3 154.8 BMI percentile (for age and sex) (kg/m 2 ) 25th 40th Resting BP (mm Hg) 118/70 123/84 Measured GFR (ml/min per 1.73 m 2 ) 59.3 70.0 CKD stage 3a 2 Tacrolimus level (ng/ml) 5.5 4.5 Medications, Dose, Frequency Procysbi (cysteamine DR) 675 mg q 12 h Cysteamine HCL (0.44%) 1 gtt. OU q h while awake Amlodipine 10 mg/d Cardura 4 mg/d — Lisinopril 10 mg/d Drisdol 50,000 IU/ q 14 d — Cellcept 500 mg BID Tacrolimus 3 mg BID 2 mg BID Synthroid 137 μg/d 125 μg/d Mg oxide 400 mg BID Bactrim 400-80 40 mg 3×/wk BID, twice a day; BMI, body mass index; BP, blood pressure; CKD, chronic kidney disease; DR, delayed release; GFR, glomerular filtration rate by plasma clearance of iohexol; gtt, drops; H, Hispanic; HCL, hydrochloride; Ht., height; IU, international units; Mg, magnesium; OU, both eyes; q, every; W, white; Wt., weight. Laboratory findings (biochemical characteristics) for both twins are shown in Table 2 . Creatinine, blood urea nitrogen, and cystatin C levels were consistent with the CKD stage of each twin. Both patients also had blood drawn for measurement of their leukocyte cystine levels, which were obtained at the time of their regular laboratory tests. Those results were 1.65 and 1.90 nmol 1/2 cystine per milligram per protein for twins 1 and 2, respectively. Because the twins exhibited leukocyte cystine levels >1 nmol 1/2 cystine per milligram per protein, it indicated they had not achieved an optimal degree of substrate depletion for cystinosis patients on cysteamine therapy. This was due to incomplete adherence with their cysteamine bitartrate therapy. Table 3 lists a summary on cystinosis. Table 2 Laboratory results Results Conventional units (SI Units) Twin # Cr BUN Cystatin C Alb Phos Na K Glucose 1 1.08 (95.47) 15 (5.35) (1.25) 4.5 (45) 3.7 (1.20) 136 (136 ) 4.0 (4.0) 98 (5.44) 2 0.81 (71.60) 13 (4.64) (1.09) 4.9 (49) 3.8 (1.23) 137 (137) 4.2 (4.2) 94 (5.22) Normal reference range 0.25−1.14 mg/dl 5.0−18.0 mg/dl 0.5−1.3 mg/l (1−17 yr) 3.6−4.7 g/dl 3.0−4.8 mg/dl 134−146 mEq/l 3.7−5.7 mEq/l 60−110 mg/dl SI units normal Reference Range 22.1−100.78 mmol/l 1.78−6.43 mmol/l 0.50−1.30 mg/l 36.0−47.0 g/l 0.97−1.55 mmol/l 134−146 mmol/l 3.7−5.7 mmol/l 3.33−6.11 mmol/l Alb, albumin; BUN, blood urea nitrogen; Cr, creatinine; K, potassium; Na, sodium; Phos, phosphorus (inorganic); SI, Standard international. Table 3 Teaching points (i) Cystinosis results from a functional defect in the lysosomal-membrane exporter protein, cystinosin (CTNS), thereby resulting in failure of cystine efflux from cell lysosomes. When untreated, cystine crystals result and are deposited throughout the body, including in the cornea, retina, and most organs. (ii) Nephropathic cystinosis (NC) is often diagnosed in infancy due to the development of severe renal Fanconi syndrome with failure to thrive. Chronic electrolyte replacement is essential. (iii) Cystine accumulation is measured in leukocytes with a cystine level < 1 nmol 1/2 cystine per milligram cell protein categorized as being consistent with optimal cystine depletion. (iv) Cysteamine bitartrate is the only Food and Drug Administration−approved therapy for cystinosis and is available in immediate and delayed release formulations. (v) In NC, the 57-kb deletion has been associated with transient receptor potential vanilloid 1 (TRPV1) gene functional impairment. (vi) Long-term extra renal manifestations of NC are frequently observed and include cognitive impairment and/or delays, altered skin and/or heat sensations, abnormal temperature regulation, heat intolerance, reduced sweating, and myopathy, the latter of which may eventually contribute to respiratory failure, all suggestive of autonomic nervous system dysfunction pertinent to thermoregulation. Both twins frequently described issues with heat intolerance and photophobia secondary to corneal cystine crystal deposition, but they demonstrated consistently normal clinical neurological examination findings. We decided to complete further testing of the twins to evaluate heat intolerance and possible associated autonomic dysfunction as opposed to what may simply be avoidance of light exposure on sunny days.', 'Clinical Testing': 'During the period before testing, a directly measured glomerular filtration rate was completed on each twin using a plasma clearance of iohexol procedure. 14 The twins then underwent 3 clinical procedures at the Center for Autonomic Medicine in Pediatrics at Ann & Robert H. Lurie Children’s Hospital of Chicago (Chicago, IL). Those procedures included the head-up tilt (HUT) test to assess baroreceptor function, a thermoregulatory sweat test (TST) to measure sudomotor function, and the quantitative sweat response test (QSWEAT), which is a sudomotor axon reflex test in which responses of the local axon reflex of sweat glands to iontophoresed acetylcholine are quantitated. 15 The use of the TST and QSWEAT procedures on patients are considered to be the gold standard for clinical evaluation, because they demonstrated a 90% sensitivity for detection of small fiber neuropathy. 16 The HUT determines whether orthostatic (in)tolerance can be demonstrated and evaluates the inter-relationship of breathing, heart rate (HR), and BP while the patient transitions from a supine to an upright position and then returns to the supine position. Simply stated, a patient lays on a tilt table in a supine horizontal position for 10 to 20 minutes while baseline measurements are taken. Then, a HUT to 70° is done with measurements collected thereafter for 10 minutes. Following this, a tilt-down to a supine horizontal position occurs and is sustained for 2 minutes of additional measurements. During the TST, the core body temperature is increased slowly to 1 ° C higher than at prewarming (baseline) or a patient reaches a core temperature of 38 ° C (whichever is greater). To prepare for the procedure, sweat-indicator powder is applied to the patient’s anterior surface while lying supine on a bed. The patient is then rolled into the chamber, and it is sealed shut, while continuous surveillance and collection of all physiological measurements of the patient, chamber, and temperatures occurs. The ambient temperature is slowly increased with an average ramp rate of 5.0 °C/hour and with a relative humidity range of 35% to 45%. Finally, for the QSWEAT, the patient is placed in a supine horizontal position. Once situated, 4 quarter-sized capsules of acetylcholine are topically applied on the forearm, proximal and distal leg, and foot. An imperceivable 2-mA current is delivered over a 5-minute period, followed by a 5-minute recovery, which results in an accurate quantitation of sweat produced in small areas of the skin.'}
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Pregnancy
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Pregnancy
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6224624
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{'Testing Results': 'Figures 1 a to d represent the continuous HR and BP recordings of twin 1 ( Figure 1 a and b) and twin 2 ( Figure 1 c and d) during the HUT over the 10-second transition from a supine horizontal position to a 70° upright tilt. As seen in Figure 1 a, the HR of twin 1 exhibited a compensatory increase to a maximum of 110 beats/min at 6.9 minutes into the HUT and remained at this level until she was returned to a horizontal and/or supine position. This was a change of 52 beats/min. In Figure 1 b, a systolic BP (SBP) decline of 29.8 mm Hg can be seen at 0.3 minutes into the HUT. The BP of twin 1 recovered quickly to pre-HUT levels and remained stable thereafter throughout the 10-minute HUT. Conversely, for twin 2, HR increased by 45 to 120 beats/min and a 30-mm Hg SBP drop occurred when transitioned from a supine position to a 70° HUT ( Figure 1 c and d). In addition, the HR and SBP remained at these levels throughout the HUT until the twin returned to the supine position. Thus, both twins exhibited orthostatic tachycardia during HUT that was maintained until returning to the supine horizontal body position, which indicated a greater than average response compared with normative data. Figure 1 Head up-tilt (HUT) of twins 1 and 2 for continuous heart rate (a,c) and blood pressure recordings (b,d). For the TST, the baseline (pre-TST) for twin 1 and twin 2 are shown in Figure 2 a and 2 c, respectively, whereas postwarming period results for each twin are found in Figure 2 b and 2 d, respectively. By referencing the temperature scale shown between Figure 2 a and 2 b and Figure 2 c and 2 d, the images clearly demonstrate both twins with cold hands and feet before warming ( Figure 2 a and 2 c). Conversely, in post-TST images, both twins displayed symmetric warming of their hands but their feet remained slightly cooler compared with other body regions ( Figure 2 b and 2 d). Figure 2 Thermoregulatory sweat test baseline and warmed (post) test twin 1 (a,b) and twin 2 (c,d), respectively. A temperature-color gauge is centered between each baseline and the warmed figure with values shown in degrees Fahrenheit. Postwarming images of twin 1 ( Figure 3 a) and twin 2 ( Figure 3 b) are shown with patchy regions of anhidrosis (in yellow) compared with the purple areas of sweat indicator powder, which demonstrated the regions where sweating occurred. Twin 1 had 53% anhidrosis but preserved sweating on the upper trunk, left abdomen, both hands, and medial legs, whereas twin 2 exhibited 50% anhidrosis and residual sweating of the upper trunk, bilateral hands, and medial legs. Figure 3 Diaphoresis patterns of twin 1 (a) and twin 2 (b) at the completion of the thermoregulatory sweat test (TST). QSWEAT results of twin 1 are shown with sweat rates of the forearm (25−50th percentile) ( Figure 4 a); proximal ( Figure 4 b) and distal leg sweat rates were each <10th percentile (abnormal for sex and age) ( Figure 4 c), and the foot was between the 10th to 25th percentile ( Figure 4 d). In addition, these abnormalities were categorized as a “latency of the sweat response” of the forearm, distal leg, and foot, as well as a “lack of recovery” of the proximal leg. Results for twin 2 showed a similar sweat response latency of the proximal leg ( Figure 5 b). Otherwise, twin 2 exhibited normal sweat volumes and rates for her age as seen for the forearm (10th−25th percentile) ( Figure 5 a), proximal leg (25th percentile) ( Figure 5 b), distal leg (25th percentile) ( Figure 5 c), and foot (50−80th percentile) ( Figure 5 d). Figure 4 Quantitative sweat rate (nanoliters per minute) of twin 1 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d). Figure 5 Quantitative sweat rate (nanoliters per minute) of twin 2 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d).', 'Case 1': 'Monozygotic female adolescent twins, aged 16 years old, were originally diagnosed in infancy with NC and found to have a 57-kb deletion of the CTNS gene, the most frequent cause of NC in Western populations. They were on cysteamine bitartrate (cystagon-immediate release) since diagnosis. Each was currently prescribed Procysbi (cysteamine-delayed release) 675 mg every 12 hours. In addition, each twin was prescribed cysteamine hydrochloride (0.44%) eye drops due to cystine crystal accumulation in the lens and cornea. Both twins were transplanted 6 years previously with kidneys from a single deceased donor source. Since that time, both twins experienced several episodes of transplant rejection, whereas twin 1 also developed Epstein-Barr virus positive posttransplant proliferative disorder. Table 1 includes clinical and medication data on the patients at the time of autonomic testing. As shown in Table 1, twin 2 exhibited a diastolic blood pressure (DBP) that exceeded the threshold for sex and height and had DBP readings 20% higher than those of twin 1. Table 1 Characteristics and medications of female monozygotic twins with nephropathic cystinosis Characteristics Twin 1 Twin 2 Age (yrs) 16 Race W Ethnicity H Wt. (kg) 43.6 46.0 Ht. (cm) 152.3 154.8 BMI percentile (for age and sex) (kg/m 2 ) 25th 40th Resting BP (mm Hg) 118/70 123/84 Measured GFR (ml/min per 1.73 m 2 ) 59.3 70.0 CKD stage 3a 2 Tacrolimus level (ng/ml) 5.5 4.5 Medications, Dose, Frequency Procysbi (cysteamine DR) 675 mg q 12 h Cysteamine HCL (0.44%) 1 gtt. OU q h while awake Amlodipine 10 mg/d Cardura 4 mg/d — Lisinopril 10 mg/d Drisdol 50,000 IU/ q 14 d — Cellcept 500 mg BID Tacrolimus 3 mg BID 2 mg BID Synthroid 137 μg/d 125 μg/d Mg oxide 400 mg BID Bactrim 400-80 40 mg 3×/wk BID, twice a day; BMI, body mass index; BP, blood pressure; CKD, chronic kidney disease; DR, delayed release; GFR, glomerular filtration rate by plasma clearance of iohexol; gtt, drops; H, Hispanic; HCL, hydrochloride; Ht., height; IU, international units; Mg, magnesium; OU, both eyes; q, every; W, white; Wt., weight. Laboratory findings (biochemical characteristics) for both twins are shown in Table 2 . Creatinine, blood urea nitrogen, and cystatin C levels were consistent with the CKD stage of each twin. Both patients also had blood drawn for measurement of their leukocyte cystine levels, which were obtained at the time of their regular laboratory tests. Those results were 1.65 and 1.90 nmol 1/2 cystine per milligram per protein for twins 1 and 2, respectively. Because the twins exhibited leukocyte cystine levels >1 nmol 1/2 cystine per milligram per protein, it indicated they had not achieved an optimal degree of substrate depletion for cystinosis patients on cysteamine therapy. This was due to incomplete adherence with their cysteamine bitartrate therapy. Table 3 lists a summary on cystinosis. Table 2 Laboratory results Results Conventional units (SI Units) Twin # Cr BUN Cystatin C Alb Phos Na K Glucose 1 1.08 (95.47) 15 (5.35) (1.25) 4.5 (45) 3.7 (1.20) 136 (136 ) 4.0 (4.0) 98 (5.44) 2 0.81 (71.60) 13 (4.64) (1.09) 4.9 (49) 3.8 (1.23) 137 (137) 4.2 (4.2) 94 (5.22) Normal reference range 0.25−1.14 mg/dl 5.0−18.0 mg/dl 0.5−1.3 mg/l (1−17 yr) 3.6−4.7 g/dl 3.0−4.8 mg/dl 134−146 mEq/l 3.7−5.7 mEq/l 60−110 mg/dl SI units normal Reference Range 22.1−100.78 mmol/l 1.78−6.43 mmol/l 0.50−1.30 mg/l 36.0−47.0 g/l 0.97−1.55 mmol/l 134−146 mmol/l 3.7−5.7 mmol/l 3.33−6.11 mmol/l Alb, albumin; BUN, blood urea nitrogen; Cr, creatinine; K, potassium; Na, sodium; Phos, phosphorus (inorganic); SI, Standard international. Table 3 Teaching points (i) Cystinosis results from a functional defect in the lysosomal-membrane exporter protein, cystinosin (CTNS), thereby resulting in failure of cystine efflux from cell lysosomes. When untreated, cystine crystals result and are deposited throughout the body, including in the cornea, retina, and most organs. (ii) Nephropathic cystinosis (NC) is often diagnosed in infancy due to the development of severe renal Fanconi syndrome with failure to thrive. Chronic electrolyte replacement is essential. (iii) Cystine accumulation is measured in leukocytes with a cystine level < 1 nmol 1/2 cystine per milligram cell protein categorized as being consistent with optimal cystine depletion. (iv) Cysteamine bitartrate is the only Food and Drug Administration−approved therapy for cystinosis and is available in immediate and delayed release formulations. (v) In NC, the 57-kb deletion has been associated with transient receptor potential vanilloid 1 (TRPV1) gene functional impairment. (vi) Long-term extra renal manifestations of NC are frequently observed and include cognitive impairment and/or delays, altered skin and/or heat sensations, abnormal temperature regulation, heat intolerance, reduced sweating, and myopathy, the latter of which may eventually contribute to respiratory failure, all suggestive of autonomic nervous system dysfunction pertinent to thermoregulation. Both twins frequently described issues with heat intolerance and photophobia secondary to corneal cystine crystal deposition, but they demonstrated consistently normal clinical neurological examination findings. We decided to complete further testing of the twins to evaluate heat intolerance and possible associated autonomic dysfunction as opposed to what may simply be avoidance of light exposure on sunny days.', 'Clinical Testing': 'During the period before testing, a directly measured glomerular filtration rate was completed on each twin using a plasma clearance of iohexol procedure. 14 The twins then underwent 3 clinical procedures at the Center for Autonomic Medicine in Pediatrics at Ann & Robert H. Lurie Children’s Hospital of Chicago (Chicago, IL). Those procedures included the head-up tilt (HUT) test to assess baroreceptor function, a thermoregulatory sweat test (TST) to measure sudomotor function, and the quantitative sweat response test (QSWEAT), which is a sudomotor axon reflex test in which responses of the local axon reflex of sweat glands to iontophoresed acetylcholine are quantitated. 15 The use of the TST and QSWEAT procedures on patients are considered to be the gold standard for clinical evaluation, because they demonstrated a 90% sensitivity for detection of small fiber neuropathy. 16 The HUT determines whether orthostatic (in)tolerance can be demonstrated and evaluates the inter-relationship of breathing, heart rate (HR), and BP while the patient transitions from a supine to an upright position and then returns to the supine position. Simply stated, a patient lays on a tilt table in a supine horizontal position for 10 to 20 minutes while baseline measurements are taken. Then, a HUT to 70° is done with measurements collected thereafter for 10 minutes. Following this, a tilt-down to a supine horizontal position occurs and is sustained for 2 minutes of additional measurements. During the TST, the core body temperature is increased slowly to 1 ° C higher than at prewarming (baseline) or a patient reaches a core temperature of 38 ° C (whichever is greater). To prepare for the procedure, sweat-indicator powder is applied to the patient’s anterior surface while lying supine on a bed. The patient is then rolled into the chamber, and it is sealed shut, while continuous surveillance and collection of all physiological measurements of the patient, chamber, and temperatures occurs. The ambient temperature is slowly increased with an average ramp rate of 5.0 °C/hour and with a relative humidity range of 35% to 45%. Finally, for the QSWEAT, the patient is placed in a supine horizontal position. Once situated, 4 quarter-sized capsules of acetylcholine are topically applied on the forearm, proximal and distal leg, and foot. An imperceivable 2-mA current is delivered over a 5-minute period, followed by a 5-minute recovery, which results in an accurate quantitation of sweat produced in small areas of the skin.'}
|
{'Testing Results': 'Figures 1 a to d represent the continuous HR and BP recordings of twin 1 ( Figure 1 a and b) and twin 2 ( Figure 1 c and d) during the HUT over the 10-second transition from a supine horizontal position to a 70° upright tilt. As seen in Figure 1 a, the HR of twin 1 exhibited a compensatory increase to a maximum of 110 beats/min at 6.9 minutes into the HUT and remained at this level until she was returned to a horizontal and/or supine position. This was a change of 52 beats/min. In Figure 1 b, a systolic BP (SBP) decline of 29.8 mm Hg can be seen at 0.3 minutes into the HUT. The BP of twin 1 recovered quickly to pre-HUT levels and remained stable thereafter throughout the 10-minute HUT. Conversely, for twin 2, HR increased by 45 to 120 beats/min and a 30-mm Hg SBP drop occurred when transitioned from a supine position to a 70° HUT ( Figure 1 c and d). In addition, the HR and SBP remained at these levels throughout the HUT until the twin returned to the supine position. Thus, both twins exhibited orthostatic tachycardia during HUT that was maintained until returning to the supine horizontal body position, which indicated a greater than average response compared with normative data. Figure 1 Head up-tilt (HUT) of twins 1 and 2 for continuous heart rate (a,c) and blood pressure recordings (b,d). For the TST, the baseline (pre-TST) for twin 1 and twin 2 are shown in Figure 2 a and 2 c, respectively, whereas postwarming period results for each twin are found in Figure 2 b and 2 d, respectively. By referencing the temperature scale shown between Figure 2 a and 2 b and Figure 2 c and 2 d, the images clearly demonstrate both twins with cold hands and feet before warming ( Figure 2 a and 2 c). Conversely, in post-TST images, both twins displayed symmetric warming of their hands but their feet remained slightly cooler compared with other body regions ( Figure 2 b and 2 d). Figure 2 Thermoregulatory sweat test baseline and warmed (post) test twin 1 (a,b) and twin 2 (c,d), respectively. A temperature-color gauge is centered between each baseline and the warmed figure with values shown in degrees Fahrenheit. Postwarming images of twin 1 ( Figure 3 a) and twin 2 ( Figure 3 b) are shown with patchy regions of anhidrosis (in yellow) compared with the purple areas of sweat indicator powder, which demonstrated the regions where sweating occurred. Twin 1 had 53% anhidrosis but preserved sweating on the upper trunk, left abdomen, both hands, and medial legs, whereas twin 2 exhibited 50% anhidrosis and residual sweating of the upper trunk, bilateral hands, and medial legs. Figure 3 Diaphoresis patterns of twin 1 (a) and twin 2 (b) at the completion of the thermoregulatory sweat test (TST). QSWEAT results of twin 1 are shown with sweat rates of the forearm (25−50th percentile) ( Figure 4 a); proximal ( Figure 4 b) and distal leg sweat rates were each <10th percentile (abnormal for sex and age) ( Figure 4 c), and the foot was between the 10th to 25th percentile ( Figure 4 d). In addition, these abnormalities were categorized as a “latency of the sweat response” of the forearm, distal leg, and foot, as well as a “lack of recovery” of the proximal leg. Results for twin 2 showed a similar sweat response latency of the proximal leg ( Figure 5 b). Otherwise, twin 2 exhibited normal sweat volumes and rates for her age as seen for the forearm (10th−25th percentile) ( Figure 5 a), proximal leg (25th percentile) ( Figure 5 b), distal leg (25th percentile) ( Figure 5 c), and foot (50−80th percentile) ( Figure 5 d). Figure 4 Quantitative sweat rate (nanoliters per minute) of twin 1 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d). Figure 5 Quantitative sweat rate (nanoliters per minute) of twin 2 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d).', 'Case 1': 'Monozygotic female adolescent twins, aged 16 years old, were originally diagnosed in infancy with NC and found to have a 57-kb deletion of the CTNS gene, the most frequent cause of NC in Western populations. They were on cysteamine bitartrate (cystagon-immediate release) since diagnosis. Each was currently prescribed Procysbi (cysteamine-delayed release) 675 mg every 12 hours. In addition, each twin was prescribed cysteamine hydrochloride (0.44%) eye drops due to cystine crystal accumulation in the lens and cornea. Both twins were transplanted 6 years previously with kidneys from a single deceased donor source. Since that time, both twins experienced several episodes of transplant rejection, whereas twin 1 also developed Epstein-Barr virus positive posttransplant proliferative disorder. Table 1 includes clinical and medication data on the patients at the time of autonomic testing. As shown in Table 1, twin 2 exhibited a diastolic blood pressure (DBP) that exceeded the threshold for sex and height and had DBP readings 20% higher than those of twin 1. Table 1 Characteristics and medications of female monozygotic twins with nephropathic cystinosis Characteristics Twin 1 Twin 2 Age (yrs) 16 Race W Ethnicity H Wt. (kg) 43.6 46.0 Ht. (cm) 152.3 154.8 BMI percentile (for age and sex) (kg/m 2 ) 25th 40th Resting BP (mm Hg) 118/70 123/84 Measured GFR (ml/min per 1.73 m 2 ) 59.3 70.0 CKD stage 3a 2 Tacrolimus level (ng/ml) 5.5 4.5 Medications, Dose, Frequency Procysbi (cysteamine DR) 675 mg q 12 h Cysteamine HCL (0.44%) 1 gtt. OU q h while awake Amlodipine 10 mg/d Cardura 4 mg/d — Lisinopril 10 mg/d Drisdol 50,000 IU/ q 14 d — Cellcept 500 mg BID Tacrolimus 3 mg BID 2 mg BID Synthroid 137 μg/d 125 μg/d Mg oxide 400 mg BID Bactrim 400-80 40 mg 3×/wk BID, twice a day; BMI, body mass index; BP, blood pressure; CKD, chronic kidney disease; DR, delayed release; GFR, glomerular filtration rate by plasma clearance of iohexol; gtt, drops; H, Hispanic; HCL, hydrochloride; Ht., height; IU, international units; Mg, magnesium; OU, both eyes; q, every; W, white; Wt., weight. Laboratory findings (biochemical characteristics) for both twins are shown in Table 2 . Creatinine, blood urea nitrogen, and cystatin C levels were consistent with the CKD stage of each twin. Both patients also had blood drawn for measurement of their leukocyte cystine levels, which were obtained at the time of their regular laboratory tests. Those results were 1.65 and 1.90 nmol 1/2 cystine per milligram per protein for twins 1 and 2, respectively. Because the twins exhibited leukocyte cystine levels >1 nmol 1/2 cystine per milligram per protein, it indicated they had not achieved an optimal degree of substrate depletion for cystinosis patients on cysteamine therapy. This was due to incomplete adherence with their cysteamine bitartrate therapy. Table 3 lists a summary on cystinosis. Table 2 Laboratory results Results Conventional units (SI Units) Twin # Cr BUN Cystatin C Alb Phos Na K Glucose 1 1.08 (95.47) 15 (5.35) (1.25) 4.5 (45) 3.7 (1.20) 136 (136 ) 4.0 (4.0) 98 (5.44) 2 0.81 (71.60) 13 (4.64) (1.09) 4.9 (49) 3.8 (1.23) 137 (137) 4.2 (4.2) 94 (5.22) Normal reference range 0.25−1.14 mg/dl 5.0−18.0 mg/dl 0.5−1.3 mg/l (1−17 yr) 3.6−4.7 g/dl 3.0−4.8 mg/dl 134−146 mEq/l 3.7−5.7 mEq/l 60−110 mg/dl SI units normal Reference Range 22.1−100.78 mmol/l 1.78−6.43 mmol/l 0.50−1.30 mg/l 36.0−47.0 g/l 0.97−1.55 mmol/l 134−146 mmol/l 3.7−5.7 mmol/l 3.33−6.11 mmol/l Alb, albumin; BUN, blood urea nitrogen; Cr, creatinine; K, potassium; Na, sodium; Phos, phosphorus (inorganic); SI, Standard international. Table 3 Teaching points (i) Cystinosis results from a functional defect in the lysosomal-membrane exporter protein, cystinosin (CTNS), thereby resulting in failure of cystine efflux from cell lysosomes. When untreated, cystine crystals result and are deposited throughout the body, including in the cornea, retina, and most organs. (ii) Nephropathic cystinosis (NC) is often diagnosed in infancy due to the development of severe renal Fanconi syndrome with failure to thrive. Chronic electrolyte replacement is essential. (iii) Cystine accumulation is measured in leukocytes with a cystine level < 1 nmol 1/2 cystine per milligram cell protein categorized as being consistent with optimal cystine depletion. (iv) Cysteamine bitartrate is the only Food and Drug Administration−approved therapy for cystinosis and is available in immediate and delayed release formulations. (v) In NC, the 57-kb deletion has been associated with transient receptor potential vanilloid 1 (TRPV1) gene functional impairment. (vi) Long-term extra renal manifestations of NC are frequently observed and include cognitive impairment and/or delays, altered skin and/or heat sensations, abnormal temperature regulation, heat intolerance, reduced sweating, and myopathy, the latter of which may eventually contribute to respiratory failure, all suggestive of autonomic nervous system dysfunction pertinent to thermoregulation. Both twins frequently described issues with heat intolerance and photophobia secondary to corneal cystine crystal deposition, but they demonstrated consistently normal clinical neurological examination findings. We decided to complete further testing of the twins to evaluate heat intolerance and possible associated autonomic dysfunction as opposed to what may simply be avoidance of light exposure on sunny days.', 'Clinical Testing': 'During the period before testing, a directly measured glomerular filtration rate was completed on each twin using a plasma clearance of iohexol procedure. 14 The twins then underwent 3 clinical procedures at the Center for Autonomic Medicine in Pediatrics at Ann & Robert H. Lurie Children’s Hospital of Chicago (Chicago, IL). Those procedures included the head-up tilt (HUT) test to assess baroreceptor function, a thermoregulatory sweat test (TST) to measure sudomotor function, and the quantitative sweat response test (QSWEAT), which is a sudomotor axon reflex test in which responses of the local axon reflex of sweat glands to iontophoresed acetylcholine are quantitated. 15 The use of the TST and QSWEAT procedures on patients are considered to be the gold standard for clinical evaluation, because they demonstrated a 90% sensitivity for detection of small fiber neuropathy. 16 The HUT determines whether orthostatic (in)tolerance can be demonstrated and evaluates the inter-relationship of breathing, heart rate (HR), and BP while the patient transitions from a supine to an upright position and then returns to the supine position. Simply stated, a patient lays on a tilt table in a supine horizontal position for 10 to 20 minutes while baseline measurements are taken. Then, a HUT to 70° is done with measurements collected thereafter for 10 minutes. Following this, a tilt-down to a supine horizontal position occurs and is sustained for 2 minutes of additional measurements. During the TST, the core body temperature is increased slowly to 1 ° C higher than at prewarming (baseline) or a patient reaches a core temperature of 38 ° C (whichever is greater). To prepare for the procedure, sweat-indicator powder is applied to the patient’s anterior surface while lying supine on a bed. The patient is then rolled into the chamber, and it is sealed shut, while continuous surveillance and collection of all physiological measurements of the patient, chamber, and temperatures occurs. The ambient temperature is slowly increased with an average ramp rate of 5.0 °C/hour and with a relative humidity range of 35% to 45%. Finally, for the QSWEAT, the patient is placed in a supine horizontal position. Once situated, 4 quarter-sized capsules of acetylcholine are topically applied on the forearm, proximal and distal leg, and foot. An imperceivable 2-mA current is delivered over a 5-minute period, followed by a 5-minute recovery, which results in an accurate quantitation of sweat produced in small areas of the skin.'}
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Lymphatic-System
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LYMPH
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[] |
6224624
|
{'Testing Results': 'Figures 1 a to d represent the continuous HR and BP recordings of twin 1 ( Figure 1 a and b) and twin 2 ( Figure 1 c and d) during the HUT over the 10-second transition from a supine horizontal position to a 70° upright tilt. As seen in Figure 1 a, the HR of twin 1 exhibited a compensatory increase to a maximum of 110 beats/min at 6.9 minutes into the HUT and remained at this level until she was returned to a horizontal and/or supine position. This was a change of 52 beats/min. In Figure 1 b, a systolic BP (SBP) decline of 29.8 mm Hg can be seen at 0.3 minutes into the HUT. The BP of twin 1 recovered quickly to pre-HUT levels and remained stable thereafter throughout the 10-minute HUT. Conversely, for twin 2, HR increased by 45 to 120 beats/min and a 30-mm Hg SBP drop occurred when transitioned from a supine position to a 70° HUT ( Figure 1 c and d). In addition, the HR and SBP remained at these levels throughout the HUT until the twin returned to the supine position. Thus, both twins exhibited orthostatic tachycardia during HUT that was maintained until returning to the supine horizontal body position, which indicated a greater than average response compared with normative data. Figure 1 Head up-tilt (HUT) of twins 1 and 2 for continuous heart rate (a,c) and blood pressure recordings (b,d). For the TST, the baseline (pre-TST) for twin 1 and twin 2 are shown in Figure 2 a and 2 c, respectively, whereas postwarming period results for each twin are found in Figure 2 b and 2 d, respectively. By referencing the temperature scale shown between Figure 2 a and 2 b and Figure 2 c and 2 d, the images clearly demonstrate both twins with cold hands and feet before warming ( Figure 2 a and 2 c). Conversely, in post-TST images, both twins displayed symmetric warming of their hands but their feet remained slightly cooler compared with other body regions ( Figure 2 b and 2 d). Figure 2 Thermoregulatory sweat test baseline and warmed (post) test twin 1 (a,b) and twin 2 (c,d), respectively. A temperature-color gauge is centered between each baseline and the warmed figure with values shown in degrees Fahrenheit. Postwarming images of twin 1 ( Figure 3 a) and twin 2 ( Figure 3 b) are shown with patchy regions of anhidrosis (in yellow) compared with the purple areas of sweat indicator powder, which demonstrated the regions where sweating occurred. Twin 1 had 53% anhidrosis but preserved sweating on the upper trunk, left abdomen, both hands, and medial legs, whereas twin 2 exhibited 50% anhidrosis and residual sweating of the upper trunk, bilateral hands, and medial legs. Figure 3 Diaphoresis patterns of twin 1 (a) and twin 2 (b) at the completion of the thermoregulatory sweat test (TST). QSWEAT results of twin 1 are shown with sweat rates of the forearm (25−50th percentile) ( Figure 4 a); proximal ( Figure 4 b) and distal leg sweat rates were each <10th percentile (abnormal for sex and age) ( Figure 4 c), and the foot was between the 10th to 25th percentile ( Figure 4 d). In addition, these abnormalities were categorized as a “latency of the sweat response” of the forearm, distal leg, and foot, as well as a “lack of recovery” of the proximal leg. Results for twin 2 showed a similar sweat response latency of the proximal leg ( Figure 5 b). Otherwise, twin 2 exhibited normal sweat volumes and rates for her age as seen for the forearm (10th−25th percentile) ( Figure 5 a), proximal leg (25th percentile) ( Figure 5 b), distal leg (25th percentile) ( Figure 5 c), and foot (50−80th percentile) ( Figure 5 d). Figure 4 Quantitative sweat rate (nanoliters per minute) of twin 1 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d). Figure 5 Quantitative sweat rate (nanoliters per minute) of twin 2 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d).', 'Case 1': 'Monozygotic female adolescent twins, aged 16 years old, were originally diagnosed in infancy with NC and found to have a 57-kb deletion of the CTNS gene, the most frequent cause of NC in Western populations. They were on cysteamine bitartrate (cystagon-immediate release) since diagnosis. Each was currently prescribed Procysbi (cysteamine-delayed release) 675 mg every 12 hours. In addition, each twin was prescribed cysteamine hydrochloride (0.44%) eye drops due to cystine crystal accumulation in the lens and cornea. Both twins were transplanted 6 years previously with kidneys from a single deceased donor source. Since that time, both twins experienced several episodes of transplant rejection, whereas twin 1 also developed Epstein-Barr virus positive posttransplant proliferative disorder. Table 1 includes clinical and medication data on the patients at the time of autonomic testing. As shown in Table 1, twin 2 exhibited a diastolic blood pressure (DBP) that exceeded the threshold for sex and height and had DBP readings 20% higher than those of twin 1. Table 1 Characteristics and medications of female monozygotic twins with nephropathic cystinosis Characteristics Twin 1 Twin 2 Age (yrs) 16 Race W Ethnicity H Wt. (kg) 43.6 46.0 Ht. (cm) 152.3 154.8 BMI percentile (for age and sex) (kg/m 2 ) 25th 40th Resting BP (mm Hg) 118/70 123/84 Measured GFR (ml/min per 1.73 m 2 ) 59.3 70.0 CKD stage 3a 2 Tacrolimus level (ng/ml) 5.5 4.5 Medications, Dose, Frequency Procysbi (cysteamine DR) 675 mg q 12 h Cysteamine HCL (0.44%) 1 gtt. OU q h while awake Amlodipine 10 mg/d Cardura 4 mg/d — Lisinopril 10 mg/d Drisdol 50,000 IU/ q 14 d — Cellcept 500 mg BID Tacrolimus 3 mg BID 2 mg BID Synthroid 137 μg/d 125 μg/d Mg oxide 400 mg BID Bactrim 400-80 40 mg 3×/wk BID, twice a day; BMI, body mass index; BP, blood pressure; CKD, chronic kidney disease; DR, delayed release; GFR, glomerular filtration rate by plasma clearance of iohexol; gtt, drops; H, Hispanic; HCL, hydrochloride; Ht., height; IU, international units; Mg, magnesium; OU, both eyes; q, every; W, white; Wt., weight. Laboratory findings (biochemical characteristics) for both twins are shown in Table 2 . Creatinine, blood urea nitrogen, and cystatin C levels were consistent with the CKD stage of each twin. Both patients also had blood drawn for measurement of their leukocyte cystine levels, which were obtained at the time of their regular laboratory tests. Those results were 1.65 and 1.90 nmol 1/2 cystine per milligram per protein for twins 1 and 2, respectively. Because the twins exhibited leukocyte cystine levels >1 nmol 1/2 cystine per milligram per protein, it indicated they had not achieved an optimal degree of substrate depletion for cystinosis patients on cysteamine therapy. This was due to incomplete adherence with their cysteamine bitartrate therapy. Table 3 lists a summary on cystinosis. Table 2 Laboratory results Results Conventional units (SI Units) Twin # Cr BUN Cystatin C Alb Phos Na K Glucose 1 1.08 (95.47) 15 (5.35) (1.25) 4.5 (45) 3.7 (1.20) 136 (136 ) 4.0 (4.0) 98 (5.44) 2 0.81 (71.60) 13 (4.64) (1.09) 4.9 (49) 3.8 (1.23) 137 (137) 4.2 (4.2) 94 (5.22) Normal reference range 0.25−1.14 mg/dl 5.0−18.0 mg/dl 0.5−1.3 mg/l (1−17 yr) 3.6−4.7 g/dl 3.0−4.8 mg/dl 134−146 mEq/l 3.7−5.7 mEq/l 60−110 mg/dl SI units normal Reference Range 22.1−100.78 mmol/l 1.78−6.43 mmol/l 0.50−1.30 mg/l 36.0−47.0 g/l 0.97−1.55 mmol/l 134−146 mmol/l 3.7−5.7 mmol/l 3.33−6.11 mmol/l Alb, albumin; BUN, blood urea nitrogen; Cr, creatinine; K, potassium; Na, sodium; Phos, phosphorus (inorganic); SI, Standard international. Table 3 Teaching points (i) Cystinosis results from a functional defect in the lysosomal-membrane exporter protein, cystinosin (CTNS), thereby resulting in failure of cystine efflux from cell lysosomes. When untreated, cystine crystals result and are deposited throughout the body, including in the cornea, retina, and most organs. (ii) Nephropathic cystinosis (NC) is often diagnosed in infancy due to the development of severe renal Fanconi syndrome with failure to thrive. Chronic electrolyte replacement is essential. (iii) Cystine accumulation is measured in leukocytes with a cystine level < 1 nmol 1/2 cystine per milligram cell protein categorized as being consistent with optimal cystine depletion. (iv) Cysteamine bitartrate is the only Food and Drug Administration−approved therapy for cystinosis and is available in immediate and delayed release formulations. (v) In NC, the 57-kb deletion has been associated with transient receptor potential vanilloid 1 (TRPV1) gene functional impairment. (vi) Long-term extra renal manifestations of NC are frequently observed and include cognitive impairment and/or delays, altered skin and/or heat sensations, abnormal temperature regulation, heat intolerance, reduced sweating, and myopathy, the latter of which may eventually contribute to respiratory failure, all suggestive of autonomic nervous system dysfunction pertinent to thermoregulation. Both twins frequently described issues with heat intolerance and photophobia secondary to corneal cystine crystal deposition, but they demonstrated consistently normal clinical neurological examination findings. We decided to complete further testing of the twins to evaluate heat intolerance and possible associated autonomic dysfunction as opposed to what may simply be avoidance of light exposure on sunny days.', 'Clinical Testing': 'During the period before testing, a directly measured glomerular filtration rate was completed on each twin using a plasma clearance of iohexol procedure. 14 The twins then underwent 3 clinical procedures at the Center for Autonomic Medicine in Pediatrics at Ann & Robert H. Lurie Children’s Hospital of Chicago (Chicago, IL). Those procedures included the head-up tilt (HUT) test to assess baroreceptor function, a thermoregulatory sweat test (TST) to measure sudomotor function, and the quantitative sweat response test (QSWEAT), which is a sudomotor axon reflex test in which responses of the local axon reflex of sweat glands to iontophoresed acetylcholine are quantitated. 15 The use of the TST and QSWEAT procedures on patients are considered to be the gold standard for clinical evaluation, because they demonstrated a 90% sensitivity for detection of small fiber neuropathy. 16 The HUT determines whether orthostatic (in)tolerance can be demonstrated and evaluates the inter-relationship of breathing, heart rate (HR), and BP while the patient transitions from a supine to an upright position and then returns to the supine position. Simply stated, a patient lays on a tilt table in a supine horizontal position for 10 to 20 minutes while baseline measurements are taken. Then, a HUT to 70° is done with measurements collected thereafter for 10 minutes. Following this, a tilt-down to a supine horizontal position occurs and is sustained for 2 minutes of additional measurements. During the TST, the core body temperature is increased slowly to 1 ° C higher than at prewarming (baseline) or a patient reaches a core temperature of 38 ° C (whichever is greater). To prepare for the procedure, sweat-indicator powder is applied to the patient’s anterior surface while lying supine on a bed. The patient is then rolled into the chamber, and it is sealed shut, while continuous surveillance and collection of all physiological measurements of the patient, chamber, and temperatures occurs. The ambient temperature is slowly increased with an average ramp rate of 5.0 °C/hour and with a relative humidity range of 35% to 45%. Finally, for the QSWEAT, the patient is placed in a supine horizontal position. Once situated, 4 quarter-sized capsules of acetylcholine are topically applied on the forearm, proximal and distal leg, and foot. An imperceivable 2-mA current is delivered over a 5-minute period, followed by a 5-minute recovery, which results in an accurate quantitation of sweat produced in small areas of the skin.'}
|
{'Testing Results': 'Figures 1 a to d represent the continuous HR and BP recordings of twin 1 ( Figure 1 a and b) and twin 2 ( Figure 1 c and d) during the HUT over the 10-second transition from a supine horizontal position to a 70° upright tilt. As seen in Figure 1 a, the HR of twin 1 exhibited a compensatory increase to a maximum of 110 beats/min at 6.9 minutes into the HUT and remained at this level until she was returned to a horizontal and/or supine position. This was a change of 52 beats/min. In Figure 1 b, a systolic BP (SBP) decline of 29.8 mm Hg can be seen at 0.3 minutes into the HUT. The BP of twin 1 recovered quickly to pre-HUT levels and remained stable thereafter throughout the 10-minute HUT. Conversely, for twin 2, HR increased by 45 to 120 beats/min and a 30-mm Hg SBP drop occurred when transitioned from a supine position to a 70° HUT ( Figure 1 c and d). In addition, the HR and SBP remained at these levels throughout the HUT until the twin returned to the supine position. Thus, both twins exhibited orthostatic tachycardia during HUT that was maintained until returning to the supine horizontal body position, which indicated a greater than average response compared with normative data. Figure 1 Head up-tilt (HUT) of twins 1 and 2 for continuous heart rate (a,c) and blood pressure recordings (b,d). For the TST, the baseline (pre-TST) for twin 1 and twin 2 are shown in Figure 2 a and 2 c, respectively, whereas postwarming period results for each twin are found in Figure 2 b and 2 d, respectively. By referencing the temperature scale shown between Figure 2 a and 2 b and Figure 2 c and 2 d, the images clearly demonstrate both twins with cold hands and feet before warming ( Figure 2 a and 2 c). Conversely, in post-TST images, both twins displayed symmetric warming of their hands but their feet remained slightly cooler compared with other body regions ( Figure 2 b and 2 d). Figure 2 Thermoregulatory sweat test baseline and warmed (post) test twin 1 (a,b) and twin 2 (c,d), respectively. A temperature-color gauge is centered between each baseline and the warmed figure with values shown in degrees Fahrenheit. Postwarming images of twin 1 ( Figure 3 a) and twin 2 ( Figure 3 b) are shown with patchy regions of anhidrosis (in yellow) compared with the purple areas of sweat indicator powder, which demonstrated the regions where sweating occurred. Twin 1 had 53% anhidrosis but preserved sweating on the upper trunk, left abdomen, both hands, and medial legs, whereas twin 2 exhibited 50% anhidrosis and residual sweating of the upper trunk, bilateral hands, and medial legs. Figure 3 Diaphoresis patterns of twin 1 (a) and twin 2 (b) at the completion of the thermoregulatory sweat test (TST). QSWEAT results of twin 1 are shown with sweat rates of the forearm (25−50th percentile) ( Figure 4 a); proximal ( Figure 4 b) and distal leg sweat rates were each <10th percentile (abnormal for sex and age) ( Figure 4 c), and the foot was between the 10th to 25th percentile ( Figure 4 d). In addition, these abnormalities were categorized as a “latency of the sweat response” of the forearm, distal leg, and foot, as well as a “lack of recovery” of the proximal leg. Results for twin 2 showed a similar sweat response latency of the proximal leg ( Figure 5 b). Otherwise, twin 2 exhibited normal sweat volumes and rates for her age as seen for the forearm (10th−25th percentile) ( Figure 5 a), proximal leg (25th percentile) ( Figure 5 b), distal leg (25th percentile) ( Figure 5 c), and foot (50−80th percentile) ( Figure 5 d). Figure 4 Quantitative sweat rate (nanoliters per minute) of twin 1 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d). Figure 5 Quantitative sweat rate (nanoliters per minute) of twin 2 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d).', 'Case 1': 'Monozygotic female adolescent twins, aged 16 years old, were originally diagnosed in infancy with NC and found to have a 57-kb deletion of the CTNS gene, the most frequent cause of NC in Western populations. They were on cysteamine bitartrate (cystagon-immediate release) since diagnosis. Each was currently prescribed Procysbi (cysteamine-delayed release) 675 mg every 12 hours. In addition, each twin was prescribed cysteamine hydrochloride (0.44%) eye drops due to cystine crystal accumulation in the lens and cornea. Both twins were transplanted 6 years previously with kidneys from a single deceased donor source. Since that time, both twins experienced several episodes of transplant rejection, whereas twin 1 also developed Epstein-Barr virus positive posttransplant proliferative disorder. Table 1 includes clinical and medication data on the patients at the time of autonomic testing. As shown in Table 1, twin 2 exhibited a diastolic blood pressure (DBP) that exceeded the threshold for sex and height and had DBP readings 20% higher than those of twin 1. Table 1 Characteristics and medications of female monozygotic twins with nephropathic cystinosis Characteristics Twin 1 Twin 2 Age (yrs) 16 Race W Ethnicity H Wt. (kg) 43.6 46.0 Ht. (cm) 152.3 154.8 BMI percentile (for age and sex) (kg/m 2 ) 25th 40th Resting BP (mm Hg) 118/70 123/84 Measured GFR (ml/min per 1.73 m 2 ) 59.3 70.0 CKD stage 3a 2 Tacrolimus level (ng/ml) 5.5 4.5 Medications, Dose, Frequency Procysbi (cysteamine DR) 675 mg q 12 h Cysteamine HCL (0.44%) 1 gtt. OU q h while awake Amlodipine 10 mg/d Cardura 4 mg/d — Lisinopril 10 mg/d Drisdol 50,000 IU/ q 14 d — Cellcept 500 mg BID Tacrolimus 3 mg BID 2 mg BID Synthroid 137 μg/d 125 μg/d Mg oxide 400 mg BID Bactrim 400-80 40 mg 3×/wk BID, twice a day; BMI, body mass index; BP, blood pressure; CKD, chronic kidney disease; DR, delayed release; GFR, glomerular filtration rate by plasma clearance of iohexol; gtt, drops; H, Hispanic; HCL, hydrochloride; Ht., height; IU, international units; Mg, magnesium; OU, both eyes; q, every; W, white; Wt., weight. Laboratory findings (biochemical characteristics) for both twins are shown in Table 2 . Creatinine, blood urea nitrogen, and cystatin C levels were consistent with the CKD stage of each twin. Both patients also had blood drawn for measurement of their leukocyte cystine levels, which were obtained at the time of their regular laboratory tests. Those results were 1.65 and 1.90 nmol 1/2 cystine per milligram per protein for twins 1 and 2, respectively. Because the twins exhibited leukocyte cystine levels >1 nmol 1/2 cystine per milligram per protein, it indicated they had not achieved an optimal degree of substrate depletion for cystinosis patients on cysteamine therapy. This was due to incomplete adherence with their cysteamine bitartrate therapy. Table 3 lists a summary on cystinosis. Table 2 Laboratory results Results Conventional units (SI Units) Twin # Cr BUN Cystatin C Alb Phos Na K Glucose 1 1.08 (95.47) 15 (5.35) (1.25) 4.5 (45) 3.7 (1.20) 136 (136 ) 4.0 (4.0) 98 (5.44) 2 0.81 (71.60) 13 (4.64) (1.09) 4.9 (49) 3.8 (1.23) 137 (137) 4.2 (4.2) 94 (5.22) Normal reference range 0.25−1.14 mg/dl 5.0−18.0 mg/dl 0.5−1.3 mg/l (1−17 yr) 3.6−4.7 g/dl 3.0−4.8 mg/dl 134−146 mEq/l 3.7−5.7 mEq/l 60−110 mg/dl SI units normal Reference Range 22.1−100.78 mmol/l 1.78−6.43 mmol/l 0.50−1.30 mg/l 36.0−47.0 g/l 0.97−1.55 mmol/l 134−146 mmol/l 3.7−5.7 mmol/l 3.33−6.11 mmol/l Alb, albumin; BUN, blood urea nitrogen; Cr, creatinine; K, potassium; Na, sodium; Phos, phosphorus (inorganic); SI, Standard international. Table 3 Teaching points (i) Cystinosis results from a functional defect in the lysosomal-membrane exporter protein, cystinosin (CTNS), thereby resulting in failure of cystine efflux from cell lysosomes. When untreated, cystine crystals result and are deposited throughout the body, including in the cornea, retina, and most organs. (ii) Nephropathic cystinosis (NC) is often diagnosed in infancy due to the development of severe renal Fanconi syndrome with failure to thrive. Chronic electrolyte replacement is essential. (iii) Cystine accumulation is measured in leukocytes with a cystine level < 1 nmol 1/2 cystine per milligram cell protein categorized as being consistent with optimal cystine depletion. (iv) Cysteamine bitartrate is the only Food and Drug Administration−approved therapy for cystinosis and is available in immediate and delayed release formulations. (v) In NC, the 57-kb deletion has been associated with transient receptor potential vanilloid 1 (TRPV1) gene functional impairment. (vi) Long-term extra renal manifestations of NC are frequently observed and include cognitive impairment and/or delays, altered skin and/or heat sensations, abnormal temperature regulation, heat intolerance, reduced sweating, and myopathy, the latter of which may eventually contribute to respiratory failure, all suggestive of autonomic nervous system dysfunction pertinent to thermoregulation. Both twins frequently described issues with heat intolerance and photophobia secondary to corneal cystine crystal deposition, but they demonstrated consistently normal clinical neurological examination findings. We decided to complete further testing of the twins to evaluate heat intolerance and possible associated autonomic dysfunction as opposed to what may simply be avoidance of light exposure on sunny days.', 'Clinical Testing': 'During the period before testing, a directly measured glomerular filtration rate was completed on each twin using a plasma clearance of iohexol procedure. 14 The twins then underwent 3 clinical procedures at the Center for Autonomic Medicine in Pediatrics at Ann & Robert H. Lurie Children’s Hospital of Chicago (Chicago, IL). Those procedures included the head-up tilt (HUT) test to assess baroreceptor function, a thermoregulatory sweat test (TST) to measure sudomotor function, and the quantitative sweat response test (QSWEAT), which is a sudomotor axon reflex test in which responses of the local axon reflex of sweat glands to iontophoresed acetylcholine are quantitated. 15 The use of the TST and QSWEAT procedures on patients are considered to be the gold standard for clinical evaluation, because they demonstrated a 90% sensitivity for detection of small fiber neuropathy. 16 The HUT determines whether orthostatic (in)tolerance can be demonstrated and evaluates the inter-relationship of breathing, heart rate (HR), and BP while the patient transitions from a supine to an upright position and then returns to the supine position. Simply stated, a patient lays on a tilt table in a supine horizontal position for 10 to 20 minutes while baseline measurements are taken. Then, a HUT to 70° is done with measurements collected thereafter for 10 minutes. Following this, a tilt-down to a supine horizontal position occurs and is sustained for 2 minutes of additional measurements. During the TST, the core body temperature is increased slowly to 1 ° C higher than at prewarming (baseline) or a patient reaches a core temperature of 38 ° C (whichever is greater). To prepare for the procedure, sweat-indicator powder is applied to the patient’s anterior surface while lying supine on a bed. The patient is then rolled into the chamber, and it is sealed shut, while continuous surveillance and collection of all physiological measurements of the patient, chamber, and temperatures occurs. The ambient temperature is slowly increased with an average ramp rate of 5.0 °C/hour and with a relative humidity range of 35% to 45%. Finally, for the QSWEAT, the patient is placed in a supine horizontal position. Once situated, 4 quarter-sized capsules of acetylcholine are topically applied on the forearm, proximal and distal leg, and foot. An imperceivable 2-mA current is delivered over a 5-minute period, followed by a 5-minute recovery, which results in an accurate quantitation of sweat produced in small areas of the skin.'}
|
Age-at-Presentation
|
Age (at case presentation)
|
[
"16 years old"
] |
6224624
|
{'Testing Results': 'Figures 1 a to d represent the continuous HR and BP recordings of twin 1 ( Figure 1 a and b) and twin 2 ( Figure 1 c and d) during the HUT over the 10-second transition from a supine horizontal position to a 70° upright tilt. As seen in Figure 1 a, the HR of twin 1 exhibited a compensatory increase to a maximum of 110 beats/min at 6.9 minutes into the HUT and remained at this level until she was returned to a horizontal and/or supine position. This was a change of 52 beats/min. In Figure 1 b, a systolic BP (SBP) decline of 29.8 mm Hg can be seen at 0.3 minutes into the HUT. The BP of twin 1 recovered quickly to pre-HUT levels and remained stable thereafter throughout the 10-minute HUT. Conversely, for twin 2, HR increased by 45 to 120 beats/min and a 30-mm Hg SBP drop occurred when transitioned from a supine position to a 70° HUT ( Figure 1 c and d). In addition, the HR and SBP remained at these levels throughout the HUT until the twin returned to the supine position. Thus, both twins exhibited orthostatic tachycardia during HUT that was maintained until returning to the supine horizontal body position, which indicated a greater than average response compared with normative data. Figure 1 Head up-tilt (HUT) of twins 1 and 2 for continuous heart rate (a,c) and blood pressure recordings (b,d). For the TST, the baseline (pre-TST) for twin 1 and twin 2 are shown in Figure 2 a and 2 c, respectively, whereas postwarming period results for each twin are found in Figure 2 b and 2 d, respectively. By referencing the temperature scale shown between Figure 2 a and 2 b and Figure 2 c and 2 d, the images clearly demonstrate both twins with cold hands and feet before warming ( Figure 2 a and 2 c). Conversely, in post-TST images, both twins displayed symmetric warming of their hands but their feet remained slightly cooler compared with other body regions ( Figure 2 b and 2 d). Figure 2 Thermoregulatory sweat test baseline and warmed (post) test twin 1 (a,b) and twin 2 (c,d), respectively. A temperature-color gauge is centered between each baseline and the warmed figure with values shown in degrees Fahrenheit. Postwarming images of twin 1 ( Figure 3 a) and twin 2 ( Figure 3 b) are shown with patchy regions of anhidrosis (in yellow) compared with the purple areas of sweat indicator powder, which demonstrated the regions where sweating occurred. Twin 1 had 53% anhidrosis but preserved sweating on the upper trunk, left abdomen, both hands, and medial legs, whereas twin 2 exhibited 50% anhidrosis and residual sweating of the upper trunk, bilateral hands, and medial legs. Figure 3 Diaphoresis patterns of twin 1 (a) and twin 2 (b) at the completion of the thermoregulatory sweat test (TST). QSWEAT results of twin 1 are shown with sweat rates of the forearm (25−50th percentile) ( Figure 4 a); proximal ( Figure 4 b) and distal leg sweat rates were each <10th percentile (abnormal for sex and age) ( Figure 4 c), and the foot was between the 10th to 25th percentile ( Figure 4 d). In addition, these abnormalities were categorized as a “latency of the sweat response” of the forearm, distal leg, and foot, as well as a “lack of recovery” of the proximal leg. Results for twin 2 showed a similar sweat response latency of the proximal leg ( Figure 5 b). Otherwise, twin 2 exhibited normal sweat volumes and rates for her age as seen for the forearm (10th−25th percentile) ( Figure 5 a), proximal leg (25th percentile) ( Figure 5 b), distal leg (25th percentile) ( Figure 5 c), and foot (50−80th percentile) ( Figure 5 d). Figure 4 Quantitative sweat rate (nanoliters per minute) of twin 1 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d). Figure 5 Quantitative sweat rate (nanoliters per minute) of twin 2 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d).', 'Case 1': 'Monozygotic female adolescent twins, aged 16 years old, were originally diagnosed in infancy with NC and found to have a 57-kb deletion of the CTNS gene, the most frequent cause of NC in Western populations. They were on cysteamine bitartrate (cystagon-immediate release) since diagnosis. Each was currently prescribed Procysbi (cysteamine-delayed release) 675 mg every 12 hours. In addition, each twin was prescribed cysteamine hydrochloride (0.44%) eye drops due to cystine crystal accumulation in the lens and cornea. Both twins were transplanted 6 years previously with kidneys from a single deceased donor source. Since that time, both twins experienced several episodes of transplant rejection, whereas twin 1 also developed Epstein-Barr virus positive posttransplant proliferative disorder. Table 1 includes clinical and medication data on the patients at the time of autonomic testing. As shown in Table 1, twin 2 exhibited a diastolic blood pressure (DBP) that exceeded the threshold for sex and height and had DBP readings 20% higher than those of twin 1. Table 1 Characteristics and medications of female monozygotic twins with nephropathic cystinosis Characteristics Twin 1 Twin 2 Age (yrs) 16 Race W Ethnicity H Wt. (kg) 43.6 46.0 Ht. (cm) 152.3 154.8 BMI percentile (for age and sex) (kg/m 2 ) 25th 40th Resting BP (mm Hg) 118/70 123/84 Measured GFR (ml/min per 1.73 m 2 ) 59.3 70.0 CKD stage 3a 2 Tacrolimus level (ng/ml) 5.5 4.5 Medications, Dose, Frequency Procysbi (cysteamine DR) 675 mg q 12 h Cysteamine HCL (0.44%) 1 gtt. OU q h while awake Amlodipine 10 mg/d Cardura 4 mg/d — Lisinopril 10 mg/d Drisdol 50,000 IU/ q 14 d — Cellcept 500 mg BID Tacrolimus 3 mg BID 2 mg BID Synthroid 137 μg/d 125 μg/d Mg oxide 400 mg BID Bactrim 400-80 40 mg 3×/wk BID, twice a day; BMI, body mass index; BP, blood pressure; CKD, chronic kidney disease; DR, delayed release; GFR, glomerular filtration rate by plasma clearance of iohexol; gtt, drops; H, Hispanic; HCL, hydrochloride; Ht., height; IU, international units; Mg, magnesium; OU, both eyes; q, every; W, white; Wt., weight. Laboratory findings (biochemical characteristics) for both twins are shown in Table 2 . Creatinine, blood urea nitrogen, and cystatin C levels were consistent with the CKD stage of each twin. Both patients also had blood drawn for measurement of their leukocyte cystine levels, which were obtained at the time of their regular laboratory tests. Those results were 1.65 and 1.90 nmol 1/2 cystine per milligram per protein for twins 1 and 2, respectively. Because the twins exhibited leukocyte cystine levels >1 nmol 1/2 cystine per milligram per protein, it indicated they had not achieved an optimal degree of substrate depletion for cystinosis patients on cysteamine therapy. This was due to incomplete adherence with their cysteamine bitartrate therapy. Table 3 lists a summary on cystinosis. Table 2 Laboratory results Results Conventional units (SI Units) Twin # Cr BUN Cystatin C Alb Phos Na K Glucose 1 1.08 (95.47) 15 (5.35) (1.25) 4.5 (45) 3.7 (1.20) 136 (136 ) 4.0 (4.0) 98 (5.44) 2 0.81 (71.60) 13 (4.64) (1.09) 4.9 (49) 3.8 (1.23) 137 (137) 4.2 (4.2) 94 (5.22) Normal reference range 0.25−1.14 mg/dl 5.0−18.0 mg/dl 0.5−1.3 mg/l (1−17 yr) 3.6−4.7 g/dl 3.0−4.8 mg/dl 134−146 mEq/l 3.7−5.7 mEq/l 60−110 mg/dl SI units normal Reference Range 22.1−100.78 mmol/l 1.78−6.43 mmol/l 0.50−1.30 mg/l 36.0−47.0 g/l 0.97−1.55 mmol/l 134−146 mmol/l 3.7−5.7 mmol/l 3.33−6.11 mmol/l Alb, albumin; BUN, blood urea nitrogen; Cr, creatinine; K, potassium; Na, sodium; Phos, phosphorus (inorganic); SI, Standard international. Table 3 Teaching points (i) Cystinosis results from a functional defect in the lysosomal-membrane exporter protein, cystinosin (CTNS), thereby resulting in failure of cystine efflux from cell lysosomes. When untreated, cystine crystals result and are deposited throughout the body, including in the cornea, retina, and most organs. (ii) Nephropathic cystinosis (NC) is often diagnosed in infancy due to the development of severe renal Fanconi syndrome with failure to thrive. Chronic electrolyte replacement is essential. (iii) Cystine accumulation is measured in leukocytes with a cystine level < 1 nmol 1/2 cystine per milligram cell protein categorized as being consistent with optimal cystine depletion. (iv) Cysteamine bitartrate is the only Food and Drug Administration−approved therapy for cystinosis and is available in immediate and delayed release formulations. (v) In NC, the 57-kb deletion has been associated with transient receptor potential vanilloid 1 (TRPV1) gene functional impairment. (vi) Long-term extra renal manifestations of NC are frequently observed and include cognitive impairment and/or delays, altered skin and/or heat sensations, abnormal temperature regulation, heat intolerance, reduced sweating, and myopathy, the latter of which may eventually contribute to respiratory failure, all suggestive of autonomic nervous system dysfunction pertinent to thermoregulation. Both twins frequently described issues with heat intolerance and photophobia secondary to corneal cystine crystal deposition, but they demonstrated consistently normal clinical neurological examination findings. We decided to complete further testing of the twins to evaluate heat intolerance and possible associated autonomic dysfunction as opposed to what may simply be avoidance of light exposure on sunny days.', 'Clinical Testing': 'During the period before testing, a directly measured glomerular filtration rate was completed on each twin using a plasma clearance of iohexol procedure. 14 The twins then underwent 3 clinical procedures at the Center for Autonomic Medicine in Pediatrics at Ann & Robert H. Lurie Children’s Hospital of Chicago (Chicago, IL). Those procedures included the head-up tilt (HUT) test to assess baroreceptor function, a thermoregulatory sweat test (TST) to measure sudomotor function, and the quantitative sweat response test (QSWEAT), which is a sudomotor axon reflex test in which responses of the local axon reflex of sweat glands to iontophoresed acetylcholine are quantitated. 15 The use of the TST and QSWEAT procedures on patients are considered to be the gold standard for clinical evaluation, because they demonstrated a 90% sensitivity for detection of small fiber neuropathy. 16 The HUT determines whether orthostatic (in)tolerance can be demonstrated and evaluates the inter-relationship of breathing, heart rate (HR), and BP while the patient transitions from a supine to an upright position and then returns to the supine position. Simply stated, a patient lays on a tilt table in a supine horizontal position for 10 to 20 minutes while baseline measurements are taken. Then, a HUT to 70° is done with measurements collected thereafter for 10 minutes. Following this, a tilt-down to a supine horizontal position occurs and is sustained for 2 minutes of additional measurements. During the TST, the core body temperature is increased slowly to 1 ° C higher than at prewarming (baseline) or a patient reaches a core temperature of 38 ° C (whichever is greater). To prepare for the procedure, sweat-indicator powder is applied to the patient’s anterior surface while lying supine on a bed. The patient is then rolled into the chamber, and it is sealed shut, while continuous surveillance and collection of all physiological measurements of the patient, chamber, and temperatures occurs. The ambient temperature is slowly increased with an average ramp rate of 5.0 °C/hour and with a relative humidity range of 35% to 45%. Finally, for the QSWEAT, the patient is placed in a supine horizontal position. Once situated, 4 quarter-sized capsules of acetylcholine are topically applied on the forearm, proximal and distal leg, and foot. An imperceivable 2-mA current is delivered over a 5-minute period, followed by a 5-minute recovery, which results in an accurate quantitation of sweat produced in small areas of the skin.'}
|
{'Testing Results': 'Figures 1 a to d represent the continuous HR and BP recordings of twin 1 ( Figure 1 a and b) and twin 2 ( Figure 1 c and d) during the HUT over the 10-second transition from a supine horizontal position to a 70° upright tilt. As seen in Figure 1 a, the HR of twin 1 exhibited a compensatory increase to a maximum of 110 beats/min at 6.9 minutes into the HUT and remained at this level until she was returned to a horizontal and/or supine position. This was a change of 52 beats/min. In Figure 1 b, a systolic BP (SBP) decline of 29.8 mm Hg can be seen at 0.3 minutes into the HUT. The BP of twin 1 recovered quickly to pre-HUT levels and remained stable thereafter throughout the 10-minute HUT. Conversely, for twin 2, HR increased by 45 to 120 beats/min and a 30-mm Hg SBP drop occurred when transitioned from a supine position to a 70° HUT ( Figure 1 c and d). In addition, the HR and SBP remained at these levels throughout the HUT until the twin returned to the supine position. Thus, both twins exhibited orthostatic tachycardia during HUT that was maintained until returning to the supine horizontal body position, which indicated a greater than average response compared with normative data. Figure 1 Head up-tilt (HUT) of twins 1 and 2 for continuous heart rate (a,c) and blood pressure recordings (b,d). For the TST, the baseline (pre-TST) for twin 1 and twin 2 are shown in Figure 2 a and 2 c, respectively, whereas postwarming period results for each twin are found in Figure 2 b and 2 d, respectively. By referencing the temperature scale shown between Figure 2 a and 2 b and Figure 2 c and 2 d, the images clearly demonstrate both twins with cold hands and feet before warming ( Figure 2 a and 2 c). Conversely, in post-TST images, both twins displayed symmetric warming of their hands but their feet remained slightly cooler compared with other body regions ( Figure 2 b and 2 d). Figure 2 Thermoregulatory sweat test baseline and warmed (post) test twin 1 (a,b) and twin 2 (c,d), respectively. A temperature-color gauge is centered between each baseline and the warmed figure with values shown in degrees Fahrenheit. Postwarming images of twin 1 ( Figure 3 a) and twin 2 ( Figure 3 b) are shown with patchy regions of anhidrosis (in yellow) compared with the purple areas of sweat indicator powder, which demonstrated the regions where sweating occurred. Twin 1 had 53% anhidrosis but preserved sweating on the upper trunk, left abdomen, both hands, and medial legs, whereas twin 2 exhibited 50% anhidrosis and residual sweating of the upper trunk, bilateral hands, and medial legs. Figure 3 Diaphoresis patterns of twin 1 (a) and twin 2 (b) at the completion of the thermoregulatory sweat test (TST). QSWEAT results of twin 1 are shown with sweat rates of the forearm (25−50th percentile) ( Figure 4 a); proximal ( Figure 4 b) and distal leg sweat rates were each <10th percentile (abnormal for sex and age) ( Figure 4 c), and the foot was between the 10th to 25th percentile ( Figure 4 d). In addition, these abnormalities were categorized as a “latency of the sweat response” of the forearm, distal leg, and foot, as well as a “lack of recovery” of the proximal leg. Results for twin 2 showed a similar sweat response latency of the proximal leg ( Figure 5 b). Otherwise, twin 2 exhibited normal sweat volumes and rates for her age as seen for the forearm (10th−25th percentile) ( Figure 5 a), proximal leg (25th percentile) ( Figure 5 b), distal leg (25th percentile) ( Figure 5 c), and foot (50−80th percentile) ( Figure 5 d). Figure 4 Quantitative sweat rate (nanoliters per minute) of twin 1 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d). Figure 5 Quantitative sweat rate (nanoliters per minute) of twin 2 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d).', 'Case 1': 'Monozygotic female adolescent twins, aged 16 years old, were originally diagnosed in infancy with NC and found to have a 57-kb deletion of the CTNS gene, the most frequent cause of NC in Western populations. They were on cysteamine bitartrate (cystagon-immediate release) since diagnosis. Each was currently prescribed Procysbi (cysteamine-delayed release) 675 mg every 12 hours. In addition, each twin was prescribed cysteamine hydrochloride (0.44%) eye drops due to cystine crystal accumulation in the lens and cornea. Both twins were transplanted 6 years previously with kidneys from a single deceased donor source. Since that time, both twins experienced several episodes of transplant rejection, whereas twin 1 also developed Epstein-Barr virus positive posttransplant proliferative disorder. Table 1 includes clinical and medication data on the patients at the time of autonomic testing. As shown in Table 1, twin 2 exhibited a diastolic blood pressure (DBP) that exceeded the threshold for sex and height and had DBP readings 20% higher than those of twin 1. Table 1 Characteristics and medications of female monozygotic twins with nephropathic cystinosis Characteristics Twin 1 Twin 2 Age (yrs) 16 Race W Ethnicity H Wt. (kg) 43.6 46.0 Ht. (cm) 152.3 154.8 BMI percentile (for age and sex) (kg/m 2 ) 25th 40th Resting BP (mm Hg) 118/70 123/84 Measured GFR (ml/min per 1.73 m 2 ) 59.3 70.0 CKD stage 3a 2 Tacrolimus level (ng/ml) 5.5 4.5 Medications, Dose, Frequency Procysbi (cysteamine DR) 675 mg q 12 h Cysteamine HCL (0.44%) 1 gtt. OU q h while awake Amlodipine 10 mg/d Cardura 4 mg/d — Lisinopril 10 mg/d Drisdol 50,000 IU/ q 14 d — Cellcept 500 mg BID Tacrolimus 3 mg BID 2 mg BID Synthroid 137 μg/d 125 μg/d Mg oxide 400 mg BID Bactrim 400-80 40 mg 3×/wk BID, twice a day; BMI, body mass index; BP, blood pressure; CKD, chronic kidney disease; DR, delayed release; GFR, glomerular filtration rate by plasma clearance of iohexol; gtt, drops; H, Hispanic; HCL, hydrochloride; Ht., height; IU, international units; Mg, magnesium; OU, both eyes; q, every; W, white; Wt., weight. Laboratory findings (biochemical characteristics) for both twins are shown in Table 2 . Creatinine, blood urea nitrogen, and cystatin C levels were consistent with the CKD stage of each twin. Both patients also had blood drawn for measurement of their leukocyte cystine levels, which were obtained at the time of their regular laboratory tests. Those results were 1.65 and 1.90 nmol 1/2 cystine per milligram per protein for twins 1 and 2, respectively. Because the twins exhibited leukocyte cystine levels >1 nmol 1/2 cystine per milligram per protein, it indicated they had not achieved an optimal degree of substrate depletion for cystinosis patients on cysteamine therapy. This was due to incomplete adherence with their cysteamine bitartrate therapy. Table 3 lists a summary on cystinosis. Table 2 Laboratory results Results Conventional units (SI Units) Twin # Cr BUN Cystatin C Alb Phos Na K Glucose 1 1.08 (95.47) 15 (5.35) (1.25) 4.5 (45) 3.7 (1.20) 136 (136 ) 4.0 (4.0) 98 (5.44) 2 0.81 (71.60) 13 (4.64) (1.09) 4.9 (49) 3.8 (1.23) 137 (137) 4.2 (4.2) 94 (5.22) Normal reference range 0.25−1.14 mg/dl 5.0−18.0 mg/dl 0.5−1.3 mg/l (1−17 yr) 3.6−4.7 g/dl 3.0−4.8 mg/dl 134−146 mEq/l 3.7−5.7 mEq/l 60−110 mg/dl SI units normal Reference Range 22.1−100.78 mmol/l 1.78−6.43 mmol/l 0.50−1.30 mg/l 36.0−47.0 g/l 0.97−1.55 mmol/l 134−146 mmol/l 3.7−5.7 mmol/l 3.33−6.11 mmol/l Alb, albumin; BUN, blood urea nitrogen; Cr, creatinine; K, potassium; Na, sodium; Phos, phosphorus (inorganic); SI, Standard international. Table 3 Teaching points (i) Cystinosis results from a functional defect in the lysosomal-membrane exporter protein, cystinosin (CTNS), thereby resulting in failure of cystine efflux from cell lysosomes. When untreated, cystine crystals result and are deposited throughout the body, including in the cornea, retina, and most organs. (ii) Nephropathic cystinosis (NC) is often diagnosed in infancy due to the development of severe renal Fanconi syndrome with failure to thrive. Chronic electrolyte replacement is essential. (iii) Cystine accumulation is measured in leukocytes with a cystine level < 1 nmol 1/2 cystine per milligram cell protein categorized as being consistent with optimal cystine depletion. (iv) Cysteamine bitartrate is the only Food and Drug Administration−approved therapy for cystinosis and is available in immediate and delayed release formulations. (v) In NC, the 57-kb deletion has been associated with transient receptor potential vanilloid 1 (TRPV1) gene functional impairment. (vi) Long-term extra renal manifestations of NC are frequently observed and include cognitive impairment and/or delays, altered skin and/or heat sensations, abnormal temperature regulation, heat intolerance, reduced sweating, and myopathy, the latter of which may eventually contribute to respiratory failure, all suggestive of autonomic nervous system dysfunction pertinent to thermoregulation. Both twins frequently described issues with heat intolerance and photophobia secondary to corneal cystine crystal deposition, but they demonstrated consistently normal clinical neurological examination findings. We decided to complete further testing of the twins to evaluate heat intolerance and possible associated autonomic dysfunction as opposed to what may simply be avoidance of light exposure on sunny days.', 'Clinical Testing': 'During the period before testing, a directly measured glomerular filtration rate was completed on each twin using a plasma clearance of iohexol procedure. 14 The twins then underwent 3 clinical procedures at the Center for Autonomic Medicine in Pediatrics at Ann & Robert H. Lurie Children’s Hospital of Chicago (Chicago, IL). Those procedures included the head-up tilt (HUT) test to assess baroreceptor function, a thermoregulatory sweat test (TST) to measure sudomotor function, and the quantitative sweat response test (QSWEAT), which is a sudomotor axon reflex test in which responses of the local axon reflex of sweat glands to iontophoresed acetylcholine are quantitated. 15 The use of the TST and QSWEAT procedures on patients are considered to be the gold standard for clinical evaluation, because they demonstrated a 90% sensitivity for detection of small fiber neuropathy. 16 The HUT determines whether orthostatic (in)tolerance can be demonstrated and evaluates the inter-relationship of breathing, heart rate (HR), and BP while the patient transitions from a supine to an upright position and then returns to the supine position. Simply stated, a patient lays on a tilt table in a supine horizontal position for 10 to 20 minutes while baseline measurements are taken. Then, a HUT to 70° is done with measurements collected thereafter for 10 minutes. Following this, a tilt-down to a supine horizontal position occurs and is sustained for 2 minutes of additional measurements. During the TST, the core body temperature is increased slowly to 1 ° C higher than at prewarming (baseline) or a patient reaches a core temperature of 38 ° C (whichever is greater). To prepare for the procedure, sweat-indicator powder is applied to the patient’s anterior surface while lying supine on a bed. The patient is then rolled into the chamber, and it is sealed shut, while continuous surveillance and collection of all physiological measurements of the patient, chamber, and temperatures occurs. The ambient temperature is slowly increased with an average ramp rate of 5.0 °C/hour and with a relative humidity range of 35% to 45%. Finally, for the QSWEAT, the patient is placed in a supine horizontal position. Once situated, 4 quarter-sized capsules of acetylcholine are topically applied on the forearm, proximal and distal leg, and foot. An imperceivable 2-mA current is delivered over a 5-minute period, followed by a 5-minute recovery, which results in an accurate quantitation of sweat produced in small areas of the skin.'}
|
Age-of-Onset
|
Age (of onset)
|
[
"infancy"
] |
6224624
|
{'Testing Results': 'Figures 1 a to d represent the continuous HR and BP recordings of twin 1 ( Figure 1 a and b) and twin 2 ( Figure 1 c and d) during the HUT over the 10-second transition from a supine horizontal position to a 70° upright tilt. As seen in Figure 1 a, the HR of twin 1 exhibited a compensatory increase to a maximum of 110 beats/min at 6.9 minutes into the HUT and remained at this level until she was returned to a horizontal and/or supine position. This was a change of 52 beats/min. In Figure 1 b, a systolic BP (SBP) decline of 29.8 mm Hg can be seen at 0.3 minutes into the HUT. The BP of twin 1 recovered quickly to pre-HUT levels and remained stable thereafter throughout the 10-minute HUT. Conversely, for twin 2, HR increased by 45 to 120 beats/min and a 30-mm Hg SBP drop occurred when transitioned from a supine position to a 70° HUT ( Figure 1 c and d). In addition, the HR and SBP remained at these levels throughout the HUT until the twin returned to the supine position. Thus, both twins exhibited orthostatic tachycardia during HUT that was maintained until returning to the supine horizontal body position, which indicated a greater than average response compared with normative data. Figure 1 Head up-tilt (HUT) of twins 1 and 2 for continuous heart rate (a,c) and blood pressure recordings (b,d). For the TST, the baseline (pre-TST) for twin 1 and twin 2 are shown in Figure 2 a and 2 c, respectively, whereas postwarming period results for each twin are found in Figure 2 b and 2 d, respectively. By referencing the temperature scale shown between Figure 2 a and 2 b and Figure 2 c and 2 d, the images clearly demonstrate both twins with cold hands and feet before warming ( Figure 2 a and 2 c). Conversely, in post-TST images, both twins displayed symmetric warming of their hands but their feet remained slightly cooler compared with other body regions ( Figure 2 b and 2 d). Figure 2 Thermoregulatory sweat test baseline and warmed (post) test twin 1 (a,b) and twin 2 (c,d), respectively. A temperature-color gauge is centered between each baseline and the warmed figure with values shown in degrees Fahrenheit. Postwarming images of twin 1 ( Figure 3 a) and twin 2 ( Figure 3 b) are shown with patchy regions of anhidrosis (in yellow) compared with the purple areas of sweat indicator powder, which demonstrated the regions where sweating occurred. Twin 1 had 53% anhidrosis but preserved sweating on the upper trunk, left abdomen, both hands, and medial legs, whereas twin 2 exhibited 50% anhidrosis and residual sweating of the upper trunk, bilateral hands, and medial legs. Figure 3 Diaphoresis patterns of twin 1 (a) and twin 2 (b) at the completion of the thermoregulatory sweat test (TST). QSWEAT results of twin 1 are shown with sweat rates of the forearm (25−50th percentile) ( Figure 4 a); proximal ( Figure 4 b) and distal leg sweat rates were each <10th percentile (abnormal for sex and age) ( Figure 4 c), and the foot was between the 10th to 25th percentile ( Figure 4 d). In addition, these abnormalities were categorized as a “latency of the sweat response” of the forearm, distal leg, and foot, as well as a “lack of recovery” of the proximal leg. Results for twin 2 showed a similar sweat response latency of the proximal leg ( Figure 5 b). Otherwise, twin 2 exhibited normal sweat volumes and rates for her age as seen for the forearm (10th−25th percentile) ( Figure 5 a), proximal leg (25th percentile) ( Figure 5 b), distal leg (25th percentile) ( Figure 5 c), and foot (50−80th percentile) ( Figure 5 d). Figure 4 Quantitative sweat rate (nanoliters per minute) of twin 1 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d). Figure 5 Quantitative sweat rate (nanoliters per minute) of twin 2 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d).', 'Case 1': 'Monozygotic female adolescent twins, aged 16 years old, were originally diagnosed in infancy with NC and found to have a 57-kb deletion of the CTNS gene, the most frequent cause of NC in Western populations. They were on cysteamine bitartrate (cystagon-immediate release) since diagnosis. Each was currently prescribed Procysbi (cysteamine-delayed release) 675 mg every 12 hours. In addition, each twin was prescribed cysteamine hydrochloride (0.44%) eye drops due to cystine crystal accumulation in the lens and cornea. Both twins were transplanted 6 years previously with kidneys from a single deceased donor source. Since that time, both twins experienced several episodes of transplant rejection, whereas twin 1 also developed Epstein-Barr virus positive posttransplant proliferative disorder. Table 1 includes clinical and medication data on the patients at the time of autonomic testing. As shown in Table 1, twin 2 exhibited a diastolic blood pressure (DBP) that exceeded the threshold for sex and height and had DBP readings 20% higher than those of twin 1. Table 1 Characteristics and medications of female monozygotic twins with nephropathic cystinosis Characteristics Twin 1 Twin 2 Age (yrs) 16 Race W Ethnicity H Wt. (kg) 43.6 46.0 Ht. (cm) 152.3 154.8 BMI percentile (for age and sex) (kg/m 2 ) 25th 40th Resting BP (mm Hg) 118/70 123/84 Measured GFR (ml/min per 1.73 m 2 ) 59.3 70.0 CKD stage 3a 2 Tacrolimus level (ng/ml) 5.5 4.5 Medications, Dose, Frequency Procysbi (cysteamine DR) 675 mg q 12 h Cysteamine HCL (0.44%) 1 gtt. OU q h while awake Amlodipine 10 mg/d Cardura 4 mg/d — Lisinopril 10 mg/d Drisdol 50,000 IU/ q 14 d — Cellcept 500 mg BID Tacrolimus 3 mg BID 2 mg BID Synthroid 137 μg/d 125 μg/d Mg oxide 400 mg BID Bactrim 400-80 40 mg 3×/wk BID, twice a day; BMI, body mass index; BP, blood pressure; CKD, chronic kidney disease; DR, delayed release; GFR, glomerular filtration rate by plasma clearance of iohexol; gtt, drops; H, Hispanic; HCL, hydrochloride; Ht., height; IU, international units; Mg, magnesium; OU, both eyes; q, every; W, white; Wt., weight. Laboratory findings (biochemical characteristics) for both twins are shown in Table 2 . Creatinine, blood urea nitrogen, and cystatin C levels were consistent with the CKD stage of each twin. Both patients also had blood drawn for measurement of their leukocyte cystine levels, which were obtained at the time of their regular laboratory tests. Those results were 1.65 and 1.90 nmol 1/2 cystine per milligram per protein for twins 1 and 2, respectively. Because the twins exhibited leukocyte cystine levels >1 nmol 1/2 cystine per milligram per protein, it indicated they had not achieved an optimal degree of substrate depletion for cystinosis patients on cysteamine therapy. This was due to incomplete adherence with their cysteamine bitartrate therapy. Table 3 lists a summary on cystinosis. Table 2 Laboratory results Results Conventional units (SI Units) Twin # Cr BUN Cystatin C Alb Phos Na K Glucose 1 1.08 (95.47) 15 (5.35) (1.25) 4.5 (45) 3.7 (1.20) 136 (136 ) 4.0 (4.0) 98 (5.44) 2 0.81 (71.60) 13 (4.64) (1.09) 4.9 (49) 3.8 (1.23) 137 (137) 4.2 (4.2) 94 (5.22) Normal reference range 0.25−1.14 mg/dl 5.0−18.0 mg/dl 0.5−1.3 mg/l (1−17 yr) 3.6−4.7 g/dl 3.0−4.8 mg/dl 134−146 mEq/l 3.7−5.7 mEq/l 60−110 mg/dl SI units normal Reference Range 22.1−100.78 mmol/l 1.78−6.43 mmol/l 0.50−1.30 mg/l 36.0−47.0 g/l 0.97−1.55 mmol/l 134−146 mmol/l 3.7−5.7 mmol/l 3.33−6.11 mmol/l Alb, albumin; BUN, blood urea nitrogen; Cr, creatinine; K, potassium; Na, sodium; Phos, phosphorus (inorganic); SI, Standard international. Table 3 Teaching points (i) Cystinosis results from a functional defect in the lysosomal-membrane exporter protein, cystinosin (CTNS), thereby resulting in failure of cystine efflux from cell lysosomes. When untreated, cystine crystals result and are deposited throughout the body, including in the cornea, retina, and most organs. (ii) Nephropathic cystinosis (NC) is often diagnosed in infancy due to the development of severe renal Fanconi syndrome with failure to thrive. Chronic electrolyte replacement is essential. (iii) Cystine accumulation is measured in leukocytes with a cystine level < 1 nmol 1/2 cystine per milligram cell protein categorized as being consistent with optimal cystine depletion. (iv) Cysteamine bitartrate is the only Food and Drug Administration−approved therapy for cystinosis and is available in immediate and delayed release formulations. (v) In NC, the 57-kb deletion has been associated with transient receptor potential vanilloid 1 (TRPV1) gene functional impairment. (vi) Long-term extra renal manifestations of NC are frequently observed and include cognitive impairment and/or delays, altered skin and/or heat sensations, abnormal temperature regulation, heat intolerance, reduced sweating, and myopathy, the latter of which may eventually contribute to respiratory failure, all suggestive of autonomic nervous system dysfunction pertinent to thermoregulation. Both twins frequently described issues with heat intolerance and photophobia secondary to corneal cystine crystal deposition, but they demonstrated consistently normal clinical neurological examination findings. We decided to complete further testing of the twins to evaluate heat intolerance and possible associated autonomic dysfunction as opposed to what may simply be avoidance of light exposure on sunny days.', 'Clinical Testing': 'During the period before testing, a directly measured glomerular filtration rate was completed on each twin using a plasma clearance of iohexol procedure. 14 The twins then underwent 3 clinical procedures at the Center for Autonomic Medicine in Pediatrics at Ann & Robert H. Lurie Children’s Hospital of Chicago (Chicago, IL). Those procedures included the head-up tilt (HUT) test to assess baroreceptor function, a thermoregulatory sweat test (TST) to measure sudomotor function, and the quantitative sweat response test (QSWEAT), which is a sudomotor axon reflex test in which responses of the local axon reflex of sweat glands to iontophoresed acetylcholine are quantitated. 15 The use of the TST and QSWEAT procedures on patients are considered to be the gold standard for clinical evaluation, because they demonstrated a 90% sensitivity for detection of small fiber neuropathy. 16 The HUT determines whether orthostatic (in)tolerance can be demonstrated and evaluates the inter-relationship of breathing, heart rate (HR), and BP while the patient transitions from a supine to an upright position and then returns to the supine position. Simply stated, a patient lays on a tilt table in a supine horizontal position for 10 to 20 minutes while baseline measurements are taken. Then, a HUT to 70° is done with measurements collected thereafter for 10 minutes. Following this, a tilt-down to a supine horizontal position occurs and is sustained for 2 minutes of additional measurements. During the TST, the core body temperature is increased slowly to 1 ° C higher than at prewarming (baseline) or a patient reaches a core temperature of 38 ° C (whichever is greater). To prepare for the procedure, sweat-indicator powder is applied to the patient’s anterior surface while lying supine on a bed. The patient is then rolled into the chamber, and it is sealed shut, while continuous surveillance and collection of all physiological measurements of the patient, chamber, and temperatures occurs. The ambient temperature is slowly increased with an average ramp rate of 5.0 °C/hour and with a relative humidity range of 35% to 45%. Finally, for the QSWEAT, the patient is placed in a supine horizontal position. Once situated, 4 quarter-sized capsules of acetylcholine are topically applied on the forearm, proximal and distal leg, and foot. An imperceivable 2-mA current is delivered over a 5-minute period, followed by a 5-minute recovery, which results in an accurate quantitation of sweat produced in small areas of the skin.'}
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{'Testing Results': 'Figures 1 a to d represent the continuous HR and BP recordings of twin 1 ( Figure 1 a and b) and twin 2 ( Figure 1 c and d) during the HUT over the 10-second transition from a supine horizontal position to a 70° upright tilt. As seen in Figure 1 a, the HR of twin 1 exhibited a compensatory increase to a maximum of 110 beats/min at 6.9 minutes into the HUT and remained at this level until she was returned to a horizontal and/or supine position. This was a change of 52 beats/min. In Figure 1 b, a systolic BP (SBP) decline of 29.8 mm Hg can be seen at 0.3 minutes into the HUT. The BP of twin 1 recovered quickly to pre-HUT levels and remained stable thereafter throughout the 10-minute HUT. Conversely, for twin 2, HR increased by 45 to 120 beats/min and a 30-mm Hg SBP drop occurred when transitioned from a supine position to a 70° HUT ( Figure 1 c and d). In addition, the HR and SBP remained at these levels throughout the HUT until the twin returned to the supine position. Thus, both twins exhibited orthostatic tachycardia during HUT that was maintained until returning to the supine horizontal body position, which indicated a greater than average response compared with normative data. Figure 1 Head up-tilt (HUT) of twins 1 and 2 for continuous heart rate (a,c) and blood pressure recordings (b,d). For the TST, the baseline (pre-TST) for twin 1 and twin 2 are shown in Figure 2 a and 2 c, respectively, whereas postwarming period results for each twin are found in Figure 2 b and 2 d, respectively. By referencing the temperature scale shown between Figure 2 a and 2 b and Figure 2 c and 2 d, the images clearly demonstrate both twins with cold hands and feet before warming ( Figure 2 a and 2 c). Conversely, in post-TST images, both twins displayed symmetric warming of their hands but their feet remained slightly cooler compared with other body regions ( Figure 2 b and 2 d). Figure 2 Thermoregulatory sweat test baseline and warmed (post) test twin 1 (a,b) and twin 2 (c,d), respectively. A temperature-color gauge is centered between each baseline and the warmed figure with values shown in degrees Fahrenheit. Postwarming images of twin 1 ( Figure 3 a) and twin 2 ( Figure 3 b) are shown with patchy regions of anhidrosis (in yellow) compared with the purple areas of sweat indicator powder, which demonstrated the regions where sweating occurred. Twin 1 had 53% anhidrosis but preserved sweating on the upper trunk, left abdomen, both hands, and medial legs, whereas twin 2 exhibited 50% anhidrosis and residual sweating of the upper trunk, bilateral hands, and medial legs. Figure 3 Diaphoresis patterns of twin 1 (a) and twin 2 (b) at the completion of the thermoregulatory sweat test (TST). QSWEAT results of twin 1 are shown with sweat rates of the forearm (25−50th percentile) ( Figure 4 a); proximal ( Figure 4 b) and distal leg sweat rates were each <10th percentile (abnormal for sex and age) ( Figure 4 c), and the foot was between the 10th to 25th percentile ( Figure 4 d). In addition, these abnormalities were categorized as a “latency of the sweat response” of the forearm, distal leg, and foot, as well as a “lack of recovery” of the proximal leg. Results for twin 2 showed a similar sweat response latency of the proximal leg ( Figure 5 b). Otherwise, twin 2 exhibited normal sweat volumes and rates for her age as seen for the forearm (10th−25th percentile) ( Figure 5 a), proximal leg (25th percentile) ( Figure 5 b), distal leg (25th percentile) ( Figure 5 c), and foot (50−80th percentile) ( Figure 5 d). Figure 4 Quantitative sweat rate (nanoliters per minute) of twin 1 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d). Figure 5 Quantitative sweat rate (nanoliters per minute) of twin 2 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d).', 'Case 1': 'Monozygotic female adolescent twins, aged 16 years old, were originally diagnosed in infancy with NC and found to have a 57-kb deletion of the CTNS gene, the most frequent cause of NC in Western populations. They were on cysteamine bitartrate (cystagon-immediate release) since diagnosis. Each was currently prescribed Procysbi (cysteamine-delayed release) 675 mg every 12 hours. In addition, each twin was prescribed cysteamine hydrochloride (0.44%) eye drops due to cystine crystal accumulation in the lens and cornea. Both twins were transplanted 6 years previously with kidneys from a single deceased donor source. Since that time, both twins experienced several episodes of transplant rejection, whereas twin 1 also developed Epstein-Barr virus positive posttransplant proliferative disorder. Table 1 includes clinical and medication data on the patients at the time of autonomic testing. As shown in Table 1, twin 2 exhibited a diastolic blood pressure (DBP) that exceeded the threshold for sex and height and had DBP readings 20% higher than those of twin 1. Table 1 Characteristics and medications of female monozygotic twins with nephropathic cystinosis Characteristics Twin 1 Twin 2 Age (yrs) 16 Race W Ethnicity H Wt. (kg) 43.6 46.0 Ht. (cm) 152.3 154.8 BMI percentile (for age and sex) (kg/m 2 ) 25th 40th Resting BP (mm Hg) 118/70 123/84 Measured GFR (ml/min per 1.73 m 2 ) 59.3 70.0 CKD stage 3a 2 Tacrolimus level (ng/ml) 5.5 4.5 Medications, Dose, Frequency Procysbi (cysteamine DR) 675 mg q 12 h Cysteamine HCL (0.44%) 1 gtt. OU q h while awake Amlodipine 10 mg/d Cardura 4 mg/d — Lisinopril 10 mg/d Drisdol 50,000 IU/ q 14 d — Cellcept 500 mg BID Tacrolimus 3 mg BID 2 mg BID Synthroid 137 μg/d 125 μg/d Mg oxide 400 mg BID Bactrim 400-80 40 mg 3×/wk BID, twice a day; BMI, body mass index; BP, blood pressure; CKD, chronic kidney disease; DR, delayed release; GFR, glomerular filtration rate by plasma clearance of iohexol; gtt, drops; H, Hispanic; HCL, hydrochloride; Ht., height; IU, international units; Mg, magnesium; OU, both eyes; q, every; W, white; Wt., weight. Laboratory findings (biochemical characteristics) for both twins are shown in Table 2 . Creatinine, blood urea nitrogen, and cystatin C levels were consistent with the CKD stage of each twin. Both patients also had blood drawn for measurement of their leukocyte cystine levels, which were obtained at the time of their regular laboratory tests. Those results were 1.65 and 1.90 nmol 1/2 cystine per milligram per protein for twins 1 and 2, respectively. Because the twins exhibited leukocyte cystine levels >1 nmol 1/2 cystine per milligram per protein, it indicated they had not achieved an optimal degree of substrate depletion for cystinosis patients on cysteamine therapy. This was due to incomplete adherence with their cysteamine bitartrate therapy. Table 3 lists a summary on cystinosis. Table 2 Laboratory results Results Conventional units (SI Units) Twin # Cr BUN Cystatin C Alb Phos Na K Glucose 1 1.08 (95.47) 15 (5.35) (1.25) 4.5 (45) 3.7 (1.20) 136 (136 ) 4.0 (4.0) 98 (5.44) 2 0.81 (71.60) 13 (4.64) (1.09) 4.9 (49) 3.8 (1.23) 137 (137) 4.2 (4.2) 94 (5.22) Normal reference range 0.25−1.14 mg/dl 5.0−18.0 mg/dl 0.5−1.3 mg/l (1−17 yr) 3.6−4.7 g/dl 3.0−4.8 mg/dl 134−146 mEq/l 3.7−5.7 mEq/l 60−110 mg/dl SI units normal Reference Range 22.1−100.78 mmol/l 1.78−6.43 mmol/l 0.50−1.30 mg/l 36.0−47.0 g/l 0.97−1.55 mmol/l 134−146 mmol/l 3.7−5.7 mmol/l 3.33−6.11 mmol/l Alb, albumin; BUN, blood urea nitrogen; Cr, creatinine; K, potassium; Na, sodium; Phos, phosphorus (inorganic); SI, Standard international. Table 3 Teaching points (i) Cystinosis results from a functional defect in the lysosomal-membrane exporter protein, cystinosin (CTNS), thereby resulting in failure of cystine efflux from cell lysosomes. When untreated, cystine crystals result and are deposited throughout the body, including in the cornea, retina, and most organs. (ii) Nephropathic cystinosis (NC) is often diagnosed in infancy due to the development of severe renal Fanconi syndrome with failure to thrive. Chronic electrolyte replacement is essential. (iii) Cystine accumulation is measured in leukocytes with a cystine level < 1 nmol 1/2 cystine per milligram cell protein categorized as being consistent with optimal cystine depletion. (iv) Cysteamine bitartrate is the only Food and Drug Administration−approved therapy for cystinosis and is available in immediate and delayed release formulations. (v) In NC, the 57-kb deletion has been associated with transient receptor potential vanilloid 1 (TRPV1) gene functional impairment. (vi) Long-term extra renal manifestations of NC are frequently observed and include cognitive impairment and/or delays, altered skin and/or heat sensations, abnormal temperature regulation, heat intolerance, reduced sweating, and myopathy, the latter of which may eventually contribute to respiratory failure, all suggestive of autonomic nervous system dysfunction pertinent to thermoregulation. Both twins frequently described issues with heat intolerance and photophobia secondary to corneal cystine crystal deposition, but they demonstrated consistently normal clinical neurological examination findings. We decided to complete further testing of the twins to evaluate heat intolerance and possible associated autonomic dysfunction as opposed to what may simply be avoidance of light exposure on sunny days.', 'Clinical Testing': 'During the period before testing, a directly measured glomerular filtration rate was completed on each twin using a plasma clearance of iohexol procedure. 14 The twins then underwent 3 clinical procedures at the Center for Autonomic Medicine in Pediatrics at Ann & Robert H. Lurie Children’s Hospital of Chicago (Chicago, IL). Those procedures included the head-up tilt (HUT) test to assess baroreceptor function, a thermoregulatory sweat test (TST) to measure sudomotor function, and the quantitative sweat response test (QSWEAT), which is a sudomotor axon reflex test in which responses of the local axon reflex of sweat glands to iontophoresed acetylcholine are quantitated. 15 The use of the TST and QSWEAT procedures on patients are considered to be the gold standard for clinical evaluation, because they demonstrated a 90% sensitivity for detection of small fiber neuropathy. 16 The HUT determines whether orthostatic (in)tolerance can be demonstrated and evaluates the inter-relationship of breathing, heart rate (HR), and BP while the patient transitions from a supine to an upright position and then returns to the supine position. Simply stated, a patient lays on a tilt table in a supine horizontal position for 10 to 20 minutes while baseline measurements are taken. Then, a HUT to 70° is done with measurements collected thereafter for 10 minutes. Following this, a tilt-down to a supine horizontal position occurs and is sustained for 2 minutes of additional measurements. During the TST, the core body temperature is increased slowly to 1 ° C higher than at prewarming (baseline) or a patient reaches a core temperature of 38 ° C (whichever is greater). To prepare for the procedure, sweat-indicator powder is applied to the patient’s anterior surface while lying supine on a bed. The patient is then rolled into the chamber, and it is sealed shut, while continuous surveillance and collection of all physiological measurements of the patient, chamber, and temperatures occurs. The ambient temperature is slowly increased with an average ramp rate of 5.0 °C/hour and with a relative humidity range of 35% to 45%. Finally, for the QSWEAT, the patient is placed in a supine horizontal position. Once situated, 4 quarter-sized capsules of acetylcholine are topically applied on the forearm, proximal and distal leg, and foot. An imperceivable 2-mA current is delivered over a 5-minute period, followed by a 5-minute recovery, which results in an accurate quantitation of sweat produced in small areas of the skin.'}
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Confirmed-Diagnosis-IEM
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Confirmed_Diagnosis(IEM)
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[
"diagnosed in infancy with NC and found to have a 57 - kb deletion of the CTNS gene , the most frequent cause of NC in Western populations ."
] |
6224624
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{'Testing Results': 'Figures 1 a to d represent the continuous HR and BP recordings of twin 1 ( Figure 1 a and b) and twin 2 ( Figure 1 c and d) during the HUT over the 10-second transition from a supine horizontal position to a 70° upright tilt. As seen in Figure 1 a, the HR of twin 1 exhibited a compensatory increase to a maximum of 110 beats/min at 6.9 minutes into the HUT and remained at this level until she was returned to a horizontal and/or supine position. This was a change of 52 beats/min. In Figure 1 b, a systolic BP (SBP) decline of 29.8 mm Hg can be seen at 0.3 minutes into the HUT. The BP of twin 1 recovered quickly to pre-HUT levels and remained stable thereafter throughout the 10-minute HUT. Conversely, for twin 2, HR increased by 45 to 120 beats/min and a 30-mm Hg SBP drop occurred when transitioned from a supine position to a 70° HUT ( Figure 1 c and d). In addition, the HR and SBP remained at these levels throughout the HUT until the twin returned to the supine position. Thus, both twins exhibited orthostatic tachycardia during HUT that was maintained until returning to the supine horizontal body position, which indicated a greater than average response compared with normative data. Figure 1 Head up-tilt (HUT) of twins 1 and 2 for continuous heart rate (a,c) and blood pressure recordings (b,d). For the TST, the baseline (pre-TST) for twin 1 and twin 2 are shown in Figure 2 a and 2 c, respectively, whereas postwarming period results for each twin are found in Figure 2 b and 2 d, respectively. By referencing the temperature scale shown between Figure 2 a and 2 b and Figure 2 c and 2 d, the images clearly demonstrate both twins with cold hands and feet before warming ( Figure 2 a and 2 c). Conversely, in post-TST images, both twins displayed symmetric warming of their hands but their feet remained slightly cooler compared with other body regions ( Figure 2 b and 2 d). Figure 2 Thermoregulatory sweat test baseline and warmed (post) test twin 1 (a,b) and twin 2 (c,d), respectively. A temperature-color gauge is centered between each baseline and the warmed figure with values shown in degrees Fahrenheit. Postwarming images of twin 1 ( Figure 3 a) and twin 2 ( Figure 3 b) are shown with patchy regions of anhidrosis (in yellow) compared with the purple areas of sweat indicator powder, which demonstrated the regions where sweating occurred. Twin 1 had 53% anhidrosis but preserved sweating on the upper trunk, left abdomen, both hands, and medial legs, whereas twin 2 exhibited 50% anhidrosis and residual sweating of the upper trunk, bilateral hands, and medial legs. Figure 3 Diaphoresis patterns of twin 1 (a) and twin 2 (b) at the completion of the thermoregulatory sweat test (TST). QSWEAT results of twin 1 are shown with sweat rates of the forearm (25−50th percentile) ( Figure 4 a); proximal ( Figure 4 b) and distal leg sweat rates were each <10th percentile (abnormal for sex and age) ( Figure 4 c), and the foot was between the 10th to 25th percentile ( Figure 4 d). In addition, these abnormalities were categorized as a “latency of the sweat response” of the forearm, distal leg, and foot, as well as a “lack of recovery” of the proximal leg. Results for twin 2 showed a similar sweat response latency of the proximal leg ( Figure 5 b). Otherwise, twin 2 exhibited normal sweat volumes and rates for her age as seen for the forearm (10th−25th percentile) ( Figure 5 a), proximal leg (25th percentile) ( Figure 5 b), distal leg (25th percentile) ( Figure 5 c), and foot (50−80th percentile) ( Figure 5 d). Figure 4 Quantitative sweat rate (nanoliters per minute) of twin 1 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d). Figure 5 Quantitative sweat rate (nanoliters per minute) of twin 2 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d).', 'Case 1': 'Monozygotic female adolescent twins, aged 16 years old, were originally diagnosed in infancy with NC and found to have a 57-kb deletion of the CTNS gene, the most frequent cause of NC in Western populations. They were on cysteamine bitartrate (cystagon-immediate release) since diagnosis. Each was currently prescribed Procysbi (cysteamine-delayed release) 675 mg every 12 hours. In addition, each twin was prescribed cysteamine hydrochloride (0.44%) eye drops due to cystine crystal accumulation in the lens and cornea. Both twins were transplanted 6 years previously with kidneys from a single deceased donor source. Since that time, both twins experienced several episodes of transplant rejection, whereas twin 1 also developed Epstein-Barr virus positive posttransplant proliferative disorder. Table 1 includes clinical and medication data on the patients at the time of autonomic testing. As shown in Table 1, twin 2 exhibited a diastolic blood pressure (DBP) that exceeded the threshold for sex and height and had DBP readings 20% higher than those of twin 1. Table 1 Characteristics and medications of female monozygotic twins with nephropathic cystinosis Characteristics Twin 1 Twin 2 Age (yrs) 16 Race W Ethnicity H Wt. (kg) 43.6 46.0 Ht. (cm) 152.3 154.8 BMI percentile (for age and sex) (kg/m 2 ) 25th 40th Resting BP (mm Hg) 118/70 123/84 Measured GFR (ml/min per 1.73 m 2 ) 59.3 70.0 CKD stage 3a 2 Tacrolimus level (ng/ml) 5.5 4.5 Medications, Dose, Frequency Procysbi (cysteamine DR) 675 mg q 12 h Cysteamine HCL (0.44%) 1 gtt. OU q h while awake Amlodipine 10 mg/d Cardura 4 mg/d — Lisinopril 10 mg/d Drisdol 50,000 IU/ q 14 d — Cellcept 500 mg BID Tacrolimus 3 mg BID 2 mg BID Synthroid 137 μg/d 125 μg/d Mg oxide 400 mg BID Bactrim 400-80 40 mg 3×/wk BID, twice a day; BMI, body mass index; BP, blood pressure; CKD, chronic kidney disease; DR, delayed release; GFR, glomerular filtration rate by plasma clearance of iohexol; gtt, drops; H, Hispanic; HCL, hydrochloride; Ht., height; IU, international units; Mg, magnesium; OU, both eyes; q, every; W, white; Wt., weight. Laboratory findings (biochemical characteristics) for both twins are shown in Table 2 . Creatinine, blood urea nitrogen, and cystatin C levels were consistent with the CKD stage of each twin. Both patients also had blood drawn for measurement of their leukocyte cystine levels, which were obtained at the time of their regular laboratory tests. Those results were 1.65 and 1.90 nmol 1/2 cystine per milligram per protein for twins 1 and 2, respectively. Because the twins exhibited leukocyte cystine levels >1 nmol 1/2 cystine per milligram per protein, it indicated they had not achieved an optimal degree of substrate depletion for cystinosis patients on cysteamine therapy. This was due to incomplete adherence with their cysteamine bitartrate therapy. Table 3 lists a summary on cystinosis. Table 2 Laboratory results Results Conventional units (SI Units) Twin # Cr BUN Cystatin C Alb Phos Na K Glucose 1 1.08 (95.47) 15 (5.35) (1.25) 4.5 (45) 3.7 (1.20) 136 (136 ) 4.0 (4.0) 98 (5.44) 2 0.81 (71.60) 13 (4.64) (1.09) 4.9 (49) 3.8 (1.23) 137 (137) 4.2 (4.2) 94 (5.22) Normal reference range 0.25−1.14 mg/dl 5.0−18.0 mg/dl 0.5−1.3 mg/l (1−17 yr) 3.6−4.7 g/dl 3.0−4.8 mg/dl 134−146 mEq/l 3.7−5.7 mEq/l 60−110 mg/dl SI units normal Reference Range 22.1−100.78 mmol/l 1.78−6.43 mmol/l 0.50−1.30 mg/l 36.0−47.0 g/l 0.97−1.55 mmol/l 134−146 mmol/l 3.7−5.7 mmol/l 3.33−6.11 mmol/l Alb, albumin; BUN, blood urea nitrogen; Cr, creatinine; K, potassium; Na, sodium; Phos, phosphorus (inorganic); SI, Standard international. Table 3 Teaching points (i) Cystinosis results from a functional defect in the lysosomal-membrane exporter protein, cystinosin (CTNS), thereby resulting in failure of cystine efflux from cell lysosomes. When untreated, cystine crystals result and are deposited throughout the body, including in the cornea, retina, and most organs. (ii) Nephropathic cystinosis (NC) is often diagnosed in infancy due to the development of severe renal Fanconi syndrome with failure to thrive. Chronic electrolyte replacement is essential. (iii) Cystine accumulation is measured in leukocytes with a cystine level < 1 nmol 1/2 cystine per milligram cell protein categorized as being consistent with optimal cystine depletion. (iv) Cysteamine bitartrate is the only Food and Drug Administration−approved therapy for cystinosis and is available in immediate and delayed release formulations. (v) In NC, the 57-kb deletion has been associated with transient receptor potential vanilloid 1 (TRPV1) gene functional impairment. (vi) Long-term extra renal manifestations of NC are frequently observed and include cognitive impairment and/or delays, altered skin and/or heat sensations, abnormal temperature regulation, heat intolerance, reduced sweating, and myopathy, the latter of which may eventually contribute to respiratory failure, all suggestive of autonomic nervous system dysfunction pertinent to thermoregulation. Both twins frequently described issues with heat intolerance and photophobia secondary to corneal cystine crystal deposition, but they demonstrated consistently normal clinical neurological examination findings. We decided to complete further testing of the twins to evaluate heat intolerance and possible associated autonomic dysfunction as opposed to what may simply be avoidance of light exposure on sunny days.', 'Clinical Testing': 'During the period before testing, a directly measured glomerular filtration rate was completed on each twin using a plasma clearance of iohexol procedure. 14 The twins then underwent 3 clinical procedures at the Center for Autonomic Medicine in Pediatrics at Ann & Robert H. Lurie Children’s Hospital of Chicago (Chicago, IL). Those procedures included the head-up tilt (HUT) test to assess baroreceptor function, a thermoregulatory sweat test (TST) to measure sudomotor function, and the quantitative sweat response test (QSWEAT), which is a sudomotor axon reflex test in which responses of the local axon reflex of sweat glands to iontophoresed acetylcholine are quantitated. 15 The use of the TST and QSWEAT procedures on patients are considered to be the gold standard for clinical evaluation, because they demonstrated a 90% sensitivity for detection of small fiber neuropathy. 16 The HUT determines whether orthostatic (in)tolerance can be demonstrated and evaluates the inter-relationship of breathing, heart rate (HR), and BP while the patient transitions from a supine to an upright position and then returns to the supine position. Simply stated, a patient lays on a tilt table in a supine horizontal position for 10 to 20 minutes while baseline measurements are taken. Then, a HUT to 70° is done with measurements collected thereafter for 10 minutes. Following this, a tilt-down to a supine horizontal position occurs and is sustained for 2 minutes of additional measurements. During the TST, the core body temperature is increased slowly to 1 ° C higher than at prewarming (baseline) or a patient reaches a core temperature of 38 ° C (whichever is greater). To prepare for the procedure, sweat-indicator powder is applied to the patient’s anterior surface while lying supine on a bed. The patient is then rolled into the chamber, and it is sealed shut, while continuous surveillance and collection of all physiological measurements of the patient, chamber, and temperatures occurs. The ambient temperature is slowly increased with an average ramp rate of 5.0 °C/hour and with a relative humidity range of 35% to 45%. Finally, for the QSWEAT, the patient is placed in a supine horizontal position. Once situated, 4 quarter-sized capsules of acetylcholine are topically applied on the forearm, proximal and distal leg, and foot. An imperceivable 2-mA current is delivered over a 5-minute period, followed by a 5-minute recovery, which results in an accurate quantitation of sweat produced in small areas of the skin.'}
|
{'Testing Results': 'Figures 1 a to d represent the continuous HR and BP recordings of twin 1 ( Figure 1 a and b) and twin 2 ( Figure 1 c and d) during the HUT over the 10-second transition from a supine horizontal position to a 70° upright tilt. As seen in Figure 1 a, the HR of twin 1 exhibited a compensatory increase to a maximum of 110 beats/min at 6.9 minutes into the HUT and remained at this level until she was returned to a horizontal and/or supine position. This was a change of 52 beats/min. In Figure 1 b, a systolic BP (SBP) decline of 29.8 mm Hg can be seen at 0.3 minutes into the HUT. The BP of twin 1 recovered quickly to pre-HUT levels and remained stable thereafter throughout the 10-minute HUT. Conversely, for twin 2, HR increased by 45 to 120 beats/min and a 30-mm Hg SBP drop occurred when transitioned from a supine position to a 70° HUT ( Figure 1 c and d). In addition, the HR and SBP remained at these levels throughout the HUT until the twin returned to the supine position. Thus, both twins exhibited orthostatic tachycardia during HUT that was maintained until returning to the supine horizontal body position, which indicated a greater than average response compared with normative data. Figure 1 Head up-tilt (HUT) of twins 1 and 2 for continuous heart rate (a,c) and blood pressure recordings (b,d). For the TST, the baseline (pre-TST) for twin 1 and twin 2 are shown in Figure 2 a and 2 c, respectively, whereas postwarming period results for each twin are found in Figure 2 b and 2 d, respectively. By referencing the temperature scale shown between Figure 2 a and 2 b and Figure 2 c and 2 d, the images clearly demonstrate both twins with cold hands and feet before warming ( Figure 2 a and 2 c). Conversely, in post-TST images, both twins displayed symmetric warming of their hands but their feet remained slightly cooler compared with other body regions ( Figure 2 b and 2 d). Figure 2 Thermoregulatory sweat test baseline and warmed (post) test twin 1 (a,b) and twin 2 (c,d), respectively. A temperature-color gauge is centered between each baseline and the warmed figure with values shown in degrees Fahrenheit. Postwarming images of twin 1 ( Figure 3 a) and twin 2 ( Figure 3 b) are shown with patchy regions of anhidrosis (in yellow) compared with the purple areas of sweat indicator powder, which demonstrated the regions where sweating occurred. Twin 1 had 53% anhidrosis but preserved sweating on the upper trunk, left abdomen, both hands, and medial legs, whereas twin 2 exhibited 50% anhidrosis and residual sweating of the upper trunk, bilateral hands, and medial legs. Figure 3 Diaphoresis patterns of twin 1 (a) and twin 2 (b) at the completion of the thermoregulatory sweat test (TST). QSWEAT results of twin 1 are shown with sweat rates of the forearm (25−50th percentile) ( Figure 4 a); proximal ( Figure 4 b) and distal leg sweat rates were each <10th percentile (abnormal for sex and age) ( Figure 4 c), and the foot was between the 10th to 25th percentile ( Figure 4 d). In addition, these abnormalities were categorized as a “latency of the sweat response” of the forearm, distal leg, and foot, as well as a “lack of recovery” of the proximal leg. Results for twin 2 showed a similar sweat response latency of the proximal leg ( Figure 5 b). Otherwise, twin 2 exhibited normal sweat volumes and rates for her age as seen for the forearm (10th−25th percentile) ( Figure 5 a), proximal leg (25th percentile) ( Figure 5 b), distal leg (25th percentile) ( Figure 5 c), and foot (50−80th percentile) ( Figure 5 d). Figure 4 Quantitative sweat rate (nanoliters per minute) of twin 1 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d). Figure 5 Quantitative sweat rate (nanoliters per minute) of twin 2 for the left forearm (a), proximal leg (b), distal leg (c), and foot (d).', 'Case 1': 'Monozygotic female adolescent twins, aged 16 years old, were originally diagnosed in infancy with NC and found to have a 57-kb deletion of the CTNS gene, the most frequent cause of NC in Western populations. They were on cysteamine bitartrate (cystagon-immediate release) since diagnosis. Each was currently prescribed Procysbi (cysteamine-delayed release) 675 mg every 12 hours. In addition, each twin was prescribed cysteamine hydrochloride (0.44%) eye drops due to cystine crystal accumulation in the lens and cornea. Both twins were transplanted 6 years previously with kidneys from a single deceased donor source. Since that time, both twins experienced several episodes of transplant rejection, whereas twin 1 also developed Epstein-Barr virus positive posttransplant proliferative disorder. Table 1 includes clinical and medication data on the patients at the time of autonomic testing. As shown in Table 1, twin 2 exhibited a diastolic blood pressure (DBP) that exceeded the threshold for sex and height and had DBP readings 20% higher than those of twin 1. Table 1 Characteristics and medications of female monozygotic twins with nephropathic cystinosis Characteristics Twin 1 Twin 2 Age (yrs) 16 Race W Ethnicity H Wt. (kg) 43.6 46.0 Ht. (cm) 152.3 154.8 BMI percentile (for age and sex) (kg/m 2 ) 25th 40th Resting BP (mm Hg) 118/70 123/84 Measured GFR (ml/min per 1.73 m 2 ) 59.3 70.0 CKD stage 3a 2 Tacrolimus level (ng/ml) 5.5 4.5 Medications, Dose, Frequency Procysbi (cysteamine DR) 675 mg q 12 h Cysteamine HCL (0.44%) 1 gtt. OU q h while awake Amlodipine 10 mg/d Cardura 4 mg/d — Lisinopril 10 mg/d Drisdol 50,000 IU/ q 14 d — Cellcept 500 mg BID Tacrolimus 3 mg BID 2 mg BID Synthroid 137 μg/d 125 μg/d Mg oxide 400 mg BID Bactrim 400-80 40 mg 3×/wk BID, twice a day; BMI, body mass index; BP, blood pressure; CKD, chronic kidney disease; DR, delayed release; GFR, glomerular filtration rate by plasma clearance of iohexol; gtt, drops; H, Hispanic; HCL, hydrochloride; Ht., height; IU, international units; Mg, magnesium; OU, both eyes; q, every; W, white; Wt., weight. Laboratory findings (biochemical characteristics) for both twins are shown in Table 2 . Creatinine, blood urea nitrogen, and cystatin C levels were consistent with the CKD stage of each twin. Both patients also had blood drawn for measurement of their leukocyte cystine levels, which were obtained at the time of their regular laboratory tests. Those results were 1.65 and 1.90 nmol 1/2 cystine per milligram per protein for twins 1 and 2, respectively. Because the twins exhibited leukocyte cystine levels >1 nmol 1/2 cystine per milligram per protein, it indicated they had not achieved an optimal degree of substrate depletion for cystinosis patients on cysteamine therapy. This was due to incomplete adherence with their cysteamine bitartrate therapy. Table 3 lists a summary on cystinosis. Table 2 Laboratory results Results Conventional units (SI Units) Twin # Cr BUN Cystatin C Alb Phos Na K Glucose 1 1.08 (95.47) 15 (5.35) (1.25) 4.5 (45) 3.7 (1.20) 136 (136 ) 4.0 (4.0) 98 (5.44) 2 0.81 (71.60) 13 (4.64) (1.09) 4.9 (49) 3.8 (1.23) 137 (137) 4.2 (4.2) 94 (5.22) Normal reference range 0.25−1.14 mg/dl 5.0−18.0 mg/dl 0.5−1.3 mg/l (1−17 yr) 3.6−4.7 g/dl 3.0−4.8 mg/dl 134−146 mEq/l 3.7−5.7 mEq/l 60−110 mg/dl SI units normal Reference Range 22.1−100.78 mmol/l 1.78−6.43 mmol/l 0.50−1.30 mg/l 36.0−47.0 g/l 0.97−1.55 mmol/l 134−146 mmol/l 3.7−5.7 mmol/l 3.33−6.11 mmol/l Alb, albumin; BUN, blood urea nitrogen; Cr, creatinine; K, potassium; Na, sodium; Phos, phosphorus (inorganic); SI, Standard international. Table 3 Teaching points (i) Cystinosis results from a functional defect in the lysosomal-membrane exporter protein, cystinosin (CTNS), thereby resulting in failure of cystine efflux from cell lysosomes. When untreated, cystine crystals result and are deposited throughout the body, including in the cornea, retina, and most organs. (ii) Nephropathic cystinosis (NC) is often diagnosed in infancy due to the development of severe renal Fanconi syndrome with failure to thrive. Chronic electrolyte replacement is essential. (iii) Cystine accumulation is measured in leukocytes with a cystine level < 1 nmol 1/2 cystine per milligram cell protein categorized as being consistent with optimal cystine depletion. (iv) Cysteamine bitartrate is the only Food and Drug Administration−approved therapy for cystinosis and is available in immediate and delayed release formulations. (v) In NC, the 57-kb deletion has been associated with transient receptor potential vanilloid 1 (TRPV1) gene functional impairment. (vi) Long-term extra renal manifestations of NC are frequently observed and include cognitive impairment and/or delays, altered skin and/or heat sensations, abnormal temperature regulation, heat intolerance, reduced sweating, and myopathy, the latter of which may eventually contribute to respiratory failure, all suggestive of autonomic nervous system dysfunction pertinent to thermoregulation. Both twins frequently described issues with heat intolerance and photophobia secondary to corneal cystine crystal deposition, but they demonstrated consistently normal clinical neurological examination findings. We decided to complete further testing of the twins to evaluate heat intolerance and possible associated autonomic dysfunction as opposed to what may simply be avoidance of light exposure on sunny days.', 'Clinical Testing': 'During the period before testing, a directly measured glomerular filtration rate was completed on each twin using a plasma clearance of iohexol procedure. 14 The twins then underwent 3 clinical procedures at the Center for Autonomic Medicine in Pediatrics at Ann & Robert H. Lurie Children’s Hospital of Chicago (Chicago, IL). Those procedures included the head-up tilt (HUT) test to assess baroreceptor function, a thermoregulatory sweat test (TST) to measure sudomotor function, and the quantitative sweat response test (QSWEAT), which is a sudomotor axon reflex test in which responses of the local axon reflex of sweat glands to iontophoresed acetylcholine are quantitated. 15 The use of the TST and QSWEAT procedures on patients are considered to be the gold standard for clinical evaluation, because they demonstrated a 90% sensitivity for detection of small fiber neuropathy. 16 The HUT determines whether orthostatic (in)tolerance can be demonstrated and evaluates the inter-relationship of breathing, heart rate (HR), and BP while the patient transitions from a supine to an upright position and then returns to the supine position. Simply stated, a patient lays on a tilt table in a supine horizontal position for 10 to 20 minutes while baseline measurements are taken. Then, a HUT to 70° is done with measurements collected thereafter for 10 minutes. Following this, a tilt-down to a supine horizontal position occurs and is sustained for 2 minutes of additional measurements. During the TST, the core body temperature is increased slowly to 1 ° C higher than at prewarming (baseline) or a patient reaches a core temperature of 38 ° C (whichever is greater). To prepare for the procedure, sweat-indicator powder is applied to the patient’s anterior surface while lying supine on a bed. The patient is then rolled into the chamber, and it is sealed shut, while continuous surveillance and collection of all physiological measurements of the patient, chamber, and temperatures occurs. The ambient temperature is slowly increased with an average ramp rate of 5.0 °C/hour and with a relative humidity range of 35% to 45%. Finally, for the QSWEAT, the patient is placed in a supine horizontal position. Once situated, 4 quarter-sized capsules of acetylcholine are topically applied on the forearm, proximal and distal leg, and foot. An imperceivable 2-mA current is delivered over a 5-minute period, followed by a 5-minute recovery, which results in an accurate quantitation of sweat produced in small areas of the skin.'}
|
IEM-Treatment
|
IEM_Treatment
|
[
"They were on cysteamine bitartrate ( cystagon - immediate release ) since diagnosis . Each was currently prescribed Procysbi ( cysteamine - delayed release ) 675 mg every 12 hours . In addition , each twin was prescribed cysteamine hydrochloride ( 0.44 % ) eye drops due to cystine crystal accumulation in the lens and cornea . Both twins were transplanted 6 years previously with kidneys from a single deceased donor source ."
] |
6246115
|
{'Clinical Presentation': 'A dichorionic diamniotic male twin was born at 35 weeks of gestation with a birth weight of 1.6 kg (small for gestational age). The baby presented with recurrent hypoglycemia shortly after birth. Blood tests on the second day of life showed cholestasis (up to 145 umol/L), hypoalbuminemia, hyperammonemia (up to 453 umol/L), and coagulopathy, which progressively worsened throughout the first week of life. Work-up for neonatal liver failure was negative for metabolic disease, and surgical and infective causes. Ferritin level was elevated at 8,397 umol/L. Biopsy of the liver and buccal mucosa was performed. This demonstrated hepatic and extrahepatic iron deposition ( Fig. 1 ) and confirmed the diagnosis of neonatal hemochromatosis (NH; likely due to gestational alloimmune liver disease, GALD). Medical treatment was given with exchange transfusion and intravenous immunoglobulin (IVIg). However, he failed to respond to medical treatment and developed worsening liver failure. Liver transplantation was considered but deemed not an option due to the low body weight and unavailability of living-related liver donor. After extensive discussion with the parents, the decision for redirection of care was made. The baby was electively extubated and eventually succumbed on day 33 of life. On the contrary, the other twin girl was born with a birth weight of 2.4 kg and suffered only from mildly deranged liver function only. Her liver function test showed mildly elevated liver enzymes (peak aspartate aminotransferase of 371 U/L and alanine aminotransferase of 162 U/L at around 3 weeks of life) and conjugated bilirubin (11 umol/L), with normal ammonia level and clotting profile all along. Metabolic, surgical, and infective work-ups were negative. Ferritin level was high at 9,801 umol/L. Liver function test subsequently normalized spontaneously upon follow-up. Family was counseled on the importance of antenatal treatment with IVIg in future pregnancies to prevent the recurrence of NH.'}
|
{'Clinical Presentation': 'A dichorionic diamniotic male twin was born at 35 weeks of gestation with a birth weight of 1.6 kg (small for gestational age). The baby presented with recurrent hypoglycemia shortly after birth. Blood tests on the second day of life showed cholestasis (up to 145 umol/L), hypoalbuminemia, hyperammonemia (up to 453 umol/L), and coagulopathy, which progressively worsened throughout the first week of life. Work-up for neonatal liver failure was negative for metabolic disease, and surgical and infective causes. Ferritin level was elevated at 8,397 umol/L. Biopsy of the liver and buccal mucosa was performed. This demonstrated hepatic and extrahepatic iron deposition ( Fig. 1 ) and confirmed the diagnosis of neonatal hemochromatosis (NH; likely due to gestational alloimmune liver disease, GALD). Medical treatment was given with exchange transfusion and intravenous immunoglobulin (IVIg). However, he failed to respond to medical treatment and developed worsening liver failure. Liver transplantation was considered but deemed not an option due to the low body weight and unavailability of living-related liver donor. After extensive discussion with the parents, the decision for redirection of care was made. The baby was electively extubated and eventually succumbed on day 33 of life. On the contrary, the other twin girl was born with a birth weight of 2.4 kg and suffered only from mildly deranged liver function only. Her liver function test showed mildly elevated liver enzymes (peak aspartate aminotransferase of 371 U/L and alanine aminotransferase of 162 U/L at around 3 weeks of life) and conjugated bilirubin (11 umol/L), with normal ammonia level and clotting profile all along. Metabolic, surgical, and infective work-ups were negative. Ferritin level was high at 9,801 umol/L. Liver function test subsequently normalized spontaneously upon follow-up. Family was counseled on the importance of antenatal treatment with IVIg in future pregnancies to prevent the recurrence of NH.'}
|
Vitals-and-Hematology
|
Vitals_Hema
|
[
"coagulopathy",
"Ferritin level was elevated at 8,397 umol / L.",
"normal ammonia level and clotting profile all along",
"Ferritin level was high at 9,801 umol / L."
] |
6246115
|
{'Clinical Presentation': 'A dichorionic diamniotic male twin was born at 35 weeks of gestation with a birth weight of 1.6 kg (small for gestational age). The baby presented with recurrent hypoglycemia shortly after birth. Blood tests on the second day of life showed cholestasis (up to 145 umol/L), hypoalbuminemia, hyperammonemia (up to 453 umol/L), and coagulopathy, which progressively worsened throughout the first week of life. Work-up for neonatal liver failure was negative for metabolic disease, and surgical and infective causes. Ferritin level was elevated at 8,397 umol/L. Biopsy of the liver and buccal mucosa was performed. This demonstrated hepatic and extrahepatic iron deposition ( Fig. 1 ) and confirmed the diagnosis of neonatal hemochromatosis (NH; likely due to gestational alloimmune liver disease, GALD). Medical treatment was given with exchange transfusion and intravenous immunoglobulin (IVIg). However, he failed to respond to medical treatment and developed worsening liver failure. Liver transplantation was considered but deemed not an option due to the low body weight and unavailability of living-related liver donor. After extensive discussion with the parents, the decision for redirection of care was made. The baby was electively extubated and eventually succumbed on day 33 of life. On the contrary, the other twin girl was born with a birth weight of 2.4 kg and suffered only from mildly deranged liver function only. Her liver function test showed mildly elevated liver enzymes (peak aspartate aminotransferase of 371 U/L and alanine aminotransferase of 162 U/L at around 3 weeks of life) and conjugated bilirubin (11 umol/L), with normal ammonia level and clotting profile all along. Metabolic, surgical, and infective work-ups were negative. Ferritin level was high at 9,801 umol/L. Liver function test subsequently normalized spontaneously upon follow-up. Family was counseled on the importance of antenatal treatment with IVIg in future pregnancies to prevent the recurrence of NH.'}
|
{'Clinical Presentation': 'A dichorionic diamniotic male twin was born at 35 weeks of gestation with a birth weight of 1.6 kg (small for gestational age). The baby presented with recurrent hypoglycemia shortly after birth. Blood tests on the second day of life showed cholestasis (up to 145 umol/L), hypoalbuminemia, hyperammonemia (up to 453 umol/L), and coagulopathy, which progressively worsened throughout the first week of life. Work-up for neonatal liver failure was negative for metabolic disease, and surgical and infective causes. Ferritin level was elevated at 8,397 umol/L. Biopsy of the liver and buccal mucosa was performed. This demonstrated hepatic and extrahepatic iron deposition ( Fig. 1 ) and confirmed the diagnosis of neonatal hemochromatosis (NH; likely due to gestational alloimmune liver disease, GALD). Medical treatment was given with exchange transfusion and intravenous immunoglobulin (IVIg). However, he failed to respond to medical treatment and developed worsening liver failure. Liver transplantation was considered but deemed not an option due to the low body weight and unavailability of living-related liver donor. After extensive discussion with the parents, the decision for redirection of care was made. The baby was electively extubated and eventually succumbed on day 33 of life. On the contrary, the other twin girl was born with a birth weight of 2.4 kg and suffered only from mildly deranged liver function only. Her liver function test showed mildly elevated liver enzymes (peak aspartate aminotransferase of 371 U/L and alanine aminotransferase of 162 U/L at around 3 weeks of life) and conjugated bilirubin (11 umol/L), with normal ammonia level and clotting profile all along. Metabolic, surgical, and infective work-ups were negative. Ferritin level was high at 9,801 umol/L. Liver function test subsequently normalized spontaneously upon follow-up. Family was counseled on the importance of antenatal treatment with IVIg in future pregnancies to prevent the recurrence of NH.'}
|
Gastrointestinal-System
|
GI
|
[] |
6246115
|
{'Clinical Presentation': 'A dichorionic diamniotic male twin was born at 35 weeks of gestation with a birth weight of 1.6 kg (small for gestational age). The baby presented with recurrent hypoglycemia shortly after birth. Blood tests on the second day of life showed cholestasis (up to 145 umol/L), hypoalbuminemia, hyperammonemia (up to 453 umol/L), and coagulopathy, which progressively worsened throughout the first week of life. Work-up for neonatal liver failure was negative for metabolic disease, and surgical and infective causes. Ferritin level was elevated at 8,397 umol/L. Biopsy of the liver and buccal mucosa was performed. This demonstrated hepatic and extrahepatic iron deposition ( Fig. 1 ) and confirmed the diagnosis of neonatal hemochromatosis (NH; likely due to gestational alloimmune liver disease, GALD). Medical treatment was given with exchange transfusion and intravenous immunoglobulin (IVIg). However, he failed to respond to medical treatment and developed worsening liver failure. Liver transplantation was considered but deemed not an option due to the low body weight and unavailability of living-related liver donor. After extensive discussion with the parents, the decision for redirection of care was made. The baby was electively extubated and eventually succumbed on day 33 of life. On the contrary, the other twin girl was born with a birth weight of 2.4 kg and suffered only from mildly deranged liver function only. Her liver function test showed mildly elevated liver enzymes (peak aspartate aminotransferase of 371 U/L and alanine aminotransferase of 162 U/L at around 3 weeks of life) and conjugated bilirubin (11 umol/L), with normal ammonia level and clotting profile all along. Metabolic, surgical, and infective work-ups were negative. Ferritin level was high at 9,801 umol/L. Liver function test subsequently normalized spontaneously upon follow-up. Family was counseled on the importance of antenatal treatment with IVIg in future pregnancies to prevent the recurrence of NH.'}
|
{'Clinical Presentation': 'A dichorionic diamniotic male twin was born at 35 weeks of gestation with a birth weight of 1.6 kg (small for gestational age). The baby presented with recurrent hypoglycemia shortly after birth. Blood tests on the second day of life showed cholestasis (up to 145 umol/L), hypoalbuminemia, hyperammonemia (up to 453 umol/L), and coagulopathy, which progressively worsened throughout the first week of life. Work-up for neonatal liver failure was negative for metabolic disease, and surgical and infective causes. Ferritin level was elevated at 8,397 umol/L. Biopsy of the liver and buccal mucosa was performed. This demonstrated hepatic and extrahepatic iron deposition ( Fig. 1 ) and confirmed the diagnosis of neonatal hemochromatosis (NH; likely due to gestational alloimmune liver disease, GALD). Medical treatment was given with exchange transfusion and intravenous immunoglobulin (IVIg). However, he failed to respond to medical treatment and developed worsening liver failure. Liver transplantation was considered but deemed not an option due to the low body weight and unavailability of living-related liver donor. After extensive discussion with the parents, the decision for redirection of care was made. The baby was electively extubated and eventually succumbed on day 33 of life. On the contrary, the other twin girl was born with a birth weight of 2.4 kg and suffered only from mildly deranged liver function only. Her liver function test showed mildly elevated liver enzymes (peak aspartate aminotransferase of 371 U/L and alanine aminotransferase of 162 U/L at around 3 weeks of life) and conjugated bilirubin (11 umol/L), with normal ammonia level and clotting profile all along. Metabolic, surgical, and infective work-ups were negative. Ferritin level was high at 9,801 umol/L. Liver function test subsequently normalized spontaneously upon follow-up. Family was counseled on the importance of antenatal treatment with IVIg in future pregnancies to prevent the recurrence of NH.'}
|
Patient-History
|
History
|
[
"The baby presented with recurrent hypoglycemia shortly after birth"
] |
6246115
|
{'Clinical Presentation': 'A dichorionic diamniotic male twin was born at 35 weeks of gestation with a birth weight of 1.6 kg (small for gestational age). The baby presented with recurrent hypoglycemia shortly after birth. Blood tests on the second day of life showed cholestasis (up to 145 umol/L), hypoalbuminemia, hyperammonemia (up to 453 umol/L), and coagulopathy, which progressively worsened throughout the first week of life. Work-up for neonatal liver failure was negative for metabolic disease, and surgical and infective causes. Ferritin level was elevated at 8,397 umol/L. Biopsy of the liver and buccal mucosa was performed. This demonstrated hepatic and extrahepatic iron deposition ( Fig. 1 ) and confirmed the diagnosis of neonatal hemochromatosis (NH; likely due to gestational alloimmune liver disease, GALD). Medical treatment was given with exchange transfusion and intravenous immunoglobulin (IVIg). However, he failed to respond to medical treatment and developed worsening liver failure. Liver transplantation was considered but deemed not an option due to the low body weight and unavailability of living-related liver donor. After extensive discussion with the parents, the decision for redirection of care was made. The baby was electively extubated and eventually succumbed on day 33 of life. On the contrary, the other twin girl was born with a birth weight of 2.4 kg and suffered only from mildly deranged liver function only. Her liver function test showed mildly elevated liver enzymes (peak aspartate aminotransferase of 371 U/L and alanine aminotransferase of 162 U/L at around 3 weeks of life) and conjugated bilirubin (11 umol/L), with normal ammonia level and clotting profile all along. Metabolic, surgical, and infective work-ups were negative. Ferritin level was high at 9,801 umol/L. Liver function test subsequently normalized spontaneously upon follow-up. Family was counseled on the importance of antenatal treatment with IVIg in future pregnancies to prevent the recurrence of NH.'}
|
{'Clinical Presentation': 'A dichorionic diamniotic male twin was born at 35 weeks of gestation with a birth weight of 1.6 kg (small for gestational age). The baby presented with recurrent hypoglycemia shortly after birth. Blood tests on the second day of life showed cholestasis (up to 145 umol/L), hypoalbuminemia, hyperammonemia (up to 453 umol/L), and coagulopathy, which progressively worsened throughout the first week of life. Work-up for neonatal liver failure was negative for metabolic disease, and surgical and infective causes. Ferritin level was elevated at 8,397 umol/L. Biopsy of the liver and buccal mucosa was performed. This demonstrated hepatic and extrahepatic iron deposition ( Fig. 1 ) and confirmed the diagnosis of neonatal hemochromatosis (NH; likely due to gestational alloimmune liver disease, GALD). Medical treatment was given with exchange transfusion and intravenous immunoglobulin (IVIg). However, he failed to respond to medical treatment and developed worsening liver failure. Liver transplantation was considered but deemed not an option due to the low body weight and unavailability of living-related liver donor. After extensive discussion with the parents, the decision for redirection of care was made. The baby was electively extubated and eventually succumbed on day 33 of life. On the contrary, the other twin girl was born with a birth weight of 2.4 kg and suffered only from mildly deranged liver function only. Her liver function test showed mildly elevated liver enzymes (peak aspartate aminotransferase of 371 U/L and alanine aminotransferase of 162 U/L at around 3 weeks of life) and conjugated bilirubin (11 umol/L), with normal ammonia level and clotting profile all along. Metabolic, surgical, and infective work-ups were negative. Ferritin level was high at 9,801 umol/L. Liver function test subsequently normalized spontaneously upon follow-up. Family was counseled on the importance of antenatal treatment with IVIg in future pregnancies to prevent the recurrence of NH.'}
|
Neurology
|
Neuro
|
[] |
6246115
|
{'Clinical Presentation': 'A dichorionic diamniotic male twin was born at 35 weeks of gestation with a birth weight of 1.6 kg (small for gestational age). The baby presented with recurrent hypoglycemia shortly after birth. Blood tests on the second day of life showed cholestasis (up to 145 umol/L), hypoalbuminemia, hyperammonemia (up to 453 umol/L), and coagulopathy, which progressively worsened throughout the first week of life. Work-up for neonatal liver failure was negative for metabolic disease, and surgical and infective causes. Ferritin level was elevated at 8,397 umol/L. Biopsy of the liver and buccal mucosa was performed. This demonstrated hepatic and extrahepatic iron deposition ( Fig. 1 ) and confirmed the diagnosis of neonatal hemochromatosis (NH; likely due to gestational alloimmune liver disease, GALD). Medical treatment was given with exchange transfusion and intravenous immunoglobulin (IVIg). However, he failed to respond to medical treatment and developed worsening liver failure. Liver transplantation was considered but deemed not an option due to the low body weight and unavailability of living-related liver donor. After extensive discussion with the parents, the decision for redirection of care was made. The baby was electively extubated and eventually succumbed on day 33 of life. On the contrary, the other twin girl was born with a birth weight of 2.4 kg and suffered only from mildly deranged liver function only. Her liver function test showed mildly elevated liver enzymes (peak aspartate aminotransferase of 371 U/L and alanine aminotransferase of 162 U/L at around 3 weeks of life) and conjugated bilirubin (11 umol/L), with normal ammonia level and clotting profile all along. Metabolic, surgical, and infective work-ups were negative. Ferritin level was high at 9,801 umol/L. Liver function test subsequently normalized spontaneously upon follow-up. Family was counseled on the importance of antenatal treatment with IVIg in future pregnancies to prevent the recurrence of NH.'}
|
{'Clinical Presentation': 'A dichorionic diamniotic male twin was born at 35 weeks of gestation with a birth weight of 1.6 kg (small for gestational age). The baby presented with recurrent hypoglycemia shortly after birth. Blood tests on the second day of life showed cholestasis (up to 145 umol/L), hypoalbuminemia, hyperammonemia (up to 453 umol/L), and coagulopathy, which progressively worsened throughout the first week of life. Work-up for neonatal liver failure was negative for metabolic disease, and surgical and infective causes. Ferritin level was elevated at 8,397 umol/L. Biopsy of the liver and buccal mucosa was performed. This demonstrated hepatic and extrahepatic iron deposition ( Fig. 1 ) and confirmed the diagnosis of neonatal hemochromatosis (NH; likely due to gestational alloimmune liver disease, GALD). Medical treatment was given with exchange transfusion and intravenous immunoglobulin (IVIg). However, he failed to respond to medical treatment and developed worsening liver failure. Liver transplantation was considered but deemed not an option due to the low body weight and unavailability of living-related liver donor. After extensive discussion with the parents, the decision for redirection of care was made. The baby was electively extubated and eventually succumbed on day 33 of life. On the contrary, the other twin girl was born with a birth weight of 2.4 kg and suffered only from mildly deranged liver function only. Her liver function test showed mildly elevated liver enzymes (peak aspartate aminotransferase of 371 U/L and alanine aminotransferase of 162 U/L at around 3 weeks of life) and conjugated bilirubin (11 umol/L), with normal ammonia level and clotting profile all along. Metabolic, surgical, and infective work-ups were negative. Ferritin level was high at 9,801 umol/L. Liver function test subsequently normalized spontaneously upon follow-up. Family was counseled on the importance of antenatal treatment with IVIg in future pregnancies to prevent the recurrence of NH.'}
|
Laboratory-and-Imaging
|
Lab_Image
|
[
"Blood tests on the second day of life showed cholestasis ( up to 145 umol / L ), hypoalbuminemia, hyperammonemia ( up to 453 umol / L ), and coagulopathy, which progressively worsened throughout the first week of life. Work - up for neonatal liver failure was negative for metabolic disease, and surgical and infective causes. Ferritin level was elevated at 8,397 umol / L.",
"Biopsy of the liver and buccal mucosa was performed. This demonstrated hepatic and extrahepatic iron deposition",
"Her liver function test showed mildly elevated liver enzymes ( peak aspartate aminotransferase of 371 U / L and alanine aminotransferase of 162 U / L at around 3 weeks of life ) and conjugated bilirubin ( 11 umol / L ), with normal ammonia level and clotting profile all along. Metabolic, surgical, and infective work - ups were negative. Ferritin level was high at 9,801 umol / L. Liver function test subsequently normalized spontaneously upon follow - up."
] |
6246115
|
{'Clinical Presentation': 'A dichorionic diamniotic male twin was born at 35 weeks of gestation with a birth weight of 1.6 kg (small for gestational age). The baby presented with recurrent hypoglycemia shortly after birth. Blood tests on the second day of life showed cholestasis (up to 145 umol/L), hypoalbuminemia, hyperammonemia (up to 453 umol/L), and coagulopathy, which progressively worsened throughout the first week of life. Work-up for neonatal liver failure was negative for metabolic disease, and surgical and infective causes. Ferritin level was elevated at 8,397 umol/L. Biopsy of the liver and buccal mucosa was performed. This demonstrated hepatic and extrahepatic iron deposition ( Fig. 1 ) and confirmed the diagnosis of neonatal hemochromatosis (NH; likely due to gestational alloimmune liver disease, GALD). Medical treatment was given with exchange transfusion and intravenous immunoglobulin (IVIg). However, he failed to respond to medical treatment and developed worsening liver failure. Liver transplantation was considered but deemed not an option due to the low body weight and unavailability of living-related liver donor. After extensive discussion with the parents, the decision for redirection of care was made. The baby was electively extubated and eventually succumbed on day 33 of life. On the contrary, the other twin girl was born with a birth weight of 2.4 kg and suffered only from mildly deranged liver function only. Her liver function test showed mildly elevated liver enzymes (peak aspartate aminotransferase of 371 U/L and alanine aminotransferase of 162 U/L at around 3 weeks of life) and conjugated bilirubin (11 umol/L), with normal ammonia level and clotting profile all along. Metabolic, surgical, and infective work-ups were negative. Ferritin level was high at 9,801 umol/L. Liver function test subsequently normalized spontaneously upon follow-up. Family was counseled on the importance of antenatal treatment with IVIg in future pregnancies to prevent the recurrence of NH.'}
|
{'Clinical Presentation': 'A dichorionic diamniotic male twin was born at 35 weeks of gestation with a birth weight of 1.6 kg (small for gestational age). The baby presented with recurrent hypoglycemia shortly after birth. Blood tests on the second day of life showed cholestasis (up to 145 umol/L), hypoalbuminemia, hyperammonemia (up to 453 umol/L), and coagulopathy, which progressively worsened throughout the first week of life. Work-up for neonatal liver failure was negative for metabolic disease, and surgical and infective causes. Ferritin level was elevated at 8,397 umol/L. Biopsy of the liver and buccal mucosa was performed. This demonstrated hepatic and extrahepatic iron deposition ( Fig. 1 ) and confirmed the diagnosis of neonatal hemochromatosis (NH; likely due to gestational alloimmune liver disease, GALD). Medical treatment was given with exchange transfusion and intravenous immunoglobulin (IVIg). However, he failed to respond to medical treatment and developed worsening liver failure. Liver transplantation was considered but deemed not an option due to the low body weight and unavailability of living-related liver donor. After extensive discussion with the parents, the decision for redirection of care was made. The baby was electively extubated and eventually succumbed on day 33 of life. On the contrary, the other twin girl was born with a birth weight of 2.4 kg and suffered only from mildly deranged liver function only. Her liver function test showed mildly elevated liver enzymes (peak aspartate aminotransferase of 371 U/L and alanine aminotransferase of 162 U/L at around 3 weeks of life) and conjugated bilirubin (11 umol/L), with normal ammonia level and clotting profile all along. Metabolic, surgical, and infective work-ups were negative. Ferritin level was high at 9,801 umol/L. Liver function test subsequently normalized spontaneously upon follow-up. Family was counseled on the importance of antenatal treatment with IVIg in future pregnancies to prevent the recurrence of NH.'}
|
Cardiovascular-System
|
CVS
|
[] |
6246115
|
{'Clinical Presentation': 'A dichorionic diamniotic male twin was born at 35 weeks of gestation with a birth weight of 1.6 kg (small for gestational age). The baby presented with recurrent hypoglycemia shortly after birth. Blood tests on the second day of life showed cholestasis (up to 145 umol/L), hypoalbuminemia, hyperammonemia (up to 453 umol/L), and coagulopathy, which progressively worsened throughout the first week of life. Work-up for neonatal liver failure was negative for metabolic disease, and surgical and infective causes. Ferritin level was elevated at 8,397 umol/L. Biopsy of the liver and buccal mucosa was performed. This demonstrated hepatic and extrahepatic iron deposition ( Fig. 1 ) and confirmed the diagnosis of neonatal hemochromatosis (NH; likely due to gestational alloimmune liver disease, GALD). Medical treatment was given with exchange transfusion and intravenous immunoglobulin (IVIg). However, he failed to respond to medical treatment and developed worsening liver failure. Liver transplantation was considered but deemed not an option due to the low body weight and unavailability of living-related liver donor. After extensive discussion with the parents, the decision for redirection of care was made. The baby was electively extubated and eventually succumbed on day 33 of life. On the contrary, the other twin girl was born with a birth weight of 2.4 kg and suffered only from mildly deranged liver function only. Her liver function test showed mildly elevated liver enzymes (peak aspartate aminotransferase of 371 U/L and alanine aminotransferase of 162 U/L at around 3 weeks of life) and conjugated bilirubin (11 umol/L), with normal ammonia level and clotting profile all along. Metabolic, surgical, and infective work-ups were negative. Ferritin level was high at 9,801 umol/L. Liver function test subsequently normalized spontaneously upon follow-up. Family was counseled on the importance of antenatal treatment with IVIg in future pregnancies to prevent the recurrence of NH.'}
|
{'Clinical Presentation': 'A dichorionic diamniotic male twin was born at 35 weeks of gestation with a birth weight of 1.6 kg (small for gestational age). The baby presented with recurrent hypoglycemia shortly after birth. Blood tests on the second day of life showed cholestasis (up to 145 umol/L), hypoalbuminemia, hyperammonemia (up to 453 umol/L), and coagulopathy, which progressively worsened throughout the first week of life. Work-up for neonatal liver failure was negative for metabolic disease, and surgical and infective causes. Ferritin level was elevated at 8,397 umol/L. Biopsy of the liver and buccal mucosa was performed. This demonstrated hepatic and extrahepatic iron deposition ( Fig. 1 ) and confirmed the diagnosis of neonatal hemochromatosis (NH; likely due to gestational alloimmune liver disease, GALD). Medical treatment was given with exchange transfusion and intravenous immunoglobulin (IVIg). However, he failed to respond to medical treatment and developed worsening liver failure. Liver transplantation was considered but deemed not an option due to the low body weight and unavailability of living-related liver donor. After extensive discussion with the parents, the decision for redirection of care was made. The baby was electively extubated and eventually succumbed on day 33 of life. On the contrary, the other twin girl was born with a birth weight of 2.4 kg and suffered only from mildly deranged liver function only. Her liver function test showed mildly elevated liver enzymes (peak aspartate aminotransferase of 371 U/L and alanine aminotransferase of 162 U/L at around 3 weeks of life) and conjugated bilirubin (11 umol/L), with normal ammonia level and clotting profile all along. Metabolic, surgical, and infective work-ups were negative. Ferritin level was high at 9,801 umol/L. Liver function test subsequently normalized spontaneously upon follow-up. Family was counseled on the importance of antenatal treatment with IVIg in future pregnancies to prevent the recurrence of NH.'}
|
Endocrinology
|
ENDO
|
[
"recurrent hypoglycemia"
] |
6246115
|
{'Clinical Presentation': 'A dichorionic diamniotic male twin was born at 35 weeks of gestation with a birth weight of 1.6 kg (small for gestational age). The baby presented with recurrent hypoglycemia shortly after birth. Blood tests on the second day of life showed cholestasis (up to 145 umol/L), hypoalbuminemia, hyperammonemia (up to 453 umol/L), and coagulopathy, which progressively worsened throughout the first week of life. Work-up for neonatal liver failure was negative for metabolic disease, and surgical and infective causes. Ferritin level was elevated at 8,397 umol/L. Biopsy of the liver and buccal mucosa was performed. This demonstrated hepatic and extrahepatic iron deposition ( Fig. 1 ) and confirmed the diagnosis of neonatal hemochromatosis (NH; likely due to gestational alloimmune liver disease, GALD). Medical treatment was given with exchange transfusion and intravenous immunoglobulin (IVIg). However, he failed to respond to medical treatment and developed worsening liver failure. Liver transplantation was considered but deemed not an option due to the low body weight and unavailability of living-related liver donor. After extensive discussion with the parents, the decision for redirection of care was made. The baby was electively extubated and eventually succumbed on day 33 of life. On the contrary, the other twin girl was born with a birth weight of 2.4 kg and suffered only from mildly deranged liver function only. Her liver function test showed mildly elevated liver enzymes (peak aspartate aminotransferase of 371 U/L and alanine aminotransferase of 162 U/L at around 3 weeks of life) and conjugated bilirubin (11 umol/L), with normal ammonia level and clotting profile all along. Metabolic, surgical, and infective work-ups were negative. Ferritin level was high at 9,801 umol/L. Liver function test subsequently normalized spontaneously upon follow-up. Family was counseled on the importance of antenatal treatment with IVIg in future pregnancies to prevent the recurrence of NH.'}
|
{'Clinical Presentation': 'A dichorionic diamniotic male twin was born at 35 weeks of gestation with a birth weight of 1.6 kg (small for gestational age). The baby presented with recurrent hypoglycemia shortly after birth. Blood tests on the second day of life showed cholestasis (up to 145 umol/L), hypoalbuminemia, hyperammonemia (up to 453 umol/L), and coagulopathy, which progressively worsened throughout the first week of life. Work-up for neonatal liver failure was negative for metabolic disease, and surgical and infective causes. Ferritin level was elevated at 8,397 umol/L. Biopsy of the liver and buccal mucosa was performed. This demonstrated hepatic and extrahepatic iron deposition ( Fig. 1 ) and confirmed the diagnosis of neonatal hemochromatosis (NH; likely due to gestational alloimmune liver disease, GALD). Medical treatment was given with exchange transfusion and intravenous immunoglobulin (IVIg). However, he failed to respond to medical treatment and developed worsening liver failure. Liver transplantation was considered but deemed not an option due to the low body weight and unavailability of living-related liver donor. After extensive discussion with the parents, the decision for redirection of care was made. The baby was electively extubated and eventually succumbed on day 33 of life. On the contrary, the other twin girl was born with a birth weight of 2.4 kg and suffered only from mildly deranged liver function only. Her liver function test showed mildly elevated liver enzymes (peak aspartate aminotransferase of 371 U/L and alanine aminotransferase of 162 U/L at around 3 weeks of life) and conjugated bilirubin (11 umol/L), with normal ammonia level and clotting profile all along. Metabolic, surgical, and infective work-ups were negative. Ferritin level was high at 9,801 umol/L. Liver function test subsequently normalized spontaneously upon follow-up. Family was counseled on the importance of antenatal treatment with IVIg in future pregnancies to prevent the recurrence of NH.'}
|
Genitourinary-System
|
GU
|
[] |
6246115
|
{'Clinical Presentation': 'A dichorionic diamniotic male twin was born at 35 weeks of gestation with a birth weight of 1.6 kg (small for gestational age). The baby presented with recurrent hypoglycemia shortly after birth. Blood tests on the second day of life showed cholestasis (up to 145 umol/L), hypoalbuminemia, hyperammonemia (up to 453 umol/L), and coagulopathy, which progressively worsened throughout the first week of life. Work-up for neonatal liver failure was negative for metabolic disease, and surgical and infective causes. Ferritin level was elevated at 8,397 umol/L. Biopsy of the liver and buccal mucosa was performed. This demonstrated hepatic and extrahepatic iron deposition ( Fig. 1 ) and confirmed the diagnosis of neonatal hemochromatosis (NH; likely due to gestational alloimmune liver disease, GALD). Medical treatment was given with exchange transfusion and intravenous immunoglobulin (IVIg). However, he failed to respond to medical treatment and developed worsening liver failure. Liver transplantation was considered but deemed not an option due to the low body weight and unavailability of living-related liver donor. After extensive discussion with the parents, the decision for redirection of care was made. The baby was electively extubated and eventually succumbed on day 33 of life. On the contrary, the other twin girl was born with a birth weight of 2.4 kg and suffered only from mildly deranged liver function only. Her liver function test showed mildly elevated liver enzymes (peak aspartate aminotransferase of 371 U/L and alanine aminotransferase of 162 U/L at around 3 weeks of life) and conjugated bilirubin (11 umol/L), with normal ammonia level and clotting profile all along. Metabolic, surgical, and infective work-ups were negative. Ferritin level was high at 9,801 umol/L. Liver function test subsequently normalized spontaneously upon follow-up. Family was counseled on the importance of antenatal treatment with IVIg in future pregnancies to prevent the recurrence of NH.'}
|
{'Clinical Presentation': 'A dichorionic diamniotic male twin was born at 35 weeks of gestation with a birth weight of 1.6 kg (small for gestational age). The baby presented with recurrent hypoglycemia shortly after birth. Blood tests on the second day of life showed cholestasis (up to 145 umol/L), hypoalbuminemia, hyperammonemia (up to 453 umol/L), and coagulopathy, which progressively worsened throughout the first week of life. Work-up for neonatal liver failure was negative for metabolic disease, and surgical and infective causes. Ferritin level was elevated at 8,397 umol/L. Biopsy of the liver and buccal mucosa was performed. This demonstrated hepatic and extrahepatic iron deposition ( Fig. 1 ) and confirmed the diagnosis of neonatal hemochromatosis (NH; likely due to gestational alloimmune liver disease, GALD). Medical treatment was given with exchange transfusion and intravenous immunoglobulin (IVIg). However, he failed to respond to medical treatment and developed worsening liver failure. Liver transplantation was considered but deemed not an option due to the low body weight and unavailability of living-related liver donor. After extensive discussion with the parents, the decision for redirection of care was made. The baby was electively extubated and eventually succumbed on day 33 of life. On the contrary, the other twin girl was born with a birth weight of 2.4 kg and suffered only from mildly deranged liver function only. Her liver function test showed mildly elevated liver enzymes (peak aspartate aminotransferase of 371 U/L and alanine aminotransferase of 162 U/L at around 3 weeks of life) and conjugated bilirubin (11 umol/L), with normal ammonia level and clotting profile all along. Metabolic, surgical, and infective work-ups were negative. Ferritin level was high at 9,801 umol/L. Liver function test subsequently normalized spontaneously upon follow-up. Family was counseled on the importance of antenatal treatment with IVIg in future pregnancies to prevent the recurrence of NH.'}
|
Respiratory-System
|
RESP
|
[] |
6246115
|
{'Clinical Presentation': 'A dichorionic diamniotic male twin was born at 35 weeks of gestation with a birth weight of 1.6 kg (small for gestational age). The baby presented with recurrent hypoglycemia shortly after birth. Blood tests on the second day of life showed cholestasis (up to 145 umol/L), hypoalbuminemia, hyperammonemia (up to 453 umol/L), and coagulopathy, which progressively worsened throughout the first week of life. Work-up for neonatal liver failure was negative for metabolic disease, and surgical and infective causes. Ferritin level was elevated at 8,397 umol/L. Biopsy of the liver and buccal mucosa was performed. This demonstrated hepatic and extrahepatic iron deposition ( Fig. 1 ) and confirmed the diagnosis of neonatal hemochromatosis (NH; likely due to gestational alloimmune liver disease, GALD). Medical treatment was given with exchange transfusion and intravenous immunoglobulin (IVIg). However, he failed to respond to medical treatment and developed worsening liver failure. Liver transplantation was considered but deemed not an option due to the low body weight and unavailability of living-related liver donor. After extensive discussion with the parents, the decision for redirection of care was made. The baby was electively extubated and eventually succumbed on day 33 of life. On the contrary, the other twin girl was born with a birth weight of 2.4 kg and suffered only from mildly deranged liver function only. Her liver function test showed mildly elevated liver enzymes (peak aspartate aminotransferase of 371 U/L and alanine aminotransferase of 162 U/L at around 3 weeks of life) and conjugated bilirubin (11 umol/L), with normal ammonia level and clotting profile all along. Metabolic, surgical, and infective work-ups were negative. Ferritin level was high at 9,801 umol/L. Liver function test subsequently normalized spontaneously upon follow-up. Family was counseled on the importance of antenatal treatment with IVIg in future pregnancies to prevent the recurrence of NH.'}
|
{'Clinical Presentation': 'A dichorionic diamniotic male twin was born at 35 weeks of gestation with a birth weight of 1.6 kg (small for gestational age). The baby presented with recurrent hypoglycemia shortly after birth. Blood tests on the second day of life showed cholestasis (up to 145 umol/L), hypoalbuminemia, hyperammonemia (up to 453 umol/L), and coagulopathy, which progressively worsened throughout the first week of life. Work-up for neonatal liver failure was negative for metabolic disease, and surgical and infective causes. Ferritin level was elevated at 8,397 umol/L. Biopsy of the liver and buccal mucosa was performed. This demonstrated hepatic and extrahepatic iron deposition ( Fig. 1 ) and confirmed the diagnosis of neonatal hemochromatosis (NH; likely due to gestational alloimmune liver disease, GALD). Medical treatment was given with exchange transfusion and intravenous immunoglobulin (IVIg). However, he failed to respond to medical treatment and developed worsening liver failure. Liver transplantation was considered but deemed not an option due to the low body weight and unavailability of living-related liver donor. After extensive discussion with the parents, the decision for redirection of care was made. The baby was electively extubated and eventually succumbed on day 33 of life. On the contrary, the other twin girl was born with a birth weight of 2.4 kg and suffered only from mildly deranged liver function only. Her liver function test showed mildly elevated liver enzymes (peak aspartate aminotransferase of 371 U/L and alanine aminotransferase of 162 U/L at around 3 weeks of life) and conjugated bilirubin (11 umol/L), with normal ammonia level and clotting profile all along. Metabolic, surgical, and infective work-ups were negative. Ferritin level was high at 9,801 umol/L. Liver function test subsequently normalized spontaneously upon follow-up. Family was counseled on the importance of antenatal treatment with IVIg in future pregnancies to prevent the recurrence of NH.'}
|
Musculoskeletal-System
|
MSK
|
[] |
6246115
|
{'Clinical Presentation': 'A dichorionic diamniotic male twin was born at 35 weeks of gestation with a birth weight of 1.6 kg (small for gestational age). The baby presented with recurrent hypoglycemia shortly after birth. Blood tests on the second day of life showed cholestasis (up to 145 umol/L), hypoalbuminemia, hyperammonemia (up to 453 umol/L), and coagulopathy, which progressively worsened throughout the first week of life. Work-up for neonatal liver failure was negative for metabolic disease, and surgical and infective causes. Ferritin level was elevated at 8,397 umol/L. Biopsy of the liver and buccal mucosa was performed. This demonstrated hepatic and extrahepatic iron deposition ( Fig. 1 ) and confirmed the diagnosis of neonatal hemochromatosis (NH; likely due to gestational alloimmune liver disease, GALD). Medical treatment was given with exchange transfusion and intravenous immunoglobulin (IVIg). However, he failed to respond to medical treatment and developed worsening liver failure. Liver transplantation was considered but deemed not an option due to the low body weight and unavailability of living-related liver donor. After extensive discussion with the parents, the decision for redirection of care was made. The baby was electively extubated and eventually succumbed on day 33 of life. On the contrary, the other twin girl was born with a birth weight of 2.4 kg and suffered only from mildly deranged liver function only. Her liver function test showed mildly elevated liver enzymes (peak aspartate aminotransferase of 371 U/L and alanine aminotransferase of 162 U/L at around 3 weeks of life) and conjugated bilirubin (11 umol/L), with normal ammonia level and clotting profile all along. Metabolic, surgical, and infective work-ups were negative. Ferritin level was high at 9,801 umol/L. Liver function test subsequently normalized spontaneously upon follow-up. Family was counseled on the importance of antenatal treatment with IVIg in future pregnancies to prevent the recurrence of NH.'}
|
{'Clinical Presentation': 'A dichorionic diamniotic male twin was born at 35 weeks of gestation with a birth weight of 1.6 kg (small for gestational age). The baby presented with recurrent hypoglycemia shortly after birth. Blood tests on the second day of life showed cholestasis (up to 145 umol/L), hypoalbuminemia, hyperammonemia (up to 453 umol/L), and coagulopathy, which progressively worsened throughout the first week of life. Work-up for neonatal liver failure was negative for metabolic disease, and surgical and infective causes. Ferritin level was elevated at 8,397 umol/L. Biopsy of the liver and buccal mucosa was performed. This demonstrated hepatic and extrahepatic iron deposition ( Fig. 1 ) and confirmed the diagnosis of neonatal hemochromatosis (NH; likely due to gestational alloimmune liver disease, GALD). Medical treatment was given with exchange transfusion and intravenous immunoglobulin (IVIg). However, he failed to respond to medical treatment and developed worsening liver failure. Liver transplantation was considered but deemed not an option due to the low body weight and unavailability of living-related liver donor. After extensive discussion with the parents, the decision for redirection of care was made. The baby was electively extubated and eventually succumbed on day 33 of life. On the contrary, the other twin girl was born with a birth weight of 2.4 kg and suffered only from mildly deranged liver function only. Her liver function test showed mildly elevated liver enzymes (peak aspartate aminotransferase of 371 U/L and alanine aminotransferase of 162 U/L at around 3 weeks of life) and conjugated bilirubin (11 umol/L), with normal ammonia level and clotting profile all along. Metabolic, surgical, and infective work-ups were negative. Ferritin level was high at 9,801 umol/L. Liver function test subsequently normalized spontaneously upon follow-up. Family was counseled on the importance of antenatal treatment with IVIg in future pregnancies to prevent the recurrence of NH.'}
|
Eyes-Ears-Nose-Throat
|
EENT
|
[] |
6246115
|
{'Clinical Presentation': 'A dichorionic diamniotic male twin was born at 35 weeks of gestation with a birth weight of 1.6 kg (small for gestational age). The baby presented with recurrent hypoglycemia shortly after birth. Blood tests on the second day of life showed cholestasis (up to 145 umol/L), hypoalbuminemia, hyperammonemia (up to 453 umol/L), and coagulopathy, which progressively worsened throughout the first week of life. Work-up for neonatal liver failure was negative for metabolic disease, and surgical and infective causes. Ferritin level was elevated at 8,397 umol/L. Biopsy of the liver and buccal mucosa was performed. This demonstrated hepatic and extrahepatic iron deposition ( Fig. 1 ) and confirmed the diagnosis of neonatal hemochromatosis (NH; likely due to gestational alloimmune liver disease, GALD). Medical treatment was given with exchange transfusion and intravenous immunoglobulin (IVIg). However, he failed to respond to medical treatment and developed worsening liver failure. Liver transplantation was considered but deemed not an option due to the low body weight and unavailability of living-related liver donor. After extensive discussion with the parents, the decision for redirection of care was made. The baby was electively extubated and eventually succumbed on day 33 of life. On the contrary, the other twin girl was born with a birth weight of 2.4 kg and suffered only from mildly deranged liver function only. Her liver function test showed mildly elevated liver enzymes (peak aspartate aminotransferase of 371 U/L and alanine aminotransferase of 162 U/L at around 3 weeks of life) and conjugated bilirubin (11 umol/L), with normal ammonia level and clotting profile all along. Metabolic, surgical, and infective work-ups were negative. Ferritin level was high at 9,801 umol/L. Liver function test subsequently normalized spontaneously upon follow-up. Family was counseled on the importance of antenatal treatment with IVIg in future pregnancies to prevent the recurrence of NH.'}
|
{'Clinical Presentation': 'A dichorionic diamniotic male twin was born at 35 weeks of gestation with a birth weight of 1.6 kg (small for gestational age). The baby presented with recurrent hypoglycemia shortly after birth. Blood tests on the second day of life showed cholestasis (up to 145 umol/L), hypoalbuminemia, hyperammonemia (up to 453 umol/L), and coagulopathy, which progressively worsened throughout the first week of life. Work-up for neonatal liver failure was negative for metabolic disease, and surgical and infective causes. Ferritin level was elevated at 8,397 umol/L. Biopsy of the liver and buccal mucosa was performed. This demonstrated hepatic and extrahepatic iron deposition ( Fig. 1 ) and confirmed the diagnosis of neonatal hemochromatosis (NH; likely due to gestational alloimmune liver disease, GALD). Medical treatment was given with exchange transfusion and intravenous immunoglobulin (IVIg). However, he failed to respond to medical treatment and developed worsening liver failure. Liver transplantation was considered but deemed not an option due to the low body weight and unavailability of living-related liver donor. After extensive discussion with the parents, the decision for redirection of care was made. The baby was electively extubated and eventually succumbed on day 33 of life. On the contrary, the other twin girl was born with a birth weight of 2.4 kg and suffered only from mildly deranged liver function only. Her liver function test showed mildly elevated liver enzymes (peak aspartate aminotransferase of 371 U/L and alanine aminotransferase of 162 U/L at around 3 weeks of life) and conjugated bilirubin (11 umol/L), with normal ammonia level and clotting profile all along. Metabolic, surgical, and infective work-ups were negative. Ferritin level was high at 9,801 umol/L. Liver function test subsequently normalized spontaneously upon follow-up. Family was counseled on the importance of antenatal treatment with IVIg in future pregnancies to prevent the recurrence of NH.'}
|
Dermatology
|
DERM
|
[] |
6246115
|
{'Clinical Presentation': 'A dichorionic diamniotic male twin was born at 35 weeks of gestation with a birth weight of 1.6 kg (small for gestational age). The baby presented with recurrent hypoglycemia shortly after birth. Blood tests on the second day of life showed cholestasis (up to 145 umol/L), hypoalbuminemia, hyperammonemia (up to 453 umol/L), and coagulopathy, which progressively worsened throughout the first week of life. Work-up for neonatal liver failure was negative for metabolic disease, and surgical and infective causes. Ferritin level was elevated at 8,397 umol/L. Biopsy of the liver and buccal mucosa was performed. This demonstrated hepatic and extrahepatic iron deposition ( Fig. 1 ) and confirmed the diagnosis of neonatal hemochromatosis (NH; likely due to gestational alloimmune liver disease, GALD). Medical treatment was given with exchange transfusion and intravenous immunoglobulin (IVIg). However, he failed to respond to medical treatment and developed worsening liver failure. Liver transplantation was considered but deemed not an option due to the low body weight and unavailability of living-related liver donor. After extensive discussion with the parents, the decision for redirection of care was made. The baby was electively extubated and eventually succumbed on day 33 of life. On the contrary, the other twin girl was born with a birth weight of 2.4 kg and suffered only from mildly deranged liver function only. Her liver function test showed mildly elevated liver enzymes (peak aspartate aminotransferase of 371 U/L and alanine aminotransferase of 162 U/L at around 3 weeks of life) and conjugated bilirubin (11 umol/L), with normal ammonia level and clotting profile all along. Metabolic, surgical, and infective work-ups were negative. Ferritin level was high at 9,801 umol/L. Liver function test subsequently normalized spontaneously upon follow-up. Family was counseled on the importance of antenatal treatment with IVIg in future pregnancies to prevent the recurrence of NH.'}
|
{'Clinical Presentation': 'A dichorionic diamniotic male twin was born at 35 weeks of gestation with a birth weight of 1.6 kg (small for gestational age). The baby presented with recurrent hypoglycemia shortly after birth. Blood tests on the second day of life showed cholestasis (up to 145 umol/L), hypoalbuminemia, hyperammonemia (up to 453 umol/L), and coagulopathy, which progressively worsened throughout the first week of life. Work-up for neonatal liver failure was negative for metabolic disease, and surgical and infective causes. Ferritin level was elevated at 8,397 umol/L. Biopsy of the liver and buccal mucosa was performed. This demonstrated hepatic and extrahepatic iron deposition ( Fig. 1 ) and confirmed the diagnosis of neonatal hemochromatosis (NH; likely due to gestational alloimmune liver disease, GALD). Medical treatment was given with exchange transfusion and intravenous immunoglobulin (IVIg). However, he failed to respond to medical treatment and developed worsening liver failure. Liver transplantation was considered but deemed not an option due to the low body weight and unavailability of living-related liver donor. After extensive discussion with the parents, the decision for redirection of care was made. The baby was electively extubated and eventually succumbed on day 33 of life. On the contrary, the other twin girl was born with a birth weight of 2.4 kg and suffered only from mildly deranged liver function only. Her liver function test showed mildly elevated liver enzymes (peak aspartate aminotransferase of 371 U/L and alanine aminotransferase of 162 U/L at around 3 weeks of life) and conjugated bilirubin (11 umol/L), with normal ammonia level and clotting profile all along. Metabolic, surgical, and infective work-ups were negative. Ferritin level was high at 9,801 umol/L. Liver function test subsequently normalized spontaneously upon follow-up. Family was counseled on the importance of antenatal treatment with IVIg in future pregnancies to prevent the recurrence of NH.'}
|
Pregnancy
|
Pregnancy
|
[
"A dichorionic diamniotic male twin was born at 35 weeks of gestation with a birth weight of 1.6 kg ( small for gestational age ).",
"the other twin girl was born with a birth weight of 2.4 kg"
] |
6246115
|
{'Clinical Presentation': 'A dichorionic diamniotic male twin was born at 35 weeks of gestation with a birth weight of 1.6 kg (small for gestational age). The baby presented with recurrent hypoglycemia shortly after birth. Blood tests on the second day of life showed cholestasis (up to 145 umol/L), hypoalbuminemia, hyperammonemia (up to 453 umol/L), and coagulopathy, which progressively worsened throughout the first week of life. Work-up for neonatal liver failure was negative for metabolic disease, and surgical and infective causes. Ferritin level was elevated at 8,397 umol/L. Biopsy of the liver and buccal mucosa was performed. This demonstrated hepatic and extrahepatic iron deposition ( Fig. 1 ) and confirmed the diagnosis of neonatal hemochromatosis (NH; likely due to gestational alloimmune liver disease, GALD). Medical treatment was given with exchange transfusion and intravenous immunoglobulin (IVIg). However, he failed to respond to medical treatment and developed worsening liver failure. Liver transplantation was considered but deemed not an option due to the low body weight and unavailability of living-related liver donor. After extensive discussion with the parents, the decision for redirection of care was made. The baby was electively extubated and eventually succumbed on day 33 of life. On the contrary, the other twin girl was born with a birth weight of 2.4 kg and suffered only from mildly deranged liver function only. Her liver function test showed mildly elevated liver enzymes (peak aspartate aminotransferase of 371 U/L and alanine aminotransferase of 162 U/L at around 3 weeks of life) and conjugated bilirubin (11 umol/L), with normal ammonia level and clotting profile all along. Metabolic, surgical, and infective work-ups were negative. Ferritin level was high at 9,801 umol/L. Liver function test subsequently normalized spontaneously upon follow-up. Family was counseled on the importance of antenatal treatment with IVIg in future pregnancies to prevent the recurrence of NH.'}
|
{'Clinical Presentation': 'A dichorionic diamniotic male twin was born at 35 weeks of gestation with a birth weight of 1.6 kg (small for gestational age). The baby presented with recurrent hypoglycemia shortly after birth. Blood tests on the second day of life showed cholestasis (up to 145 umol/L), hypoalbuminemia, hyperammonemia (up to 453 umol/L), and coagulopathy, which progressively worsened throughout the first week of life. Work-up for neonatal liver failure was negative for metabolic disease, and surgical and infective causes. Ferritin level was elevated at 8,397 umol/L. Biopsy of the liver and buccal mucosa was performed. This demonstrated hepatic and extrahepatic iron deposition ( Fig. 1 ) and confirmed the diagnosis of neonatal hemochromatosis (NH; likely due to gestational alloimmune liver disease, GALD). Medical treatment was given with exchange transfusion and intravenous immunoglobulin (IVIg). However, he failed to respond to medical treatment and developed worsening liver failure. Liver transplantation was considered but deemed not an option due to the low body weight and unavailability of living-related liver donor. After extensive discussion with the parents, the decision for redirection of care was made. The baby was electively extubated and eventually succumbed on day 33 of life. On the contrary, the other twin girl was born with a birth weight of 2.4 kg and suffered only from mildly deranged liver function only. Her liver function test showed mildly elevated liver enzymes (peak aspartate aminotransferase of 371 U/L and alanine aminotransferase of 162 U/L at around 3 weeks of life) and conjugated bilirubin (11 umol/L), with normal ammonia level and clotting profile all along. Metabolic, surgical, and infective work-ups were negative. Ferritin level was high at 9,801 umol/L. Liver function test subsequently normalized spontaneously upon follow-up. Family was counseled on the importance of antenatal treatment with IVIg in future pregnancies to prevent the recurrence of NH.'}
|
Lymphatic-System
|
LYMPH
|
[] |
6246115
|
{'Clinical Presentation': 'A dichorionic diamniotic male twin was born at 35 weeks of gestation with a birth weight of 1.6 kg (small for gestational age). The baby presented with recurrent hypoglycemia shortly after birth. Blood tests on the second day of life showed cholestasis (up to 145 umol/L), hypoalbuminemia, hyperammonemia (up to 453 umol/L), and coagulopathy, which progressively worsened throughout the first week of life. Work-up for neonatal liver failure was negative for metabolic disease, and surgical and infective causes. Ferritin level was elevated at 8,397 umol/L. Biopsy of the liver and buccal mucosa was performed. This demonstrated hepatic and extrahepatic iron deposition ( Fig. 1 ) and confirmed the diagnosis of neonatal hemochromatosis (NH; likely due to gestational alloimmune liver disease, GALD). Medical treatment was given with exchange transfusion and intravenous immunoglobulin (IVIg). However, he failed to respond to medical treatment and developed worsening liver failure. Liver transplantation was considered but deemed not an option due to the low body weight and unavailability of living-related liver donor. After extensive discussion with the parents, the decision for redirection of care was made. The baby was electively extubated and eventually succumbed on day 33 of life. On the contrary, the other twin girl was born with a birth weight of 2.4 kg and suffered only from mildly deranged liver function only. Her liver function test showed mildly elevated liver enzymes (peak aspartate aminotransferase of 371 U/L and alanine aminotransferase of 162 U/L at around 3 weeks of life) and conjugated bilirubin (11 umol/L), with normal ammonia level and clotting profile all along. Metabolic, surgical, and infective work-ups were negative. Ferritin level was high at 9,801 umol/L. Liver function test subsequently normalized spontaneously upon follow-up. Family was counseled on the importance of antenatal treatment with IVIg in future pregnancies to prevent the recurrence of NH.'}
|
{'Clinical Presentation': 'A dichorionic diamniotic male twin was born at 35 weeks of gestation with a birth weight of 1.6 kg (small for gestational age). The baby presented with recurrent hypoglycemia shortly after birth. Blood tests on the second day of life showed cholestasis (up to 145 umol/L), hypoalbuminemia, hyperammonemia (up to 453 umol/L), and coagulopathy, which progressively worsened throughout the first week of life. Work-up for neonatal liver failure was negative for metabolic disease, and surgical and infective causes. Ferritin level was elevated at 8,397 umol/L. Biopsy of the liver and buccal mucosa was performed. This demonstrated hepatic and extrahepatic iron deposition ( Fig. 1 ) and confirmed the diagnosis of neonatal hemochromatosis (NH; likely due to gestational alloimmune liver disease, GALD). Medical treatment was given with exchange transfusion and intravenous immunoglobulin (IVIg). However, he failed to respond to medical treatment and developed worsening liver failure. Liver transplantation was considered but deemed not an option due to the low body weight and unavailability of living-related liver donor. After extensive discussion with the parents, the decision for redirection of care was made. The baby was electively extubated and eventually succumbed on day 33 of life. On the contrary, the other twin girl was born with a birth weight of 2.4 kg and suffered only from mildly deranged liver function only. Her liver function test showed mildly elevated liver enzymes (peak aspartate aminotransferase of 371 U/L and alanine aminotransferase of 162 U/L at around 3 weeks of life) and conjugated bilirubin (11 umol/L), with normal ammonia level and clotting profile all along. Metabolic, surgical, and infective work-ups were negative. Ferritin level was high at 9,801 umol/L. Liver function test subsequently normalized spontaneously upon follow-up. Family was counseled on the importance of antenatal treatment with IVIg in future pregnancies to prevent the recurrence of NH.'}
|
Age-at-Presentation
|
Age (at case presentation)
|
[
"shortly after birth"
] |
6246115
|
{'Clinical Presentation': 'A dichorionic diamniotic male twin was born at 35 weeks of gestation with a birth weight of 1.6 kg (small for gestational age). The baby presented with recurrent hypoglycemia shortly after birth. Blood tests on the second day of life showed cholestasis (up to 145 umol/L), hypoalbuminemia, hyperammonemia (up to 453 umol/L), and coagulopathy, which progressively worsened throughout the first week of life. Work-up for neonatal liver failure was negative for metabolic disease, and surgical and infective causes. Ferritin level was elevated at 8,397 umol/L. Biopsy of the liver and buccal mucosa was performed. This demonstrated hepatic and extrahepatic iron deposition ( Fig. 1 ) and confirmed the diagnosis of neonatal hemochromatosis (NH; likely due to gestational alloimmune liver disease, GALD). Medical treatment was given with exchange transfusion and intravenous immunoglobulin (IVIg). However, he failed to respond to medical treatment and developed worsening liver failure. Liver transplantation was considered but deemed not an option due to the low body weight and unavailability of living-related liver donor. After extensive discussion with the parents, the decision for redirection of care was made. The baby was electively extubated and eventually succumbed on day 33 of life. On the contrary, the other twin girl was born with a birth weight of 2.4 kg and suffered only from mildly deranged liver function only. Her liver function test showed mildly elevated liver enzymes (peak aspartate aminotransferase of 371 U/L and alanine aminotransferase of 162 U/L at around 3 weeks of life) and conjugated bilirubin (11 umol/L), with normal ammonia level and clotting profile all along. Metabolic, surgical, and infective work-ups were negative. Ferritin level was high at 9,801 umol/L. Liver function test subsequently normalized spontaneously upon follow-up. Family was counseled on the importance of antenatal treatment with IVIg in future pregnancies to prevent the recurrence of NH.'}
|
{'Clinical Presentation': 'A dichorionic diamniotic male twin was born at 35 weeks of gestation with a birth weight of 1.6 kg (small for gestational age). The baby presented with recurrent hypoglycemia shortly after birth. Blood tests on the second day of life showed cholestasis (up to 145 umol/L), hypoalbuminemia, hyperammonemia (up to 453 umol/L), and coagulopathy, which progressively worsened throughout the first week of life. Work-up for neonatal liver failure was negative for metabolic disease, and surgical and infective causes. Ferritin level was elevated at 8,397 umol/L. Biopsy of the liver and buccal mucosa was performed. This demonstrated hepatic and extrahepatic iron deposition ( Fig. 1 ) and confirmed the diagnosis of neonatal hemochromatosis (NH; likely due to gestational alloimmune liver disease, GALD). Medical treatment was given with exchange transfusion and intravenous immunoglobulin (IVIg). However, he failed to respond to medical treatment and developed worsening liver failure. Liver transplantation was considered but deemed not an option due to the low body weight and unavailability of living-related liver donor. After extensive discussion with the parents, the decision for redirection of care was made. The baby was electively extubated and eventually succumbed on day 33 of life. On the contrary, the other twin girl was born with a birth weight of 2.4 kg and suffered only from mildly deranged liver function only. Her liver function test showed mildly elevated liver enzymes (peak aspartate aminotransferase of 371 U/L and alanine aminotransferase of 162 U/L at around 3 weeks of life) and conjugated bilirubin (11 umol/L), with normal ammonia level and clotting profile all along. Metabolic, surgical, and infective work-ups were negative. Ferritin level was high at 9,801 umol/L. Liver function test subsequently normalized spontaneously upon follow-up. Family was counseled on the importance of antenatal treatment with IVIg in future pregnancies to prevent the recurrence of NH.'}
|
Age-of-Onset
|
Age (of onset)
|
[
"shortly after birth"
] |
6246115
|
{'Clinical Presentation': 'A dichorionic diamniotic male twin was born at 35 weeks of gestation with a birth weight of 1.6 kg (small for gestational age). The baby presented with recurrent hypoglycemia shortly after birth. Blood tests on the second day of life showed cholestasis (up to 145 umol/L), hypoalbuminemia, hyperammonemia (up to 453 umol/L), and coagulopathy, which progressively worsened throughout the first week of life. Work-up for neonatal liver failure was negative for metabolic disease, and surgical and infective causes. Ferritin level was elevated at 8,397 umol/L. Biopsy of the liver and buccal mucosa was performed. This demonstrated hepatic and extrahepatic iron deposition ( Fig. 1 ) and confirmed the diagnosis of neonatal hemochromatosis (NH; likely due to gestational alloimmune liver disease, GALD). Medical treatment was given with exchange transfusion and intravenous immunoglobulin (IVIg). However, he failed to respond to medical treatment and developed worsening liver failure. Liver transplantation was considered but deemed not an option due to the low body weight and unavailability of living-related liver donor. After extensive discussion with the parents, the decision for redirection of care was made. The baby was electively extubated and eventually succumbed on day 33 of life. On the contrary, the other twin girl was born with a birth weight of 2.4 kg and suffered only from mildly deranged liver function only. Her liver function test showed mildly elevated liver enzymes (peak aspartate aminotransferase of 371 U/L and alanine aminotransferase of 162 U/L at around 3 weeks of life) and conjugated bilirubin (11 umol/L), with normal ammonia level and clotting profile all along. Metabolic, surgical, and infective work-ups were negative. Ferritin level was high at 9,801 umol/L. Liver function test subsequently normalized spontaneously upon follow-up. Family was counseled on the importance of antenatal treatment with IVIg in future pregnancies to prevent the recurrence of NH.'}
|
{'Clinical Presentation': 'A dichorionic diamniotic male twin was born at 35 weeks of gestation with a birth weight of 1.6 kg (small for gestational age). The baby presented with recurrent hypoglycemia shortly after birth. Blood tests on the second day of life showed cholestasis (up to 145 umol/L), hypoalbuminemia, hyperammonemia (up to 453 umol/L), and coagulopathy, which progressively worsened throughout the first week of life. Work-up for neonatal liver failure was negative for metabolic disease, and surgical and infective causes. Ferritin level was elevated at 8,397 umol/L. Biopsy of the liver and buccal mucosa was performed. This demonstrated hepatic and extrahepatic iron deposition ( Fig. 1 ) and confirmed the diagnosis of neonatal hemochromatosis (NH; likely due to gestational alloimmune liver disease, GALD). Medical treatment was given with exchange transfusion and intravenous immunoglobulin (IVIg). However, he failed to respond to medical treatment and developed worsening liver failure. Liver transplantation was considered but deemed not an option due to the low body weight and unavailability of living-related liver donor. After extensive discussion with the parents, the decision for redirection of care was made. The baby was electively extubated and eventually succumbed on day 33 of life. On the contrary, the other twin girl was born with a birth weight of 2.4 kg and suffered only from mildly deranged liver function only. Her liver function test showed mildly elevated liver enzymes (peak aspartate aminotransferase of 371 U/L and alanine aminotransferase of 162 U/L at around 3 weeks of life) and conjugated bilirubin (11 umol/L), with normal ammonia level and clotting profile all along. Metabolic, surgical, and infective work-ups were negative. Ferritin level was high at 9,801 umol/L. Liver function test subsequently normalized spontaneously upon follow-up. Family was counseled on the importance of antenatal treatment with IVIg in future pregnancies to prevent the recurrence of NH.'}
|
Confirmed-Diagnosis-IEM
|
Confirmed_Diagnosis(IEM)
|
[
"confirmed the diagnosis of neonatal hemochromatosis ( NH ; likely due to gestational alloimmune liver disease , GALD ) ."
] |
6246115
|
{'Clinical Presentation': 'A dichorionic diamniotic male twin was born at 35 weeks of gestation with a birth weight of 1.6 kg (small for gestational age). The baby presented with recurrent hypoglycemia shortly after birth. Blood tests on the second day of life showed cholestasis (up to 145 umol/L), hypoalbuminemia, hyperammonemia (up to 453 umol/L), and coagulopathy, which progressively worsened throughout the first week of life. Work-up for neonatal liver failure was negative for metabolic disease, and surgical and infective causes. Ferritin level was elevated at 8,397 umol/L. Biopsy of the liver and buccal mucosa was performed. This demonstrated hepatic and extrahepatic iron deposition ( Fig. 1 ) and confirmed the diagnosis of neonatal hemochromatosis (NH; likely due to gestational alloimmune liver disease, GALD). Medical treatment was given with exchange transfusion and intravenous immunoglobulin (IVIg). However, he failed to respond to medical treatment and developed worsening liver failure. Liver transplantation was considered but deemed not an option due to the low body weight and unavailability of living-related liver donor. After extensive discussion with the parents, the decision for redirection of care was made. The baby was electively extubated and eventually succumbed on day 33 of life. On the contrary, the other twin girl was born with a birth weight of 2.4 kg and suffered only from mildly deranged liver function only. Her liver function test showed mildly elevated liver enzymes (peak aspartate aminotransferase of 371 U/L and alanine aminotransferase of 162 U/L at around 3 weeks of life) and conjugated bilirubin (11 umol/L), with normal ammonia level and clotting profile all along. Metabolic, surgical, and infective work-ups were negative. Ferritin level was high at 9,801 umol/L. Liver function test subsequently normalized spontaneously upon follow-up. Family was counseled on the importance of antenatal treatment with IVIg in future pregnancies to prevent the recurrence of NH.'}
|
{'Clinical Presentation': 'A dichorionic diamniotic male twin was born at 35 weeks of gestation with a birth weight of 1.6 kg (small for gestational age). The baby presented with recurrent hypoglycemia shortly after birth. Blood tests on the second day of life showed cholestasis (up to 145 umol/L), hypoalbuminemia, hyperammonemia (up to 453 umol/L), and coagulopathy, which progressively worsened throughout the first week of life. Work-up for neonatal liver failure was negative for metabolic disease, and surgical and infective causes. Ferritin level was elevated at 8,397 umol/L. Biopsy of the liver and buccal mucosa was performed. This demonstrated hepatic and extrahepatic iron deposition ( Fig. 1 ) and confirmed the diagnosis of neonatal hemochromatosis (NH; likely due to gestational alloimmune liver disease, GALD). Medical treatment was given with exchange transfusion and intravenous immunoglobulin (IVIg). However, he failed to respond to medical treatment and developed worsening liver failure. Liver transplantation was considered but deemed not an option due to the low body weight and unavailability of living-related liver donor. After extensive discussion with the parents, the decision for redirection of care was made. The baby was electively extubated and eventually succumbed on day 33 of life. On the contrary, the other twin girl was born with a birth weight of 2.4 kg and suffered only from mildly deranged liver function only. Her liver function test showed mildly elevated liver enzymes (peak aspartate aminotransferase of 371 U/L and alanine aminotransferase of 162 U/L at around 3 weeks of life) and conjugated bilirubin (11 umol/L), with normal ammonia level and clotting profile all along. Metabolic, surgical, and infective work-ups were negative. Ferritin level was high at 9,801 umol/L. Liver function test subsequently normalized spontaneously upon follow-up. Family was counseled on the importance of antenatal treatment with IVIg in future pregnancies to prevent the recurrence of NH.'}
|
IEM-Treatment
|
IEM_Treatment
|
[
"Medical treatment was given with exchange transfusion and intravenous immunoglobulin ( IVIg )"
] |
6801357
|
{'Case 2': 'The male patient who was born at 36 wk of gestational age was the younger (3 yr younger) brother of case 1. He also showed apparent reduction of the subcutaneous adipose tissue at 1 mo of age. At that time, he already had characteristic symptoms of CGL, including an inverted triangular face, sparse subcutaneous tissue, and hepatomegaly. Laboratory examination demonstrated extremely high triglyceride level and low leptin level ( Table 1 ). Compound heterozygous variants of BSCL2 gene were identified; these were identical to the gene variants found in his sister. The clinical course is shown in Fig. 1B . Serum triglyceride and insulin levels increased to more than 2000 mg/dL and 700 μU/mL, respectively, at 2 mo of age. Following this, low-fat dietary formula was introduced (calories, 350 Cal/d; fat ratio, 20%). Metformin therapy was initiated at 7 mo of age (250 mg/d). At approximately 1 yr of age, when he started eating solid foods, hyperlipidemia and hyperinsulinemia resolved. Thereafter, his examination findings remained relatively stable for approximately 10 yr under management with nutritional and metformin therapies. His insulin resistance worsened and his triglyceride level increased during puberty ( Fig. 1B . OGTT③). At 11 yr and 6 mo of age, metreleptin was introduced at a dose of 0.04 mg/kg/d, and there was an immediate improvement of hyperinsulinemia and hyperlipidemia resulting in discontinuation of metformin. A few months later, hyperinsulinemia and liver dysfunction reappeared, and metformin treatment was reinitiated. An intelligence test (WISC-IV) at 12 yr of age demonstrated that his full-scale intelligence quotient was 58, indicating slightly retarded mental development with mild intellectual disability. At the time of writing this report, he was 16 yr and 4 mo of age and has received metreleptin therapy for approximately 4 yr.', 'Case 1': 'The female patient was born to non-consanguineous Japanese parents at 38 wk of gestational age. Poor weight gain was seen during a health checkup at 3 mo of age, and her parents consulted a pediatrician. Physical examination showed a generalized reduction in the subcutaneous adipose tissue with marked hepatomegaly. Laboratory analysis revealed notable hyperinsulinemia and hypertriglyceridemia. Generalized lipoatrophy was suspected and the patient was introduced to our department, Oita University Hospital at 5 mo of age. The characteristic physical findings of CGL were detected as shown in Table 1 Table 1. Physical manifestations and laboratory data for the siblings at their respective first clinical evaluations . Cardiac ultrasonography demonstrated hypertrophic cardiomyopathy. The serum leptin concentration was markedly low (0.9 ng/mL) ( 13 ). Genetic testing revealed compound heterozygous pathogenic variants of BSCL2 gene; the already reported variant (c.823C>T) and the unreported variant (c.576C>A). She was therefore diagnosed with CGL (Berardinelli-Seip syndrome). The clinical course is shown in Fig. 1A Fig. 1. Clinical courses of the siblings. (A) Case 1 and (B) Case 2. Each figure shows the serial data or parameters. The upper portions show the physical symptoms of CGL and its medical interventions. The middle portions show the serum triglyceride (TG), IRI, and HbA1c levels. The lower portions show the oral glucose tolerance test (OGTT) data. . At 5 mo of age, dietary management was initiated for calorie and lipid restriction (calorie 90 Cal/kg/d; carbohydrate 55%, lipid 20%, protein 20%). At 2 yr and 6 mo of age, metformin treatment (500 mg/d: 30 mg/kg/d) commenced because of marked insulin resistance with hepatic dysfunction. Metformin treatment seemed effective for insulin resistance ( Fig. 1A . OGTT①②). At approximately 4 yr of age, obstructive sleep apnea, which is known as a characteristic complication of CGL appeared, and insulin resistance and lipid metabolism also worsened. Artificial respiratory support for continuous positive airway pressure was introduced, which stabilized her sleeping status with stable oxygenation. Her glucose metabolism with insulin resistance then partially improved ( Fig. 1A . OGTT③④). At the beginning of puberty (approximately 10 yr of age), hyperglycemia with hyperinsulinemia gradually deteriorated and the oral glucose tolerance test (OGTT) showed diabetic glucose response (Fig. 1A.OGTT⑤). At 11 yr and 5 mo of age, she was enrolled in a clinical trial of metreleptin. Metreleptin treatment was initiated at a dose of 0.06 mg/kg/d. Marked effectiveness of metreleptin appeared as early as 1 mo after the initiation, and metformin treatment was discontinued. Based on the results of the metreleptin trial, treatment with metreleptin was approved in 2013. Continuous treatment had consistent effects on patient’s glucose and fat metabolism. At approximately 13 yr of age, she sometimes had insomnia, headaches, and abdominal pains, followed by aggravation of her HbA1c and triglyceride levels, due to stressful relationship with her friends. Oral administration of metformin was then resumed, and socio-psychological counseling by a child psychiatrist was initiated. Her glycolipid metabolism status fluctuated according to her psychological state that is in line with her school year, and combined management with metreleptin, metformin, dietary therapy, and socio-psychological intervention were continued. As a result, the headaches and insomnia gradually decreased, and there was also an improvement in her glycolipid metabolism. Anti-metreleptin antibodies were detected (titer: 1:25) at 14 yr and 4 mo old. At 14 yr and 8 mo of age, Kauffman therapy was initiated due to irregular menstruation. At 18 yr and 8 mo of age and 7 yr after the commencement of metreleptin therapy, she began receiving metreleptin (3.8 mg/d), metformin (2250 mg/d), as well as dietary management to regulate the levels of calorie and lipid. Her height was 154 cm, weight 48 kg, and her HbA1c level was 6.0% in a stable state. She graduated from high school and entered the university without apparent hindrance in her daily life.'}
|
{'Case 2': 'The male patient who was born at 36 wk of gestational age was the younger (3 yr younger) brother of case 1. He also showed apparent reduction of the subcutaneous adipose tissue at 1 mo of age. At that time, he already had characteristic symptoms of CGL, including an inverted triangular face, sparse subcutaneous tissue, and hepatomegaly. Laboratory examination demonstrated extremely high triglyceride level and low leptin level ( Table 1 ). Compound heterozygous variants of BSCL2 gene were identified; these were identical to the gene variants found in his sister. The clinical course is shown in Fig. 1B . Serum triglyceride and insulin levels increased to more than 2000 mg/dL and 700 μU/mL, respectively, at 2 mo of age. Following this, low-fat dietary formula was introduced (calories, 350 Cal/d; fat ratio, 20%). Metformin therapy was initiated at 7 mo of age (250 mg/d). At approximately 1 yr of age, when he started eating solid foods, hyperlipidemia and hyperinsulinemia resolved. Thereafter, his examination findings remained relatively stable for approximately 10 yr under management with nutritional and metformin therapies. His insulin resistance worsened and his triglyceride level increased during puberty ( Fig. 1B . OGTT③). At 11 yr and 6 mo of age, metreleptin was introduced at a dose of 0.04 mg/kg/d, and there was an immediate improvement of hyperinsulinemia and hyperlipidemia resulting in discontinuation of metformin. A few months later, hyperinsulinemia and liver dysfunction reappeared, and metformin treatment was reinitiated. An intelligence test (WISC-IV) at 12 yr of age demonstrated that his full-scale intelligence quotient was 58, indicating slightly retarded mental development with mild intellectual disability. At the time of writing this report, he was 16 yr and 4 mo of age and has received metreleptin therapy for approximately 4 yr.', 'Case 1': 'The female patient was born to non-consanguineous Japanese parents at 38 wk of gestational age. Poor weight gain was seen during a health checkup at 3 mo of age, and her parents consulted a pediatrician. Physical examination showed a generalized reduction in the subcutaneous adipose tissue with marked hepatomegaly. Laboratory analysis revealed notable hyperinsulinemia and hypertriglyceridemia. Generalized lipoatrophy was suspected and the patient was introduced to our department, Oita University Hospital at 5 mo of age. The characteristic physical findings of CGL were detected as shown in Table 1 Table 1. Physical manifestations and laboratory data for the siblings at their respective first clinical evaluations . Cardiac ultrasonography demonstrated hypertrophic cardiomyopathy. The serum leptin concentration was markedly low (0.9 ng/mL) ( 13 ). Genetic testing revealed compound heterozygous pathogenic variants of BSCL2 gene; the already reported variant (c.823C>T) and the unreported variant (c.576C>A). She was therefore diagnosed with CGL (Berardinelli-Seip syndrome). The clinical course is shown in Fig. 1A Fig. 1. Clinical courses of the siblings. (A) Case 1 and (B) Case 2. Each figure shows the serial data or parameters. The upper portions show the physical symptoms of CGL and its medical interventions. The middle portions show the serum triglyceride (TG), IRI, and HbA1c levels. The lower portions show the oral glucose tolerance test (OGTT) data. . At 5 mo of age, dietary management was initiated for calorie and lipid restriction (calorie 90 Cal/kg/d; carbohydrate 55%, lipid 20%, protein 20%). At 2 yr and 6 mo of age, metformin treatment (500 mg/d: 30 mg/kg/d) commenced because of marked insulin resistance with hepatic dysfunction. Metformin treatment seemed effective for insulin resistance ( Fig. 1A . OGTT①②). At approximately 4 yr of age, obstructive sleep apnea, which is known as a characteristic complication of CGL appeared, and insulin resistance and lipid metabolism also worsened. Artificial respiratory support for continuous positive airway pressure was introduced, which stabilized her sleeping status with stable oxygenation. Her glucose metabolism with insulin resistance then partially improved ( Fig. 1A . OGTT③④). At the beginning of puberty (approximately 10 yr of age), hyperglycemia with hyperinsulinemia gradually deteriorated and the oral glucose tolerance test (OGTT) showed diabetic glucose response (Fig. 1A.OGTT⑤). At 11 yr and 5 mo of age, she was enrolled in a clinical trial of metreleptin. Metreleptin treatment was initiated at a dose of 0.06 mg/kg/d. Marked effectiveness of metreleptin appeared as early as 1 mo after the initiation, and metformin treatment was discontinued. Based on the results of the metreleptin trial, treatment with metreleptin was approved in 2013. Continuous treatment had consistent effects on patient’s glucose and fat metabolism. At approximately 13 yr of age, she sometimes had insomnia, headaches, and abdominal pains, followed by aggravation of her HbA1c and triglyceride levels, due to stressful relationship with her friends. Oral administration of metformin was then resumed, and socio-psychological counseling by a child psychiatrist was initiated. Her glycolipid metabolism status fluctuated according to her psychological state that is in line with her school year, and combined management with metreleptin, metformin, dietary therapy, and socio-psychological intervention were continued. As a result, the headaches and insomnia gradually decreased, and there was also an improvement in her glycolipid metabolism. Anti-metreleptin antibodies were detected (titer: 1:25) at 14 yr and 4 mo old. At 14 yr and 8 mo of age, Kauffman therapy was initiated due to irregular menstruation. At 18 yr and 8 mo of age and 7 yr after the commencement of metreleptin therapy, she began receiving metreleptin (3.8 mg/d), metformin (2250 mg/d), as well as dietary management to regulate the levels of calorie and lipid. Her height was 154 cm, weight 48 kg, and her HbA1c level was 6.0% in a stable state. She graduated from high school and entered the university without apparent hindrance in her daily life.'}
|
Vitals-and-Hematology
|
Vitals_Hema
|
[
"Her height was 154 cm, weight 48 kg"
] |
6801357
|
{'Case 2': 'The male patient who was born at 36 wk of gestational age was the younger (3 yr younger) brother of case 1. He also showed apparent reduction of the subcutaneous adipose tissue at 1 mo of age. At that time, he already had characteristic symptoms of CGL, including an inverted triangular face, sparse subcutaneous tissue, and hepatomegaly. Laboratory examination demonstrated extremely high triglyceride level and low leptin level ( Table 1 ). Compound heterozygous variants of BSCL2 gene were identified; these were identical to the gene variants found in his sister. The clinical course is shown in Fig. 1B . Serum triglyceride and insulin levels increased to more than 2000 mg/dL and 700 μU/mL, respectively, at 2 mo of age. Following this, low-fat dietary formula was introduced (calories, 350 Cal/d; fat ratio, 20%). Metformin therapy was initiated at 7 mo of age (250 mg/d). At approximately 1 yr of age, when he started eating solid foods, hyperlipidemia and hyperinsulinemia resolved. Thereafter, his examination findings remained relatively stable for approximately 10 yr under management with nutritional and metformin therapies. His insulin resistance worsened and his triglyceride level increased during puberty ( Fig. 1B . OGTT③). At 11 yr and 6 mo of age, metreleptin was introduced at a dose of 0.04 mg/kg/d, and there was an immediate improvement of hyperinsulinemia and hyperlipidemia resulting in discontinuation of metformin. A few months later, hyperinsulinemia and liver dysfunction reappeared, and metformin treatment was reinitiated. An intelligence test (WISC-IV) at 12 yr of age demonstrated that his full-scale intelligence quotient was 58, indicating slightly retarded mental development with mild intellectual disability. At the time of writing this report, he was 16 yr and 4 mo of age and has received metreleptin therapy for approximately 4 yr.', 'Case 1': 'The female patient was born to non-consanguineous Japanese parents at 38 wk of gestational age. Poor weight gain was seen during a health checkup at 3 mo of age, and her parents consulted a pediatrician. Physical examination showed a generalized reduction in the subcutaneous adipose tissue with marked hepatomegaly. Laboratory analysis revealed notable hyperinsulinemia and hypertriglyceridemia. Generalized lipoatrophy was suspected and the patient was introduced to our department, Oita University Hospital at 5 mo of age. The characteristic physical findings of CGL were detected as shown in Table 1 Table 1. Physical manifestations and laboratory data for the siblings at their respective first clinical evaluations . Cardiac ultrasonography demonstrated hypertrophic cardiomyopathy. The serum leptin concentration was markedly low (0.9 ng/mL) ( 13 ). Genetic testing revealed compound heterozygous pathogenic variants of BSCL2 gene; the already reported variant (c.823C>T) and the unreported variant (c.576C>A). She was therefore diagnosed with CGL (Berardinelli-Seip syndrome). The clinical course is shown in Fig. 1A Fig. 1. Clinical courses of the siblings. (A) Case 1 and (B) Case 2. Each figure shows the serial data or parameters. The upper portions show the physical symptoms of CGL and its medical interventions. The middle portions show the serum triglyceride (TG), IRI, and HbA1c levels. The lower portions show the oral glucose tolerance test (OGTT) data. . At 5 mo of age, dietary management was initiated for calorie and lipid restriction (calorie 90 Cal/kg/d; carbohydrate 55%, lipid 20%, protein 20%). At 2 yr and 6 mo of age, metformin treatment (500 mg/d: 30 mg/kg/d) commenced because of marked insulin resistance with hepatic dysfunction. Metformin treatment seemed effective for insulin resistance ( Fig. 1A . OGTT①②). At approximately 4 yr of age, obstructive sleep apnea, which is known as a characteristic complication of CGL appeared, and insulin resistance and lipid metabolism also worsened. Artificial respiratory support for continuous positive airway pressure was introduced, which stabilized her sleeping status with stable oxygenation. Her glucose metabolism with insulin resistance then partially improved ( Fig. 1A . OGTT③④). At the beginning of puberty (approximately 10 yr of age), hyperglycemia with hyperinsulinemia gradually deteriorated and the oral glucose tolerance test (OGTT) showed diabetic glucose response (Fig. 1A.OGTT⑤). At 11 yr and 5 mo of age, she was enrolled in a clinical trial of metreleptin. Metreleptin treatment was initiated at a dose of 0.06 mg/kg/d. Marked effectiveness of metreleptin appeared as early as 1 mo after the initiation, and metformin treatment was discontinued. Based on the results of the metreleptin trial, treatment with metreleptin was approved in 2013. Continuous treatment had consistent effects on patient’s glucose and fat metabolism. At approximately 13 yr of age, she sometimes had insomnia, headaches, and abdominal pains, followed by aggravation of her HbA1c and triglyceride levels, due to stressful relationship with her friends. Oral administration of metformin was then resumed, and socio-psychological counseling by a child psychiatrist was initiated. Her glycolipid metabolism status fluctuated according to her psychological state that is in line with her school year, and combined management with metreleptin, metformin, dietary therapy, and socio-psychological intervention were continued. As a result, the headaches and insomnia gradually decreased, and there was also an improvement in her glycolipid metabolism. Anti-metreleptin antibodies were detected (titer: 1:25) at 14 yr and 4 mo old. At 14 yr and 8 mo of age, Kauffman therapy was initiated due to irregular menstruation. At 18 yr and 8 mo of age and 7 yr after the commencement of metreleptin therapy, she began receiving metreleptin (3.8 mg/d), metformin (2250 mg/d), as well as dietary management to regulate the levels of calorie and lipid. Her height was 154 cm, weight 48 kg, and her HbA1c level was 6.0% in a stable state. She graduated from high school and entered the university without apparent hindrance in her daily life.'}
|
{'Case 2': 'The male patient who was born at 36 wk of gestational age was the younger (3 yr younger) brother of case 1. He also showed apparent reduction of the subcutaneous adipose tissue at 1 mo of age. At that time, he already had characteristic symptoms of CGL, including an inverted triangular face, sparse subcutaneous tissue, and hepatomegaly. Laboratory examination demonstrated extremely high triglyceride level and low leptin level ( Table 1 ). Compound heterozygous variants of BSCL2 gene were identified; these were identical to the gene variants found in his sister. The clinical course is shown in Fig. 1B . Serum triglyceride and insulin levels increased to more than 2000 mg/dL and 700 μU/mL, respectively, at 2 mo of age. Following this, low-fat dietary formula was introduced (calories, 350 Cal/d; fat ratio, 20%). Metformin therapy was initiated at 7 mo of age (250 mg/d). At approximately 1 yr of age, when he started eating solid foods, hyperlipidemia and hyperinsulinemia resolved. Thereafter, his examination findings remained relatively stable for approximately 10 yr under management with nutritional and metformin therapies. His insulin resistance worsened and his triglyceride level increased during puberty ( Fig. 1B . OGTT③). At 11 yr and 6 mo of age, metreleptin was introduced at a dose of 0.04 mg/kg/d, and there was an immediate improvement of hyperinsulinemia and hyperlipidemia resulting in discontinuation of metformin. A few months later, hyperinsulinemia and liver dysfunction reappeared, and metformin treatment was reinitiated. An intelligence test (WISC-IV) at 12 yr of age demonstrated that his full-scale intelligence quotient was 58, indicating slightly retarded mental development with mild intellectual disability. At the time of writing this report, he was 16 yr and 4 mo of age and has received metreleptin therapy for approximately 4 yr.', 'Case 1': 'The female patient was born to non-consanguineous Japanese parents at 38 wk of gestational age. Poor weight gain was seen during a health checkup at 3 mo of age, and her parents consulted a pediatrician. Physical examination showed a generalized reduction in the subcutaneous adipose tissue with marked hepatomegaly. Laboratory analysis revealed notable hyperinsulinemia and hypertriglyceridemia. Generalized lipoatrophy was suspected and the patient was introduced to our department, Oita University Hospital at 5 mo of age. The characteristic physical findings of CGL were detected as shown in Table 1 Table 1. Physical manifestations and laboratory data for the siblings at their respective first clinical evaluations . Cardiac ultrasonography demonstrated hypertrophic cardiomyopathy. The serum leptin concentration was markedly low (0.9 ng/mL) ( 13 ). Genetic testing revealed compound heterozygous pathogenic variants of BSCL2 gene; the already reported variant (c.823C>T) and the unreported variant (c.576C>A). She was therefore diagnosed with CGL (Berardinelli-Seip syndrome). The clinical course is shown in Fig. 1A Fig. 1. Clinical courses of the siblings. (A) Case 1 and (B) Case 2. Each figure shows the serial data or parameters. The upper portions show the physical symptoms of CGL and its medical interventions. The middle portions show the serum triglyceride (TG), IRI, and HbA1c levels. The lower portions show the oral glucose tolerance test (OGTT) data. . At 5 mo of age, dietary management was initiated for calorie and lipid restriction (calorie 90 Cal/kg/d; carbohydrate 55%, lipid 20%, protein 20%). At 2 yr and 6 mo of age, metformin treatment (500 mg/d: 30 mg/kg/d) commenced because of marked insulin resistance with hepatic dysfunction. Metformin treatment seemed effective for insulin resistance ( Fig. 1A . OGTT①②). At approximately 4 yr of age, obstructive sleep apnea, which is known as a characteristic complication of CGL appeared, and insulin resistance and lipid metabolism also worsened. Artificial respiratory support for continuous positive airway pressure was introduced, which stabilized her sleeping status with stable oxygenation. Her glucose metabolism with insulin resistance then partially improved ( Fig. 1A . OGTT③④). At the beginning of puberty (approximately 10 yr of age), hyperglycemia with hyperinsulinemia gradually deteriorated and the oral glucose tolerance test (OGTT) showed diabetic glucose response (Fig. 1A.OGTT⑤). At 11 yr and 5 mo of age, she was enrolled in a clinical trial of metreleptin. Metreleptin treatment was initiated at a dose of 0.06 mg/kg/d. Marked effectiveness of metreleptin appeared as early as 1 mo after the initiation, and metformin treatment was discontinued. Based on the results of the metreleptin trial, treatment with metreleptin was approved in 2013. Continuous treatment had consistent effects on patient’s glucose and fat metabolism. At approximately 13 yr of age, she sometimes had insomnia, headaches, and abdominal pains, followed by aggravation of her HbA1c and triglyceride levels, due to stressful relationship with her friends. Oral administration of metformin was then resumed, and socio-psychological counseling by a child psychiatrist was initiated. Her glycolipid metabolism status fluctuated according to her psychological state that is in line with her school year, and combined management with metreleptin, metformin, dietary therapy, and socio-psychological intervention were continued. As a result, the headaches and insomnia gradually decreased, and there was also an improvement in her glycolipid metabolism. Anti-metreleptin antibodies were detected (titer: 1:25) at 14 yr and 4 mo old. At 14 yr and 8 mo of age, Kauffman therapy was initiated due to irregular menstruation. At 18 yr and 8 mo of age and 7 yr after the commencement of metreleptin therapy, she began receiving metreleptin (3.8 mg/d), metformin (2250 mg/d), as well as dietary management to regulate the levels of calorie and lipid. Her height was 154 cm, weight 48 kg, and her HbA1c level was 6.0% in a stable state. She graduated from high school and entered the university without apparent hindrance in her daily life.'}
|
Gastrointestinal-System
|
GI
|
[
"hepatomegaly",
"marked hepatomegaly",
"hepatic dysfunction",
"abdominal pains"
] |
6801357
|
{'Case 2': 'The male patient who was born at 36 wk of gestational age was the younger (3 yr younger) brother of case 1. He also showed apparent reduction of the subcutaneous adipose tissue at 1 mo of age. At that time, he already had characteristic symptoms of CGL, including an inverted triangular face, sparse subcutaneous tissue, and hepatomegaly. Laboratory examination demonstrated extremely high triglyceride level and low leptin level ( Table 1 ). Compound heterozygous variants of BSCL2 gene were identified; these were identical to the gene variants found in his sister. The clinical course is shown in Fig. 1B . Serum triglyceride and insulin levels increased to more than 2000 mg/dL and 700 μU/mL, respectively, at 2 mo of age. Following this, low-fat dietary formula was introduced (calories, 350 Cal/d; fat ratio, 20%). Metformin therapy was initiated at 7 mo of age (250 mg/d). At approximately 1 yr of age, when he started eating solid foods, hyperlipidemia and hyperinsulinemia resolved. Thereafter, his examination findings remained relatively stable for approximately 10 yr under management with nutritional and metformin therapies. His insulin resistance worsened and his triglyceride level increased during puberty ( Fig. 1B . OGTT③). At 11 yr and 6 mo of age, metreleptin was introduced at a dose of 0.04 mg/kg/d, and there was an immediate improvement of hyperinsulinemia and hyperlipidemia resulting in discontinuation of metformin. A few months later, hyperinsulinemia and liver dysfunction reappeared, and metformin treatment was reinitiated. An intelligence test (WISC-IV) at 12 yr of age demonstrated that his full-scale intelligence quotient was 58, indicating slightly retarded mental development with mild intellectual disability. At the time of writing this report, he was 16 yr and 4 mo of age and has received metreleptin therapy for approximately 4 yr.', 'Case 1': 'The female patient was born to non-consanguineous Japanese parents at 38 wk of gestational age. Poor weight gain was seen during a health checkup at 3 mo of age, and her parents consulted a pediatrician. Physical examination showed a generalized reduction in the subcutaneous adipose tissue with marked hepatomegaly. Laboratory analysis revealed notable hyperinsulinemia and hypertriglyceridemia. Generalized lipoatrophy was suspected and the patient was introduced to our department, Oita University Hospital at 5 mo of age. The characteristic physical findings of CGL were detected as shown in Table 1 Table 1. Physical manifestations and laboratory data for the siblings at their respective first clinical evaluations . Cardiac ultrasonography demonstrated hypertrophic cardiomyopathy. The serum leptin concentration was markedly low (0.9 ng/mL) ( 13 ). Genetic testing revealed compound heterozygous pathogenic variants of BSCL2 gene; the already reported variant (c.823C>T) and the unreported variant (c.576C>A). She was therefore diagnosed with CGL (Berardinelli-Seip syndrome). The clinical course is shown in Fig. 1A Fig. 1. Clinical courses of the siblings. (A) Case 1 and (B) Case 2. Each figure shows the serial data or parameters. The upper portions show the physical symptoms of CGL and its medical interventions. The middle portions show the serum triglyceride (TG), IRI, and HbA1c levels. The lower portions show the oral glucose tolerance test (OGTT) data. . At 5 mo of age, dietary management was initiated for calorie and lipid restriction (calorie 90 Cal/kg/d; carbohydrate 55%, lipid 20%, protein 20%). At 2 yr and 6 mo of age, metformin treatment (500 mg/d: 30 mg/kg/d) commenced because of marked insulin resistance with hepatic dysfunction. Metformin treatment seemed effective for insulin resistance ( Fig. 1A . OGTT①②). At approximately 4 yr of age, obstructive sleep apnea, which is known as a characteristic complication of CGL appeared, and insulin resistance and lipid metabolism also worsened. Artificial respiratory support for continuous positive airway pressure was introduced, which stabilized her sleeping status with stable oxygenation. Her glucose metabolism with insulin resistance then partially improved ( Fig. 1A . OGTT③④). At the beginning of puberty (approximately 10 yr of age), hyperglycemia with hyperinsulinemia gradually deteriorated and the oral glucose tolerance test (OGTT) showed diabetic glucose response (Fig. 1A.OGTT⑤). At 11 yr and 5 mo of age, she was enrolled in a clinical trial of metreleptin. Metreleptin treatment was initiated at a dose of 0.06 mg/kg/d. Marked effectiveness of metreleptin appeared as early as 1 mo after the initiation, and metformin treatment was discontinued. Based on the results of the metreleptin trial, treatment with metreleptin was approved in 2013. Continuous treatment had consistent effects on patient’s glucose and fat metabolism. At approximately 13 yr of age, she sometimes had insomnia, headaches, and abdominal pains, followed by aggravation of her HbA1c and triglyceride levels, due to stressful relationship with her friends. Oral administration of metformin was then resumed, and socio-psychological counseling by a child psychiatrist was initiated. Her glycolipid metabolism status fluctuated according to her psychological state that is in line with her school year, and combined management with metreleptin, metformin, dietary therapy, and socio-psychological intervention were continued. As a result, the headaches and insomnia gradually decreased, and there was also an improvement in her glycolipid metabolism. Anti-metreleptin antibodies were detected (titer: 1:25) at 14 yr and 4 mo old. At 14 yr and 8 mo of age, Kauffman therapy was initiated due to irregular menstruation. At 18 yr and 8 mo of age and 7 yr after the commencement of metreleptin therapy, she began receiving metreleptin (3.8 mg/d), metformin (2250 mg/d), as well as dietary management to regulate the levels of calorie and lipid. Her height was 154 cm, weight 48 kg, and her HbA1c level was 6.0% in a stable state. She graduated from high school and entered the university without apparent hindrance in her daily life.'}
|
{'Case 2': 'The male patient who was born at 36 wk of gestational age was the younger (3 yr younger) brother of case 1. He also showed apparent reduction of the subcutaneous adipose tissue at 1 mo of age. At that time, he already had characteristic symptoms of CGL, including an inverted triangular face, sparse subcutaneous tissue, and hepatomegaly. Laboratory examination demonstrated extremely high triglyceride level and low leptin level ( Table 1 ). Compound heterozygous variants of BSCL2 gene were identified; these were identical to the gene variants found in his sister. The clinical course is shown in Fig. 1B . Serum triglyceride and insulin levels increased to more than 2000 mg/dL and 700 μU/mL, respectively, at 2 mo of age. Following this, low-fat dietary formula was introduced (calories, 350 Cal/d; fat ratio, 20%). Metformin therapy was initiated at 7 mo of age (250 mg/d). At approximately 1 yr of age, when he started eating solid foods, hyperlipidemia and hyperinsulinemia resolved. Thereafter, his examination findings remained relatively stable for approximately 10 yr under management with nutritional and metformin therapies. His insulin resistance worsened and his triglyceride level increased during puberty ( Fig. 1B . OGTT③). At 11 yr and 6 mo of age, metreleptin was introduced at a dose of 0.04 mg/kg/d, and there was an immediate improvement of hyperinsulinemia and hyperlipidemia resulting in discontinuation of metformin. A few months later, hyperinsulinemia and liver dysfunction reappeared, and metformin treatment was reinitiated. An intelligence test (WISC-IV) at 12 yr of age demonstrated that his full-scale intelligence quotient was 58, indicating slightly retarded mental development with mild intellectual disability. At the time of writing this report, he was 16 yr and 4 mo of age and has received metreleptin therapy for approximately 4 yr.', 'Case 1': 'The female patient was born to non-consanguineous Japanese parents at 38 wk of gestational age. Poor weight gain was seen during a health checkup at 3 mo of age, and her parents consulted a pediatrician. Physical examination showed a generalized reduction in the subcutaneous adipose tissue with marked hepatomegaly. Laboratory analysis revealed notable hyperinsulinemia and hypertriglyceridemia. Generalized lipoatrophy was suspected and the patient was introduced to our department, Oita University Hospital at 5 mo of age. The characteristic physical findings of CGL were detected as shown in Table 1 Table 1. Physical manifestations and laboratory data for the siblings at their respective first clinical evaluations . Cardiac ultrasonography demonstrated hypertrophic cardiomyopathy. The serum leptin concentration was markedly low (0.9 ng/mL) ( 13 ). Genetic testing revealed compound heterozygous pathogenic variants of BSCL2 gene; the already reported variant (c.823C>T) and the unreported variant (c.576C>A). She was therefore diagnosed with CGL (Berardinelli-Seip syndrome). The clinical course is shown in Fig. 1A Fig. 1. Clinical courses of the siblings. (A) Case 1 and (B) Case 2. Each figure shows the serial data or parameters. The upper portions show the physical symptoms of CGL and its medical interventions. The middle portions show the serum triglyceride (TG), IRI, and HbA1c levels. The lower portions show the oral glucose tolerance test (OGTT) data. . At 5 mo of age, dietary management was initiated for calorie and lipid restriction (calorie 90 Cal/kg/d; carbohydrate 55%, lipid 20%, protein 20%). At 2 yr and 6 mo of age, metformin treatment (500 mg/d: 30 mg/kg/d) commenced because of marked insulin resistance with hepatic dysfunction. Metformin treatment seemed effective for insulin resistance ( Fig. 1A . OGTT①②). At approximately 4 yr of age, obstructive sleep apnea, which is known as a characteristic complication of CGL appeared, and insulin resistance and lipid metabolism also worsened. Artificial respiratory support for continuous positive airway pressure was introduced, which stabilized her sleeping status with stable oxygenation. Her glucose metabolism with insulin resistance then partially improved ( Fig. 1A . OGTT③④). At the beginning of puberty (approximately 10 yr of age), hyperglycemia with hyperinsulinemia gradually deteriorated and the oral glucose tolerance test (OGTT) showed diabetic glucose response (Fig. 1A.OGTT⑤). At 11 yr and 5 mo of age, she was enrolled in a clinical trial of metreleptin. Metreleptin treatment was initiated at a dose of 0.06 mg/kg/d. Marked effectiveness of metreleptin appeared as early as 1 mo after the initiation, and metformin treatment was discontinued. Based on the results of the metreleptin trial, treatment with metreleptin was approved in 2013. Continuous treatment had consistent effects on patient’s glucose and fat metabolism. At approximately 13 yr of age, she sometimes had insomnia, headaches, and abdominal pains, followed by aggravation of her HbA1c and triglyceride levels, due to stressful relationship with her friends. Oral administration of metformin was then resumed, and socio-psychological counseling by a child psychiatrist was initiated. Her glycolipid metabolism status fluctuated according to her psychological state that is in line with her school year, and combined management with metreleptin, metformin, dietary therapy, and socio-psychological intervention were continued. As a result, the headaches and insomnia gradually decreased, and there was also an improvement in her glycolipid metabolism. Anti-metreleptin antibodies were detected (titer: 1:25) at 14 yr and 4 mo old. At 14 yr and 8 mo of age, Kauffman therapy was initiated due to irregular menstruation. At 18 yr and 8 mo of age and 7 yr after the commencement of metreleptin therapy, she began receiving metreleptin (3.8 mg/d), metformin (2250 mg/d), as well as dietary management to regulate the levels of calorie and lipid. Her height was 154 cm, weight 48 kg, and her HbA1c level was 6.0% in a stable state. She graduated from high school and entered the university without apparent hindrance in her daily life.'}
|
Patient-History
|
History
|
[
"apparent reduction of the subcutaneous adipose tissue at 1 mo of age",
"Poor weight gain was seen during a health checkup at 3 mo of age"
] |
6801357
|
{'Case 2': 'The male patient who was born at 36 wk of gestational age was the younger (3 yr younger) brother of case 1. He also showed apparent reduction of the subcutaneous adipose tissue at 1 mo of age. At that time, he already had characteristic symptoms of CGL, including an inverted triangular face, sparse subcutaneous tissue, and hepatomegaly. Laboratory examination demonstrated extremely high triglyceride level and low leptin level ( Table 1 ). Compound heterozygous variants of BSCL2 gene were identified; these were identical to the gene variants found in his sister. The clinical course is shown in Fig. 1B . Serum triglyceride and insulin levels increased to more than 2000 mg/dL and 700 μU/mL, respectively, at 2 mo of age. Following this, low-fat dietary formula was introduced (calories, 350 Cal/d; fat ratio, 20%). Metformin therapy was initiated at 7 mo of age (250 mg/d). At approximately 1 yr of age, when he started eating solid foods, hyperlipidemia and hyperinsulinemia resolved. Thereafter, his examination findings remained relatively stable for approximately 10 yr under management with nutritional and metformin therapies. His insulin resistance worsened and his triglyceride level increased during puberty ( Fig. 1B . OGTT③). At 11 yr and 6 mo of age, metreleptin was introduced at a dose of 0.04 mg/kg/d, and there was an immediate improvement of hyperinsulinemia and hyperlipidemia resulting in discontinuation of metformin. A few months later, hyperinsulinemia and liver dysfunction reappeared, and metformin treatment was reinitiated. An intelligence test (WISC-IV) at 12 yr of age demonstrated that his full-scale intelligence quotient was 58, indicating slightly retarded mental development with mild intellectual disability. At the time of writing this report, he was 16 yr and 4 mo of age and has received metreleptin therapy for approximately 4 yr.', 'Case 1': 'The female patient was born to non-consanguineous Japanese parents at 38 wk of gestational age. Poor weight gain was seen during a health checkup at 3 mo of age, and her parents consulted a pediatrician. Physical examination showed a generalized reduction in the subcutaneous adipose tissue with marked hepatomegaly. Laboratory analysis revealed notable hyperinsulinemia and hypertriglyceridemia. Generalized lipoatrophy was suspected and the patient was introduced to our department, Oita University Hospital at 5 mo of age. The characteristic physical findings of CGL were detected as shown in Table 1 Table 1. Physical manifestations and laboratory data for the siblings at their respective first clinical evaluations . Cardiac ultrasonography demonstrated hypertrophic cardiomyopathy. The serum leptin concentration was markedly low (0.9 ng/mL) ( 13 ). Genetic testing revealed compound heterozygous pathogenic variants of BSCL2 gene; the already reported variant (c.823C>T) and the unreported variant (c.576C>A). She was therefore diagnosed with CGL (Berardinelli-Seip syndrome). The clinical course is shown in Fig. 1A Fig. 1. Clinical courses of the siblings. (A) Case 1 and (B) Case 2. Each figure shows the serial data or parameters. The upper portions show the physical symptoms of CGL and its medical interventions. The middle portions show the serum triglyceride (TG), IRI, and HbA1c levels. The lower portions show the oral glucose tolerance test (OGTT) data. . At 5 mo of age, dietary management was initiated for calorie and lipid restriction (calorie 90 Cal/kg/d; carbohydrate 55%, lipid 20%, protein 20%). At 2 yr and 6 mo of age, metformin treatment (500 mg/d: 30 mg/kg/d) commenced because of marked insulin resistance with hepatic dysfunction. Metformin treatment seemed effective for insulin resistance ( Fig. 1A . OGTT①②). At approximately 4 yr of age, obstructive sleep apnea, which is known as a characteristic complication of CGL appeared, and insulin resistance and lipid metabolism also worsened. Artificial respiratory support for continuous positive airway pressure was introduced, which stabilized her sleeping status with stable oxygenation. Her glucose metabolism with insulin resistance then partially improved ( Fig. 1A . OGTT③④). At the beginning of puberty (approximately 10 yr of age), hyperglycemia with hyperinsulinemia gradually deteriorated and the oral glucose tolerance test (OGTT) showed diabetic glucose response (Fig. 1A.OGTT⑤). At 11 yr and 5 mo of age, she was enrolled in a clinical trial of metreleptin. Metreleptin treatment was initiated at a dose of 0.06 mg/kg/d. Marked effectiveness of metreleptin appeared as early as 1 mo after the initiation, and metformin treatment was discontinued. Based on the results of the metreleptin trial, treatment with metreleptin was approved in 2013. Continuous treatment had consistent effects on patient’s glucose and fat metabolism. At approximately 13 yr of age, she sometimes had insomnia, headaches, and abdominal pains, followed by aggravation of her HbA1c and triglyceride levels, due to stressful relationship with her friends. Oral administration of metformin was then resumed, and socio-psychological counseling by a child psychiatrist was initiated. Her glycolipid metabolism status fluctuated according to her psychological state that is in line with her school year, and combined management with metreleptin, metformin, dietary therapy, and socio-psychological intervention were continued. As a result, the headaches and insomnia gradually decreased, and there was also an improvement in her glycolipid metabolism. Anti-metreleptin antibodies were detected (titer: 1:25) at 14 yr and 4 mo old. At 14 yr and 8 mo of age, Kauffman therapy was initiated due to irregular menstruation. At 18 yr and 8 mo of age and 7 yr after the commencement of metreleptin therapy, she began receiving metreleptin (3.8 mg/d), metformin (2250 mg/d), as well as dietary management to regulate the levels of calorie and lipid. Her height was 154 cm, weight 48 kg, and her HbA1c level was 6.0% in a stable state. She graduated from high school and entered the university without apparent hindrance in her daily life.'}
|
{'Case 2': 'The male patient who was born at 36 wk of gestational age was the younger (3 yr younger) brother of case 1. He also showed apparent reduction of the subcutaneous adipose tissue at 1 mo of age. At that time, he already had characteristic symptoms of CGL, including an inverted triangular face, sparse subcutaneous tissue, and hepatomegaly. Laboratory examination demonstrated extremely high triglyceride level and low leptin level ( Table 1 ). Compound heterozygous variants of BSCL2 gene were identified; these were identical to the gene variants found in his sister. The clinical course is shown in Fig. 1B . Serum triglyceride and insulin levels increased to more than 2000 mg/dL and 700 μU/mL, respectively, at 2 mo of age. Following this, low-fat dietary formula was introduced (calories, 350 Cal/d; fat ratio, 20%). Metformin therapy was initiated at 7 mo of age (250 mg/d). At approximately 1 yr of age, when he started eating solid foods, hyperlipidemia and hyperinsulinemia resolved. Thereafter, his examination findings remained relatively stable for approximately 10 yr under management with nutritional and metformin therapies. His insulin resistance worsened and his triglyceride level increased during puberty ( Fig. 1B . OGTT③). At 11 yr and 6 mo of age, metreleptin was introduced at a dose of 0.04 mg/kg/d, and there was an immediate improvement of hyperinsulinemia and hyperlipidemia resulting in discontinuation of metformin. A few months later, hyperinsulinemia and liver dysfunction reappeared, and metformin treatment was reinitiated. An intelligence test (WISC-IV) at 12 yr of age demonstrated that his full-scale intelligence quotient was 58, indicating slightly retarded mental development with mild intellectual disability. At the time of writing this report, he was 16 yr and 4 mo of age and has received metreleptin therapy for approximately 4 yr.', 'Case 1': 'The female patient was born to non-consanguineous Japanese parents at 38 wk of gestational age. Poor weight gain was seen during a health checkup at 3 mo of age, and her parents consulted a pediatrician. Physical examination showed a generalized reduction in the subcutaneous adipose tissue with marked hepatomegaly. Laboratory analysis revealed notable hyperinsulinemia and hypertriglyceridemia. Generalized lipoatrophy was suspected and the patient was introduced to our department, Oita University Hospital at 5 mo of age. The characteristic physical findings of CGL were detected as shown in Table 1 Table 1. Physical manifestations and laboratory data for the siblings at their respective first clinical evaluations . Cardiac ultrasonography demonstrated hypertrophic cardiomyopathy. The serum leptin concentration was markedly low (0.9 ng/mL) ( 13 ). Genetic testing revealed compound heterozygous pathogenic variants of BSCL2 gene; the already reported variant (c.823C>T) and the unreported variant (c.576C>A). She was therefore diagnosed with CGL (Berardinelli-Seip syndrome). The clinical course is shown in Fig. 1A Fig. 1. Clinical courses of the siblings. (A) Case 1 and (B) Case 2. Each figure shows the serial data or parameters. The upper portions show the physical symptoms of CGL and its medical interventions. The middle portions show the serum triglyceride (TG), IRI, and HbA1c levels. The lower portions show the oral glucose tolerance test (OGTT) data. . At 5 mo of age, dietary management was initiated for calorie and lipid restriction (calorie 90 Cal/kg/d; carbohydrate 55%, lipid 20%, protein 20%). At 2 yr and 6 mo of age, metformin treatment (500 mg/d: 30 mg/kg/d) commenced because of marked insulin resistance with hepatic dysfunction. Metformin treatment seemed effective for insulin resistance ( Fig. 1A . OGTT①②). At approximately 4 yr of age, obstructive sleep apnea, which is known as a characteristic complication of CGL appeared, and insulin resistance and lipid metabolism also worsened. Artificial respiratory support for continuous positive airway pressure was introduced, which stabilized her sleeping status with stable oxygenation. Her glucose metabolism with insulin resistance then partially improved ( Fig. 1A . OGTT③④). At the beginning of puberty (approximately 10 yr of age), hyperglycemia with hyperinsulinemia gradually deteriorated and the oral glucose tolerance test (OGTT) showed diabetic glucose response (Fig. 1A.OGTT⑤). At 11 yr and 5 mo of age, she was enrolled in a clinical trial of metreleptin. Metreleptin treatment was initiated at a dose of 0.06 mg/kg/d. Marked effectiveness of metreleptin appeared as early as 1 mo after the initiation, and metformin treatment was discontinued. Based on the results of the metreleptin trial, treatment with metreleptin was approved in 2013. Continuous treatment had consistent effects on patient’s glucose and fat metabolism. At approximately 13 yr of age, she sometimes had insomnia, headaches, and abdominal pains, followed by aggravation of her HbA1c and triglyceride levels, due to stressful relationship with her friends. Oral administration of metformin was then resumed, and socio-psychological counseling by a child psychiatrist was initiated. Her glycolipid metabolism status fluctuated according to her psychological state that is in line with her school year, and combined management with metreleptin, metformin, dietary therapy, and socio-psychological intervention were continued. As a result, the headaches and insomnia gradually decreased, and there was also an improvement in her glycolipid metabolism. Anti-metreleptin antibodies were detected (titer: 1:25) at 14 yr and 4 mo old. At 14 yr and 8 mo of age, Kauffman therapy was initiated due to irregular menstruation. At 18 yr and 8 mo of age and 7 yr after the commencement of metreleptin therapy, she began receiving metreleptin (3.8 mg/d), metformin (2250 mg/d), as well as dietary management to regulate the levels of calorie and lipid. Her height was 154 cm, weight 48 kg, and her HbA1c level was 6.0% in a stable state. She graduated from high school and entered the university without apparent hindrance in her daily life.'}
|
Neurology
|
Neuro
|
[
"An intelligence test ( WISC - IV ) at 12 yr of age demonstrated that his full - scale intelligence quotient was 58, indicating slightly retarded mental development with mild intellectual disability",
"insomnia, headaches",
"her psychological state that is in line with her school year",
"headaches and insomnia gradually decreased"
] |
6801357
|
{'Case 2': 'The male patient who was born at 36 wk of gestational age was the younger (3 yr younger) brother of case 1. He also showed apparent reduction of the subcutaneous adipose tissue at 1 mo of age. At that time, he already had characteristic symptoms of CGL, including an inverted triangular face, sparse subcutaneous tissue, and hepatomegaly. Laboratory examination demonstrated extremely high triglyceride level and low leptin level ( Table 1 ). Compound heterozygous variants of BSCL2 gene were identified; these were identical to the gene variants found in his sister. The clinical course is shown in Fig. 1B . Serum triglyceride and insulin levels increased to more than 2000 mg/dL and 700 μU/mL, respectively, at 2 mo of age. Following this, low-fat dietary formula was introduced (calories, 350 Cal/d; fat ratio, 20%). Metformin therapy was initiated at 7 mo of age (250 mg/d). At approximately 1 yr of age, when he started eating solid foods, hyperlipidemia and hyperinsulinemia resolved. Thereafter, his examination findings remained relatively stable for approximately 10 yr under management with nutritional and metformin therapies. His insulin resistance worsened and his triglyceride level increased during puberty ( Fig. 1B . OGTT③). At 11 yr and 6 mo of age, metreleptin was introduced at a dose of 0.04 mg/kg/d, and there was an immediate improvement of hyperinsulinemia and hyperlipidemia resulting in discontinuation of metformin. A few months later, hyperinsulinemia and liver dysfunction reappeared, and metformin treatment was reinitiated. An intelligence test (WISC-IV) at 12 yr of age demonstrated that his full-scale intelligence quotient was 58, indicating slightly retarded mental development with mild intellectual disability. At the time of writing this report, he was 16 yr and 4 mo of age and has received metreleptin therapy for approximately 4 yr.', 'Case 1': 'The female patient was born to non-consanguineous Japanese parents at 38 wk of gestational age. Poor weight gain was seen during a health checkup at 3 mo of age, and her parents consulted a pediatrician. Physical examination showed a generalized reduction in the subcutaneous adipose tissue with marked hepatomegaly. Laboratory analysis revealed notable hyperinsulinemia and hypertriglyceridemia. Generalized lipoatrophy was suspected and the patient was introduced to our department, Oita University Hospital at 5 mo of age. The characteristic physical findings of CGL were detected as shown in Table 1 Table 1. Physical manifestations and laboratory data for the siblings at their respective first clinical evaluations . Cardiac ultrasonography demonstrated hypertrophic cardiomyopathy. The serum leptin concentration was markedly low (0.9 ng/mL) ( 13 ). Genetic testing revealed compound heterozygous pathogenic variants of BSCL2 gene; the already reported variant (c.823C>T) and the unreported variant (c.576C>A). She was therefore diagnosed with CGL (Berardinelli-Seip syndrome). The clinical course is shown in Fig. 1A Fig. 1. Clinical courses of the siblings. (A) Case 1 and (B) Case 2. Each figure shows the serial data or parameters. The upper portions show the physical symptoms of CGL and its medical interventions. The middle portions show the serum triglyceride (TG), IRI, and HbA1c levels. The lower portions show the oral glucose tolerance test (OGTT) data. . At 5 mo of age, dietary management was initiated for calorie and lipid restriction (calorie 90 Cal/kg/d; carbohydrate 55%, lipid 20%, protein 20%). At 2 yr and 6 mo of age, metformin treatment (500 mg/d: 30 mg/kg/d) commenced because of marked insulin resistance with hepatic dysfunction. Metformin treatment seemed effective for insulin resistance ( Fig. 1A . OGTT①②). At approximately 4 yr of age, obstructive sleep apnea, which is known as a characteristic complication of CGL appeared, and insulin resistance and lipid metabolism also worsened. Artificial respiratory support for continuous positive airway pressure was introduced, which stabilized her sleeping status with stable oxygenation. Her glucose metabolism with insulin resistance then partially improved ( Fig. 1A . OGTT③④). At the beginning of puberty (approximately 10 yr of age), hyperglycemia with hyperinsulinemia gradually deteriorated and the oral glucose tolerance test (OGTT) showed diabetic glucose response (Fig. 1A.OGTT⑤). At 11 yr and 5 mo of age, she was enrolled in a clinical trial of metreleptin. Metreleptin treatment was initiated at a dose of 0.06 mg/kg/d. Marked effectiveness of metreleptin appeared as early as 1 mo after the initiation, and metformin treatment was discontinued. Based on the results of the metreleptin trial, treatment with metreleptin was approved in 2013. Continuous treatment had consistent effects on patient’s glucose and fat metabolism. At approximately 13 yr of age, she sometimes had insomnia, headaches, and abdominal pains, followed by aggravation of her HbA1c and triglyceride levels, due to stressful relationship with her friends. Oral administration of metformin was then resumed, and socio-psychological counseling by a child psychiatrist was initiated. Her glycolipid metabolism status fluctuated according to her psychological state that is in line with her school year, and combined management with metreleptin, metformin, dietary therapy, and socio-psychological intervention were continued. As a result, the headaches and insomnia gradually decreased, and there was also an improvement in her glycolipid metabolism. Anti-metreleptin antibodies were detected (titer: 1:25) at 14 yr and 4 mo old. At 14 yr and 8 mo of age, Kauffman therapy was initiated due to irregular menstruation. At 18 yr and 8 mo of age and 7 yr after the commencement of metreleptin therapy, she began receiving metreleptin (3.8 mg/d), metformin (2250 mg/d), as well as dietary management to regulate the levels of calorie and lipid. Her height was 154 cm, weight 48 kg, and her HbA1c level was 6.0% in a stable state. She graduated from high school and entered the university without apparent hindrance in her daily life.'}
|
{'Case 2': 'The male patient who was born at 36 wk of gestational age was the younger (3 yr younger) brother of case 1. He also showed apparent reduction of the subcutaneous adipose tissue at 1 mo of age. At that time, he already had characteristic symptoms of CGL, including an inverted triangular face, sparse subcutaneous tissue, and hepatomegaly. Laboratory examination demonstrated extremely high triglyceride level and low leptin level ( Table 1 ). Compound heterozygous variants of BSCL2 gene were identified; these were identical to the gene variants found in his sister. The clinical course is shown in Fig. 1B . Serum triglyceride and insulin levels increased to more than 2000 mg/dL and 700 μU/mL, respectively, at 2 mo of age. Following this, low-fat dietary formula was introduced (calories, 350 Cal/d; fat ratio, 20%). Metformin therapy was initiated at 7 mo of age (250 mg/d). At approximately 1 yr of age, when he started eating solid foods, hyperlipidemia and hyperinsulinemia resolved. Thereafter, his examination findings remained relatively stable for approximately 10 yr under management with nutritional and metformin therapies. His insulin resistance worsened and his triglyceride level increased during puberty ( Fig. 1B . OGTT③). At 11 yr and 6 mo of age, metreleptin was introduced at a dose of 0.04 mg/kg/d, and there was an immediate improvement of hyperinsulinemia and hyperlipidemia resulting in discontinuation of metformin. A few months later, hyperinsulinemia and liver dysfunction reappeared, and metformin treatment was reinitiated. An intelligence test (WISC-IV) at 12 yr of age demonstrated that his full-scale intelligence quotient was 58, indicating slightly retarded mental development with mild intellectual disability. At the time of writing this report, he was 16 yr and 4 mo of age and has received metreleptin therapy for approximately 4 yr.', 'Case 1': 'The female patient was born to non-consanguineous Japanese parents at 38 wk of gestational age. Poor weight gain was seen during a health checkup at 3 mo of age, and her parents consulted a pediatrician. Physical examination showed a generalized reduction in the subcutaneous adipose tissue with marked hepatomegaly. Laboratory analysis revealed notable hyperinsulinemia and hypertriglyceridemia. Generalized lipoatrophy was suspected and the patient was introduced to our department, Oita University Hospital at 5 mo of age. The characteristic physical findings of CGL were detected as shown in Table 1 Table 1. Physical manifestations and laboratory data for the siblings at their respective first clinical evaluations . Cardiac ultrasonography demonstrated hypertrophic cardiomyopathy. The serum leptin concentration was markedly low (0.9 ng/mL) ( 13 ). Genetic testing revealed compound heterozygous pathogenic variants of BSCL2 gene; the already reported variant (c.823C>T) and the unreported variant (c.576C>A). She was therefore diagnosed with CGL (Berardinelli-Seip syndrome). The clinical course is shown in Fig. 1A Fig. 1. Clinical courses of the siblings. (A) Case 1 and (B) Case 2. Each figure shows the serial data or parameters. The upper portions show the physical symptoms of CGL and its medical interventions. The middle portions show the serum triglyceride (TG), IRI, and HbA1c levels. The lower portions show the oral glucose tolerance test (OGTT) data. . At 5 mo of age, dietary management was initiated for calorie and lipid restriction (calorie 90 Cal/kg/d; carbohydrate 55%, lipid 20%, protein 20%). At 2 yr and 6 mo of age, metformin treatment (500 mg/d: 30 mg/kg/d) commenced because of marked insulin resistance with hepatic dysfunction. Metformin treatment seemed effective for insulin resistance ( Fig. 1A . OGTT①②). At approximately 4 yr of age, obstructive sleep apnea, which is known as a characteristic complication of CGL appeared, and insulin resistance and lipid metabolism also worsened. Artificial respiratory support for continuous positive airway pressure was introduced, which stabilized her sleeping status with stable oxygenation. Her glucose metabolism with insulin resistance then partially improved ( Fig. 1A . OGTT③④). At the beginning of puberty (approximately 10 yr of age), hyperglycemia with hyperinsulinemia gradually deteriorated and the oral glucose tolerance test (OGTT) showed diabetic glucose response (Fig. 1A.OGTT⑤). At 11 yr and 5 mo of age, she was enrolled in a clinical trial of metreleptin. Metreleptin treatment was initiated at a dose of 0.06 mg/kg/d. Marked effectiveness of metreleptin appeared as early as 1 mo after the initiation, and metformin treatment was discontinued. Based on the results of the metreleptin trial, treatment with metreleptin was approved in 2013. Continuous treatment had consistent effects on patient’s glucose and fat metabolism. At approximately 13 yr of age, she sometimes had insomnia, headaches, and abdominal pains, followed by aggravation of her HbA1c and triglyceride levels, due to stressful relationship with her friends. Oral administration of metformin was then resumed, and socio-psychological counseling by a child psychiatrist was initiated. Her glycolipid metabolism status fluctuated according to her psychological state that is in line with her school year, and combined management with metreleptin, metformin, dietary therapy, and socio-psychological intervention were continued. As a result, the headaches and insomnia gradually decreased, and there was also an improvement in her glycolipid metabolism. Anti-metreleptin antibodies were detected (titer: 1:25) at 14 yr and 4 mo old. At 14 yr and 8 mo of age, Kauffman therapy was initiated due to irregular menstruation. At 18 yr and 8 mo of age and 7 yr after the commencement of metreleptin therapy, she began receiving metreleptin (3.8 mg/d), metformin (2250 mg/d), as well as dietary management to regulate the levels of calorie and lipid. Her height was 154 cm, weight 48 kg, and her HbA1c level was 6.0% in a stable state. She graduated from high school and entered the university without apparent hindrance in her daily life.'}
|
Laboratory-and-Imaging
|
Lab_Image
|
[
"Laboratory examination demonstrated extremely high triglyceride level and low leptin level ( Table 1 ). Compound heterozygous variants of BSCL2 gene were identified; these were identical to the gene variants found in his sister",
"Serum triglyceride and insulin levels increased to more than 2000 mg / dL and 700 μU / mL, respectively, at 2 mo of age",
"notable hyperinsulinemia and hypertriglyceridemia",
"Cardiac ultrasonography demonstrated hypertrophic cardiomyopathy. The serum leptin concentration was markedly low ( 0.9 ng / mL ) ( 13 ). Genetic testing revealed compound heterozygous pathogenic variants of BSCL2 gene; the already reported variant ( c.823C > T ) and the unreported variant ( c.576C > A )",
"oral glucose tolerance test ( OGTT ) showed diabetic glucose response (",
"aggravation of her HbA1c and triglyceride levels",
"HbA1c level was 6.0 % in a stable state"
] |
6801357
|
{'Case 2': 'The male patient who was born at 36 wk of gestational age was the younger (3 yr younger) brother of case 1. He also showed apparent reduction of the subcutaneous adipose tissue at 1 mo of age. At that time, he already had characteristic symptoms of CGL, including an inverted triangular face, sparse subcutaneous tissue, and hepatomegaly. Laboratory examination demonstrated extremely high triglyceride level and low leptin level ( Table 1 ). Compound heterozygous variants of BSCL2 gene were identified; these were identical to the gene variants found in his sister. The clinical course is shown in Fig. 1B . Serum triglyceride and insulin levels increased to more than 2000 mg/dL and 700 μU/mL, respectively, at 2 mo of age. Following this, low-fat dietary formula was introduced (calories, 350 Cal/d; fat ratio, 20%). Metformin therapy was initiated at 7 mo of age (250 mg/d). At approximately 1 yr of age, when he started eating solid foods, hyperlipidemia and hyperinsulinemia resolved. Thereafter, his examination findings remained relatively stable for approximately 10 yr under management with nutritional and metformin therapies. His insulin resistance worsened and his triglyceride level increased during puberty ( Fig. 1B . OGTT③). At 11 yr and 6 mo of age, metreleptin was introduced at a dose of 0.04 mg/kg/d, and there was an immediate improvement of hyperinsulinemia and hyperlipidemia resulting in discontinuation of metformin. A few months later, hyperinsulinemia and liver dysfunction reappeared, and metformin treatment was reinitiated. An intelligence test (WISC-IV) at 12 yr of age demonstrated that his full-scale intelligence quotient was 58, indicating slightly retarded mental development with mild intellectual disability. At the time of writing this report, he was 16 yr and 4 mo of age and has received metreleptin therapy for approximately 4 yr.', 'Case 1': 'The female patient was born to non-consanguineous Japanese parents at 38 wk of gestational age. Poor weight gain was seen during a health checkup at 3 mo of age, and her parents consulted a pediatrician. Physical examination showed a generalized reduction in the subcutaneous adipose tissue with marked hepatomegaly. Laboratory analysis revealed notable hyperinsulinemia and hypertriglyceridemia. Generalized lipoatrophy was suspected and the patient was introduced to our department, Oita University Hospital at 5 mo of age. The characteristic physical findings of CGL were detected as shown in Table 1 Table 1. Physical manifestations and laboratory data for the siblings at their respective first clinical evaluations . Cardiac ultrasonography demonstrated hypertrophic cardiomyopathy. The serum leptin concentration was markedly low (0.9 ng/mL) ( 13 ). Genetic testing revealed compound heterozygous pathogenic variants of BSCL2 gene; the already reported variant (c.823C>T) and the unreported variant (c.576C>A). She was therefore diagnosed with CGL (Berardinelli-Seip syndrome). The clinical course is shown in Fig. 1A Fig. 1. Clinical courses of the siblings. (A) Case 1 and (B) Case 2. Each figure shows the serial data or parameters. The upper portions show the physical symptoms of CGL and its medical interventions. The middle portions show the serum triglyceride (TG), IRI, and HbA1c levels. The lower portions show the oral glucose tolerance test (OGTT) data. . At 5 mo of age, dietary management was initiated for calorie and lipid restriction (calorie 90 Cal/kg/d; carbohydrate 55%, lipid 20%, protein 20%). At 2 yr and 6 mo of age, metformin treatment (500 mg/d: 30 mg/kg/d) commenced because of marked insulin resistance with hepatic dysfunction. Metformin treatment seemed effective for insulin resistance ( Fig. 1A . OGTT①②). At approximately 4 yr of age, obstructive sleep apnea, which is known as a characteristic complication of CGL appeared, and insulin resistance and lipid metabolism also worsened. Artificial respiratory support for continuous positive airway pressure was introduced, which stabilized her sleeping status with stable oxygenation. Her glucose metabolism with insulin resistance then partially improved ( Fig. 1A . OGTT③④). At the beginning of puberty (approximately 10 yr of age), hyperglycemia with hyperinsulinemia gradually deteriorated and the oral glucose tolerance test (OGTT) showed diabetic glucose response (Fig. 1A.OGTT⑤). At 11 yr and 5 mo of age, she was enrolled in a clinical trial of metreleptin. Metreleptin treatment was initiated at a dose of 0.06 mg/kg/d. Marked effectiveness of metreleptin appeared as early as 1 mo after the initiation, and metformin treatment was discontinued. Based on the results of the metreleptin trial, treatment with metreleptin was approved in 2013. Continuous treatment had consistent effects on patient’s glucose and fat metabolism. At approximately 13 yr of age, she sometimes had insomnia, headaches, and abdominal pains, followed by aggravation of her HbA1c and triglyceride levels, due to stressful relationship with her friends. Oral administration of metformin was then resumed, and socio-psychological counseling by a child psychiatrist was initiated. Her glycolipid metabolism status fluctuated according to her psychological state that is in line with her school year, and combined management with metreleptin, metformin, dietary therapy, and socio-psychological intervention were continued. As a result, the headaches and insomnia gradually decreased, and there was also an improvement in her glycolipid metabolism. Anti-metreleptin antibodies were detected (titer: 1:25) at 14 yr and 4 mo old. At 14 yr and 8 mo of age, Kauffman therapy was initiated due to irregular menstruation. At 18 yr and 8 mo of age and 7 yr after the commencement of metreleptin therapy, she began receiving metreleptin (3.8 mg/d), metformin (2250 mg/d), as well as dietary management to regulate the levels of calorie and lipid. Her height was 154 cm, weight 48 kg, and her HbA1c level was 6.0% in a stable state. She graduated from high school and entered the university without apparent hindrance in her daily life.'}
|
{'Case 2': 'The male patient who was born at 36 wk of gestational age was the younger (3 yr younger) brother of case 1. He also showed apparent reduction of the subcutaneous adipose tissue at 1 mo of age. At that time, he already had characteristic symptoms of CGL, including an inverted triangular face, sparse subcutaneous tissue, and hepatomegaly. Laboratory examination demonstrated extremely high triglyceride level and low leptin level ( Table 1 ). Compound heterozygous variants of BSCL2 gene were identified; these were identical to the gene variants found in his sister. The clinical course is shown in Fig. 1B . Serum triglyceride and insulin levels increased to more than 2000 mg/dL and 700 μU/mL, respectively, at 2 mo of age. Following this, low-fat dietary formula was introduced (calories, 350 Cal/d; fat ratio, 20%). Metformin therapy was initiated at 7 mo of age (250 mg/d). At approximately 1 yr of age, when he started eating solid foods, hyperlipidemia and hyperinsulinemia resolved. Thereafter, his examination findings remained relatively stable for approximately 10 yr under management with nutritional and metformin therapies. His insulin resistance worsened and his triglyceride level increased during puberty ( Fig. 1B . OGTT③). At 11 yr and 6 mo of age, metreleptin was introduced at a dose of 0.04 mg/kg/d, and there was an immediate improvement of hyperinsulinemia and hyperlipidemia resulting in discontinuation of metformin. A few months later, hyperinsulinemia and liver dysfunction reappeared, and metformin treatment was reinitiated. An intelligence test (WISC-IV) at 12 yr of age demonstrated that his full-scale intelligence quotient was 58, indicating slightly retarded mental development with mild intellectual disability. At the time of writing this report, he was 16 yr and 4 mo of age and has received metreleptin therapy for approximately 4 yr.', 'Case 1': 'The female patient was born to non-consanguineous Japanese parents at 38 wk of gestational age. Poor weight gain was seen during a health checkup at 3 mo of age, and her parents consulted a pediatrician. Physical examination showed a generalized reduction in the subcutaneous adipose tissue with marked hepatomegaly. Laboratory analysis revealed notable hyperinsulinemia and hypertriglyceridemia. Generalized lipoatrophy was suspected and the patient was introduced to our department, Oita University Hospital at 5 mo of age. The characteristic physical findings of CGL were detected as shown in Table 1 Table 1. Physical manifestations and laboratory data for the siblings at their respective first clinical evaluations . Cardiac ultrasonography demonstrated hypertrophic cardiomyopathy. The serum leptin concentration was markedly low (0.9 ng/mL) ( 13 ). Genetic testing revealed compound heterozygous pathogenic variants of BSCL2 gene; the already reported variant (c.823C>T) and the unreported variant (c.576C>A). She was therefore diagnosed with CGL (Berardinelli-Seip syndrome). The clinical course is shown in Fig. 1A Fig. 1. Clinical courses of the siblings. (A) Case 1 and (B) Case 2. Each figure shows the serial data or parameters. The upper portions show the physical symptoms of CGL and its medical interventions. The middle portions show the serum triglyceride (TG), IRI, and HbA1c levels. The lower portions show the oral glucose tolerance test (OGTT) data. . At 5 mo of age, dietary management was initiated for calorie and lipid restriction (calorie 90 Cal/kg/d; carbohydrate 55%, lipid 20%, protein 20%). At 2 yr and 6 mo of age, metformin treatment (500 mg/d: 30 mg/kg/d) commenced because of marked insulin resistance with hepatic dysfunction. Metformin treatment seemed effective for insulin resistance ( Fig. 1A . OGTT①②). At approximately 4 yr of age, obstructive sleep apnea, which is known as a characteristic complication of CGL appeared, and insulin resistance and lipid metabolism also worsened. Artificial respiratory support for continuous positive airway pressure was introduced, which stabilized her sleeping status with stable oxygenation. Her glucose metabolism with insulin resistance then partially improved ( Fig. 1A . OGTT③④). At the beginning of puberty (approximately 10 yr of age), hyperglycemia with hyperinsulinemia gradually deteriorated and the oral glucose tolerance test (OGTT) showed diabetic glucose response (Fig. 1A.OGTT⑤). At 11 yr and 5 mo of age, she was enrolled in a clinical trial of metreleptin. Metreleptin treatment was initiated at a dose of 0.06 mg/kg/d. Marked effectiveness of metreleptin appeared as early as 1 mo after the initiation, and metformin treatment was discontinued. Based on the results of the metreleptin trial, treatment with metreleptin was approved in 2013. Continuous treatment had consistent effects on patient’s glucose and fat metabolism. At approximately 13 yr of age, she sometimes had insomnia, headaches, and abdominal pains, followed by aggravation of her HbA1c and triglyceride levels, due to stressful relationship with her friends. Oral administration of metformin was then resumed, and socio-psychological counseling by a child psychiatrist was initiated. Her glycolipid metabolism status fluctuated according to her psychological state that is in line with her school year, and combined management with metreleptin, metformin, dietary therapy, and socio-psychological intervention were continued. As a result, the headaches and insomnia gradually decreased, and there was also an improvement in her glycolipid metabolism. Anti-metreleptin antibodies were detected (titer: 1:25) at 14 yr and 4 mo old. At 14 yr and 8 mo of age, Kauffman therapy was initiated due to irregular menstruation. At 18 yr and 8 mo of age and 7 yr after the commencement of metreleptin therapy, she began receiving metreleptin (3.8 mg/d), metformin (2250 mg/d), as well as dietary management to regulate the levels of calorie and lipid. Her height was 154 cm, weight 48 kg, and her HbA1c level was 6.0% in a stable state. She graduated from high school and entered the university without apparent hindrance in her daily life.'}
|
Cardiovascular-System
|
CVS
|
[
"Cardiac ultrasonography demonstrated hypertrophic cardiomyopathy"
] |
6801357
|
{'Case 2': 'The male patient who was born at 36 wk of gestational age was the younger (3 yr younger) brother of case 1. He also showed apparent reduction of the subcutaneous adipose tissue at 1 mo of age. At that time, he already had characteristic symptoms of CGL, including an inverted triangular face, sparse subcutaneous tissue, and hepatomegaly. Laboratory examination demonstrated extremely high triglyceride level and low leptin level ( Table 1 ). Compound heterozygous variants of BSCL2 gene were identified; these were identical to the gene variants found in his sister. The clinical course is shown in Fig. 1B . Serum triglyceride and insulin levels increased to more than 2000 mg/dL and 700 μU/mL, respectively, at 2 mo of age. Following this, low-fat dietary formula was introduced (calories, 350 Cal/d; fat ratio, 20%). Metformin therapy was initiated at 7 mo of age (250 mg/d). At approximately 1 yr of age, when he started eating solid foods, hyperlipidemia and hyperinsulinemia resolved. Thereafter, his examination findings remained relatively stable for approximately 10 yr under management with nutritional and metformin therapies. His insulin resistance worsened and his triglyceride level increased during puberty ( Fig. 1B . OGTT③). At 11 yr and 6 mo of age, metreleptin was introduced at a dose of 0.04 mg/kg/d, and there was an immediate improvement of hyperinsulinemia and hyperlipidemia resulting in discontinuation of metformin. A few months later, hyperinsulinemia and liver dysfunction reappeared, and metformin treatment was reinitiated. An intelligence test (WISC-IV) at 12 yr of age demonstrated that his full-scale intelligence quotient was 58, indicating slightly retarded mental development with mild intellectual disability. At the time of writing this report, he was 16 yr and 4 mo of age and has received metreleptin therapy for approximately 4 yr.', 'Case 1': 'The female patient was born to non-consanguineous Japanese parents at 38 wk of gestational age. Poor weight gain was seen during a health checkup at 3 mo of age, and her parents consulted a pediatrician. Physical examination showed a generalized reduction in the subcutaneous adipose tissue with marked hepatomegaly. Laboratory analysis revealed notable hyperinsulinemia and hypertriglyceridemia. Generalized lipoatrophy was suspected and the patient was introduced to our department, Oita University Hospital at 5 mo of age. The characteristic physical findings of CGL were detected as shown in Table 1 Table 1. Physical manifestations and laboratory data for the siblings at their respective first clinical evaluations . Cardiac ultrasonography demonstrated hypertrophic cardiomyopathy. The serum leptin concentration was markedly low (0.9 ng/mL) ( 13 ). Genetic testing revealed compound heterozygous pathogenic variants of BSCL2 gene; the already reported variant (c.823C>T) and the unreported variant (c.576C>A). She was therefore diagnosed with CGL (Berardinelli-Seip syndrome). The clinical course is shown in Fig. 1A Fig. 1. Clinical courses of the siblings. (A) Case 1 and (B) Case 2. Each figure shows the serial data or parameters. The upper portions show the physical symptoms of CGL and its medical interventions. The middle portions show the serum triglyceride (TG), IRI, and HbA1c levels. The lower portions show the oral glucose tolerance test (OGTT) data. . At 5 mo of age, dietary management was initiated for calorie and lipid restriction (calorie 90 Cal/kg/d; carbohydrate 55%, lipid 20%, protein 20%). At 2 yr and 6 mo of age, metformin treatment (500 mg/d: 30 mg/kg/d) commenced because of marked insulin resistance with hepatic dysfunction. Metformin treatment seemed effective for insulin resistance ( Fig. 1A . OGTT①②). At approximately 4 yr of age, obstructive sleep apnea, which is known as a characteristic complication of CGL appeared, and insulin resistance and lipid metabolism also worsened. Artificial respiratory support for continuous positive airway pressure was introduced, which stabilized her sleeping status with stable oxygenation. Her glucose metabolism with insulin resistance then partially improved ( Fig. 1A . OGTT③④). At the beginning of puberty (approximately 10 yr of age), hyperglycemia with hyperinsulinemia gradually deteriorated and the oral glucose tolerance test (OGTT) showed diabetic glucose response (Fig. 1A.OGTT⑤). At 11 yr and 5 mo of age, she was enrolled in a clinical trial of metreleptin. Metreleptin treatment was initiated at a dose of 0.06 mg/kg/d. Marked effectiveness of metreleptin appeared as early as 1 mo after the initiation, and metformin treatment was discontinued. Based on the results of the metreleptin trial, treatment with metreleptin was approved in 2013. Continuous treatment had consistent effects on patient’s glucose and fat metabolism. At approximately 13 yr of age, she sometimes had insomnia, headaches, and abdominal pains, followed by aggravation of her HbA1c and triglyceride levels, due to stressful relationship with her friends. Oral administration of metformin was then resumed, and socio-psychological counseling by a child psychiatrist was initiated. Her glycolipid metabolism status fluctuated according to her psychological state that is in line with her school year, and combined management with metreleptin, metformin, dietary therapy, and socio-psychological intervention were continued. As a result, the headaches and insomnia gradually decreased, and there was also an improvement in her glycolipid metabolism. Anti-metreleptin antibodies were detected (titer: 1:25) at 14 yr and 4 mo old. At 14 yr and 8 mo of age, Kauffman therapy was initiated due to irregular menstruation. At 18 yr and 8 mo of age and 7 yr after the commencement of metreleptin therapy, she began receiving metreleptin (3.8 mg/d), metformin (2250 mg/d), as well as dietary management to regulate the levels of calorie and lipid. Her height was 154 cm, weight 48 kg, and her HbA1c level was 6.0% in a stable state. She graduated from high school and entered the university without apparent hindrance in her daily life.'}
|
{'Case 2': 'The male patient who was born at 36 wk of gestational age was the younger (3 yr younger) brother of case 1. He also showed apparent reduction of the subcutaneous adipose tissue at 1 mo of age. At that time, he already had characteristic symptoms of CGL, including an inverted triangular face, sparse subcutaneous tissue, and hepatomegaly. Laboratory examination demonstrated extremely high triglyceride level and low leptin level ( Table 1 ). Compound heterozygous variants of BSCL2 gene were identified; these were identical to the gene variants found in his sister. The clinical course is shown in Fig. 1B . Serum triglyceride and insulin levels increased to more than 2000 mg/dL and 700 μU/mL, respectively, at 2 mo of age. Following this, low-fat dietary formula was introduced (calories, 350 Cal/d; fat ratio, 20%). Metformin therapy was initiated at 7 mo of age (250 mg/d). At approximately 1 yr of age, when he started eating solid foods, hyperlipidemia and hyperinsulinemia resolved. Thereafter, his examination findings remained relatively stable for approximately 10 yr under management with nutritional and metformin therapies. His insulin resistance worsened and his triglyceride level increased during puberty ( Fig. 1B . OGTT③). At 11 yr and 6 mo of age, metreleptin was introduced at a dose of 0.04 mg/kg/d, and there was an immediate improvement of hyperinsulinemia and hyperlipidemia resulting in discontinuation of metformin. A few months later, hyperinsulinemia and liver dysfunction reappeared, and metformin treatment was reinitiated. An intelligence test (WISC-IV) at 12 yr of age demonstrated that his full-scale intelligence quotient was 58, indicating slightly retarded mental development with mild intellectual disability. At the time of writing this report, he was 16 yr and 4 mo of age and has received metreleptin therapy for approximately 4 yr.', 'Case 1': 'The female patient was born to non-consanguineous Japanese parents at 38 wk of gestational age. Poor weight gain was seen during a health checkup at 3 mo of age, and her parents consulted a pediatrician. Physical examination showed a generalized reduction in the subcutaneous adipose tissue with marked hepatomegaly. Laboratory analysis revealed notable hyperinsulinemia and hypertriglyceridemia. Generalized lipoatrophy was suspected and the patient was introduced to our department, Oita University Hospital at 5 mo of age. The characteristic physical findings of CGL were detected as shown in Table 1 Table 1. Physical manifestations and laboratory data for the siblings at their respective first clinical evaluations . Cardiac ultrasonography demonstrated hypertrophic cardiomyopathy. The serum leptin concentration was markedly low (0.9 ng/mL) ( 13 ). Genetic testing revealed compound heterozygous pathogenic variants of BSCL2 gene; the already reported variant (c.823C>T) and the unreported variant (c.576C>A). She was therefore diagnosed with CGL (Berardinelli-Seip syndrome). The clinical course is shown in Fig. 1A Fig. 1. Clinical courses of the siblings. (A) Case 1 and (B) Case 2. Each figure shows the serial data or parameters. The upper portions show the physical symptoms of CGL and its medical interventions. The middle portions show the serum triglyceride (TG), IRI, and HbA1c levels. The lower portions show the oral glucose tolerance test (OGTT) data. . At 5 mo of age, dietary management was initiated for calorie and lipid restriction (calorie 90 Cal/kg/d; carbohydrate 55%, lipid 20%, protein 20%). At 2 yr and 6 mo of age, metformin treatment (500 mg/d: 30 mg/kg/d) commenced because of marked insulin resistance with hepatic dysfunction. Metformin treatment seemed effective for insulin resistance ( Fig. 1A . OGTT①②). At approximately 4 yr of age, obstructive sleep apnea, which is known as a characteristic complication of CGL appeared, and insulin resistance and lipid metabolism also worsened. Artificial respiratory support for continuous positive airway pressure was introduced, which stabilized her sleeping status with stable oxygenation. Her glucose metabolism with insulin resistance then partially improved ( Fig. 1A . OGTT③④). At the beginning of puberty (approximately 10 yr of age), hyperglycemia with hyperinsulinemia gradually deteriorated and the oral glucose tolerance test (OGTT) showed diabetic glucose response (Fig. 1A.OGTT⑤). At 11 yr and 5 mo of age, she was enrolled in a clinical trial of metreleptin. Metreleptin treatment was initiated at a dose of 0.06 mg/kg/d. Marked effectiveness of metreleptin appeared as early as 1 mo after the initiation, and metformin treatment was discontinued. Based on the results of the metreleptin trial, treatment with metreleptin was approved in 2013. Continuous treatment had consistent effects on patient’s glucose and fat metabolism. At approximately 13 yr of age, she sometimes had insomnia, headaches, and abdominal pains, followed by aggravation of her HbA1c and triglyceride levels, due to stressful relationship with her friends. Oral administration of metformin was then resumed, and socio-psychological counseling by a child psychiatrist was initiated. Her glycolipid metabolism status fluctuated according to her psychological state that is in line with her school year, and combined management with metreleptin, metformin, dietary therapy, and socio-psychological intervention were continued. As a result, the headaches and insomnia gradually decreased, and there was also an improvement in her glycolipid metabolism. Anti-metreleptin antibodies were detected (titer: 1:25) at 14 yr and 4 mo old. At 14 yr and 8 mo of age, Kauffman therapy was initiated due to irregular menstruation. At 18 yr and 8 mo of age and 7 yr after the commencement of metreleptin therapy, she began receiving metreleptin (3.8 mg/d), metformin (2250 mg/d), as well as dietary management to regulate the levels of calorie and lipid. Her height was 154 cm, weight 48 kg, and her HbA1c level was 6.0% in a stable state. She graduated from high school and entered the university without apparent hindrance in her daily life.'}
|
Endocrinology
|
ENDO
|
[
"extremely high triglyceride level and low leptin level",
"Serum triglyceride and insulin levels increased to more than 2000 mg / dL and 700 μU / mL, respectively, at 2 mo of age",
"hyperlipidemia and hyperinsulinemia resolved",
"His insulin resistance worsened and his triglyceride level increased during puberty",
"hyperinsulinemia and hyperlipidemia",
"hyperinsulinemia",
"Poor weight gain",
"notable hyperinsulinemia and hypertriglyceridemia",
"The serum leptin concentration was markedly low ( 0.9 ng / mL ) ( 13 ).",
"marked insulin resistance",
"insulin resistance and lipid metabolism also worsened",
"hyperglycemia with hyperinsulinemia gradually deteriorated",
"diabetic glucose response",
"aggravation of her HbA1c and triglyceride levels",
"irregular menstruation"
] |
6801357
|
{'Case 2': 'The male patient who was born at 36 wk of gestational age was the younger (3 yr younger) brother of case 1. He also showed apparent reduction of the subcutaneous adipose tissue at 1 mo of age. At that time, he already had characteristic symptoms of CGL, including an inverted triangular face, sparse subcutaneous tissue, and hepatomegaly. Laboratory examination demonstrated extremely high triglyceride level and low leptin level ( Table 1 ). Compound heterozygous variants of BSCL2 gene were identified; these were identical to the gene variants found in his sister. The clinical course is shown in Fig. 1B . Serum triglyceride and insulin levels increased to more than 2000 mg/dL and 700 μU/mL, respectively, at 2 mo of age. Following this, low-fat dietary formula was introduced (calories, 350 Cal/d; fat ratio, 20%). Metformin therapy was initiated at 7 mo of age (250 mg/d). At approximately 1 yr of age, when he started eating solid foods, hyperlipidemia and hyperinsulinemia resolved. Thereafter, his examination findings remained relatively stable for approximately 10 yr under management with nutritional and metformin therapies. His insulin resistance worsened and his triglyceride level increased during puberty ( Fig. 1B . OGTT③). At 11 yr and 6 mo of age, metreleptin was introduced at a dose of 0.04 mg/kg/d, and there was an immediate improvement of hyperinsulinemia and hyperlipidemia resulting in discontinuation of metformin. A few months later, hyperinsulinemia and liver dysfunction reappeared, and metformin treatment was reinitiated. An intelligence test (WISC-IV) at 12 yr of age demonstrated that his full-scale intelligence quotient was 58, indicating slightly retarded mental development with mild intellectual disability. At the time of writing this report, he was 16 yr and 4 mo of age and has received metreleptin therapy for approximately 4 yr.', 'Case 1': 'The female patient was born to non-consanguineous Japanese parents at 38 wk of gestational age. Poor weight gain was seen during a health checkup at 3 mo of age, and her parents consulted a pediatrician. Physical examination showed a generalized reduction in the subcutaneous adipose tissue with marked hepatomegaly. Laboratory analysis revealed notable hyperinsulinemia and hypertriglyceridemia. Generalized lipoatrophy was suspected and the patient was introduced to our department, Oita University Hospital at 5 mo of age. The characteristic physical findings of CGL were detected as shown in Table 1 Table 1. Physical manifestations and laboratory data for the siblings at their respective first clinical evaluations . Cardiac ultrasonography demonstrated hypertrophic cardiomyopathy. The serum leptin concentration was markedly low (0.9 ng/mL) ( 13 ). Genetic testing revealed compound heterozygous pathogenic variants of BSCL2 gene; the already reported variant (c.823C>T) and the unreported variant (c.576C>A). She was therefore diagnosed with CGL (Berardinelli-Seip syndrome). The clinical course is shown in Fig. 1A Fig. 1. Clinical courses of the siblings. (A) Case 1 and (B) Case 2. Each figure shows the serial data or parameters. The upper portions show the physical symptoms of CGL and its medical interventions. The middle portions show the serum triglyceride (TG), IRI, and HbA1c levels. The lower portions show the oral glucose tolerance test (OGTT) data. . At 5 mo of age, dietary management was initiated for calorie and lipid restriction (calorie 90 Cal/kg/d; carbohydrate 55%, lipid 20%, protein 20%). At 2 yr and 6 mo of age, metformin treatment (500 mg/d: 30 mg/kg/d) commenced because of marked insulin resistance with hepatic dysfunction. Metformin treatment seemed effective for insulin resistance ( Fig. 1A . OGTT①②). At approximately 4 yr of age, obstructive sleep apnea, which is known as a characteristic complication of CGL appeared, and insulin resistance and lipid metabolism also worsened. Artificial respiratory support for continuous positive airway pressure was introduced, which stabilized her sleeping status with stable oxygenation. Her glucose metabolism with insulin resistance then partially improved ( Fig. 1A . OGTT③④). At the beginning of puberty (approximately 10 yr of age), hyperglycemia with hyperinsulinemia gradually deteriorated and the oral glucose tolerance test (OGTT) showed diabetic glucose response (Fig. 1A.OGTT⑤). At 11 yr and 5 mo of age, she was enrolled in a clinical trial of metreleptin. Metreleptin treatment was initiated at a dose of 0.06 mg/kg/d. Marked effectiveness of metreleptin appeared as early as 1 mo after the initiation, and metformin treatment was discontinued. Based on the results of the metreleptin trial, treatment with metreleptin was approved in 2013. Continuous treatment had consistent effects on patient’s glucose and fat metabolism. At approximately 13 yr of age, she sometimes had insomnia, headaches, and abdominal pains, followed by aggravation of her HbA1c and triglyceride levels, due to stressful relationship with her friends. Oral administration of metformin was then resumed, and socio-psychological counseling by a child psychiatrist was initiated. Her glycolipid metabolism status fluctuated according to her psychological state that is in line with her school year, and combined management with metreleptin, metformin, dietary therapy, and socio-psychological intervention were continued. As a result, the headaches and insomnia gradually decreased, and there was also an improvement in her glycolipid metabolism. Anti-metreleptin antibodies were detected (titer: 1:25) at 14 yr and 4 mo old. At 14 yr and 8 mo of age, Kauffman therapy was initiated due to irregular menstruation. At 18 yr and 8 mo of age and 7 yr after the commencement of metreleptin therapy, she began receiving metreleptin (3.8 mg/d), metformin (2250 mg/d), as well as dietary management to regulate the levels of calorie and lipid. Her height was 154 cm, weight 48 kg, and her HbA1c level was 6.0% in a stable state. She graduated from high school and entered the university without apparent hindrance in her daily life.'}
|
{'Case 2': 'The male patient who was born at 36 wk of gestational age was the younger (3 yr younger) brother of case 1. He also showed apparent reduction of the subcutaneous adipose tissue at 1 mo of age. At that time, he already had characteristic symptoms of CGL, including an inverted triangular face, sparse subcutaneous tissue, and hepatomegaly. Laboratory examination demonstrated extremely high triglyceride level and low leptin level ( Table 1 ). Compound heterozygous variants of BSCL2 gene were identified; these were identical to the gene variants found in his sister. The clinical course is shown in Fig. 1B . Serum triglyceride and insulin levels increased to more than 2000 mg/dL and 700 μU/mL, respectively, at 2 mo of age. Following this, low-fat dietary formula was introduced (calories, 350 Cal/d; fat ratio, 20%). Metformin therapy was initiated at 7 mo of age (250 mg/d). At approximately 1 yr of age, when he started eating solid foods, hyperlipidemia and hyperinsulinemia resolved. Thereafter, his examination findings remained relatively stable for approximately 10 yr under management with nutritional and metformin therapies. His insulin resistance worsened and his triglyceride level increased during puberty ( Fig. 1B . OGTT③). At 11 yr and 6 mo of age, metreleptin was introduced at a dose of 0.04 mg/kg/d, and there was an immediate improvement of hyperinsulinemia and hyperlipidemia resulting in discontinuation of metformin. A few months later, hyperinsulinemia and liver dysfunction reappeared, and metformin treatment was reinitiated. An intelligence test (WISC-IV) at 12 yr of age demonstrated that his full-scale intelligence quotient was 58, indicating slightly retarded mental development with mild intellectual disability. At the time of writing this report, he was 16 yr and 4 mo of age and has received metreleptin therapy for approximately 4 yr.', 'Case 1': 'The female patient was born to non-consanguineous Japanese parents at 38 wk of gestational age. Poor weight gain was seen during a health checkup at 3 mo of age, and her parents consulted a pediatrician. Physical examination showed a generalized reduction in the subcutaneous adipose tissue with marked hepatomegaly. Laboratory analysis revealed notable hyperinsulinemia and hypertriglyceridemia. Generalized lipoatrophy was suspected and the patient was introduced to our department, Oita University Hospital at 5 mo of age. The characteristic physical findings of CGL were detected as shown in Table 1 Table 1. Physical manifestations and laboratory data for the siblings at their respective first clinical evaluations . Cardiac ultrasonography demonstrated hypertrophic cardiomyopathy. The serum leptin concentration was markedly low (0.9 ng/mL) ( 13 ). Genetic testing revealed compound heterozygous pathogenic variants of BSCL2 gene; the already reported variant (c.823C>T) and the unreported variant (c.576C>A). She was therefore diagnosed with CGL (Berardinelli-Seip syndrome). The clinical course is shown in Fig. 1A Fig. 1. Clinical courses of the siblings. (A) Case 1 and (B) Case 2. Each figure shows the serial data or parameters. The upper portions show the physical symptoms of CGL and its medical interventions. The middle portions show the serum triglyceride (TG), IRI, and HbA1c levels. The lower portions show the oral glucose tolerance test (OGTT) data. . At 5 mo of age, dietary management was initiated for calorie and lipid restriction (calorie 90 Cal/kg/d; carbohydrate 55%, lipid 20%, protein 20%). At 2 yr and 6 mo of age, metformin treatment (500 mg/d: 30 mg/kg/d) commenced because of marked insulin resistance with hepatic dysfunction. Metformin treatment seemed effective for insulin resistance ( Fig. 1A . OGTT①②). At approximately 4 yr of age, obstructive sleep apnea, which is known as a characteristic complication of CGL appeared, and insulin resistance and lipid metabolism also worsened. Artificial respiratory support for continuous positive airway pressure was introduced, which stabilized her sleeping status with stable oxygenation. Her glucose metabolism with insulin resistance then partially improved ( Fig. 1A . OGTT③④). At the beginning of puberty (approximately 10 yr of age), hyperglycemia with hyperinsulinemia gradually deteriorated and the oral glucose tolerance test (OGTT) showed diabetic glucose response (Fig. 1A.OGTT⑤). At 11 yr and 5 mo of age, she was enrolled in a clinical trial of metreleptin. Metreleptin treatment was initiated at a dose of 0.06 mg/kg/d. Marked effectiveness of metreleptin appeared as early as 1 mo after the initiation, and metformin treatment was discontinued. Based on the results of the metreleptin trial, treatment with metreleptin was approved in 2013. Continuous treatment had consistent effects on patient’s glucose and fat metabolism. At approximately 13 yr of age, she sometimes had insomnia, headaches, and abdominal pains, followed by aggravation of her HbA1c and triglyceride levels, due to stressful relationship with her friends. Oral administration of metformin was then resumed, and socio-psychological counseling by a child psychiatrist was initiated. Her glycolipid metabolism status fluctuated according to her psychological state that is in line with her school year, and combined management with metreleptin, metformin, dietary therapy, and socio-psychological intervention were continued. As a result, the headaches and insomnia gradually decreased, and there was also an improvement in her glycolipid metabolism. Anti-metreleptin antibodies were detected (titer: 1:25) at 14 yr and 4 mo old. At 14 yr and 8 mo of age, Kauffman therapy was initiated due to irregular menstruation. At 18 yr and 8 mo of age and 7 yr after the commencement of metreleptin therapy, she began receiving metreleptin (3.8 mg/d), metformin (2250 mg/d), as well as dietary management to regulate the levels of calorie and lipid. Her height was 154 cm, weight 48 kg, and her HbA1c level was 6.0% in a stable state. She graduated from high school and entered the university without apparent hindrance in her daily life.'}
|
Genitourinary-System
|
GU
|
[
"irregular menstruation"
] |
6801357
|
{'Case 2': 'The male patient who was born at 36 wk of gestational age was the younger (3 yr younger) brother of case 1. He also showed apparent reduction of the subcutaneous adipose tissue at 1 mo of age. At that time, he already had characteristic symptoms of CGL, including an inverted triangular face, sparse subcutaneous tissue, and hepatomegaly. Laboratory examination demonstrated extremely high triglyceride level and low leptin level ( Table 1 ). Compound heterozygous variants of BSCL2 gene were identified; these were identical to the gene variants found in his sister. The clinical course is shown in Fig. 1B . Serum triglyceride and insulin levels increased to more than 2000 mg/dL and 700 μU/mL, respectively, at 2 mo of age. Following this, low-fat dietary formula was introduced (calories, 350 Cal/d; fat ratio, 20%). Metformin therapy was initiated at 7 mo of age (250 mg/d). At approximately 1 yr of age, when he started eating solid foods, hyperlipidemia and hyperinsulinemia resolved. Thereafter, his examination findings remained relatively stable for approximately 10 yr under management with nutritional and metformin therapies. His insulin resistance worsened and his triglyceride level increased during puberty ( Fig. 1B . OGTT③). At 11 yr and 6 mo of age, metreleptin was introduced at a dose of 0.04 mg/kg/d, and there was an immediate improvement of hyperinsulinemia and hyperlipidemia resulting in discontinuation of metformin. A few months later, hyperinsulinemia and liver dysfunction reappeared, and metformin treatment was reinitiated. An intelligence test (WISC-IV) at 12 yr of age demonstrated that his full-scale intelligence quotient was 58, indicating slightly retarded mental development with mild intellectual disability. At the time of writing this report, he was 16 yr and 4 mo of age and has received metreleptin therapy for approximately 4 yr.', 'Case 1': 'The female patient was born to non-consanguineous Japanese parents at 38 wk of gestational age. Poor weight gain was seen during a health checkup at 3 mo of age, and her parents consulted a pediatrician. Physical examination showed a generalized reduction in the subcutaneous adipose tissue with marked hepatomegaly. Laboratory analysis revealed notable hyperinsulinemia and hypertriglyceridemia. Generalized lipoatrophy was suspected and the patient was introduced to our department, Oita University Hospital at 5 mo of age. The characteristic physical findings of CGL were detected as shown in Table 1 Table 1. Physical manifestations and laboratory data for the siblings at their respective first clinical evaluations . Cardiac ultrasonography demonstrated hypertrophic cardiomyopathy. The serum leptin concentration was markedly low (0.9 ng/mL) ( 13 ). Genetic testing revealed compound heterozygous pathogenic variants of BSCL2 gene; the already reported variant (c.823C>T) and the unreported variant (c.576C>A). She was therefore diagnosed with CGL (Berardinelli-Seip syndrome). The clinical course is shown in Fig. 1A Fig. 1. Clinical courses of the siblings. (A) Case 1 and (B) Case 2. Each figure shows the serial data or parameters. The upper portions show the physical symptoms of CGL and its medical interventions. The middle portions show the serum triglyceride (TG), IRI, and HbA1c levels. The lower portions show the oral glucose tolerance test (OGTT) data. . At 5 mo of age, dietary management was initiated for calorie and lipid restriction (calorie 90 Cal/kg/d; carbohydrate 55%, lipid 20%, protein 20%). At 2 yr and 6 mo of age, metformin treatment (500 mg/d: 30 mg/kg/d) commenced because of marked insulin resistance with hepatic dysfunction. Metformin treatment seemed effective for insulin resistance ( Fig. 1A . OGTT①②). At approximately 4 yr of age, obstructive sleep apnea, which is known as a characteristic complication of CGL appeared, and insulin resistance and lipid metabolism also worsened. Artificial respiratory support for continuous positive airway pressure was introduced, which stabilized her sleeping status with stable oxygenation. Her glucose metabolism with insulin resistance then partially improved ( Fig. 1A . OGTT③④). At the beginning of puberty (approximately 10 yr of age), hyperglycemia with hyperinsulinemia gradually deteriorated and the oral glucose tolerance test (OGTT) showed diabetic glucose response (Fig. 1A.OGTT⑤). At 11 yr and 5 mo of age, she was enrolled in a clinical trial of metreleptin. Metreleptin treatment was initiated at a dose of 0.06 mg/kg/d. Marked effectiveness of metreleptin appeared as early as 1 mo after the initiation, and metformin treatment was discontinued. Based on the results of the metreleptin trial, treatment with metreleptin was approved in 2013. Continuous treatment had consistent effects on patient’s glucose and fat metabolism. At approximately 13 yr of age, she sometimes had insomnia, headaches, and abdominal pains, followed by aggravation of her HbA1c and triglyceride levels, due to stressful relationship with her friends. Oral administration of metformin was then resumed, and socio-psychological counseling by a child psychiatrist was initiated. Her glycolipid metabolism status fluctuated according to her psychological state that is in line with her school year, and combined management with metreleptin, metformin, dietary therapy, and socio-psychological intervention were continued. As a result, the headaches and insomnia gradually decreased, and there was also an improvement in her glycolipid metabolism. Anti-metreleptin antibodies were detected (titer: 1:25) at 14 yr and 4 mo old. At 14 yr and 8 mo of age, Kauffman therapy was initiated due to irregular menstruation. At 18 yr and 8 mo of age and 7 yr after the commencement of metreleptin therapy, she began receiving metreleptin (3.8 mg/d), metformin (2250 mg/d), as well as dietary management to regulate the levels of calorie and lipid. Her height was 154 cm, weight 48 kg, and her HbA1c level was 6.0% in a stable state. She graduated from high school and entered the university without apparent hindrance in her daily life.'}
|
{'Case 2': 'The male patient who was born at 36 wk of gestational age was the younger (3 yr younger) brother of case 1. He also showed apparent reduction of the subcutaneous adipose tissue at 1 mo of age. At that time, he already had characteristic symptoms of CGL, including an inverted triangular face, sparse subcutaneous tissue, and hepatomegaly. Laboratory examination demonstrated extremely high triglyceride level and low leptin level ( Table 1 ). Compound heterozygous variants of BSCL2 gene were identified; these were identical to the gene variants found in his sister. The clinical course is shown in Fig. 1B . Serum triglyceride and insulin levels increased to more than 2000 mg/dL and 700 μU/mL, respectively, at 2 mo of age. Following this, low-fat dietary formula was introduced (calories, 350 Cal/d; fat ratio, 20%). Metformin therapy was initiated at 7 mo of age (250 mg/d). At approximately 1 yr of age, when he started eating solid foods, hyperlipidemia and hyperinsulinemia resolved. Thereafter, his examination findings remained relatively stable for approximately 10 yr under management with nutritional and metformin therapies. His insulin resistance worsened and his triglyceride level increased during puberty ( Fig. 1B . OGTT③). At 11 yr and 6 mo of age, metreleptin was introduced at a dose of 0.04 mg/kg/d, and there was an immediate improvement of hyperinsulinemia and hyperlipidemia resulting in discontinuation of metformin. A few months later, hyperinsulinemia and liver dysfunction reappeared, and metformin treatment was reinitiated. An intelligence test (WISC-IV) at 12 yr of age demonstrated that his full-scale intelligence quotient was 58, indicating slightly retarded mental development with mild intellectual disability. At the time of writing this report, he was 16 yr and 4 mo of age and has received metreleptin therapy for approximately 4 yr.', 'Case 1': 'The female patient was born to non-consanguineous Japanese parents at 38 wk of gestational age. Poor weight gain was seen during a health checkup at 3 mo of age, and her parents consulted a pediatrician. Physical examination showed a generalized reduction in the subcutaneous adipose tissue with marked hepatomegaly. Laboratory analysis revealed notable hyperinsulinemia and hypertriglyceridemia. Generalized lipoatrophy was suspected and the patient was introduced to our department, Oita University Hospital at 5 mo of age. The characteristic physical findings of CGL were detected as shown in Table 1 Table 1. Physical manifestations and laboratory data for the siblings at their respective first clinical evaluations . Cardiac ultrasonography demonstrated hypertrophic cardiomyopathy. The serum leptin concentration was markedly low (0.9 ng/mL) ( 13 ). Genetic testing revealed compound heterozygous pathogenic variants of BSCL2 gene; the already reported variant (c.823C>T) and the unreported variant (c.576C>A). She was therefore diagnosed with CGL (Berardinelli-Seip syndrome). The clinical course is shown in Fig. 1A Fig. 1. Clinical courses of the siblings. (A) Case 1 and (B) Case 2. Each figure shows the serial data or parameters. The upper portions show the physical symptoms of CGL and its medical interventions. The middle portions show the serum triglyceride (TG), IRI, and HbA1c levels. The lower portions show the oral glucose tolerance test (OGTT) data. . At 5 mo of age, dietary management was initiated for calorie and lipid restriction (calorie 90 Cal/kg/d; carbohydrate 55%, lipid 20%, protein 20%). At 2 yr and 6 mo of age, metformin treatment (500 mg/d: 30 mg/kg/d) commenced because of marked insulin resistance with hepatic dysfunction. Metformin treatment seemed effective for insulin resistance ( Fig. 1A . OGTT①②). At approximately 4 yr of age, obstructive sleep apnea, which is known as a characteristic complication of CGL appeared, and insulin resistance and lipid metabolism also worsened. Artificial respiratory support for continuous positive airway pressure was introduced, which stabilized her sleeping status with stable oxygenation. Her glucose metabolism with insulin resistance then partially improved ( Fig. 1A . OGTT③④). At the beginning of puberty (approximately 10 yr of age), hyperglycemia with hyperinsulinemia gradually deteriorated and the oral glucose tolerance test (OGTT) showed diabetic glucose response (Fig. 1A.OGTT⑤). At 11 yr and 5 mo of age, she was enrolled in a clinical trial of metreleptin. Metreleptin treatment was initiated at a dose of 0.06 mg/kg/d. Marked effectiveness of metreleptin appeared as early as 1 mo after the initiation, and metformin treatment was discontinued. Based on the results of the metreleptin trial, treatment with metreleptin was approved in 2013. Continuous treatment had consistent effects on patient’s glucose and fat metabolism. At approximately 13 yr of age, she sometimes had insomnia, headaches, and abdominal pains, followed by aggravation of her HbA1c and triglyceride levels, due to stressful relationship with her friends. Oral administration of metformin was then resumed, and socio-psychological counseling by a child psychiatrist was initiated. Her glycolipid metabolism status fluctuated according to her psychological state that is in line with her school year, and combined management with metreleptin, metformin, dietary therapy, and socio-psychological intervention were continued. As a result, the headaches and insomnia gradually decreased, and there was also an improvement in her glycolipid metabolism. Anti-metreleptin antibodies were detected (titer: 1:25) at 14 yr and 4 mo old. At 14 yr and 8 mo of age, Kauffman therapy was initiated due to irregular menstruation. At 18 yr and 8 mo of age and 7 yr after the commencement of metreleptin therapy, she began receiving metreleptin (3.8 mg/d), metformin (2250 mg/d), as well as dietary management to regulate the levels of calorie and lipid. Her height was 154 cm, weight 48 kg, and her HbA1c level was 6.0% in a stable state. She graduated from high school and entered the university without apparent hindrance in her daily life.'}
|
Respiratory-System
|
RESP
|
[
"obstructive sleep apnea"
] |
6801357
|
{'Case 2': 'The male patient who was born at 36 wk of gestational age was the younger (3 yr younger) brother of case 1. He also showed apparent reduction of the subcutaneous adipose tissue at 1 mo of age. At that time, he already had characteristic symptoms of CGL, including an inverted triangular face, sparse subcutaneous tissue, and hepatomegaly. Laboratory examination demonstrated extremely high triglyceride level and low leptin level ( Table 1 ). Compound heterozygous variants of BSCL2 gene were identified; these were identical to the gene variants found in his sister. The clinical course is shown in Fig. 1B . Serum triglyceride and insulin levels increased to more than 2000 mg/dL and 700 μU/mL, respectively, at 2 mo of age. Following this, low-fat dietary formula was introduced (calories, 350 Cal/d; fat ratio, 20%). Metformin therapy was initiated at 7 mo of age (250 mg/d). At approximately 1 yr of age, when he started eating solid foods, hyperlipidemia and hyperinsulinemia resolved. Thereafter, his examination findings remained relatively stable for approximately 10 yr under management with nutritional and metformin therapies. His insulin resistance worsened and his triglyceride level increased during puberty ( Fig. 1B . OGTT③). At 11 yr and 6 mo of age, metreleptin was introduced at a dose of 0.04 mg/kg/d, and there was an immediate improvement of hyperinsulinemia and hyperlipidemia resulting in discontinuation of metformin. A few months later, hyperinsulinemia and liver dysfunction reappeared, and metformin treatment was reinitiated. An intelligence test (WISC-IV) at 12 yr of age demonstrated that his full-scale intelligence quotient was 58, indicating slightly retarded mental development with mild intellectual disability. At the time of writing this report, he was 16 yr and 4 mo of age and has received metreleptin therapy for approximately 4 yr.', 'Case 1': 'The female patient was born to non-consanguineous Japanese parents at 38 wk of gestational age. Poor weight gain was seen during a health checkup at 3 mo of age, and her parents consulted a pediatrician. Physical examination showed a generalized reduction in the subcutaneous adipose tissue with marked hepatomegaly. Laboratory analysis revealed notable hyperinsulinemia and hypertriglyceridemia. Generalized lipoatrophy was suspected and the patient was introduced to our department, Oita University Hospital at 5 mo of age. The characteristic physical findings of CGL were detected as shown in Table 1 Table 1. Physical manifestations and laboratory data for the siblings at their respective first clinical evaluations . Cardiac ultrasonography demonstrated hypertrophic cardiomyopathy. The serum leptin concentration was markedly low (0.9 ng/mL) ( 13 ). Genetic testing revealed compound heterozygous pathogenic variants of BSCL2 gene; the already reported variant (c.823C>T) and the unreported variant (c.576C>A). She was therefore diagnosed with CGL (Berardinelli-Seip syndrome). The clinical course is shown in Fig. 1A Fig. 1. Clinical courses of the siblings. (A) Case 1 and (B) Case 2. Each figure shows the serial data or parameters. The upper portions show the physical symptoms of CGL and its medical interventions. The middle portions show the serum triglyceride (TG), IRI, and HbA1c levels. The lower portions show the oral glucose tolerance test (OGTT) data. . At 5 mo of age, dietary management was initiated for calorie and lipid restriction (calorie 90 Cal/kg/d; carbohydrate 55%, lipid 20%, protein 20%). At 2 yr and 6 mo of age, metformin treatment (500 mg/d: 30 mg/kg/d) commenced because of marked insulin resistance with hepatic dysfunction. Metformin treatment seemed effective for insulin resistance ( Fig. 1A . OGTT①②). At approximately 4 yr of age, obstructive sleep apnea, which is known as a characteristic complication of CGL appeared, and insulin resistance and lipid metabolism also worsened. Artificial respiratory support for continuous positive airway pressure was introduced, which stabilized her sleeping status with stable oxygenation. Her glucose metabolism with insulin resistance then partially improved ( Fig. 1A . OGTT③④). At the beginning of puberty (approximately 10 yr of age), hyperglycemia with hyperinsulinemia gradually deteriorated and the oral glucose tolerance test (OGTT) showed diabetic glucose response (Fig. 1A.OGTT⑤). At 11 yr and 5 mo of age, she was enrolled in a clinical trial of metreleptin. Metreleptin treatment was initiated at a dose of 0.06 mg/kg/d. Marked effectiveness of metreleptin appeared as early as 1 mo after the initiation, and metformin treatment was discontinued. Based on the results of the metreleptin trial, treatment with metreleptin was approved in 2013. Continuous treatment had consistent effects on patient’s glucose and fat metabolism. At approximately 13 yr of age, she sometimes had insomnia, headaches, and abdominal pains, followed by aggravation of her HbA1c and triglyceride levels, due to stressful relationship with her friends. Oral administration of metformin was then resumed, and socio-psychological counseling by a child psychiatrist was initiated. Her glycolipid metabolism status fluctuated according to her psychological state that is in line with her school year, and combined management with metreleptin, metformin, dietary therapy, and socio-psychological intervention were continued. As a result, the headaches and insomnia gradually decreased, and there was also an improvement in her glycolipid metabolism. Anti-metreleptin antibodies were detected (titer: 1:25) at 14 yr and 4 mo old. At 14 yr and 8 mo of age, Kauffman therapy was initiated due to irregular menstruation. At 18 yr and 8 mo of age and 7 yr after the commencement of metreleptin therapy, she began receiving metreleptin (3.8 mg/d), metformin (2250 mg/d), as well as dietary management to regulate the levels of calorie and lipid. Her height was 154 cm, weight 48 kg, and her HbA1c level was 6.0% in a stable state. She graduated from high school and entered the university without apparent hindrance in her daily life.'}
|
{'Case 2': 'The male patient who was born at 36 wk of gestational age was the younger (3 yr younger) brother of case 1. He also showed apparent reduction of the subcutaneous adipose tissue at 1 mo of age. At that time, he already had characteristic symptoms of CGL, including an inverted triangular face, sparse subcutaneous tissue, and hepatomegaly. Laboratory examination demonstrated extremely high triglyceride level and low leptin level ( Table 1 ). Compound heterozygous variants of BSCL2 gene were identified; these were identical to the gene variants found in his sister. The clinical course is shown in Fig. 1B . Serum triglyceride and insulin levels increased to more than 2000 mg/dL and 700 μU/mL, respectively, at 2 mo of age. Following this, low-fat dietary formula was introduced (calories, 350 Cal/d; fat ratio, 20%). Metformin therapy was initiated at 7 mo of age (250 mg/d). At approximately 1 yr of age, when he started eating solid foods, hyperlipidemia and hyperinsulinemia resolved. Thereafter, his examination findings remained relatively stable for approximately 10 yr under management with nutritional and metformin therapies. His insulin resistance worsened and his triglyceride level increased during puberty ( Fig. 1B . OGTT③). At 11 yr and 6 mo of age, metreleptin was introduced at a dose of 0.04 mg/kg/d, and there was an immediate improvement of hyperinsulinemia and hyperlipidemia resulting in discontinuation of metformin. A few months later, hyperinsulinemia and liver dysfunction reappeared, and metformin treatment was reinitiated. An intelligence test (WISC-IV) at 12 yr of age demonstrated that his full-scale intelligence quotient was 58, indicating slightly retarded mental development with mild intellectual disability. At the time of writing this report, he was 16 yr and 4 mo of age and has received metreleptin therapy for approximately 4 yr.', 'Case 1': 'The female patient was born to non-consanguineous Japanese parents at 38 wk of gestational age. Poor weight gain was seen during a health checkup at 3 mo of age, and her parents consulted a pediatrician. Physical examination showed a generalized reduction in the subcutaneous adipose tissue with marked hepatomegaly. Laboratory analysis revealed notable hyperinsulinemia and hypertriglyceridemia. Generalized lipoatrophy was suspected and the patient was introduced to our department, Oita University Hospital at 5 mo of age. The characteristic physical findings of CGL were detected as shown in Table 1 Table 1. Physical manifestations and laboratory data for the siblings at their respective first clinical evaluations . Cardiac ultrasonography demonstrated hypertrophic cardiomyopathy. The serum leptin concentration was markedly low (0.9 ng/mL) ( 13 ). Genetic testing revealed compound heterozygous pathogenic variants of BSCL2 gene; the already reported variant (c.823C>T) and the unreported variant (c.576C>A). She was therefore diagnosed with CGL (Berardinelli-Seip syndrome). The clinical course is shown in Fig. 1A Fig. 1. Clinical courses of the siblings. (A) Case 1 and (B) Case 2. Each figure shows the serial data or parameters. The upper portions show the physical symptoms of CGL and its medical interventions. The middle portions show the serum triglyceride (TG), IRI, and HbA1c levels. The lower portions show the oral glucose tolerance test (OGTT) data. . At 5 mo of age, dietary management was initiated for calorie and lipid restriction (calorie 90 Cal/kg/d; carbohydrate 55%, lipid 20%, protein 20%). At 2 yr and 6 mo of age, metformin treatment (500 mg/d: 30 mg/kg/d) commenced because of marked insulin resistance with hepatic dysfunction. Metformin treatment seemed effective for insulin resistance ( Fig. 1A . OGTT①②). At approximately 4 yr of age, obstructive sleep apnea, which is known as a characteristic complication of CGL appeared, and insulin resistance and lipid metabolism also worsened. Artificial respiratory support for continuous positive airway pressure was introduced, which stabilized her sleeping status with stable oxygenation. Her glucose metabolism with insulin resistance then partially improved ( Fig. 1A . OGTT③④). At the beginning of puberty (approximately 10 yr of age), hyperglycemia with hyperinsulinemia gradually deteriorated and the oral glucose tolerance test (OGTT) showed diabetic glucose response (Fig. 1A.OGTT⑤). At 11 yr and 5 mo of age, she was enrolled in a clinical trial of metreleptin. Metreleptin treatment was initiated at a dose of 0.06 mg/kg/d. Marked effectiveness of metreleptin appeared as early as 1 mo after the initiation, and metformin treatment was discontinued. Based on the results of the metreleptin trial, treatment with metreleptin was approved in 2013. Continuous treatment had consistent effects on patient’s glucose and fat metabolism. At approximately 13 yr of age, she sometimes had insomnia, headaches, and abdominal pains, followed by aggravation of her HbA1c and triglyceride levels, due to stressful relationship with her friends. Oral administration of metformin was then resumed, and socio-psychological counseling by a child psychiatrist was initiated. Her glycolipid metabolism status fluctuated according to her psychological state that is in line with her school year, and combined management with metreleptin, metformin, dietary therapy, and socio-psychological intervention were continued. As a result, the headaches and insomnia gradually decreased, and there was also an improvement in her glycolipid metabolism. Anti-metreleptin antibodies were detected (titer: 1:25) at 14 yr and 4 mo old. At 14 yr and 8 mo of age, Kauffman therapy was initiated due to irregular menstruation. At 18 yr and 8 mo of age and 7 yr after the commencement of metreleptin therapy, she began receiving metreleptin (3.8 mg/d), metformin (2250 mg/d), as well as dietary management to regulate the levels of calorie and lipid. Her height was 154 cm, weight 48 kg, and her HbA1c level was 6.0% in a stable state. She graduated from high school and entered the university without apparent hindrance in her daily life.'}
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Musculoskeletal-System
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MSK
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