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test-1901
|
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.'}
|
Eyes-Ears-Nose-Throat
|
EENT
|
[] |
test-1902
|
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.'}
|
Dermatology
|
DERM
|
[
"apparent reduction of the subcutaneous adipose tissue",
"inverted triangular face, sparse subcutaneous tissue",
"generalized reduction in the subcutaneous adipose tissue"
] |
test-1903
|
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.'}
|
Pregnancy
|
Pregnancy
|
[
"born at 36 wk of gestational age",
"born to non - consanguineous Japanese parents at 38 wk of gestational age"
] |
test-1904
|
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.'}
|
Lymphatic-System
|
LYMPH
|
[] |
test-1905
|
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.'}
|
Age-at-Presentation
|
Age (at case presentation)
|
[
"16 yr and 4 mo of age"
] |
test-1906
|
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.'}
|
Age-of-Onset
|
Age (of onset)
|
[
"1 mo of age .",
"3 mo of age"
] |
test-1907
|
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.'}
|
Confirmed-Diagnosis-IEM
|
Confirmed_Diagnosis(IEM)
|
[
"CGL",
"She was therefore diagnosed with CGL ( Berardinelli - Seip syndrome ) ."
] |
test-1908
|
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.'}
|
IEM-Treatment
|
IEM_Treatment
|
[
"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",
"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"
] |
test-1909
|
6177667
|
{'Case report': 'This research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenants of the Helsinki declaration, and has been approved by the author\'s or equivalent committee. Informed consent was obtained from the parents of the patients. The proband was a male born to consanguineous parents ( Fig. 1 ). He had an acute viral fever at 4 years of age, and was found to have mild hyponatremia and hyperkalemia (sodium 131 mEq/L and potassium 6.1 mEq/L, respectively). Further investigation revealed increased 17-hydroxyprogesterone (17-OHP) and adrenocorticotropic hormone (ACTH) levels ( Table 1 ), and a suboptimal rise in cortisol levels following ACTH1-24 stimulation (13.4 μg/dL after 60 minutes). At the time of diagnosis proband was of normal growth and stature (height=107 cm, z -score=-0.4, 32nd percentile; weight=20.8 kg, z -score=+0.8, 80th percentile; body mass index=18.2 kg/m 2 ). Treatment was thus begun for presumed salt wasting (SW) CAH using replacement doses of hydrocortisone and fludrocortisone. He had normal male genitalia, descended testes, and no evidence of precocious adrenarche or puberty. He was seen by various providers sporadically over the years, and finally was reviewed in our pediatric endocrinology clinic at 17 years of age. He was on subphysiologic hydrocortisone replacement (7.7 mg/m 2 /day) as well as fludrocortisone (0.2 mg per day), without any symptoms, no history of prostration with illness, and normally-timed pubertal changes. He was obese with normal stature (height=170 cm, z -score=-0.8, 21st percentile; weight=110 kg, z -score=+2.4, 99th percentile; BMI=38.1 kg/m 2 ), and had normal testes with Tanner stage V pubic hair. After his diagnosis, the 3-year-old sister was screened for increased 17-OHP and ACTH levels, which were found to be mildly elevated ( Table 2 ). At the time of her diagnosis she was also of normal growth and stature (height=94 cm, z -score=-0.05, 48th percentile; weight=14 kg, z -score=0.03, 51st percentile; BMI=15.8 kg/m 2 ). She was also started on physiologic doses of hydrocortisone after ACTH1-24 -stimulation showed suboptimal rise in cortisol levels (13.12 μg/dL after 60 minutes). She also presented to us in the Pediatric Endocrinology clinic at the age of 15 and 11 months, on subphysiologic hydrocortisone replacement (8.33 g/m 2 /day), with no history of virilization, precocious puberty or prostration with illness. She was obese (height=158 m, z -score=-0.7, 23rd percentile; weight=73.6 kg, z -score=1.4, 92nd percentile; BMI=29.5 kg/m 2 ), with no hirsutism and normal female genitalia (Tanner V breasts and pubic hair). We questioned the diagnosis of SW CAH, since they were both asymptomatic on subphysiologic hydrocortisone replacement. Work up revealed normal serum electrolytes, mildly increased ACTH and stimulated 17-OHP levels, which when combined with the lack of any symptoms, led us to suspect NC CAH ( Tables 1, 2 ).Thus samples were taken from the family and sent for molecular testing. Participants were tested for the presence of mutation(s) within the CYP21A2 gene and large rearrangements between CYP21A2 and the CYP21A1P pseudogene. The method used was sequencing and multiplex ligation-dependent probe amplification. Molecular testing revealed that the proband had one deleted copy of CYP21A2, whereas the other copy harbored a likely pathogenic sequence variant (c.748C>T, p.R124C). The p.R124C variant has been reported previously in an individual with a diagnosis of CAH. Previous functional studies indicated that this variant has approximately 16% residual activity. The arginine (R) at this position is highly conserved across species and there is a large physicochemical difference between arginine (R) and cysteine (C). In silico analysis, based on SIFT, PolyPhen-2, MutationTaster, and Align GVGD suggests that this variant might affect protein function based on the amino acid change. SIFT categorized these changes as damaging. PolyPhen-2 scored it as probably damaging with HumDiv and HumVar scores of 1.000 and 0.997, respectively (scale: 0.000 – not damaging – to 1.000 – damaging). MutationTaster classified it as "disease causing" with a score of 180 (scale: 0.0 – not disease causing – to 215 – disease causing). Finally, AlignGVGD gave it a GD score of 70.97, which puts it into the most "likely damaging" prediction Class C65 (scale: Class C0 – not damaging – to C65 – most likely to be damaging). Taken together, these findings suggested that p.R124C is likely pathogenic. If p.R124C is pathogenic, the most likely phenotype due to compound heterozygosity for p.R124C and a large deletion would be NC CAH. The proband’s sister had the same genotype. To our surprise, family studies indicated that the father had the same genotype as the 2 children, with one copy deleted and the other harboring the p.R124C mutation. The mother was heterozygous for the large deletion. Therefore, a diagnosis of NC CAH was confirmed, and consequently, we discontinued the current treatment regimen, with regular follow-up visits. Both siblings remain asymptomatic without medication, with mild, expected laboratory derangements, proband’s sister had a 17-OHP levels (9,072 ng/dL) 1 year after the cessation of medication. Follow-up testing could not be performed on the proband.'}
|
{'Case report': 'This research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenants of the Helsinki declaration, and has been approved by the author\'s or equivalent committee. Informed consent was obtained from the parents of the patients. The proband was a male born to consanguineous parents ( Fig. 1 ). He had an acute viral fever at 4 years of age, and was found to have mild hyponatremia and hyperkalemia (sodium 131 mEq/L and potassium 6.1 mEq/L, respectively). Further investigation revealed increased 17-hydroxyprogesterone (17-OHP) and adrenocorticotropic hormone (ACTH) levels ( Table 1 ), and a suboptimal rise in cortisol levels following ACTH1-24 stimulation (13.4 μg/dL after 60 minutes). At the time of diagnosis proband was of normal growth and stature (height=107 cm, z -score=-0.4, 32nd percentile; weight=20.8 kg, z -score=+0.8, 80th percentile; body mass index=18.2 kg/m 2 ). Treatment was thus begun for presumed salt wasting (SW) CAH using replacement doses of hydrocortisone and fludrocortisone. He had normal male genitalia, descended testes, and no evidence of precocious adrenarche or puberty. He was seen by various providers sporadically over the years, and finally was reviewed in our pediatric endocrinology clinic at 17 years of age. He was on subphysiologic hydrocortisone replacement (7.7 mg/m 2 /day) as well as fludrocortisone (0.2 mg per day), without any symptoms, no history of prostration with illness, and normally-timed pubertal changes. He was obese with normal stature (height=170 cm, z -score=-0.8, 21st percentile; weight=110 kg, z -score=+2.4, 99th percentile; BMI=38.1 kg/m 2 ), and had normal testes with Tanner stage V pubic hair. After his diagnosis, the 3-year-old sister was screened for increased 17-OHP and ACTH levels, which were found to be mildly elevated ( Table 2 ). At the time of her diagnosis she was also of normal growth and stature (height=94 cm, z -score=-0.05, 48th percentile; weight=14 kg, z -score=0.03, 51st percentile; BMI=15.8 kg/m 2 ). She was also started on physiologic doses of hydrocortisone after ACTH1-24 -stimulation showed suboptimal rise in cortisol levels (13.12 μg/dL after 60 minutes). She also presented to us in the Pediatric Endocrinology clinic at the age of 15 and 11 months, on subphysiologic hydrocortisone replacement (8.33 g/m 2 /day), with no history of virilization, precocious puberty or prostration with illness. She was obese (height=158 m, z -score=-0.7, 23rd percentile; weight=73.6 kg, z -score=1.4, 92nd percentile; BMI=29.5 kg/m 2 ), with no hirsutism and normal female genitalia (Tanner V breasts and pubic hair). We questioned the diagnosis of SW CAH, since they were both asymptomatic on subphysiologic hydrocortisone replacement. Work up revealed normal serum electrolytes, mildly increased ACTH and stimulated 17-OHP levels, which when combined with the lack of any symptoms, led us to suspect NC CAH ( Tables 1, 2 ).Thus samples were taken from the family and sent for molecular testing. Participants were tested for the presence of mutation(s) within the CYP21A2 gene and large rearrangements between CYP21A2 and the CYP21A1P pseudogene. The method used was sequencing and multiplex ligation-dependent probe amplification. Molecular testing revealed that the proband had one deleted copy of CYP21A2, whereas the other copy harbored a likely pathogenic sequence variant (c.748C>T, p.R124C). The p.R124C variant has been reported previously in an individual with a diagnosis of CAH. Previous functional studies indicated that this variant has approximately 16% residual activity. The arginine (R) at this position is highly conserved across species and there is a large physicochemical difference between arginine (R) and cysteine (C). In silico analysis, based on SIFT, PolyPhen-2, MutationTaster, and Align GVGD suggests that this variant might affect protein function based on the amino acid change. SIFT categorized these changes as damaging. PolyPhen-2 scored it as probably damaging with HumDiv and HumVar scores of 1.000 and 0.997, respectively (scale: 0.000 – not damaging – to 1.000 – damaging). MutationTaster classified it as "disease causing" with a score of 180 (scale: 0.0 – not disease causing – to 215 – disease causing). Finally, AlignGVGD gave it a GD score of 70.97, which puts it into the most "likely damaging" prediction Class C65 (scale: Class C0 – not damaging – to C65 – most likely to be damaging). Taken together, these findings suggested that p.R124C is likely pathogenic. If p.R124C is pathogenic, the most likely phenotype due to compound heterozygosity for p.R124C and a large deletion would be NC CAH. The proband’s sister had the same genotype. To our surprise, family studies indicated that the father had the same genotype as the 2 children, with one copy deleted and the other harboring the p.R124C mutation. The mother was heterozygous for the large deletion. Therefore, a diagnosis of NC CAH was confirmed, and consequently, we discontinued the current treatment regimen, with regular follow-up visits. Both siblings remain asymptomatic without medication, with mild, expected laboratory derangements, proband’s sister had a 17-OHP levels (9,072 ng/dL) 1 year after the cessation of medication. Follow-up testing could not be performed on the proband.'}
|
Vitals-and-Hematology
|
Vitals_Hema
|
[
"( height=107 cm, z -score=-0.4, 32nd percentile; weight=20.8 kg, z -score=+0.8, 80th percentile; body mass index=18.2 kg / m 2 )",
"height=170 cm, z -score=-0.8, 21st percentile; weight=110 kg, z -score=+2.4, 99th percentile; BMI=38.1 kg / m 2",
"height=94 cm, z -score=-0.05, 48th percentile; weight=14 kg, z -score=0.03, 51st percentile; BMI=15.8 kg / m 2",
"height=158 m, z -score=-0.7, 23rd percentile; weight=73.6 kg, z -score=1.4, 92nd percentile; BMI=29.5 kg / m 2"
] |
test-1910
|
6177667
|
{'Case report': 'This research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenants of the Helsinki declaration, and has been approved by the author\'s or equivalent committee. Informed consent was obtained from the parents of the patients. The proband was a male born to consanguineous parents ( Fig. 1 ). He had an acute viral fever at 4 years of age, and was found to have mild hyponatremia and hyperkalemia (sodium 131 mEq/L and potassium 6.1 mEq/L, respectively). Further investigation revealed increased 17-hydroxyprogesterone (17-OHP) and adrenocorticotropic hormone (ACTH) levels ( Table 1 ), and a suboptimal rise in cortisol levels following ACTH1-24 stimulation (13.4 μg/dL after 60 minutes). At the time of diagnosis proband was of normal growth and stature (height=107 cm, z -score=-0.4, 32nd percentile; weight=20.8 kg, z -score=+0.8, 80th percentile; body mass index=18.2 kg/m 2 ). Treatment was thus begun for presumed salt wasting (SW) CAH using replacement doses of hydrocortisone and fludrocortisone. He had normal male genitalia, descended testes, and no evidence of precocious adrenarche or puberty. He was seen by various providers sporadically over the years, and finally was reviewed in our pediatric endocrinology clinic at 17 years of age. He was on subphysiologic hydrocortisone replacement (7.7 mg/m 2 /day) as well as fludrocortisone (0.2 mg per day), without any symptoms, no history of prostration with illness, and normally-timed pubertal changes. He was obese with normal stature (height=170 cm, z -score=-0.8, 21st percentile; weight=110 kg, z -score=+2.4, 99th percentile; BMI=38.1 kg/m 2 ), and had normal testes with Tanner stage V pubic hair. After his diagnosis, the 3-year-old sister was screened for increased 17-OHP and ACTH levels, which were found to be mildly elevated ( Table 2 ). At the time of her diagnosis she was also of normal growth and stature (height=94 cm, z -score=-0.05, 48th percentile; weight=14 kg, z -score=0.03, 51st percentile; BMI=15.8 kg/m 2 ). She was also started on physiologic doses of hydrocortisone after ACTH1-24 -stimulation showed suboptimal rise in cortisol levels (13.12 μg/dL after 60 minutes). She also presented to us in the Pediatric Endocrinology clinic at the age of 15 and 11 months, on subphysiologic hydrocortisone replacement (8.33 g/m 2 /day), with no history of virilization, precocious puberty or prostration with illness. She was obese (height=158 m, z -score=-0.7, 23rd percentile; weight=73.6 kg, z -score=1.4, 92nd percentile; BMI=29.5 kg/m 2 ), with no hirsutism and normal female genitalia (Tanner V breasts and pubic hair). We questioned the diagnosis of SW CAH, since they were both asymptomatic on subphysiologic hydrocortisone replacement. Work up revealed normal serum electrolytes, mildly increased ACTH and stimulated 17-OHP levels, which when combined with the lack of any symptoms, led us to suspect NC CAH ( Tables 1, 2 ).Thus samples were taken from the family and sent for molecular testing. Participants were tested for the presence of mutation(s) within the CYP21A2 gene and large rearrangements between CYP21A2 and the CYP21A1P pseudogene. The method used was sequencing and multiplex ligation-dependent probe amplification. Molecular testing revealed that the proband had one deleted copy of CYP21A2, whereas the other copy harbored a likely pathogenic sequence variant (c.748C>T, p.R124C). The p.R124C variant has been reported previously in an individual with a diagnosis of CAH. Previous functional studies indicated that this variant has approximately 16% residual activity. The arginine (R) at this position is highly conserved across species and there is a large physicochemical difference between arginine (R) and cysteine (C). In silico analysis, based on SIFT, PolyPhen-2, MutationTaster, and Align GVGD suggests that this variant might affect protein function based on the amino acid change. SIFT categorized these changes as damaging. PolyPhen-2 scored it as probably damaging with HumDiv and HumVar scores of 1.000 and 0.997, respectively (scale: 0.000 – not damaging – to 1.000 – damaging). MutationTaster classified it as "disease causing" with a score of 180 (scale: 0.0 – not disease causing – to 215 – disease causing). Finally, AlignGVGD gave it a GD score of 70.97, which puts it into the most "likely damaging" prediction Class C65 (scale: Class C0 – not damaging – to C65 – most likely to be damaging). Taken together, these findings suggested that p.R124C is likely pathogenic. If p.R124C is pathogenic, the most likely phenotype due to compound heterozygosity for p.R124C and a large deletion would be NC CAH. The proband’s sister had the same genotype. To our surprise, family studies indicated that the father had the same genotype as the 2 children, with one copy deleted and the other harboring the p.R124C mutation. The mother was heterozygous for the large deletion. Therefore, a diagnosis of NC CAH was confirmed, and consequently, we discontinued the current treatment regimen, with regular follow-up visits. Both siblings remain asymptomatic without medication, with mild, expected laboratory derangements, proband’s sister had a 17-OHP levels (9,072 ng/dL) 1 year after the cessation of medication. Follow-up testing could not be performed on the proband.'}
|
{'Case report': 'This research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenants of the Helsinki declaration, and has been approved by the author\'s or equivalent committee. Informed consent was obtained from the parents of the patients. The proband was a male born to consanguineous parents ( Fig. 1 ). He had an acute viral fever at 4 years of age, and was found to have mild hyponatremia and hyperkalemia (sodium 131 mEq/L and potassium 6.1 mEq/L, respectively). Further investigation revealed increased 17-hydroxyprogesterone (17-OHP) and adrenocorticotropic hormone (ACTH) levels ( Table 1 ), and a suboptimal rise in cortisol levels following ACTH1-24 stimulation (13.4 μg/dL after 60 minutes). At the time of diagnosis proband was of normal growth and stature (height=107 cm, z -score=-0.4, 32nd percentile; weight=20.8 kg, z -score=+0.8, 80th percentile; body mass index=18.2 kg/m 2 ). Treatment was thus begun for presumed salt wasting (SW) CAH using replacement doses of hydrocortisone and fludrocortisone. He had normal male genitalia, descended testes, and no evidence of precocious adrenarche or puberty. He was seen by various providers sporadically over the years, and finally was reviewed in our pediatric endocrinology clinic at 17 years of age. He was on subphysiologic hydrocortisone replacement (7.7 mg/m 2 /day) as well as fludrocortisone (0.2 mg per day), without any symptoms, no history of prostration with illness, and normally-timed pubertal changes. He was obese with normal stature (height=170 cm, z -score=-0.8, 21st percentile; weight=110 kg, z -score=+2.4, 99th percentile; BMI=38.1 kg/m 2 ), and had normal testes with Tanner stage V pubic hair. After his diagnosis, the 3-year-old sister was screened for increased 17-OHP and ACTH levels, which were found to be mildly elevated ( Table 2 ). At the time of her diagnosis she was also of normal growth and stature (height=94 cm, z -score=-0.05, 48th percentile; weight=14 kg, z -score=0.03, 51st percentile; BMI=15.8 kg/m 2 ). She was also started on physiologic doses of hydrocortisone after ACTH1-24 -stimulation showed suboptimal rise in cortisol levels (13.12 μg/dL after 60 minutes). She also presented to us in the Pediatric Endocrinology clinic at the age of 15 and 11 months, on subphysiologic hydrocortisone replacement (8.33 g/m 2 /day), with no history of virilization, precocious puberty or prostration with illness. She was obese (height=158 m, z -score=-0.7, 23rd percentile; weight=73.6 kg, z -score=1.4, 92nd percentile; BMI=29.5 kg/m 2 ), with no hirsutism and normal female genitalia (Tanner V breasts and pubic hair). We questioned the diagnosis of SW CAH, since they were both asymptomatic on subphysiologic hydrocortisone replacement. Work up revealed normal serum electrolytes, mildly increased ACTH and stimulated 17-OHP levels, which when combined with the lack of any symptoms, led us to suspect NC CAH ( Tables 1, 2 ).Thus samples were taken from the family and sent for molecular testing. Participants were tested for the presence of mutation(s) within the CYP21A2 gene and large rearrangements between CYP21A2 and the CYP21A1P pseudogene. The method used was sequencing and multiplex ligation-dependent probe amplification. Molecular testing revealed that the proband had one deleted copy of CYP21A2, whereas the other copy harbored a likely pathogenic sequence variant (c.748C>T, p.R124C). The p.R124C variant has been reported previously in an individual with a diagnosis of CAH. Previous functional studies indicated that this variant has approximately 16% residual activity. The arginine (R) at this position is highly conserved across species and there is a large physicochemical difference between arginine (R) and cysteine (C). In silico analysis, based on SIFT, PolyPhen-2, MutationTaster, and Align GVGD suggests that this variant might affect protein function based on the amino acid change. SIFT categorized these changes as damaging. PolyPhen-2 scored it as probably damaging with HumDiv and HumVar scores of 1.000 and 0.997, respectively (scale: 0.000 – not damaging – to 1.000 – damaging). MutationTaster classified it as "disease causing" with a score of 180 (scale: 0.0 – not disease causing – to 215 – disease causing). Finally, AlignGVGD gave it a GD score of 70.97, which puts it into the most "likely damaging" prediction Class C65 (scale: Class C0 – not damaging – to C65 – most likely to be damaging). Taken together, these findings suggested that p.R124C is likely pathogenic. If p.R124C is pathogenic, the most likely phenotype due to compound heterozygosity for p.R124C and a large deletion would be NC CAH. The proband’s sister had the same genotype. To our surprise, family studies indicated that the father had the same genotype as the 2 children, with one copy deleted and the other harboring the p.R124C mutation. The mother was heterozygous for the large deletion. Therefore, a diagnosis of NC CAH was confirmed, and consequently, we discontinued the current treatment regimen, with regular follow-up visits. Both siblings remain asymptomatic without medication, with mild, expected laboratory derangements, proband’s sister had a 17-OHP levels (9,072 ng/dL) 1 year after the cessation of medication. Follow-up testing could not be performed on the proband.'}
|
Gastrointestinal-System
|
GI
|
[] |
test-1911
|
6177667
|
{'Case report': 'This research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenants of the Helsinki declaration, and has been approved by the author\'s or equivalent committee. Informed consent was obtained from the parents of the patients. The proband was a male born to consanguineous parents ( Fig. 1 ). He had an acute viral fever at 4 years of age, and was found to have mild hyponatremia and hyperkalemia (sodium 131 mEq/L and potassium 6.1 mEq/L, respectively). Further investigation revealed increased 17-hydroxyprogesterone (17-OHP) and adrenocorticotropic hormone (ACTH) levels ( Table 1 ), and a suboptimal rise in cortisol levels following ACTH1-24 stimulation (13.4 μg/dL after 60 minutes). At the time of diagnosis proband was of normal growth and stature (height=107 cm, z -score=-0.4, 32nd percentile; weight=20.8 kg, z -score=+0.8, 80th percentile; body mass index=18.2 kg/m 2 ). Treatment was thus begun for presumed salt wasting (SW) CAH using replacement doses of hydrocortisone and fludrocortisone. He had normal male genitalia, descended testes, and no evidence of precocious adrenarche or puberty. He was seen by various providers sporadically over the years, and finally was reviewed in our pediatric endocrinology clinic at 17 years of age. He was on subphysiologic hydrocortisone replacement (7.7 mg/m 2 /day) as well as fludrocortisone (0.2 mg per day), without any symptoms, no history of prostration with illness, and normally-timed pubertal changes. He was obese with normal stature (height=170 cm, z -score=-0.8, 21st percentile; weight=110 kg, z -score=+2.4, 99th percentile; BMI=38.1 kg/m 2 ), and had normal testes with Tanner stage V pubic hair. After his diagnosis, the 3-year-old sister was screened for increased 17-OHP and ACTH levels, which were found to be mildly elevated ( Table 2 ). At the time of her diagnosis she was also of normal growth and stature (height=94 cm, z -score=-0.05, 48th percentile; weight=14 kg, z -score=0.03, 51st percentile; BMI=15.8 kg/m 2 ). She was also started on physiologic doses of hydrocortisone after ACTH1-24 -stimulation showed suboptimal rise in cortisol levels (13.12 μg/dL after 60 minutes). She also presented to us in the Pediatric Endocrinology clinic at the age of 15 and 11 months, on subphysiologic hydrocortisone replacement (8.33 g/m 2 /day), with no history of virilization, precocious puberty or prostration with illness. She was obese (height=158 m, z -score=-0.7, 23rd percentile; weight=73.6 kg, z -score=1.4, 92nd percentile; BMI=29.5 kg/m 2 ), with no hirsutism and normal female genitalia (Tanner V breasts and pubic hair). We questioned the diagnosis of SW CAH, since they were both asymptomatic on subphysiologic hydrocortisone replacement. Work up revealed normal serum electrolytes, mildly increased ACTH and stimulated 17-OHP levels, which when combined with the lack of any symptoms, led us to suspect NC CAH ( Tables 1, 2 ).Thus samples were taken from the family and sent for molecular testing. Participants were tested for the presence of mutation(s) within the CYP21A2 gene and large rearrangements between CYP21A2 and the CYP21A1P pseudogene. The method used was sequencing and multiplex ligation-dependent probe amplification. Molecular testing revealed that the proband had one deleted copy of CYP21A2, whereas the other copy harbored a likely pathogenic sequence variant (c.748C>T, p.R124C). The p.R124C variant has been reported previously in an individual with a diagnosis of CAH. Previous functional studies indicated that this variant has approximately 16% residual activity. The arginine (R) at this position is highly conserved across species and there is a large physicochemical difference between arginine (R) and cysteine (C). In silico analysis, based on SIFT, PolyPhen-2, MutationTaster, and Align GVGD suggests that this variant might affect protein function based on the amino acid change. SIFT categorized these changes as damaging. PolyPhen-2 scored it as probably damaging with HumDiv and HumVar scores of 1.000 and 0.997, respectively (scale: 0.000 – not damaging – to 1.000 – damaging). MutationTaster classified it as "disease causing" with a score of 180 (scale: 0.0 – not disease causing – to 215 – disease causing). Finally, AlignGVGD gave it a GD score of 70.97, which puts it into the most "likely damaging" prediction Class C65 (scale: Class C0 – not damaging – to C65 – most likely to be damaging). Taken together, these findings suggested that p.R124C is likely pathogenic. If p.R124C is pathogenic, the most likely phenotype due to compound heterozygosity for p.R124C and a large deletion would be NC CAH. The proband’s sister had the same genotype. To our surprise, family studies indicated that the father had the same genotype as the 2 children, with one copy deleted and the other harboring the p.R124C mutation. The mother was heterozygous for the large deletion. Therefore, a diagnosis of NC CAH was confirmed, and consequently, we discontinued the current treatment regimen, with regular follow-up visits. Both siblings remain asymptomatic without medication, with mild, expected laboratory derangements, proband’s sister had a 17-OHP levels (9,072 ng/dL) 1 year after the cessation of medication. Follow-up testing could not be performed on the proband.'}
|
{'Case report': 'This research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenants of the Helsinki declaration, and has been approved by the author\'s or equivalent committee. Informed consent was obtained from the parents of the patients. The proband was a male born to consanguineous parents ( Fig. 1 ). He had an acute viral fever at 4 years of age, and was found to have mild hyponatremia and hyperkalemia (sodium 131 mEq/L and potassium 6.1 mEq/L, respectively). Further investigation revealed increased 17-hydroxyprogesterone (17-OHP) and adrenocorticotropic hormone (ACTH) levels ( Table 1 ), and a suboptimal rise in cortisol levels following ACTH1-24 stimulation (13.4 μg/dL after 60 minutes). At the time of diagnosis proband was of normal growth and stature (height=107 cm, z -score=-0.4, 32nd percentile; weight=20.8 kg, z -score=+0.8, 80th percentile; body mass index=18.2 kg/m 2 ). Treatment was thus begun for presumed salt wasting (SW) CAH using replacement doses of hydrocortisone and fludrocortisone. He had normal male genitalia, descended testes, and no evidence of precocious adrenarche or puberty. He was seen by various providers sporadically over the years, and finally was reviewed in our pediatric endocrinology clinic at 17 years of age. He was on subphysiologic hydrocortisone replacement (7.7 mg/m 2 /day) as well as fludrocortisone (0.2 mg per day), without any symptoms, no history of prostration with illness, and normally-timed pubertal changes. He was obese with normal stature (height=170 cm, z -score=-0.8, 21st percentile; weight=110 kg, z -score=+2.4, 99th percentile; BMI=38.1 kg/m 2 ), and had normal testes with Tanner stage V pubic hair. After his diagnosis, the 3-year-old sister was screened for increased 17-OHP and ACTH levels, which were found to be mildly elevated ( Table 2 ). At the time of her diagnosis she was also of normal growth and stature (height=94 cm, z -score=-0.05, 48th percentile; weight=14 kg, z -score=0.03, 51st percentile; BMI=15.8 kg/m 2 ). She was also started on physiologic doses of hydrocortisone after ACTH1-24 -stimulation showed suboptimal rise in cortisol levels (13.12 μg/dL after 60 minutes). She also presented to us in the Pediatric Endocrinology clinic at the age of 15 and 11 months, on subphysiologic hydrocortisone replacement (8.33 g/m 2 /day), with no history of virilization, precocious puberty or prostration with illness. She was obese (height=158 m, z -score=-0.7, 23rd percentile; weight=73.6 kg, z -score=1.4, 92nd percentile; BMI=29.5 kg/m 2 ), with no hirsutism and normal female genitalia (Tanner V breasts and pubic hair). We questioned the diagnosis of SW CAH, since they were both asymptomatic on subphysiologic hydrocortisone replacement. Work up revealed normal serum electrolytes, mildly increased ACTH and stimulated 17-OHP levels, which when combined with the lack of any symptoms, led us to suspect NC CAH ( Tables 1, 2 ).Thus samples were taken from the family and sent for molecular testing. Participants were tested for the presence of mutation(s) within the CYP21A2 gene and large rearrangements between CYP21A2 and the CYP21A1P pseudogene. The method used was sequencing and multiplex ligation-dependent probe amplification. Molecular testing revealed that the proband had one deleted copy of CYP21A2, whereas the other copy harbored a likely pathogenic sequence variant (c.748C>T, p.R124C). The p.R124C variant has been reported previously in an individual with a diagnosis of CAH. Previous functional studies indicated that this variant has approximately 16% residual activity. The arginine (R) at this position is highly conserved across species and there is a large physicochemical difference between arginine (R) and cysteine (C). In silico analysis, based on SIFT, PolyPhen-2, MutationTaster, and Align GVGD suggests that this variant might affect protein function based on the amino acid change. SIFT categorized these changes as damaging. PolyPhen-2 scored it as probably damaging with HumDiv and HumVar scores of 1.000 and 0.997, respectively (scale: 0.000 – not damaging – to 1.000 – damaging). MutationTaster classified it as "disease causing" with a score of 180 (scale: 0.0 – not disease causing – to 215 – disease causing). Finally, AlignGVGD gave it a GD score of 70.97, which puts it into the most "likely damaging" prediction Class C65 (scale: Class C0 – not damaging – to C65 – most likely to be damaging). Taken together, these findings suggested that p.R124C is likely pathogenic. If p.R124C is pathogenic, the most likely phenotype due to compound heterozygosity for p.R124C and a large deletion would be NC CAH. The proband’s sister had the same genotype. To our surprise, family studies indicated that the father had the same genotype as the 2 children, with one copy deleted and the other harboring the p.R124C mutation. The mother was heterozygous for the large deletion. Therefore, a diagnosis of NC CAH was confirmed, and consequently, we discontinued the current treatment regimen, with regular follow-up visits. Both siblings remain asymptomatic without medication, with mild, expected laboratory derangements, proband’s sister had a 17-OHP levels (9,072 ng/dL) 1 year after the cessation of medication. Follow-up testing could not be performed on the proband.'}
|
Patient-History
|
History
|
[
"The proband was a male born to consanguineous parents ( Fig. 1 ). He had an acute viral fever at 4 years of age, and was found to have mild hyponatremia and hyperkalemia ( sodium 131 mEq / L and potassium 6.1 mEq / L, respectively )",
"no history of prostration with illness, and normally - timed pubertal changes",
"the 3 - year - old sister was screened for increased 17 - OHP and ACTH levels, which were found to be mildly elevated",
"no history of virilization, precocious puberty or prostration with illness",
"family studies indicated that the father had the same genotype as the 2 children, with one copy deleted and the other harboring the p. R124C mutation. The mother was heterozygous for the large deletion."
] |
test-1912
|
6177667
|
{'Case report': 'This research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenants of the Helsinki declaration, and has been approved by the author\'s or equivalent committee. Informed consent was obtained from the parents of the patients. The proband was a male born to consanguineous parents ( Fig. 1 ). He had an acute viral fever at 4 years of age, and was found to have mild hyponatremia and hyperkalemia (sodium 131 mEq/L and potassium 6.1 mEq/L, respectively). Further investigation revealed increased 17-hydroxyprogesterone (17-OHP) and adrenocorticotropic hormone (ACTH) levels ( Table 1 ), and a suboptimal rise in cortisol levels following ACTH1-24 stimulation (13.4 μg/dL after 60 minutes). At the time of diagnosis proband was of normal growth and stature (height=107 cm, z -score=-0.4, 32nd percentile; weight=20.8 kg, z -score=+0.8, 80th percentile; body mass index=18.2 kg/m 2 ). Treatment was thus begun for presumed salt wasting (SW) CAH using replacement doses of hydrocortisone and fludrocortisone. He had normal male genitalia, descended testes, and no evidence of precocious adrenarche or puberty. He was seen by various providers sporadically over the years, and finally was reviewed in our pediatric endocrinology clinic at 17 years of age. He was on subphysiologic hydrocortisone replacement (7.7 mg/m 2 /day) as well as fludrocortisone (0.2 mg per day), without any symptoms, no history of prostration with illness, and normally-timed pubertal changes. He was obese with normal stature (height=170 cm, z -score=-0.8, 21st percentile; weight=110 kg, z -score=+2.4, 99th percentile; BMI=38.1 kg/m 2 ), and had normal testes with Tanner stage V pubic hair. After his diagnosis, the 3-year-old sister was screened for increased 17-OHP and ACTH levels, which were found to be mildly elevated ( Table 2 ). At the time of her diagnosis she was also of normal growth and stature (height=94 cm, z -score=-0.05, 48th percentile; weight=14 kg, z -score=0.03, 51st percentile; BMI=15.8 kg/m 2 ). She was also started on physiologic doses of hydrocortisone after ACTH1-24 -stimulation showed suboptimal rise in cortisol levels (13.12 μg/dL after 60 minutes). She also presented to us in the Pediatric Endocrinology clinic at the age of 15 and 11 months, on subphysiologic hydrocortisone replacement (8.33 g/m 2 /day), with no history of virilization, precocious puberty or prostration with illness. She was obese (height=158 m, z -score=-0.7, 23rd percentile; weight=73.6 kg, z -score=1.4, 92nd percentile; BMI=29.5 kg/m 2 ), with no hirsutism and normal female genitalia (Tanner V breasts and pubic hair). We questioned the diagnosis of SW CAH, since they were both asymptomatic on subphysiologic hydrocortisone replacement. Work up revealed normal serum electrolytes, mildly increased ACTH and stimulated 17-OHP levels, which when combined with the lack of any symptoms, led us to suspect NC CAH ( Tables 1, 2 ).Thus samples were taken from the family and sent for molecular testing. Participants were tested for the presence of mutation(s) within the CYP21A2 gene and large rearrangements between CYP21A2 and the CYP21A1P pseudogene. The method used was sequencing and multiplex ligation-dependent probe amplification. Molecular testing revealed that the proband had one deleted copy of CYP21A2, whereas the other copy harbored a likely pathogenic sequence variant (c.748C>T, p.R124C). The p.R124C variant has been reported previously in an individual with a diagnosis of CAH. Previous functional studies indicated that this variant has approximately 16% residual activity. The arginine (R) at this position is highly conserved across species and there is a large physicochemical difference between arginine (R) and cysteine (C). In silico analysis, based on SIFT, PolyPhen-2, MutationTaster, and Align GVGD suggests that this variant might affect protein function based on the amino acid change. SIFT categorized these changes as damaging. PolyPhen-2 scored it as probably damaging with HumDiv and HumVar scores of 1.000 and 0.997, respectively (scale: 0.000 – not damaging – to 1.000 – damaging). MutationTaster classified it as "disease causing" with a score of 180 (scale: 0.0 – not disease causing – to 215 – disease causing). Finally, AlignGVGD gave it a GD score of 70.97, which puts it into the most "likely damaging" prediction Class C65 (scale: Class C0 – not damaging – to C65 – most likely to be damaging). Taken together, these findings suggested that p.R124C is likely pathogenic. If p.R124C is pathogenic, the most likely phenotype due to compound heterozygosity for p.R124C and a large deletion would be NC CAH. The proband’s sister had the same genotype. To our surprise, family studies indicated that the father had the same genotype as the 2 children, with one copy deleted and the other harboring the p.R124C mutation. The mother was heterozygous for the large deletion. Therefore, a diagnosis of NC CAH was confirmed, and consequently, we discontinued the current treatment regimen, with regular follow-up visits. Both siblings remain asymptomatic without medication, with mild, expected laboratory derangements, proband’s sister had a 17-OHP levels (9,072 ng/dL) 1 year after the cessation of medication. Follow-up testing could not be performed on the proband.'}
|
{'Case report': 'This research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenants of the Helsinki declaration, and has been approved by the author\'s or equivalent committee. Informed consent was obtained from the parents of the patients. The proband was a male born to consanguineous parents ( Fig. 1 ). He had an acute viral fever at 4 years of age, and was found to have mild hyponatremia and hyperkalemia (sodium 131 mEq/L and potassium 6.1 mEq/L, respectively). Further investigation revealed increased 17-hydroxyprogesterone (17-OHP) and adrenocorticotropic hormone (ACTH) levels ( Table 1 ), and a suboptimal rise in cortisol levels following ACTH1-24 stimulation (13.4 μg/dL after 60 minutes). At the time of diagnosis proband was of normal growth and stature (height=107 cm, z -score=-0.4, 32nd percentile; weight=20.8 kg, z -score=+0.8, 80th percentile; body mass index=18.2 kg/m 2 ). Treatment was thus begun for presumed salt wasting (SW) CAH using replacement doses of hydrocortisone and fludrocortisone. He had normal male genitalia, descended testes, and no evidence of precocious adrenarche or puberty. He was seen by various providers sporadically over the years, and finally was reviewed in our pediatric endocrinology clinic at 17 years of age. He was on subphysiologic hydrocortisone replacement (7.7 mg/m 2 /day) as well as fludrocortisone (0.2 mg per day), without any symptoms, no history of prostration with illness, and normally-timed pubertal changes. He was obese with normal stature (height=170 cm, z -score=-0.8, 21st percentile; weight=110 kg, z -score=+2.4, 99th percentile; BMI=38.1 kg/m 2 ), and had normal testes with Tanner stage V pubic hair. After his diagnosis, the 3-year-old sister was screened for increased 17-OHP and ACTH levels, which were found to be mildly elevated ( Table 2 ). At the time of her diagnosis she was also of normal growth and stature (height=94 cm, z -score=-0.05, 48th percentile; weight=14 kg, z -score=0.03, 51st percentile; BMI=15.8 kg/m 2 ). She was also started on physiologic doses of hydrocortisone after ACTH1-24 -stimulation showed suboptimal rise in cortisol levels (13.12 μg/dL after 60 minutes). She also presented to us in the Pediatric Endocrinology clinic at the age of 15 and 11 months, on subphysiologic hydrocortisone replacement (8.33 g/m 2 /day), with no history of virilization, precocious puberty or prostration with illness. She was obese (height=158 m, z -score=-0.7, 23rd percentile; weight=73.6 kg, z -score=1.4, 92nd percentile; BMI=29.5 kg/m 2 ), with no hirsutism and normal female genitalia (Tanner V breasts and pubic hair). We questioned the diagnosis of SW CAH, since they were both asymptomatic on subphysiologic hydrocortisone replacement. Work up revealed normal serum electrolytes, mildly increased ACTH and stimulated 17-OHP levels, which when combined with the lack of any symptoms, led us to suspect NC CAH ( Tables 1, 2 ).Thus samples were taken from the family and sent for molecular testing. Participants were tested for the presence of mutation(s) within the CYP21A2 gene and large rearrangements between CYP21A2 and the CYP21A1P pseudogene. The method used was sequencing and multiplex ligation-dependent probe amplification. Molecular testing revealed that the proband had one deleted copy of CYP21A2, whereas the other copy harbored a likely pathogenic sequence variant (c.748C>T, p.R124C). The p.R124C variant has been reported previously in an individual with a diagnosis of CAH. Previous functional studies indicated that this variant has approximately 16% residual activity. The arginine (R) at this position is highly conserved across species and there is a large physicochemical difference between arginine (R) and cysteine (C). In silico analysis, based on SIFT, PolyPhen-2, MutationTaster, and Align GVGD suggests that this variant might affect protein function based on the amino acid change. SIFT categorized these changes as damaging. PolyPhen-2 scored it as probably damaging with HumDiv and HumVar scores of 1.000 and 0.997, respectively (scale: 0.000 – not damaging – to 1.000 – damaging). MutationTaster classified it as "disease causing" with a score of 180 (scale: 0.0 – not disease causing – to 215 – disease causing). Finally, AlignGVGD gave it a GD score of 70.97, which puts it into the most "likely damaging" prediction Class C65 (scale: Class C0 – not damaging – to C65 – most likely to be damaging). Taken together, these findings suggested that p.R124C is likely pathogenic. If p.R124C is pathogenic, the most likely phenotype due to compound heterozygosity for p.R124C and a large deletion would be NC CAH. The proband’s sister had the same genotype. To our surprise, family studies indicated that the father had the same genotype as the 2 children, with one copy deleted and the other harboring the p.R124C mutation. The mother was heterozygous for the large deletion. Therefore, a diagnosis of NC CAH was confirmed, and consequently, we discontinued the current treatment regimen, with regular follow-up visits. Both siblings remain asymptomatic without medication, with mild, expected laboratory derangements, proband’s sister had a 17-OHP levels (9,072 ng/dL) 1 year after the cessation of medication. Follow-up testing could not be performed on the proband.'}
|
Neurology
|
Neuro
|
[] |
test-1913
|
6177667
|
{'Case report': 'This research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenants of the Helsinki declaration, and has been approved by the author\'s or equivalent committee. Informed consent was obtained from the parents of the patients. The proband was a male born to consanguineous parents ( Fig. 1 ). He had an acute viral fever at 4 years of age, and was found to have mild hyponatremia and hyperkalemia (sodium 131 mEq/L and potassium 6.1 mEq/L, respectively). Further investigation revealed increased 17-hydroxyprogesterone (17-OHP) and adrenocorticotropic hormone (ACTH) levels ( Table 1 ), and a suboptimal rise in cortisol levels following ACTH1-24 stimulation (13.4 μg/dL after 60 minutes). At the time of diagnosis proband was of normal growth and stature (height=107 cm, z -score=-0.4, 32nd percentile; weight=20.8 kg, z -score=+0.8, 80th percentile; body mass index=18.2 kg/m 2 ). Treatment was thus begun for presumed salt wasting (SW) CAH using replacement doses of hydrocortisone and fludrocortisone. He had normal male genitalia, descended testes, and no evidence of precocious adrenarche or puberty. He was seen by various providers sporadically over the years, and finally was reviewed in our pediatric endocrinology clinic at 17 years of age. He was on subphysiologic hydrocortisone replacement (7.7 mg/m 2 /day) as well as fludrocortisone (0.2 mg per day), without any symptoms, no history of prostration with illness, and normally-timed pubertal changes. He was obese with normal stature (height=170 cm, z -score=-0.8, 21st percentile; weight=110 kg, z -score=+2.4, 99th percentile; BMI=38.1 kg/m 2 ), and had normal testes with Tanner stage V pubic hair. After his diagnosis, the 3-year-old sister was screened for increased 17-OHP and ACTH levels, which were found to be mildly elevated ( Table 2 ). At the time of her diagnosis she was also of normal growth and stature (height=94 cm, z -score=-0.05, 48th percentile; weight=14 kg, z -score=0.03, 51st percentile; BMI=15.8 kg/m 2 ). She was also started on physiologic doses of hydrocortisone after ACTH1-24 -stimulation showed suboptimal rise in cortisol levels (13.12 μg/dL after 60 minutes). She also presented to us in the Pediatric Endocrinology clinic at the age of 15 and 11 months, on subphysiologic hydrocortisone replacement (8.33 g/m 2 /day), with no history of virilization, precocious puberty or prostration with illness. She was obese (height=158 m, z -score=-0.7, 23rd percentile; weight=73.6 kg, z -score=1.4, 92nd percentile; BMI=29.5 kg/m 2 ), with no hirsutism and normal female genitalia (Tanner V breasts and pubic hair). We questioned the diagnosis of SW CAH, since they were both asymptomatic on subphysiologic hydrocortisone replacement. Work up revealed normal serum electrolytes, mildly increased ACTH and stimulated 17-OHP levels, which when combined with the lack of any symptoms, led us to suspect NC CAH ( Tables 1, 2 ).Thus samples were taken from the family and sent for molecular testing. Participants were tested for the presence of mutation(s) within the CYP21A2 gene and large rearrangements between CYP21A2 and the CYP21A1P pseudogene. The method used was sequencing and multiplex ligation-dependent probe amplification. Molecular testing revealed that the proband had one deleted copy of CYP21A2, whereas the other copy harbored a likely pathogenic sequence variant (c.748C>T, p.R124C). The p.R124C variant has been reported previously in an individual with a diagnosis of CAH. Previous functional studies indicated that this variant has approximately 16% residual activity. The arginine (R) at this position is highly conserved across species and there is a large physicochemical difference between arginine (R) and cysteine (C). In silico analysis, based on SIFT, PolyPhen-2, MutationTaster, and Align GVGD suggests that this variant might affect protein function based on the amino acid change. SIFT categorized these changes as damaging. PolyPhen-2 scored it as probably damaging with HumDiv and HumVar scores of 1.000 and 0.997, respectively (scale: 0.000 – not damaging – to 1.000 – damaging). MutationTaster classified it as "disease causing" with a score of 180 (scale: 0.0 – not disease causing – to 215 – disease causing). Finally, AlignGVGD gave it a GD score of 70.97, which puts it into the most "likely damaging" prediction Class C65 (scale: Class C0 – not damaging – to C65 – most likely to be damaging). Taken together, these findings suggested that p.R124C is likely pathogenic. If p.R124C is pathogenic, the most likely phenotype due to compound heterozygosity for p.R124C and a large deletion would be NC CAH. The proband’s sister had the same genotype. To our surprise, family studies indicated that the father had the same genotype as the 2 children, with one copy deleted and the other harboring the p.R124C mutation. The mother was heterozygous for the large deletion. Therefore, a diagnosis of NC CAH was confirmed, and consequently, we discontinued the current treatment regimen, with regular follow-up visits. Both siblings remain asymptomatic without medication, with mild, expected laboratory derangements, proband’s sister had a 17-OHP levels (9,072 ng/dL) 1 year after the cessation of medication. Follow-up testing could not be performed on the proband.'}
|
{'Case report': 'This research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenants of the Helsinki declaration, and has been approved by the author\'s or equivalent committee. Informed consent was obtained from the parents of the patients. The proband was a male born to consanguineous parents ( Fig. 1 ). He had an acute viral fever at 4 years of age, and was found to have mild hyponatremia and hyperkalemia (sodium 131 mEq/L and potassium 6.1 mEq/L, respectively). Further investigation revealed increased 17-hydroxyprogesterone (17-OHP) and adrenocorticotropic hormone (ACTH) levels ( Table 1 ), and a suboptimal rise in cortisol levels following ACTH1-24 stimulation (13.4 μg/dL after 60 minutes). At the time of diagnosis proband was of normal growth and stature (height=107 cm, z -score=-0.4, 32nd percentile; weight=20.8 kg, z -score=+0.8, 80th percentile; body mass index=18.2 kg/m 2 ). Treatment was thus begun for presumed salt wasting (SW) CAH using replacement doses of hydrocortisone and fludrocortisone. He had normal male genitalia, descended testes, and no evidence of precocious adrenarche or puberty. He was seen by various providers sporadically over the years, and finally was reviewed in our pediatric endocrinology clinic at 17 years of age. He was on subphysiologic hydrocortisone replacement (7.7 mg/m 2 /day) as well as fludrocortisone (0.2 mg per day), without any symptoms, no history of prostration with illness, and normally-timed pubertal changes. He was obese with normal stature (height=170 cm, z -score=-0.8, 21st percentile; weight=110 kg, z -score=+2.4, 99th percentile; BMI=38.1 kg/m 2 ), and had normal testes with Tanner stage V pubic hair. After his diagnosis, the 3-year-old sister was screened for increased 17-OHP and ACTH levels, which were found to be mildly elevated ( Table 2 ). At the time of her diagnosis she was also of normal growth and stature (height=94 cm, z -score=-0.05, 48th percentile; weight=14 kg, z -score=0.03, 51st percentile; BMI=15.8 kg/m 2 ). She was also started on physiologic doses of hydrocortisone after ACTH1-24 -stimulation showed suboptimal rise in cortisol levels (13.12 μg/dL after 60 minutes). She also presented to us in the Pediatric Endocrinology clinic at the age of 15 and 11 months, on subphysiologic hydrocortisone replacement (8.33 g/m 2 /day), with no history of virilization, precocious puberty or prostration with illness. She was obese (height=158 m, z -score=-0.7, 23rd percentile; weight=73.6 kg, z -score=1.4, 92nd percentile; BMI=29.5 kg/m 2 ), with no hirsutism and normal female genitalia (Tanner V breasts and pubic hair). We questioned the diagnosis of SW CAH, since they were both asymptomatic on subphysiologic hydrocortisone replacement. Work up revealed normal serum electrolytes, mildly increased ACTH and stimulated 17-OHP levels, which when combined with the lack of any symptoms, led us to suspect NC CAH ( Tables 1, 2 ).Thus samples were taken from the family and sent for molecular testing. Participants were tested for the presence of mutation(s) within the CYP21A2 gene and large rearrangements between CYP21A2 and the CYP21A1P pseudogene. The method used was sequencing and multiplex ligation-dependent probe amplification. Molecular testing revealed that the proband had one deleted copy of CYP21A2, whereas the other copy harbored a likely pathogenic sequence variant (c.748C>T, p.R124C). The p.R124C variant has been reported previously in an individual with a diagnosis of CAH. Previous functional studies indicated that this variant has approximately 16% residual activity. The arginine (R) at this position is highly conserved across species and there is a large physicochemical difference between arginine (R) and cysteine (C). In silico analysis, based on SIFT, PolyPhen-2, MutationTaster, and Align GVGD suggests that this variant might affect protein function based on the amino acid change. SIFT categorized these changes as damaging. PolyPhen-2 scored it as probably damaging with HumDiv and HumVar scores of 1.000 and 0.997, respectively (scale: 0.000 – not damaging – to 1.000 – damaging). MutationTaster classified it as "disease causing" with a score of 180 (scale: 0.0 – not disease causing – to 215 – disease causing). Finally, AlignGVGD gave it a GD score of 70.97, which puts it into the most "likely damaging" prediction Class C65 (scale: Class C0 – not damaging – to C65 – most likely to be damaging). Taken together, these findings suggested that p.R124C is likely pathogenic. If p.R124C is pathogenic, the most likely phenotype due to compound heterozygosity for p.R124C and a large deletion would be NC CAH. The proband’s sister had the same genotype. To our surprise, family studies indicated that the father had the same genotype as the 2 children, with one copy deleted and the other harboring the p.R124C mutation. The mother was heterozygous for the large deletion. Therefore, a diagnosis of NC CAH was confirmed, and consequently, we discontinued the current treatment regimen, with regular follow-up visits. Both siblings remain asymptomatic without medication, with mild, expected laboratory derangements, proband’s sister had a 17-OHP levels (9,072 ng/dL) 1 year after the cessation of medication. Follow-up testing could not be performed on the proband.'}
|
Laboratory-and-Imaging
|
Lab_Image
|
[
"mild hyponatremia and hyperkalemia ( sodium 131 mEq / L and potassium 6.1 mEq / L, respectively ). Further investigation revealed increased 17 - hydroxyprogesterone ( 17 - OHP ) and adrenocorticotropic hormone ( ACTH ) levels ( Table 1 ), and a suboptimal rise in cortisol levels following ACTH1 - 24 stimulation ( 13.4 μg / dL after 60 minutes )",
"screened for increased 17 - OHP and ACTH levels, which were found to be mildly elevated",
"ACTH1 - 24 -stimulation showed suboptimal rise in cortisol levels ( 13.12 μg / dL after 60 minutes )",
"normal serum electrolytes, mildly increased ACTH and stimulated 17 - OHP levels",
"Molecular testing revealed that the proband had one deleted copy of CYP21A2, whereas the other copy harbored a likely pathogenic sequence variant ( c.748C > T, p. R124C )",
"with mild, expected laboratory derangements, proband ’s sister had a 17 - OHP levels ( 9,072 ng / dL )"
] |
test-1914
|
6177667
|
{'Case report': 'This research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenants of the Helsinki declaration, and has been approved by the author\'s or equivalent committee. Informed consent was obtained from the parents of the patients. The proband was a male born to consanguineous parents ( Fig. 1 ). He had an acute viral fever at 4 years of age, and was found to have mild hyponatremia and hyperkalemia (sodium 131 mEq/L and potassium 6.1 mEq/L, respectively). Further investigation revealed increased 17-hydroxyprogesterone (17-OHP) and adrenocorticotropic hormone (ACTH) levels ( Table 1 ), and a suboptimal rise in cortisol levels following ACTH1-24 stimulation (13.4 μg/dL after 60 minutes). At the time of diagnosis proband was of normal growth and stature (height=107 cm, z -score=-0.4, 32nd percentile; weight=20.8 kg, z -score=+0.8, 80th percentile; body mass index=18.2 kg/m 2 ). Treatment was thus begun for presumed salt wasting (SW) CAH using replacement doses of hydrocortisone and fludrocortisone. He had normal male genitalia, descended testes, and no evidence of precocious adrenarche or puberty. He was seen by various providers sporadically over the years, and finally was reviewed in our pediatric endocrinology clinic at 17 years of age. He was on subphysiologic hydrocortisone replacement (7.7 mg/m 2 /day) as well as fludrocortisone (0.2 mg per day), without any symptoms, no history of prostration with illness, and normally-timed pubertal changes. He was obese with normal stature (height=170 cm, z -score=-0.8, 21st percentile; weight=110 kg, z -score=+2.4, 99th percentile; BMI=38.1 kg/m 2 ), and had normal testes with Tanner stage V pubic hair. After his diagnosis, the 3-year-old sister was screened for increased 17-OHP and ACTH levels, which were found to be mildly elevated ( Table 2 ). At the time of her diagnosis she was also of normal growth and stature (height=94 cm, z -score=-0.05, 48th percentile; weight=14 kg, z -score=0.03, 51st percentile; BMI=15.8 kg/m 2 ). She was also started on physiologic doses of hydrocortisone after ACTH1-24 -stimulation showed suboptimal rise in cortisol levels (13.12 μg/dL after 60 minutes). She also presented to us in the Pediatric Endocrinology clinic at the age of 15 and 11 months, on subphysiologic hydrocortisone replacement (8.33 g/m 2 /day), with no history of virilization, precocious puberty or prostration with illness. She was obese (height=158 m, z -score=-0.7, 23rd percentile; weight=73.6 kg, z -score=1.4, 92nd percentile; BMI=29.5 kg/m 2 ), with no hirsutism and normal female genitalia (Tanner V breasts and pubic hair). We questioned the diagnosis of SW CAH, since they were both asymptomatic on subphysiologic hydrocortisone replacement. Work up revealed normal serum electrolytes, mildly increased ACTH and stimulated 17-OHP levels, which when combined with the lack of any symptoms, led us to suspect NC CAH ( Tables 1, 2 ).Thus samples were taken from the family and sent for molecular testing. Participants were tested for the presence of mutation(s) within the CYP21A2 gene and large rearrangements between CYP21A2 and the CYP21A1P pseudogene. The method used was sequencing and multiplex ligation-dependent probe amplification. Molecular testing revealed that the proband had one deleted copy of CYP21A2, whereas the other copy harbored a likely pathogenic sequence variant (c.748C>T, p.R124C). The p.R124C variant has been reported previously in an individual with a diagnosis of CAH. Previous functional studies indicated that this variant has approximately 16% residual activity. The arginine (R) at this position is highly conserved across species and there is a large physicochemical difference between arginine (R) and cysteine (C). In silico analysis, based on SIFT, PolyPhen-2, MutationTaster, and Align GVGD suggests that this variant might affect protein function based on the amino acid change. SIFT categorized these changes as damaging. PolyPhen-2 scored it as probably damaging with HumDiv and HumVar scores of 1.000 and 0.997, respectively (scale: 0.000 – not damaging – to 1.000 – damaging). MutationTaster classified it as "disease causing" with a score of 180 (scale: 0.0 – not disease causing – to 215 – disease causing). Finally, AlignGVGD gave it a GD score of 70.97, which puts it into the most "likely damaging" prediction Class C65 (scale: Class C0 – not damaging – to C65 – most likely to be damaging). Taken together, these findings suggested that p.R124C is likely pathogenic. If p.R124C is pathogenic, the most likely phenotype due to compound heterozygosity for p.R124C and a large deletion would be NC CAH. The proband’s sister had the same genotype. To our surprise, family studies indicated that the father had the same genotype as the 2 children, with one copy deleted and the other harboring the p.R124C mutation. The mother was heterozygous for the large deletion. Therefore, a diagnosis of NC CAH was confirmed, and consequently, we discontinued the current treatment regimen, with regular follow-up visits. Both siblings remain asymptomatic without medication, with mild, expected laboratory derangements, proband’s sister had a 17-OHP levels (9,072 ng/dL) 1 year after the cessation of medication. Follow-up testing could not be performed on the proband.'}
|
{'Case report': 'This research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenants of the Helsinki declaration, and has been approved by the author\'s or equivalent committee. Informed consent was obtained from the parents of the patients. The proband was a male born to consanguineous parents ( Fig. 1 ). He had an acute viral fever at 4 years of age, and was found to have mild hyponatremia and hyperkalemia (sodium 131 mEq/L and potassium 6.1 mEq/L, respectively). Further investigation revealed increased 17-hydroxyprogesterone (17-OHP) and adrenocorticotropic hormone (ACTH) levels ( Table 1 ), and a suboptimal rise in cortisol levels following ACTH1-24 stimulation (13.4 μg/dL after 60 minutes). At the time of diagnosis proband was of normal growth and stature (height=107 cm, z -score=-0.4, 32nd percentile; weight=20.8 kg, z -score=+0.8, 80th percentile; body mass index=18.2 kg/m 2 ). Treatment was thus begun for presumed salt wasting (SW) CAH using replacement doses of hydrocortisone and fludrocortisone. He had normal male genitalia, descended testes, and no evidence of precocious adrenarche or puberty. He was seen by various providers sporadically over the years, and finally was reviewed in our pediatric endocrinology clinic at 17 years of age. He was on subphysiologic hydrocortisone replacement (7.7 mg/m 2 /day) as well as fludrocortisone (0.2 mg per day), without any symptoms, no history of prostration with illness, and normally-timed pubertal changes. He was obese with normal stature (height=170 cm, z -score=-0.8, 21st percentile; weight=110 kg, z -score=+2.4, 99th percentile; BMI=38.1 kg/m 2 ), and had normal testes with Tanner stage V pubic hair. After his diagnosis, the 3-year-old sister was screened for increased 17-OHP and ACTH levels, which were found to be mildly elevated ( Table 2 ). At the time of her diagnosis she was also of normal growth and stature (height=94 cm, z -score=-0.05, 48th percentile; weight=14 kg, z -score=0.03, 51st percentile; BMI=15.8 kg/m 2 ). She was also started on physiologic doses of hydrocortisone after ACTH1-24 -stimulation showed suboptimal rise in cortisol levels (13.12 μg/dL after 60 minutes). She also presented to us in the Pediatric Endocrinology clinic at the age of 15 and 11 months, on subphysiologic hydrocortisone replacement (8.33 g/m 2 /day), with no history of virilization, precocious puberty or prostration with illness. She was obese (height=158 m, z -score=-0.7, 23rd percentile; weight=73.6 kg, z -score=1.4, 92nd percentile; BMI=29.5 kg/m 2 ), with no hirsutism and normal female genitalia (Tanner V breasts and pubic hair). We questioned the diagnosis of SW CAH, since they were both asymptomatic on subphysiologic hydrocortisone replacement. Work up revealed normal serum electrolytes, mildly increased ACTH and stimulated 17-OHP levels, which when combined with the lack of any symptoms, led us to suspect NC CAH ( Tables 1, 2 ).Thus samples were taken from the family and sent for molecular testing. Participants were tested for the presence of mutation(s) within the CYP21A2 gene and large rearrangements between CYP21A2 and the CYP21A1P pseudogene. The method used was sequencing and multiplex ligation-dependent probe amplification. Molecular testing revealed that the proband had one deleted copy of CYP21A2, whereas the other copy harbored a likely pathogenic sequence variant (c.748C>T, p.R124C). The p.R124C variant has been reported previously in an individual with a diagnosis of CAH. Previous functional studies indicated that this variant has approximately 16% residual activity. The arginine (R) at this position is highly conserved across species and there is a large physicochemical difference between arginine (R) and cysteine (C). In silico analysis, based on SIFT, PolyPhen-2, MutationTaster, and Align GVGD suggests that this variant might affect protein function based on the amino acid change. SIFT categorized these changes as damaging. PolyPhen-2 scored it as probably damaging with HumDiv and HumVar scores of 1.000 and 0.997, respectively (scale: 0.000 – not damaging – to 1.000 – damaging). MutationTaster classified it as "disease causing" with a score of 180 (scale: 0.0 – not disease causing – to 215 – disease causing). Finally, AlignGVGD gave it a GD score of 70.97, which puts it into the most "likely damaging" prediction Class C65 (scale: Class C0 – not damaging – to C65 – most likely to be damaging). Taken together, these findings suggested that p.R124C is likely pathogenic. If p.R124C is pathogenic, the most likely phenotype due to compound heterozygosity for p.R124C and a large deletion would be NC CAH. The proband’s sister had the same genotype. To our surprise, family studies indicated that the father had the same genotype as the 2 children, with one copy deleted and the other harboring the p.R124C mutation. The mother was heterozygous for the large deletion. Therefore, a diagnosis of NC CAH was confirmed, and consequently, we discontinued the current treatment regimen, with regular follow-up visits. Both siblings remain asymptomatic without medication, with mild, expected laboratory derangements, proband’s sister had a 17-OHP levels (9,072 ng/dL) 1 year after the cessation of medication. Follow-up testing could not be performed on the proband.'}
|
Cardiovascular-System
|
CVS
|
[] |
test-1915
|
6177667
|
{'Case report': 'This research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenants of the Helsinki declaration, and has been approved by the author\'s or equivalent committee. Informed consent was obtained from the parents of the patients. The proband was a male born to consanguineous parents ( Fig. 1 ). He had an acute viral fever at 4 years of age, and was found to have mild hyponatremia and hyperkalemia (sodium 131 mEq/L and potassium 6.1 mEq/L, respectively). Further investigation revealed increased 17-hydroxyprogesterone (17-OHP) and adrenocorticotropic hormone (ACTH) levels ( Table 1 ), and a suboptimal rise in cortisol levels following ACTH1-24 stimulation (13.4 μg/dL after 60 minutes). At the time of diagnosis proband was of normal growth and stature (height=107 cm, z -score=-0.4, 32nd percentile; weight=20.8 kg, z -score=+0.8, 80th percentile; body mass index=18.2 kg/m 2 ). Treatment was thus begun for presumed salt wasting (SW) CAH using replacement doses of hydrocortisone and fludrocortisone. He had normal male genitalia, descended testes, and no evidence of precocious adrenarche or puberty. He was seen by various providers sporadically over the years, and finally was reviewed in our pediatric endocrinology clinic at 17 years of age. He was on subphysiologic hydrocortisone replacement (7.7 mg/m 2 /day) as well as fludrocortisone (0.2 mg per day), without any symptoms, no history of prostration with illness, and normally-timed pubertal changes. He was obese with normal stature (height=170 cm, z -score=-0.8, 21st percentile; weight=110 kg, z -score=+2.4, 99th percentile; BMI=38.1 kg/m 2 ), and had normal testes with Tanner stage V pubic hair. After his diagnosis, the 3-year-old sister was screened for increased 17-OHP and ACTH levels, which were found to be mildly elevated ( Table 2 ). At the time of her diagnosis she was also of normal growth and stature (height=94 cm, z -score=-0.05, 48th percentile; weight=14 kg, z -score=0.03, 51st percentile; BMI=15.8 kg/m 2 ). She was also started on physiologic doses of hydrocortisone after ACTH1-24 -stimulation showed suboptimal rise in cortisol levels (13.12 μg/dL after 60 minutes). She also presented to us in the Pediatric Endocrinology clinic at the age of 15 and 11 months, on subphysiologic hydrocortisone replacement (8.33 g/m 2 /day), with no history of virilization, precocious puberty or prostration with illness. She was obese (height=158 m, z -score=-0.7, 23rd percentile; weight=73.6 kg, z -score=1.4, 92nd percentile; BMI=29.5 kg/m 2 ), with no hirsutism and normal female genitalia (Tanner V breasts and pubic hair). We questioned the diagnosis of SW CAH, since they were both asymptomatic on subphysiologic hydrocortisone replacement. Work up revealed normal serum electrolytes, mildly increased ACTH and stimulated 17-OHP levels, which when combined with the lack of any symptoms, led us to suspect NC CAH ( Tables 1, 2 ).Thus samples were taken from the family and sent for molecular testing. Participants were tested for the presence of mutation(s) within the CYP21A2 gene and large rearrangements between CYP21A2 and the CYP21A1P pseudogene. The method used was sequencing and multiplex ligation-dependent probe amplification. Molecular testing revealed that the proband had one deleted copy of CYP21A2, whereas the other copy harbored a likely pathogenic sequence variant (c.748C>T, p.R124C). The p.R124C variant has been reported previously in an individual with a diagnosis of CAH. Previous functional studies indicated that this variant has approximately 16% residual activity. The arginine (R) at this position is highly conserved across species and there is a large physicochemical difference between arginine (R) and cysteine (C). In silico analysis, based on SIFT, PolyPhen-2, MutationTaster, and Align GVGD suggests that this variant might affect protein function based on the amino acid change. SIFT categorized these changes as damaging. PolyPhen-2 scored it as probably damaging with HumDiv and HumVar scores of 1.000 and 0.997, respectively (scale: 0.000 – not damaging – to 1.000 – damaging). MutationTaster classified it as "disease causing" with a score of 180 (scale: 0.0 – not disease causing – to 215 – disease causing). Finally, AlignGVGD gave it a GD score of 70.97, which puts it into the most "likely damaging" prediction Class C65 (scale: Class C0 – not damaging – to C65 – most likely to be damaging). Taken together, these findings suggested that p.R124C is likely pathogenic. If p.R124C is pathogenic, the most likely phenotype due to compound heterozygosity for p.R124C and a large deletion would be NC CAH. The proband’s sister had the same genotype. To our surprise, family studies indicated that the father had the same genotype as the 2 children, with one copy deleted and the other harboring the p.R124C mutation. The mother was heterozygous for the large deletion. Therefore, a diagnosis of NC CAH was confirmed, and consequently, we discontinued the current treatment regimen, with regular follow-up visits. Both siblings remain asymptomatic without medication, with mild, expected laboratory derangements, proband’s sister had a 17-OHP levels (9,072 ng/dL) 1 year after the cessation of medication. Follow-up testing could not be performed on the proband.'}
|
{'Case report': 'This research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenants of the Helsinki declaration, and has been approved by the author\'s or equivalent committee. Informed consent was obtained from the parents of the patients. The proband was a male born to consanguineous parents ( Fig. 1 ). He had an acute viral fever at 4 years of age, and was found to have mild hyponatremia and hyperkalemia (sodium 131 mEq/L and potassium 6.1 mEq/L, respectively). Further investigation revealed increased 17-hydroxyprogesterone (17-OHP) and adrenocorticotropic hormone (ACTH) levels ( Table 1 ), and a suboptimal rise in cortisol levels following ACTH1-24 stimulation (13.4 μg/dL after 60 minutes). At the time of diagnosis proband was of normal growth and stature (height=107 cm, z -score=-0.4, 32nd percentile; weight=20.8 kg, z -score=+0.8, 80th percentile; body mass index=18.2 kg/m 2 ). Treatment was thus begun for presumed salt wasting (SW) CAH using replacement doses of hydrocortisone and fludrocortisone. He had normal male genitalia, descended testes, and no evidence of precocious adrenarche or puberty. He was seen by various providers sporadically over the years, and finally was reviewed in our pediatric endocrinology clinic at 17 years of age. He was on subphysiologic hydrocortisone replacement (7.7 mg/m 2 /day) as well as fludrocortisone (0.2 mg per day), without any symptoms, no history of prostration with illness, and normally-timed pubertal changes. He was obese with normal stature (height=170 cm, z -score=-0.8, 21st percentile; weight=110 kg, z -score=+2.4, 99th percentile; BMI=38.1 kg/m 2 ), and had normal testes with Tanner stage V pubic hair. After his diagnosis, the 3-year-old sister was screened for increased 17-OHP and ACTH levels, which were found to be mildly elevated ( Table 2 ). At the time of her diagnosis she was also of normal growth and stature (height=94 cm, z -score=-0.05, 48th percentile; weight=14 kg, z -score=0.03, 51st percentile; BMI=15.8 kg/m 2 ). She was also started on physiologic doses of hydrocortisone after ACTH1-24 -stimulation showed suboptimal rise in cortisol levels (13.12 μg/dL after 60 minutes). She also presented to us in the Pediatric Endocrinology clinic at the age of 15 and 11 months, on subphysiologic hydrocortisone replacement (8.33 g/m 2 /day), with no history of virilization, precocious puberty or prostration with illness. She was obese (height=158 m, z -score=-0.7, 23rd percentile; weight=73.6 kg, z -score=1.4, 92nd percentile; BMI=29.5 kg/m 2 ), with no hirsutism and normal female genitalia (Tanner V breasts and pubic hair). We questioned the diagnosis of SW CAH, since they were both asymptomatic on subphysiologic hydrocortisone replacement. Work up revealed normal serum electrolytes, mildly increased ACTH and stimulated 17-OHP levels, which when combined with the lack of any symptoms, led us to suspect NC CAH ( Tables 1, 2 ).Thus samples were taken from the family and sent for molecular testing. Participants were tested for the presence of mutation(s) within the CYP21A2 gene and large rearrangements between CYP21A2 and the CYP21A1P pseudogene. The method used was sequencing and multiplex ligation-dependent probe amplification. Molecular testing revealed that the proband had one deleted copy of CYP21A2, whereas the other copy harbored a likely pathogenic sequence variant (c.748C>T, p.R124C). The p.R124C variant has been reported previously in an individual with a diagnosis of CAH. Previous functional studies indicated that this variant has approximately 16% residual activity. The arginine (R) at this position is highly conserved across species and there is a large physicochemical difference between arginine (R) and cysteine (C). In silico analysis, based on SIFT, PolyPhen-2, MutationTaster, and Align GVGD suggests that this variant might affect protein function based on the amino acid change. SIFT categorized these changes as damaging. PolyPhen-2 scored it as probably damaging with HumDiv and HumVar scores of 1.000 and 0.997, respectively (scale: 0.000 – not damaging – to 1.000 – damaging). MutationTaster classified it as "disease causing" with a score of 180 (scale: 0.0 – not disease causing – to 215 – disease causing). Finally, AlignGVGD gave it a GD score of 70.97, which puts it into the most "likely damaging" prediction Class C65 (scale: Class C0 – not damaging – to C65 – most likely to be damaging). Taken together, these findings suggested that p.R124C is likely pathogenic. If p.R124C is pathogenic, the most likely phenotype due to compound heterozygosity for p.R124C and a large deletion would be NC CAH. The proband’s sister had the same genotype. To our surprise, family studies indicated that the father had the same genotype as the 2 children, with one copy deleted and the other harboring the p.R124C mutation. The mother was heterozygous for the large deletion. Therefore, a diagnosis of NC CAH was confirmed, and consequently, we discontinued the current treatment regimen, with regular follow-up visits. Both siblings remain asymptomatic without medication, with mild, expected laboratory derangements, proband’s sister had a 17-OHP levels (9,072 ng/dL) 1 year after the cessation of medication. Follow-up testing could not be performed on the proband.'}
|
Endocrinology
|
ENDO
|
[
"mild hyponatremia and hyperkalemia ( sodium 131 mEq / L and potassium 6.1 mEq / L, respectively ). Further investigation revealed increased 17 - hydroxyprogesterone ( 17 - OHP ) and adrenocorticotropic hormone ( ACTH ) levels ( Table 1 ), and a suboptimal rise in cortisol levels following ACTH1 - 24 stimulation ( 13.4 μg / dL after 60 minutes ).",
"normal growth and stature",
"no evidence of precocious adrenarche or puberty",
"no history of prostration with illness, and normally - timed pubertal changes",
"obese with normal stature",
"normal testes with Tanner stage V pubic hair",
"screened for increased 17 - OHP and ACTH levels, which were found to be mildly elevated",
"normal growth and stature",
"ACTH1 - 24 -stimulation showed suboptimal rise in cortisol levels ( 13.12 μg / dL after 60 minutes ).",
"no history of virilization, precocious puberty or prostration with illness",
"obese",
"with no hirsutism and normal female genitalia ( Tanner V breasts and pubic hair",
"normal serum electrolytes, mildly increased ACTH and stimulated 17 - OHP levels",
"had a 17 - OHP levels ( 9,072 ng / dL )"
] |
test-1916
|
6177667
|
{'Case report': 'This research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenants of the Helsinki declaration, and has been approved by the author\'s or equivalent committee. Informed consent was obtained from the parents of the patients. The proband was a male born to consanguineous parents ( Fig. 1 ). He had an acute viral fever at 4 years of age, and was found to have mild hyponatremia and hyperkalemia (sodium 131 mEq/L and potassium 6.1 mEq/L, respectively). Further investigation revealed increased 17-hydroxyprogesterone (17-OHP) and adrenocorticotropic hormone (ACTH) levels ( Table 1 ), and a suboptimal rise in cortisol levels following ACTH1-24 stimulation (13.4 μg/dL after 60 minutes). At the time of diagnosis proband was of normal growth and stature (height=107 cm, z -score=-0.4, 32nd percentile; weight=20.8 kg, z -score=+0.8, 80th percentile; body mass index=18.2 kg/m 2 ). Treatment was thus begun for presumed salt wasting (SW) CAH using replacement doses of hydrocortisone and fludrocortisone. He had normal male genitalia, descended testes, and no evidence of precocious adrenarche or puberty. He was seen by various providers sporadically over the years, and finally was reviewed in our pediatric endocrinology clinic at 17 years of age. He was on subphysiologic hydrocortisone replacement (7.7 mg/m 2 /day) as well as fludrocortisone (0.2 mg per day), without any symptoms, no history of prostration with illness, and normally-timed pubertal changes. He was obese with normal stature (height=170 cm, z -score=-0.8, 21st percentile; weight=110 kg, z -score=+2.4, 99th percentile; BMI=38.1 kg/m 2 ), and had normal testes with Tanner stage V pubic hair. After his diagnosis, the 3-year-old sister was screened for increased 17-OHP and ACTH levels, which were found to be mildly elevated ( Table 2 ). At the time of her diagnosis she was also of normal growth and stature (height=94 cm, z -score=-0.05, 48th percentile; weight=14 kg, z -score=0.03, 51st percentile; BMI=15.8 kg/m 2 ). She was also started on physiologic doses of hydrocortisone after ACTH1-24 -stimulation showed suboptimal rise in cortisol levels (13.12 μg/dL after 60 minutes). She also presented to us in the Pediatric Endocrinology clinic at the age of 15 and 11 months, on subphysiologic hydrocortisone replacement (8.33 g/m 2 /day), with no history of virilization, precocious puberty or prostration with illness. She was obese (height=158 m, z -score=-0.7, 23rd percentile; weight=73.6 kg, z -score=1.4, 92nd percentile; BMI=29.5 kg/m 2 ), with no hirsutism and normal female genitalia (Tanner V breasts and pubic hair). We questioned the diagnosis of SW CAH, since they were both asymptomatic on subphysiologic hydrocortisone replacement. Work up revealed normal serum electrolytes, mildly increased ACTH and stimulated 17-OHP levels, which when combined with the lack of any symptoms, led us to suspect NC CAH ( Tables 1, 2 ).Thus samples were taken from the family and sent for molecular testing. Participants were tested for the presence of mutation(s) within the CYP21A2 gene and large rearrangements between CYP21A2 and the CYP21A1P pseudogene. The method used was sequencing and multiplex ligation-dependent probe amplification. Molecular testing revealed that the proband had one deleted copy of CYP21A2, whereas the other copy harbored a likely pathogenic sequence variant (c.748C>T, p.R124C). The p.R124C variant has been reported previously in an individual with a diagnosis of CAH. Previous functional studies indicated that this variant has approximately 16% residual activity. The arginine (R) at this position is highly conserved across species and there is a large physicochemical difference between arginine (R) and cysteine (C). In silico analysis, based on SIFT, PolyPhen-2, MutationTaster, and Align GVGD suggests that this variant might affect protein function based on the amino acid change. SIFT categorized these changes as damaging. PolyPhen-2 scored it as probably damaging with HumDiv and HumVar scores of 1.000 and 0.997, respectively (scale: 0.000 – not damaging – to 1.000 – damaging). MutationTaster classified it as "disease causing" with a score of 180 (scale: 0.0 – not disease causing – to 215 – disease causing). Finally, AlignGVGD gave it a GD score of 70.97, which puts it into the most "likely damaging" prediction Class C65 (scale: Class C0 – not damaging – to C65 – most likely to be damaging). Taken together, these findings suggested that p.R124C is likely pathogenic. If p.R124C is pathogenic, the most likely phenotype due to compound heterozygosity for p.R124C and a large deletion would be NC CAH. The proband’s sister had the same genotype. To our surprise, family studies indicated that the father had the same genotype as the 2 children, with one copy deleted and the other harboring the p.R124C mutation. The mother was heterozygous for the large deletion. Therefore, a diagnosis of NC CAH was confirmed, and consequently, we discontinued the current treatment regimen, with regular follow-up visits. Both siblings remain asymptomatic without medication, with mild, expected laboratory derangements, proband’s sister had a 17-OHP levels (9,072 ng/dL) 1 year after the cessation of medication. Follow-up testing could not be performed on the proband.'}
|
{'Case report': 'This research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenants of the Helsinki declaration, and has been approved by the author\'s or equivalent committee. Informed consent was obtained from the parents of the patients. The proband was a male born to consanguineous parents ( Fig. 1 ). He had an acute viral fever at 4 years of age, and was found to have mild hyponatremia and hyperkalemia (sodium 131 mEq/L and potassium 6.1 mEq/L, respectively). Further investigation revealed increased 17-hydroxyprogesterone (17-OHP) and adrenocorticotropic hormone (ACTH) levels ( Table 1 ), and a suboptimal rise in cortisol levels following ACTH1-24 stimulation (13.4 μg/dL after 60 minutes). At the time of diagnosis proband was of normal growth and stature (height=107 cm, z -score=-0.4, 32nd percentile; weight=20.8 kg, z -score=+0.8, 80th percentile; body mass index=18.2 kg/m 2 ). Treatment was thus begun for presumed salt wasting (SW) CAH using replacement doses of hydrocortisone and fludrocortisone. He had normal male genitalia, descended testes, and no evidence of precocious adrenarche or puberty. He was seen by various providers sporadically over the years, and finally was reviewed in our pediatric endocrinology clinic at 17 years of age. He was on subphysiologic hydrocortisone replacement (7.7 mg/m 2 /day) as well as fludrocortisone (0.2 mg per day), without any symptoms, no history of prostration with illness, and normally-timed pubertal changes. He was obese with normal stature (height=170 cm, z -score=-0.8, 21st percentile; weight=110 kg, z -score=+2.4, 99th percentile; BMI=38.1 kg/m 2 ), and had normal testes with Tanner stage V pubic hair. After his diagnosis, the 3-year-old sister was screened for increased 17-OHP and ACTH levels, which were found to be mildly elevated ( Table 2 ). At the time of her diagnosis she was also of normal growth and stature (height=94 cm, z -score=-0.05, 48th percentile; weight=14 kg, z -score=0.03, 51st percentile; BMI=15.8 kg/m 2 ). She was also started on physiologic doses of hydrocortisone after ACTH1-24 -stimulation showed suboptimal rise in cortisol levels (13.12 μg/dL after 60 minutes). She also presented to us in the Pediatric Endocrinology clinic at the age of 15 and 11 months, on subphysiologic hydrocortisone replacement (8.33 g/m 2 /day), with no history of virilization, precocious puberty or prostration with illness. She was obese (height=158 m, z -score=-0.7, 23rd percentile; weight=73.6 kg, z -score=1.4, 92nd percentile; BMI=29.5 kg/m 2 ), with no hirsutism and normal female genitalia (Tanner V breasts and pubic hair). We questioned the diagnosis of SW CAH, since they were both asymptomatic on subphysiologic hydrocortisone replacement. Work up revealed normal serum electrolytes, mildly increased ACTH and stimulated 17-OHP levels, which when combined with the lack of any symptoms, led us to suspect NC CAH ( Tables 1, 2 ).Thus samples were taken from the family and sent for molecular testing. Participants were tested for the presence of mutation(s) within the CYP21A2 gene and large rearrangements between CYP21A2 and the CYP21A1P pseudogene. The method used was sequencing and multiplex ligation-dependent probe amplification. Molecular testing revealed that the proband had one deleted copy of CYP21A2, whereas the other copy harbored a likely pathogenic sequence variant (c.748C>T, p.R124C). The p.R124C variant has been reported previously in an individual with a diagnosis of CAH. Previous functional studies indicated that this variant has approximately 16% residual activity. The arginine (R) at this position is highly conserved across species and there is a large physicochemical difference between arginine (R) and cysteine (C). In silico analysis, based on SIFT, PolyPhen-2, MutationTaster, and Align GVGD suggests that this variant might affect protein function based on the amino acid change. SIFT categorized these changes as damaging. PolyPhen-2 scored it as probably damaging with HumDiv and HumVar scores of 1.000 and 0.997, respectively (scale: 0.000 – not damaging – to 1.000 – damaging). MutationTaster classified it as "disease causing" with a score of 180 (scale: 0.0 – not disease causing – to 215 – disease causing). Finally, AlignGVGD gave it a GD score of 70.97, which puts it into the most "likely damaging" prediction Class C65 (scale: Class C0 – not damaging – to C65 – most likely to be damaging). Taken together, these findings suggested that p.R124C is likely pathogenic. If p.R124C is pathogenic, the most likely phenotype due to compound heterozygosity for p.R124C and a large deletion would be NC CAH. The proband’s sister had the same genotype. To our surprise, family studies indicated that the father had the same genotype as the 2 children, with one copy deleted and the other harboring the p.R124C mutation. The mother was heterozygous for the large deletion. Therefore, a diagnosis of NC CAH was confirmed, and consequently, we discontinued the current treatment regimen, with regular follow-up visits. Both siblings remain asymptomatic without medication, with mild, expected laboratory derangements, proband’s sister had a 17-OHP levels (9,072 ng/dL) 1 year after the cessation of medication. Follow-up testing could not be performed on the proband.'}
|
Genitourinary-System
|
GU
|
[
"mild hyponatremia and hyperkalemia ( sodium 131 mEq / L and potassium 6.1 mEq / L, respectively )",
"normal male genitalia, descended testes, and no evidence of precocious adrenarche or puberty",
"normal testes with Tanner stage V pubic hair",
"normal serum electrolytes"
] |
test-1917
|
6177667
|
{'Case report': 'This research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenants of the Helsinki declaration, and has been approved by the author\'s or equivalent committee. Informed consent was obtained from the parents of the patients. The proband was a male born to consanguineous parents ( Fig. 1 ). He had an acute viral fever at 4 years of age, and was found to have mild hyponatremia and hyperkalemia (sodium 131 mEq/L and potassium 6.1 mEq/L, respectively). Further investigation revealed increased 17-hydroxyprogesterone (17-OHP) and adrenocorticotropic hormone (ACTH) levels ( Table 1 ), and a suboptimal rise in cortisol levels following ACTH1-24 stimulation (13.4 μg/dL after 60 minutes). At the time of diagnosis proband was of normal growth and stature (height=107 cm, z -score=-0.4, 32nd percentile; weight=20.8 kg, z -score=+0.8, 80th percentile; body mass index=18.2 kg/m 2 ). Treatment was thus begun for presumed salt wasting (SW) CAH using replacement doses of hydrocortisone and fludrocortisone. He had normal male genitalia, descended testes, and no evidence of precocious adrenarche or puberty. He was seen by various providers sporadically over the years, and finally was reviewed in our pediatric endocrinology clinic at 17 years of age. He was on subphysiologic hydrocortisone replacement (7.7 mg/m 2 /day) as well as fludrocortisone (0.2 mg per day), without any symptoms, no history of prostration with illness, and normally-timed pubertal changes. He was obese with normal stature (height=170 cm, z -score=-0.8, 21st percentile; weight=110 kg, z -score=+2.4, 99th percentile; BMI=38.1 kg/m 2 ), and had normal testes with Tanner stage V pubic hair. After his diagnosis, the 3-year-old sister was screened for increased 17-OHP and ACTH levels, which were found to be mildly elevated ( Table 2 ). At the time of her diagnosis she was also of normal growth and stature (height=94 cm, z -score=-0.05, 48th percentile; weight=14 kg, z -score=0.03, 51st percentile; BMI=15.8 kg/m 2 ). She was also started on physiologic doses of hydrocortisone after ACTH1-24 -stimulation showed suboptimal rise in cortisol levels (13.12 μg/dL after 60 minutes). She also presented to us in the Pediatric Endocrinology clinic at the age of 15 and 11 months, on subphysiologic hydrocortisone replacement (8.33 g/m 2 /day), with no history of virilization, precocious puberty or prostration with illness. She was obese (height=158 m, z -score=-0.7, 23rd percentile; weight=73.6 kg, z -score=1.4, 92nd percentile; BMI=29.5 kg/m 2 ), with no hirsutism and normal female genitalia (Tanner V breasts and pubic hair). We questioned the diagnosis of SW CAH, since they were both asymptomatic on subphysiologic hydrocortisone replacement. Work up revealed normal serum electrolytes, mildly increased ACTH and stimulated 17-OHP levels, which when combined with the lack of any symptoms, led us to suspect NC CAH ( Tables 1, 2 ).Thus samples were taken from the family and sent for molecular testing. Participants were tested for the presence of mutation(s) within the CYP21A2 gene and large rearrangements between CYP21A2 and the CYP21A1P pseudogene. The method used was sequencing and multiplex ligation-dependent probe amplification. Molecular testing revealed that the proband had one deleted copy of CYP21A2, whereas the other copy harbored a likely pathogenic sequence variant (c.748C>T, p.R124C). The p.R124C variant has been reported previously in an individual with a diagnosis of CAH. Previous functional studies indicated that this variant has approximately 16% residual activity. The arginine (R) at this position is highly conserved across species and there is a large physicochemical difference between arginine (R) and cysteine (C). In silico analysis, based on SIFT, PolyPhen-2, MutationTaster, and Align GVGD suggests that this variant might affect protein function based on the amino acid change. SIFT categorized these changes as damaging. PolyPhen-2 scored it as probably damaging with HumDiv and HumVar scores of 1.000 and 0.997, respectively (scale: 0.000 – not damaging – to 1.000 – damaging). MutationTaster classified it as "disease causing" with a score of 180 (scale: 0.0 – not disease causing – to 215 – disease causing). Finally, AlignGVGD gave it a GD score of 70.97, which puts it into the most "likely damaging" prediction Class C65 (scale: Class C0 – not damaging – to C65 – most likely to be damaging). Taken together, these findings suggested that p.R124C is likely pathogenic. If p.R124C is pathogenic, the most likely phenotype due to compound heterozygosity for p.R124C and a large deletion would be NC CAH. The proband’s sister had the same genotype. To our surprise, family studies indicated that the father had the same genotype as the 2 children, with one copy deleted and the other harboring the p.R124C mutation. The mother was heterozygous for the large deletion. Therefore, a diagnosis of NC CAH was confirmed, and consequently, we discontinued the current treatment regimen, with regular follow-up visits. Both siblings remain asymptomatic without medication, with mild, expected laboratory derangements, proband’s sister had a 17-OHP levels (9,072 ng/dL) 1 year after the cessation of medication. Follow-up testing could not be performed on the proband.'}
|
{'Case report': 'This research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenants of the Helsinki declaration, and has been approved by the author\'s or equivalent committee. Informed consent was obtained from the parents of the patients. The proband was a male born to consanguineous parents ( Fig. 1 ). He had an acute viral fever at 4 years of age, and was found to have mild hyponatremia and hyperkalemia (sodium 131 mEq/L and potassium 6.1 mEq/L, respectively). Further investigation revealed increased 17-hydroxyprogesterone (17-OHP) and adrenocorticotropic hormone (ACTH) levels ( Table 1 ), and a suboptimal rise in cortisol levels following ACTH1-24 stimulation (13.4 μg/dL after 60 minutes). At the time of diagnosis proband was of normal growth and stature (height=107 cm, z -score=-0.4, 32nd percentile; weight=20.8 kg, z -score=+0.8, 80th percentile; body mass index=18.2 kg/m 2 ). Treatment was thus begun for presumed salt wasting (SW) CAH using replacement doses of hydrocortisone and fludrocortisone. He had normal male genitalia, descended testes, and no evidence of precocious adrenarche or puberty. He was seen by various providers sporadically over the years, and finally was reviewed in our pediatric endocrinology clinic at 17 years of age. He was on subphysiologic hydrocortisone replacement (7.7 mg/m 2 /day) as well as fludrocortisone (0.2 mg per day), without any symptoms, no history of prostration with illness, and normally-timed pubertal changes. He was obese with normal stature (height=170 cm, z -score=-0.8, 21st percentile; weight=110 kg, z -score=+2.4, 99th percentile; BMI=38.1 kg/m 2 ), and had normal testes with Tanner stage V pubic hair. After his diagnosis, the 3-year-old sister was screened for increased 17-OHP and ACTH levels, which were found to be mildly elevated ( Table 2 ). At the time of her diagnosis she was also of normal growth and stature (height=94 cm, z -score=-0.05, 48th percentile; weight=14 kg, z -score=0.03, 51st percentile; BMI=15.8 kg/m 2 ). She was also started on physiologic doses of hydrocortisone after ACTH1-24 -stimulation showed suboptimal rise in cortisol levels (13.12 μg/dL after 60 minutes). She also presented to us in the Pediatric Endocrinology clinic at the age of 15 and 11 months, on subphysiologic hydrocortisone replacement (8.33 g/m 2 /day), with no history of virilization, precocious puberty or prostration with illness. She was obese (height=158 m, z -score=-0.7, 23rd percentile; weight=73.6 kg, z -score=1.4, 92nd percentile; BMI=29.5 kg/m 2 ), with no hirsutism and normal female genitalia (Tanner V breasts and pubic hair). We questioned the diagnosis of SW CAH, since they were both asymptomatic on subphysiologic hydrocortisone replacement. Work up revealed normal serum electrolytes, mildly increased ACTH and stimulated 17-OHP levels, which when combined with the lack of any symptoms, led us to suspect NC CAH ( Tables 1, 2 ).Thus samples were taken from the family and sent for molecular testing. Participants were tested for the presence of mutation(s) within the CYP21A2 gene and large rearrangements between CYP21A2 and the CYP21A1P pseudogene. The method used was sequencing and multiplex ligation-dependent probe amplification. Molecular testing revealed that the proband had one deleted copy of CYP21A2, whereas the other copy harbored a likely pathogenic sequence variant (c.748C>T, p.R124C). The p.R124C variant has been reported previously in an individual with a diagnosis of CAH. Previous functional studies indicated that this variant has approximately 16% residual activity. The arginine (R) at this position is highly conserved across species and there is a large physicochemical difference between arginine (R) and cysteine (C). In silico analysis, based on SIFT, PolyPhen-2, MutationTaster, and Align GVGD suggests that this variant might affect protein function based on the amino acid change. SIFT categorized these changes as damaging. PolyPhen-2 scored it as probably damaging with HumDiv and HumVar scores of 1.000 and 0.997, respectively (scale: 0.000 – not damaging – to 1.000 – damaging). MutationTaster classified it as "disease causing" with a score of 180 (scale: 0.0 – not disease causing – to 215 – disease causing). Finally, AlignGVGD gave it a GD score of 70.97, which puts it into the most "likely damaging" prediction Class C65 (scale: Class C0 – not damaging – to C65 – most likely to be damaging). Taken together, these findings suggested that p.R124C is likely pathogenic. If p.R124C is pathogenic, the most likely phenotype due to compound heterozygosity for p.R124C and a large deletion would be NC CAH. The proband’s sister had the same genotype. To our surprise, family studies indicated that the father had the same genotype as the 2 children, with one copy deleted and the other harboring the p.R124C mutation. The mother was heterozygous for the large deletion. Therefore, a diagnosis of NC CAH was confirmed, and consequently, we discontinued the current treatment regimen, with regular follow-up visits. Both siblings remain asymptomatic without medication, with mild, expected laboratory derangements, proband’s sister had a 17-OHP levels (9,072 ng/dL) 1 year after the cessation of medication. Follow-up testing could not be performed on the proband.'}
|
Respiratory-System
|
RESP
|
[] |
test-1918
|
6177667
|
{'Case report': 'This research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenants of the Helsinki declaration, and has been approved by the author\'s or equivalent committee. Informed consent was obtained from the parents of the patients. The proband was a male born to consanguineous parents ( Fig. 1 ). He had an acute viral fever at 4 years of age, and was found to have mild hyponatremia and hyperkalemia (sodium 131 mEq/L and potassium 6.1 mEq/L, respectively). Further investigation revealed increased 17-hydroxyprogesterone (17-OHP) and adrenocorticotropic hormone (ACTH) levels ( Table 1 ), and a suboptimal rise in cortisol levels following ACTH1-24 stimulation (13.4 μg/dL after 60 minutes). At the time of diagnosis proband was of normal growth and stature (height=107 cm, z -score=-0.4, 32nd percentile; weight=20.8 kg, z -score=+0.8, 80th percentile; body mass index=18.2 kg/m 2 ). Treatment was thus begun for presumed salt wasting (SW) CAH using replacement doses of hydrocortisone and fludrocortisone. He had normal male genitalia, descended testes, and no evidence of precocious adrenarche or puberty. He was seen by various providers sporadically over the years, and finally was reviewed in our pediatric endocrinology clinic at 17 years of age. He was on subphysiologic hydrocortisone replacement (7.7 mg/m 2 /day) as well as fludrocortisone (0.2 mg per day), without any symptoms, no history of prostration with illness, and normally-timed pubertal changes. He was obese with normal stature (height=170 cm, z -score=-0.8, 21st percentile; weight=110 kg, z -score=+2.4, 99th percentile; BMI=38.1 kg/m 2 ), and had normal testes with Tanner stage V pubic hair. After his diagnosis, the 3-year-old sister was screened for increased 17-OHP and ACTH levels, which were found to be mildly elevated ( Table 2 ). At the time of her diagnosis she was also of normal growth and stature (height=94 cm, z -score=-0.05, 48th percentile; weight=14 kg, z -score=0.03, 51st percentile; BMI=15.8 kg/m 2 ). She was also started on physiologic doses of hydrocortisone after ACTH1-24 -stimulation showed suboptimal rise in cortisol levels (13.12 μg/dL after 60 minutes). She also presented to us in the Pediatric Endocrinology clinic at the age of 15 and 11 months, on subphysiologic hydrocortisone replacement (8.33 g/m 2 /day), with no history of virilization, precocious puberty or prostration with illness. She was obese (height=158 m, z -score=-0.7, 23rd percentile; weight=73.6 kg, z -score=1.4, 92nd percentile; BMI=29.5 kg/m 2 ), with no hirsutism and normal female genitalia (Tanner V breasts and pubic hair). We questioned the diagnosis of SW CAH, since they were both asymptomatic on subphysiologic hydrocortisone replacement. Work up revealed normal serum electrolytes, mildly increased ACTH and stimulated 17-OHP levels, which when combined with the lack of any symptoms, led us to suspect NC CAH ( Tables 1, 2 ).Thus samples were taken from the family and sent for molecular testing. Participants were tested for the presence of mutation(s) within the CYP21A2 gene and large rearrangements between CYP21A2 and the CYP21A1P pseudogene. The method used was sequencing and multiplex ligation-dependent probe amplification. Molecular testing revealed that the proband had one deleted copy of CYP21A2, whereas the other copy harbored a likely pathogenic sequence variant (c.748C>T, p.R124C). The p.R124C variant has been reported previously in an individual with a diagnosis of CAH. Previous functional studies indicated that this variant has approximately 16% residual activity. The arginine (R) at this position is highly conserved across species and there is a large physicochemical difference between arginine (R) and cysteine (C). In silico analysis, based on SIFT, PolyPhen-2, MutationTaster, and Align GVGD suggests that this variant might affect protein function based on the amino acid change. SIFT categorized these changes as damaging. PolyPhen-2 scored it as probably damaging with HumDiv and HumVar scores of 1.000 and 0.997, respectively (scale: 0.000 – not damaging – to 1.000 – damaging). MutationTaster classified it as "disease causing" with a score of 180 (scale: 0.0 – not disease causing – to 215 – disease causing). Finally, AlignGVGD gave it a GD score of 70.97, which puts it into the most "likely damaging" prediction Class C65 (scale: Class C0 – not damaging – to C65 – most likely to be damaging). Taken together, these findings suggested that p.R124C is likely pathogenic. If p.R124C is pathogenic, the most likely phenotype due to compound heterozygosity for p.R124C and a large deletion would be NC CAH. The proband’s sister had the same genotype. To our surprise, family studies indicated that the father had the same genotype as the 2 children, with one copy deleted and the other harboring the p.R124C mutation. The mother was heterozygous for the large deletion. Therefore, a diagnosis of NC CAH was confirmed, and consequently, we discontinued the current treatment regimen, with regular follow-up visits. Both siblings remain asymptomatic without medication, with mild, expected laboratory derangements, proband’s sister had a 17-OHP levels (9,072 ng/dL) 1 year after the cessation of medication. Follow-up testing could not be performed on the proband.'}
|
{'Case report': 'This research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenants of the Helsinki declaration, and has been approved by the author\'s or equivalent committee. Informed consent was obtained from the parents of the patients. The proband was a male born to consanguineous parents ( Fig. 1 ). He had an acute viral fever at 4 years of age, and was found to have mild hyponatremia and hyperkalemia (sodium 131 mEq/L and potassium 6.1 mEq/L, respectively). Further investigation revealed increased 17-hydroxyprogesterone (17-OHP) and adrenocorticotropic hormone (ACTH) levels ( Table 1 ), and a suboptimal rise in cortisol levels following ACTH1-24 stimulation (13.4 μg/dL after 60 minutes). At the time of diagnosis proband was of normal growth and stature (height=107 cm, z -score=-0.4, 32nd percentile; weight=20.8 kg, z -score=+0.8, 80th percentile; body mass index=18.2 kg/m 2 ). Treatment was thus begun for presumed salt wasting (SW) CAH using replacement doses of hydrocortisone and fludrocortisone. He had normal male genitalia, descended testes, and no evidence of precocious adrenarche or puberty. He was seen by various providers sporadically over the years, and finally was reviewed in our pediatric endocrinology clinic at 17 years of age. He was on subphysiologic hydrocortisone replacement (7.7 mg/m 2 /day) as well as fludrocortisone (0.2 mg per day), without any symptoms, no history of prostration with illness, and normally-timed pubertal changes. He was obese with normal stature (height=170 cm, z -score=-0.8, 21st percentile; weight=110 kg, z -score=+2.4, 99th percentile; BMI=38.1 kg/m 2 ), and had normal testes with Tanner stage V pubic hair. After his diagnosis, the 3-year-old sister was screened for increased 17-OHP and ACTH levels, which were found to be mildly elevated ( Table 2 ). At the time of her diagnosis she was also of normal growth and stature (height=94 cm, z -score=-0.05, 48th percentile; weight=14 kg, z -score=0.03, 51st percentile; BMI=15.8 kg/m 2 ). She was also started on physiologic doses of hydrocortisone after ACTH1-24 -stimulation showed suboptimal rise in cortisol levels (13.12 μg/dL after 60 minutes). She also presented to us in the Pediatric Endocrinology clinic at the age of 15 and 11 months, on subphysiologic hydrocortisone replacement (8.33 g/m 2 /day), with no history of virilization, precocious puberty or prostration with illness. She was obese (height=158 m, z -score=-0.7, 23rd percentile; weight=73.6 kg, z -score=1.4, 92nd percentile; BMI=29.5 kg/m 2 ), with no hirsutism and normal female genitalia (Tanner V breasts and pubic hair). We questioned the diagnosis of SW CAH, since they were both asymptomatic on subphysiologic hydrocortisone replacement. Work up revealed normal serum electrolytes, mildly increased ACTH and stimulated 17-OHP levels, which when combined with the lack of any symptoms, led us to suspect NC CAH ( Tables 1, 2 ).Thus samples were taken from the family and sent for molecular testing. Participants were tested for the presence of mutation(s) within the CYP21A2 gene and large rearrangements between CYP21A2 and the CYP21A1P pseudogene. The method used was sequencing and multiplex ligation-dependent probe amplification. Molecular testing revealed that the proband had one deleted copy of CYP21A2, whereas the other copy harbored a likely pathogenic sequence variant (c.748C>T, p.R124C). The p.R124C variant has been reported previously in an individual with a diagnosis of CAH. Previous functional studies indicated that this variant has approximately 16% residual activity. The arginine (R) at this position is highly conserved across species and there is a large physicochemical difference between arginine (R) and cysteine (C). In silico analysis, based on SIFT, PolyPhen-2, MutationTaster, and Align GVGD suggests that this variant might affect protein function based on the amino acid change. SIFT categorized these changes as damaging. PolyPhen-2 scored it as probably damaging with HumDiv and HumVar scores of 1.000 and 0.997, respectively (scale: 0.000 – not damaging – to 1.000 – damaging). MutationTaster classified it as "disease causing" with a score of 180 (scale: 0.0 – not disease causing – to 215 – disease causing). Finally, AlignGVGD gave it a GD score of 70.97, which puts it into the most "likely damaging" prediction Class C65 (scale: Class C0 – not damaging – to C65 – most likely to be damaging). Taken together, these findings suggested that p.R124C is likely pathogenic. If p.R124C is pathogenic, the most likely phenotype due to compound heterozygosity for p.R124C and a large deletion would be NC CAH. The proband’s sister had the same genotype. To our surprise, family studies indicated that the father had the same genotype as the 2 children, with one copy deleted and the other harboring the p.R124C mutation. The mother was heterozygous for the large deletion. Therefore, a diagnosis of NC CAH was confirmed, and consequently, we discontinued the current treatment regimen, with regular follow-up visits. Both siblings remain asymptomatic without medication, with mild, expected laboratory derangements, proband’s sister had a 17-OHP levels (9,072 ng/dL) 1 year after the cessation of medication. Follow-up testing could not be performed on the proband.'}
|
Musculoskeletal-System
|
MSK
|
[
". At the time of diagnosis proband was of normal growth and stature ( height=107 cm, z -score=-0.4, 32nd percentile; weight=20.8 kg, z -score=+0.8, 80th percentile; body mass index=18.2 kg / m 2 ).",
"He was obese with normal stature ( height=170 cm, z -score=-0.8, 21st percentile; weight=110 kg, z -score=+2.4, 99th percentile; BMI=38.1 kg / m 2 )"
] |
test-1919
|
6177667
|
{'Case report': 'This research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenants of the Helsinki declaration, and has been approved by the author\'s or equivalent committee. Informed consent was obtained from the parents of the patients. The proband was a male born to consanguineous parents ( Fig. 1 ). He had an acute viral fever at 4 years of age, and was found to have mild hyponatremia and hyperkalemia (sodium 131 mEq/L and potassium 6.1 mEq/L, respectively). Further investigation revealed increased 17-hydroxyprogesterone (17-OHP) and adrenocorticotropic hormone (ACTH) levels ( Table 1 ), and a suboptimal rise in cortisol levels following ACTH1-24 stimulation (13.4 μg/dL after 60 minutes). At the time of diagnosis proband was of normal growth and stature (height=107 cm, z -score=-0.4, 32nd percentile; weight=20.8 kg, z -score=+0.8, 80th percentile; body mass index=18.2 kg/m 2 ). Treatment was thus begun for presumed salt wasting (SW) CAH using replacement doses of hydrocortisone and fludrocortisone. He had normal male genitalia, descended testes, and no evidence of precocious adrenarche or puberty. He was seen by various providers sporadically over the years, and finally was reviewed in our pediatric endocrinology clinic at 17 years of age. He was on subphysiologic hydrocortisone replacement (7.7 mg/m 2 /day) as well as fludrocortisone (0.2 mg per day), without any symptoms, no history of prostration with illness, and normally-timed pubertal changes. He was obese with normal stature (height=170 cm, z -score=-0.8, 21st percentile; weight=110 kg, z -score=+2.4, 99th percentile; BMI=38.1 kg/m 2 ), and had normal testes with Tanner stage V pubic hair. After his diagnosis, the 3-year-old sister was screened for increased 17-OHP and ACTH levels, which were found to be mildly elevated ( Table 2 ). At the time of her diagnosis she was also of normal growth and stature (height=94 cm, z -score=-0.05, 48th percentile; weight=14 kg, z -score=0.03, 51st percentile; BMI=15.8 kg/m 2 ). She was also started on physiologic doses of hydrocortisone after ACTH1-24 -stimulation showed suboptimal rise in cortisol levels (13.12 μg/dL after 60 minutes). She also presented to us in the Pediatric Endocrinology clinic at the age of 15 and 11 months, on subphysiologic hydrocortisone replacement (8.33 g/m 2 /day), with no history of virilization, precocious puberty or prostration with illness. She was obese (height=158 m, z -score=-0.7, 23rd percentile; weight=73.6 kg, z -score=1.4, 92nd percentile; BMI=29.5 kg/m 2 ), with no hirsutism and normal female genitalia (Tanner V breasts and pubic hair). We questioned the diagnosis of SW CAH, since they were both asymptomatic on subphysiologic hydrocortisone replacement. Work up revealed normal serum electrolytes, mildly increased ACTH and stimulated 17-OHP levels, which when combined with the lack of any symptoms, led us to suspect NC CAH ( Tables 1, 2 ).Thus samples were taken from the family and sent for molecular testing. Participants were tested for the presence of mutation(s) within the CYP21A2 gene and large rearrangements between CYP21A2 and the CYP21A1P pseudogene. The method used was sequencing and multiplex ligation-dependent probe amplification. Molecular testing revealed that the proband had one deleted copy of CYP21A2, whereas the other copy harbored a likely pathogenic sequence variant (c.748C>T, p.R124C). The p.R124C variant has been reported previously in an individual with a diagnosis of CAH. Previous functional studies indicated that this variant has approximately 16% residual activity. The arginine (R) at this position is highly conserved across species and there is a large physicochemical difference between arginine (R) and cysteine (C). In silico analysis, based on SIFT, PolyPhen-2, MutationTaster, and Align GVGD suggests that this variant might affect protein function based on the amino acid change. SIFT categorized these changes as damaging. PolyPhen-2 scored it as probably damaging with HumDiv and HumVar scores of 1.000 and 0.997, respectively (scale: 0.000 – not damaging – to 1.000 – damaging). MutationTaster classified it as "disease causing" with a score of 180 (scale: 0.0 – not disease causing – to 215 – disease causing). Finally, AlignGVGD gave it a GD score of 70.97, which puts it into the most "likely damaging" prediction Class C65 (scale: Class C0 – not damaging – to C65 – most likely to be damaging). Taken together, these findings suggested that p.R124C is likely pathogenic. If p.R124C is pathogenic, the most likely phenotype due to compound heterozygosity for p.R124C and a large deletion would be NC CAH. The proband’s sister had the same genotype. To our surprise, family studies indicated that the father had the same genotype as the 2 children, with one copy deleted and the other harboring the p.R124C mutation. The mother was heterozygous for the large deletion. Therefore, a diagnosis of NC CAH was confirmed, and consequently, we discontinued the current treatment regimen, with regular follow-up visits. Both siblings remain asymptomatic without medication, with mild, expected laboratory derangements, proband’s sister had a 17-OHP levels (9,072 ng/dL) 1 year after the cessation of medication. Follow-up testing could not be performed on the proband.'}
|
{'Case report': 'This research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenants of the Helsinki declaration, and has been approved by the author\'s or equivalent committee. Informed consent was obtained from the parents of the patients. The proband was a male born to consanguineous parents ( Fig. 1 ). He had an acute viral fever at 4 years of age, and was found to have mild hyponatremia and hyperkalemia (sodium 131 mEq/L and potassium 6.1 mEq/L, respectively). Further investigation revealed increased 17-hydroxyprogesterone (17-OHP) and adrenocorticotropic hormone (ACTH) levels ( Table 1 ), and a suboptimal rise in cortisol levels following ACTH1-24 stimulation (13.4 μg/dL after 60 minutes). At the time of diagnosis proband was of normal growth and stature (height=107 cm, z -score=-0.4, 32nd percentile; weight=20.8 kg, z -score=+0.8, 80th percentile; body mass index=18.2 kg/m 2 ). Treatment was thus begun for presumed salt wasting (SW) CAH using replacement doses of hydrocortisone and fludrocortisone. He had normal male genitalia, descended testes, and no evidence of precocious adrenarche or puberty. He was seen by various providers sporadically over the years, and finally was reviewed in our pediatric endocrinology clinic at 17 years of age. He was on subphysiologic hydrocortisone replacement (7.7 mg/m 2 /day) as well as fludrocortisone (0.2 mg per day), without any symptoms, no history of prostration with illness, and normally-timed pubertal changes. He was obese with normal stature (height=170 cm, z -score=-0.8, 21st percentile; weight=110 kg, z -score=+2.4, 99th percentile; BMI=38.1 kg/m 2 ), and had normal testes with Tanner stage V pubic hair. After his diagnosis, the 3-year-old sister was screened for increased 17-OHP and ACTH levels, which were found to be mildly elevated ( Table 2 ). At the time of her diagnosis she was also of normal growth and stature (height=94 cm, z -score=-0.05, 48th percentile; weight=14 kg, z -score=0.03, 51st percentile; BMI=15.8 kg/m 2 ). She was also started on physiologic doses of hydrocortisone after ACTH1-24 -stimulation showed suboptimal rise in cortisol levels (13.12 μg/dL after 60 minutes). She also presented to us in the Pediatric Endocrinology clinic at the age of 15 and 11 months, on subphysiologic hydrocortisone replacement (8.33 g/m 2 /day), with no history of virilization, precocious puberty or prostration with illness. She was obese (height=158 m, z -score=-0.7, 23rd percentile; weight=73.6 kg, z -score=1.4, 92nd percentile; BMI=29.5 kg/m 2 ), with no hirsutism and normal female genitalia (Tanner V breasts and pubic hair). We questioned the diagnosis of SW CAH, since they were both asymptomatic on subphysiologic hydrocortisone replacement. Work up revealed normal serum electrolytes, mildly increased ACTH and stimulated 17-OHP levels, which when combined with the lack of any symptoms, led us to suspect NC CAH ( Tables 1, 2 ).Thus samples were taken from the family and sent for molecular testing. Participants were tested for the presence of mutation(s) within the CYP21A2 gene and large rearrangements between CYP21A2 and the CYP21A1P pseudogene. The method used was sequencing and multiplex ligation-dependent probe amplification. Molecular testing revealed that the proband had one deleted copy of CYP21A2, whereas the other copy harbored a likely pathogenic sequence variant (c.748C>T, p.R124C). The p.R124C variant has been reported previously in an individual with a diagnosis of CAH. Previous functional studies indicated that this variant has approximately 16% residual activity. The arginine (R) at this position is highly conserved across species and there is a large physicochemical difference between arginine (R) and cysteine (C). In silico analysis, based on SIFT, PolyPhen-2, MutationTaster, and Align GVGD suggests that this variant might affect protein function based on the amino acid change. SIFT categorized these changes as damaging. PolyPhen-2 scored it as probably damaging with HumDiv and HumVar scores of 1.000 and 0.997, respectively (scale: 0.000 – not damaging – to 1.000 – damaging). MutationTaster classified it as "disease causing" with a score of 180 (scale: 0.0 – not disease causing – to 215 – disease causing). Finally, AlignGVGD gave it a GD score of 70.97, which puts it into the most "likely damaging" prediction Class C65 (scale: Class C0 – not damaging – to C65 – most likely to be damaging). Taken together, these findings suggested that p.R124C is likely pathogenic. If p.R124C is pathogenic, the most likely phenotype due to compound heterozygosity for p.R124C and a large deletion would be NC CAH. The proband’s sister had the same genotype. To our surprise, family studies indicated that the father had the same genotype as the 2 children, with one copy deleted and the other harboring the p.R124C mutation. The mother was heterozygous for the large deletion. Therefore, a diagnosis of NC CAH was confirmed, and consequently, we discontinued the current treatment regimen, with regular follow-up visits. Both siblings remain asymptomatic without medication, with mild, expected laboratory derangements, proband’s sister had a 17-OHP levels (9,072 ng/dL) 1 year after the cessation of medication. Follow-up testing could not be performed on the proband.'}
|
Eyes-Ears-Nose-Throat
|
EENT
|
[] |
test-1920
|
6177667
|
{'Case report': 'This research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenants of the Helsinki declaration, and has been approved by the author\'s or equivalent committee. Informed consent was obtained from the parents of the patients. The proband was a male born to consanguineous parents ( Fig. 1 ). He had an acute viral fever at 4 years of age, and was found to have mild hyponatremia and hyperkalemia (sodium 131 mEq/L and potassium 6.1 mEq/L, respectively). Further investigation revealed increased 17-hydroxyprogesterone (17-OHP) and adrenocorticotropic hormone (ACTH) levels ( Table 1 ), and a suboptimal rise in cortisol levels following ACTH1-24 stimulation (13.4 μg/dL after 60 minutes). At the time of diagnosis proband was of normal growth and stature (height=107 cm, z -score=-0.4, 32nd percentile; weight=20.8 kg, z -score=+0.8, 80th percentile; body mass index=18.2 kg/m 2 ). Treatment was thus begun for presumed salt wasting (SW) CAH using replacement doses of hydrocortisone and fludrocortisone. He had normal male genitalia, descended testes, and no evidence of precocious adrenarche or puberty. He was seen by various providers sporadically over the years, and finally was reviewed in our pediatric endocrinology clinic at 17 years of age. He was on subphysiologic hydrocortisone replacement (7.7 mg/m 2 /day) as well as fludrocortisone (0.2 mg per day), without any symptoms, no history of prostration with illness, and normally-timed pubertal changes. He was obese with normal stature (height=170 cm, z -score=-0.8, 21st percentile; weight=110 kg, z -score=+2.4, 99th percentile; BMI=38.1 kg/m 2 ), and had normal testes with Tanner stage V pubic hair. After his diagnosis, the 3-year-old sister was screened for increased 17-OHP and ACTH levels, which were found to be mildly elevated ( Table 2 ). At the time of her diagnosis she was also of normal growth and stature (height=94 cm, z -score=-0.05, 48th percentile; weight=14 kg, z -score=0.03, 51st percentile; BMI=15.8 kg/m 2 ). She was also started on physiologic doses of hydrocortisone after ACTH1-24 -stimulation showed suboptimal rise in cortisol levels (13.12 μg/dL after 60 minutes). She also presented to us in the Pediatric Endocrinology clinic at the age of 15 and 11 months, on subphysiologic hydrocortisone replacement (8.33 g/m 2 /day), with no history of virilization, precocious puberty or prostration with illness. She was obese (height=158 m, z -score=-0.7, 23rd percentile; weight=73.6 kg, z -score=1.4, 92nd percentile; BMI=29.5 kg/m 2 ), with no hirsutism and normal female genitalia (Tanner V breasts and pubic hair). We questioned the diagnosis of SW CAH, since they were both asymptomatic on subphysiologic hydrocortisone replacement. Work up revealed normal serum electrolytes, mildly increased ACTH and stimulated 17-OHP levels, which when combined with the lack of any symptoms, led us to suspect NC CAH ( Tables 1, 2 ).Thus samples were taken from the family and sent for molecular testing. Participants were tested for the presence of mutation(s) within the CYP21A2 gene and large rearrangements between CYP21A2 and the CYP21A1P pseudogene. The method used was sequencing and multiplex ligation-dependent probe amplification. Molecular testing revealed that the proband had one deleted copy of CYP21A2, whereas the other copy harbored a likely pathogenic sequence variant (c.748C>T, p.R124C). The p.R124C variant has been reported previously in an individual with a diagnosis of CAH. Previous functional studies indicated that this variant has approximately 16% residual activity. The arginine (R) at this position is highly conserved across species and there is a large physicochemical difference between arginine (R) and cysteine (C). In silico analysis, based on SIFT, PolyPhen-2, MutationTaster, and Align GVGD suggests that this variant might affect protein function based on the amino acid change. SIFT categorized these changes as damaging. PolyPhen-2 scored it as probably damaging with HumDiv and HumVar scores of 1.000 and 0.997, respectively (scale: 0.000 – not damaging – to 1.000 – damaging). MutationTaster classified it as "disease causing" with a score of 180 (scale: 0.0 – not disease causing – to 215 – disease causing). Finally, AlignGVGD gave it a GD score of 70.97, which puts it into the most "likely damaging" prediction Class C65 (scale: Class C0 – not damaging – to C65 – most likely to be damaging). Taken together, these findings suggested that p.R124C is likely pathogenic. If p.R124C is pathogenic, the most likely phenotype due to compound heterozygosity for p.R124C and a large deletion would be NC CAH. The proband’s sister had the same genotype. To our surprise, family studies indicated that the father had the same genotype as the 2 children, with one copy deleted and the other harboring the p.R124C mutation. The mother was heterozygous for the large deletion. Therefore, a diagnosis of NC CAH was confirmed, and consequently, we discontinued the current treatment regimen, with regular follow-up visits. Both siblings remain asymptomatic without medication, with mild, expected laboratory derangements, proband’s sister had a 17-OHP levels (9,072 ng/dL) 1 year after the cessation of medication. Follow-up testing could not be performed on the proband.'}
|
{'Case report': 'This research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenants of the Helsinki declaration, and has been approved by the author\'s or equivalent committee. Informed consent was obtained from the parents of the patients. The proband was a male born to consanguineous parents ( Fig. 1 ). He had an acute viral fever at 4 years of age, and was found to have mild hyponatremia and hyperkalemia (sodium 131 mEq/L and potassium 6.1 mEq/L, respectively). Further investigation revealed increased 17-hydroxyprogesterone (17-OHP) and adrenocorticotropic hormone (ACTH) levels ( Table 1 ), and a suboptimal rise in cortisol levels following ACTH1-24 stimulation (13.4 μg/dL after 60 minutes). At the time of diagnosis proband was of normal growth and stature (height=107 cm, z -score=-0.4, 32nd percentile; weight=20.8 kg, z -score=+0.8, 80th percentile; body mass index=18.2 kg/m 2 ). Treatment was thus begun for presumed salt wasting (SW) CAH using replacement doses of hydrocortisone and fludrocortisone. He had normal male genitalia, descended testes, and no evidence of precocious adrenarche or puberty. He was seen by various providers sporadically over the years, and finally was reviewed in our pediatric endocrinology clinic at 17 years of age. He was on subphysiologic hydrocortisone replacement (7.7 mg/m 2 /day) as well as fludrocortisone (0.2 mg per day), without any symptoms, no history of prostration with illness, and normally-timed pubertal changes. He was obese with normal stature (height=170 cm, z -score=-0.8, 21st percentile; weight=110 kg, z -score=+2.4, 99th percentile; BMI=38.1 kg/m 2 ), and had normal testes with Tanner stage V pubic hair. After his diagnosis, the 3-year-old sister was screened for increased 17-OHP and ACTH levels, which were found to be mildly elevated ( Table 2 ). At the time of her diagnosis she was also of normal growth and stature (height=94 cm, z -score=-0.05, 48th percentile; weight=14 kg, z -score=0.03, 51st percentile; BMI=15.8 kg/m 2 ). She was also started on physiologic doses of hydrocortisone after ACTH1-24 -stimulation showed suboptimal rise in cortisol levels (13.12 μg/dL after 60 minutes). She also presented to us in the Pediatric Endocrinology clinic at the age of 15 and 11 months, on subphysiologic hydrocortisone replacement (8.33 g/m 2 /day), with no history of virilization, precocious puberty or prostration with illness. She was obese (height=158 m, z -score=-0.7, 23rd percentile; weight=73.6 kg, z -score=1.4, 92nd percentile; BMI=29.5 kg/m 2 ), with no hirsutism and normal female genitalia (Tanner V breasts and pubic hair). We questioned the diagnosis of SW CAH, since they were both asymptomatic on subphysiologic hydrocortisone replacement. Work up revealed normal serum electrolytes, mildly increased ACTH and stimulated 17-OHP levels, which when combined with the lack of any symptoms, led us to suspect NC CAH ( Tables 1, 2 ).Thus samples were taken from the family and sent for molecular testing. Participants were tested for the presence of mutation(s) within the CYP21A2 gene and large rearrangements between CYP21A2 and the CYP21A1P pseudogene. The method used was sequencing and multiplex ligation-dependent probe amplification. Molecular testing revealed that the proband had one deleted copy of CYP21A2, whereas the other copy harbored a likely pathogenic sequence variant (c.748C>T, p.R124C). The p.R124C variant has been reported previously in an individual with a diagnosis of CAH. Previous functional studies indicated that this variant has approximately 16% residual activity. The arginine (R) at this position is highly conserved across species and there is a large physicochemical difference between arginine (R) and cysteine (C). In silico analysis, based on SIFT, PolyPhen-2, MutationTaster, and Align GVGD suggests that this variant might affect protein function based on the amino acid change. SIFT categorized these changes as damaging. PolyPhen-2 scored it as probably damaging with HumDiv and HumVar scores of 1.000 and 0.997, respectively (scale: 0.000 – not damaging – to 1.000 – damaging). MutationTaster classified it as "disease causing" with a score of 180 (scale: 0.0 – not disease causing – to 215 – disease causing). Finally, AlignGVGD gave it a GD score of 70.97, which puts it into the most "likely damaging" prediction Class C65 (scale: Class C0 – not damaging – to C65 – most likely to be damaging). Taken together, these findings suggested that p.R124C is likely pathogenic. If p.R124C is pathogenic, the most likely phenotype due to compound heterozygosity for p.R124C and a large deletion would be NC CAH. The proband’s sister had the same genotype. To our surprise, family studies indicated that the father had the same genotype as the 2 children, with one copy deleted and the other harboring the p.R124C mutation. The mother was heterozygous for the large deletion. Therefore, a diagnosis of NC CAH was confirmed, and consequently, we discontinued the current treatment regimen, with regular follow-up visits. Both siblings remain asymptomatic without medication, with mild, expected laboratory derangements, proband’s sister had a 17-OHP levels (9,072 ng/dL) 1 year after the cessation of medication. Follow-up testing could not be performed on the proband.'}
|
Dermatology
|
DERM
|
[
"no hirsutism"
] |
test-1921
|
6177667
|
{'Case report': 'This research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenants of the Helsinki declaration, and has been approved by the author\'s or equivalent committee. Informed consent was obtained from the parents of the patients. The proband was a male born to consanguineous parents ( Fig. 1 ). He had an acute viral fever at 4 years of age, and was found to have mild hyponatremia and hyperkalemia (sodium 131 mEq/L and potassium 6.1 mEq/L, respectively). Further investigation revealed increased 17-hydroxyprogesterone (17-OHP) and adrenocorticotropic hormone (ACTH) levels ( Table 1 ), and a suboptimal rise in cortisol levels following ACTH1-24 stimulation (13.4 μg/dL after 60 minutes). At the time of diagnosis proband was of normal growth and stature (height=107 cm, z -score=-0.4, 32nd percentile; weight=20.8 kg, z -score=+0.8, 80th percentile; body mass index=18.2 kg/m 2 ). Treatment was thus begun for presumed salt wasting (SW) CAH using replacement doses of hydrocortisone and fludrocortisone. He had normal male genitalia, descended testes, and no evidence of precocious adrenarche or puberty. He was seen by various providers sporadically over the years, and finally was reviewed in our pediatric endocrinology clinic at 17 years of age. He was on subphysiologic hydrocortisone replacement (7.7 mg/m 2 /day) as well as fludrocortisone (0.2 mg per day), without any symptoms, no history of prostration with illness, and normally-timed pubertal changes. He was obese with normal stature (height=170 cm, z -score=-0.8, 21st percentile; weight=110 kg, z -score=+2.4, 99th percentile; BMI=38.1 kg/m 2 ), and had normal testes with Tanner stage V pubic hair. After his diagnosis, the 3-year-old sister was screened for increased 17-OHP and ACTH levels, which were found to be mildly elevated ( Table 2 ). At the time of her diagnosis she was also of normal growth and stature (height=94 cm, z -score=-0.05, 48th percentile; weight=14 kg, z -score=0.03, 51st percentile; BMI=15.8 kg/m 2 ). She was also started on physiologic doses of hydrocortisone after ACTH1-24 -stimulation showed suboptimal rise in cortisol levels (13.12 μg/dL after 60 minutes). She also presented to us in the Pediatric Endocrinology clinic at the age of 15 and 11 months, on subphysiologic hydrocortisone replacement (8.33 g/m 2 /day), with no history of virilization, precocious puberty or prostration with illness. She was obese (height=158 m, z -score=-0.7, 23rd percentile; weight=73.6 kg, z -score=1.4, 92nd percentile; BMI=29.5 kg/m 2 ), with no hirsutism and normal female genitalia (Tanner V breasts and pubic hair). We questioned the diagnosis of SW CAH, since they were both asymptomatic on subphysiologic hydrocortisone replacement. Work up revealed normal serum electrolytes, mildly increased ACTH and stimulated 17-OHP levels, which when combined with the lack of any symptoms, led us to suspect NC CAH ( Tables 1, 2 ).Thus samples were taken from the family and sent for molecular testing. Participants were tested for the presence of mutation(s) within the CYP21A2 gene and large rearrangements between CYP21A2 and the CYP21A1P pseudogene. The method used was sequencing and multiplex ligation-dependent probe amplification. Molecular testing revealed that the proband had one deleted copy of CYP21A2, whereas the other copy harbored a likely pathogenic sequence variant (c.748C>T, p.R124C). The p.R124C variant has been reported previously in an individual with a diagnosis of CAH. Previous functional studies indicated that this variant has approximately 16% residual activity. The arginine (R) at this position is highly conserved across species and there is a large physicochemical difference between arginine (R) and cysteine (C). In silico analysis, based on SIFT, PolyPhen-2, MutationTaster, and Align GVGD suggests that this variant might affect protein function based on the amino acid change. SIFT categorized these changes as damaging. PolyPhen-2 scored it as probably damaging with HumDiv and HumVar scores of 1.000 and 0.997, respectively (scale: 0.000 – not damaging – to 1.000 – damaging). MutationTaster classified it as "disease causing" with a score of 180 (scale: 0.0 – not disease causing – to 215 – disease causing). Finally, AlignGVGD gave it a GD score of 70.97, which puts it into the most "likely damaging" prediction Class C65 (scale: Class C0 – not damaging – to C65 – most likely to be damaging). Taken together, these findings suggested that p.R124C is likely pathogenic. If p.R124C is pathogenic, the most likely phenotype due to compound heterozygosity for p.R124C and a large deletion would be NC CAH. The proband’s sister had the same genotype. To our surprise, family studies indicated that the father had the same genotype as the 2 children, with one copy deleted and the other harboring the p.R124C mutation. The mother was heterozygous for the large deletion. Therefore, a diagnosis of NC CAH was confirmed, and consequently, we discontinued the current treatment regimen, with regular follow-up visits. Both siblings remain asymptomatic without medication, with mild, expected laboratory derangements, proband’s sister had a 17-OHP levels (9,072 ng/dL) 1 year after the cessation of medication. Follow-up testing could not be performed on the proband.'}
|
{'Case report': 'This research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenants of the Helsinki declaration, and has been approved by the author\'s or equivalent committee. Informed consent was obtained from the parents of the patients. The proband was a male born to consanguineous parents ( Fig. 1 ). He had an acute viral fever at 4 years of age, and was found to have mild hyponatremia and hyperkalemia (sodium 131 mEq/L and potassium 6.1 mEq/L, respectively). Further investigation revealed increased 17-hydroxyprogesterone (17-OHP) and adrenocorticotropic hormone (ACTH) levels ( Table 1 ), and a suboptimal rise in cortisol levels following ACTH1-24 stimulation (13.4 μg/dL after 60 minutes). At the time of diagnosis proband was of normal growth and stature (height=107 cm, z -score=-0.4, 32nd percentile; weight=20.8 kg, z -score=+0.8, 80th percentile; body mass index=18.2 kg/m 2 ). Treatment was thus begun for presumed salt wasting (SW) CAH using replacement doses of hydrocortisone and fludrocortisone. He had normal male genitalia, descended testes, and no evidence of precocious adrenarche or puberty. He was seen by various providers sporadically over the years, and finally was reviewed in our pediatric endocrinology clinic at 17 years of age. He was on subphysiologic hydrocortisone replacement (7.7 mg/m 2 /day) as well as fludrocortisone (0.2 mg per day), without any symptoms, no history of prostration with illness, and normally-timed pubertal changes. He was obese with normal stature (height=170 cm, z -score=-0.8, 21st percentile; weight=110 kg, z -score=+2.4, 99th percentile; BMI=38.1 kg/m 2 ), and had normal testes with Tanner stage V pubic hair. After his diagnosis, the 3-year-old sister was screened for increased 17-OHP and ACTH levels, which were found to be mildly elevated ( Table 2 ). At the time of her diagnosis she was also of normal growth and stature (height=94 cm, z -score=-0.05, 48th percentile; weight=14 kg, z -score=0.03, 51st percentile; BMI=15.8 kg/m 2 ). She was also started on physiologic doses of hydrocortisone after ACTH1-24 -stimulation showed suboptimal rise in cortisol levels (13.12 μg/dL after 60 minutes). She also presented to us in the Pediatric Endocrinology clinic at the age of 15 and 11 months, on subphysiologic hydrocortisone replacement (8.33 g/m 2 /day), with no history of virilization, precocious puberty or prostration with illness. She was obese (height=158 m, z -score=-0.7, 23rd percentile; weight=73.6 kg, z -score=1.4, 92nd percentile; BMI=29.5 kg/m 2 ), with no hirsutism and normal female genitalia (Tanner V breasts and pubic hair). We questioned the diagnosis of SW CAH, since they were both asymptomatic on subphysiologic hydrocortisone replacement. Work up revealed normal serum electrolytes, mildly increased ACTH and stimulated 17-OHP levels, which when combined with the lack of any symptoms, led us to suspect NC CAH ( Tables 1, 2 ).Thus samples were taken from the family and sent for molecular testing. Participants were tested for the presence of mutation(s) within the CYP21A2 gene and large rearrangements between CYP21A2 and the CYP21A1P pseudogene. The method used was sequencing and multiplex ligation-dependent probe amplification. Molecular testing revealed that the proband had one deleted copy of CYP21A2, whereas the other copy harbored a likely pathogenic sequence variant (c.748C>T, p.R124C). The p.R124C variant has been reported previously in an individual with a diagnosis of CAH. Previous functional studies indicated that this variant has approximately 16% residual activity. The arginine (R) at this position is highly conserved across species and there is a large physicochemical difference between arginine (R) and cysteine (C). In silico analysis, based on SIFT, PolyPhen-2, MutationTaster, and Align GVGD suggests that this variant might affect protein function based on the amino acid change. SIFT categorized these changes as damaging. PolyPhen-2 scored it as probably damaging with HumDiv and HumVar scores of 1.000 and 0.997, respectively (scale: 0.000 – not damaging – to 1.000 – damaging). MutationTaster classified it as "disease causing" with a score of 180 (scale: 0.0 – not disease causing – to 215 – disease causing). Finally, AlignGVGD gave it a GD score of 70.97, which puts it into the most "likely damaging" prediction Class C65 (scale: Class C0 – not damaging – to C65 – most likely to be damaging). Taken together, these findings suggested that p.R124C is likely pathogenic. If p.R124C is pathogenic, the most likely phenotype due to compound heterozygosity for p.R124C and a large deletion would be NC CAH. The proband’s sister had the same genotype. To our surprise, family studies indicated that the father had the same genotype as the 2 children, with one copy deleted and the other harboring the p.R124C mutation. The mother was heterozygous for the large deletion. Therefore, a diagnosis of NC CAH was confirmed, and consequently, we discontinued the current treatment regimen, with regular follow-up visits. Both siblings remain asymptomatic without medication, with mild, expected laboratory derangements, proband’s sister had a 17-OHP levels (9,072 ng/dL) 1 year after the cessation of medication. Follow-up testing could not be performed on the proband.'}
|
Pregnancy
|
Pregnancy
|
[] |
test-1922
|
6177667
|
{'Case report': 'This research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenants of the Helsinki declaration, and has been approved by the author\'s or equivalent committee. Informed consent was obtained from the parents of the patients. The proband was a male born to consanguineous parents ( Fig. 1 ). He had an acute viral fever at 4 years of age, and was found to have mild hyponatremia and hyperkalemia (sodium 131 mEq/L and potassium 6.1 mEq/L, respectively). Further investigation revealed increased 17-hydroxyprogesterone (17-OHP) and adrenocorticotropic hormone (ACTH) levels ( Table 1 ), and a suboptimal rise in cortisol levels following ACTH1-24 stimulation (13.4 μg/dL after 60 minutes). At the time of diagnosis proband was of normal growth and stature (height=107 cm, z -score=-0.4, 32nd percentile; weight=20.8 kg, z -score=+0.8, 80th percentile; body mass index=18.2 kg/m 2 ). Treatment was thus begun for presumed salt wasting (SW) CAH using replacement doses of hydrocortisone and fludrocortisone. He had normal male genitalia, descended testes, and no evidence of precocious adrenarche or puberty. He was seen by various providers sporadically over the years, and finally was reviewed in our pediatric endocrinology clinic at 17 years of age. He was on subphysiologic hydrocortisone replacement (7.7 mg/m 2 /day) as well as fludrocortisone (0.2 mg per day), without any symptoms, no history of prostration with illness, and normally-timed pubertal changes. He was obese with normal stature (height=170 cm, z -score=-0.8, 21st percentile; weight=110 kg, z -score=+2.4, 99th percentile; BMI=38.1 kg/m 2 ), and had normal testes with Tanner stage V pubic hair. After his diagnosis, the 3-year-old sister was screened for increased 17-OHP and ACTH levels, which were found to be mildly elevated ( Table 2 ). At the time of her diagnosis she was also of normal growth and stature (height=94 cm, z -score=-0.05, 48th percentile; weight=14 kg, z -score=0.03, 51st percentile; BMI=15.8 kg/m 2 ). She was also started on physiologic doses of hydrocortisone after ACTH1-24 -stimulation showed suboptimal rise in cortisol levels (13.12 μg/dL after 60 minutes). She also presented to us in the Pediatric Endocrinology clinic at the age of 15 and 11 months, on subphysiologic hydrocortisone replacement (8.33 g/m 2 /day), with no history of virilization, precocious puberty or prostration with illness. She was obese (height=158 m, z -score=-0.7, 23rd percentile; weight=73.6 kg, z -score=1.4, 92nd percentile; BMI=29.5 kg/m 2 ), with no hirsutism and normal female genitalia (Tanner V breasts and pubic hair). We questioned the diagnosis of SW CAH, since they were both asymptomatic on subphysiologic hydrocortisone replacement. Work up revealed normal serum electrolytes, mildly increased ACTH and stimulated 17-OHP levels, which when combined with the lack of any symptoms, led us to suspect NC CAH ( Tables 1, 2 ).Thus samples were taken from the family and sent for molecular testing. Participants were tested for the presence of mutation(s) within the CYP21A2 gene and large rearrangements between CYP21A2 and the CYP21A1P pseudogene. The method used was sequencing and multiplex ligation-dependent probe amplification. Molecular testing revealed that the proband had one deleted copy of CYP21A2, whereas the other copy harbored a likely pathogenic sequence variant (c.748C>T, p.R124C). The p.R124C variant has been reported previously in an individual with a diagnosis of CAH. Previous functional studies indicated that this variant has approximately 16% residual activity. The arginine (R) at this position is highly conserved across species and there is a large physicochemical difference between arginine (R) and cysteine (C). In silico analysis, based on SIFT, PolyPhen-2, MutationTaster, and Align GVGD suggests that this variant might affect protein function based on the amino acid change. SIFT categorized these changes as damaging. PolyPhen-2 scored it as probably damaging with HumDiv and HumVar scores of 1.000 and 0.997, respectively (scale: 0.000 – not damaging – to 1.000 – damaging). MutationTaster classified it as "disease causing" with a score of 180 (scale: 0.0 – not disease causing – to 215 – disease causing). Finally, AlignGVGD gave it a GD score of 70.97, which puts it into the most "likely damaging" prediction Class C65 (scale: Class C0 – not damaging – to C65 – most likely to be damaging). Taken together, these findings suggested that p.R124C is likely pathogenic. If p.R124C is pathogenic, the most likely phenotype due to compound heterozygosity for p.R124C and a large deletion would be NC CAH. The proband’s sister had the same genotype. To our surprise, family studies indicated that the father had the same genotype as the 2 children, with one copy deleted and the other harboring the p.R124C mutation. The mother was heterozygous for the large deletion. Therefore, a diagnosis of NC CAH was confirmed, and consequently, we discontinued the current treatment regimen, with regular follow-up visits. Both siblings remain asymptomatic without medication, with mild, expected laboratory derangements, proband’s sister had a 17-OHP levels (9,072 ng/dL) 1 year after the cessation of medication. Follow-up testing could not be performed on the proband.'}
|
{'Case report': 'This research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenants of the Helsinki declaration, and has been approved by the author\'s or equivalent committee. Informed consent was obtained from the parents of the patients. The proband was a male born to consanguineous parents ( Fig. 1 ). He had an acute viral fever at 4 years of age, and was found to have mild hyponatremia and hyperkalemia (sodium 131 mEq/L and potassium 6.1 mEq/L, respectively). Further investigation revealed increased 17-hydroxyprogesterone (17-OHP) and adrenocorticotropic hormone (ACTH) levels ( Table 1 ), and a suboptimal rise in cortisol levels following ACTH1-24 stimulation (13.4 μg/dL after 60 minutes). At the time of diagnosis proband was of normal growth and stature (height=107 cm, z -score=-0.4, 32nd percentile; weight=20.8 kg, z -score=+0.8, 80th percentile; body mass index=18.2 kg/m 2 ). Treatment was thus begun for presumed salt wasting (SW) CAH using replacement doses of hydrocortisone and fludrocortisone. He had normal male genitalia, descended testes, and no evidence of precocious adrenarche or puberty. He was seen by various providers sporadically over the years, and finally was reviewed in our pediatric endocrinology clinic at 17 years of age. He was on subphysiologic hydrocortisone replacement (7.7 mg/m 2 /day) as well as fludrocortisone (0.2 mg per day), without any symptoms, no history of prostration with illness, and normally-timed pubertal changes. He was obese with normal stature (height=170 cm, z -score=-0.8, 21st percentile; weight=110 kg, z -score=+2.4, 99th percentile; BMI=38.1 kg/m 2 ), and had normal testes with Tanner stage V pubic hair. After his diagnosis, the 3-year-old sister was screened for increased 17-OHP and ACTH levels, which were found to be mildly elevated ( Table 2 ). At the time of her diagnosis she was also of normal growth and stature (height=94 cm, z -score=-0.05, 48th percentile; weight=14 kg, z -score=0.03, 51st percentile; BMI=15.8 kg/m 2 ). She was also started on physiologic doses of hydrocortisone after ACTH1-24 -stimulation showed suboptimal rise in cortisol levels (13.12 μg/dL after 60 minutes). She also presented to us in the Pediatric Endocrinology clinic at the age of 15 and 11 months, on subphysiologic hydrocortisone replacement (8.33 g/m 2 /day), with no history of virilization, precocious puberty or prostration with illness. She was obese (height=158 m, z -score=-0.7, 23rd percentile; weight=73.6 kg, z -score=1.4, 92nd percentile; BMI=29.5 kg/m 2 ), with no hirsutism and normal female genitalia (Tanner V breasts and pubic hair). We questioned the diagnosis of SW CAH, since they were both asymptomatic on subphysiologic hydrocortisone replacement. Work up revealed normal serum electrolytes, mildly increased ACTH and stimulated 17-OHP levels, which when combined with the lack of any symptoms, led us to suspect NC CAH ( Tables 1, 2 ).Thus samples were taken from the family and sent for molecular testing. Participants were tested for the presence of mutation(s) within the CYP21A2 gene and large rearrangements between CYP21A2 and the CYP21A1P pseudogene. The method used was sequencing and multiplex ligation-dependent probe amplification. Molecular testing revealed that the proband had one deleted copy of CYP21A2, whereas the other copy harbored a likely pathogenic sequence variant (c.748C>T, p.R124C). The p.R124C variant has been reported previously in an individual with a diagnosis of CAH. Previous functional studies indicated that this variant has approximately 16% residual activity. The arginine (R) at this position is highly conserved across species and there is a large physicochemical difference between arginine (R) and cysteine (C). In silico analysis, based on SIFT, PolyPhen-2, MutationTaster, and Align GVGD suggests that this variant might affect protein function based on the amino acid change. SIFT categorized these changes as damaging. PolyPhen-2 scored it as probably damaging with HumDiv and HumVar scores of 1.000 and 0.997, respectively (scale: 0.000 – not damaging – to 1.000 – damaging). MutationTaster classified it as "disease causing" with a score of 180 (scale: 0.0 – not disease causing – to 215 – disease causing). Finally, AlignGVGD gave it a GD score of 70.97, which puts it into the most "likely damaging" prediction Class C65 (scale: Class C0 – not damaging – to C65 – most likely to be damaging). Taken together, these findings suggested that p.R124C is likely pathogenic. If p.R124C is pathogenic, the most likely phenotype due to compound heterozygosity for p.R124C and a large deletion would be NC CAH. The proband’s sister had the same genotype. To our surprise, family studies indicated that the father had the same genotype as the 2 children, with one copy deleted and the other harboring the p.R124C mutation. The mother was heterozygous for the large deletion. Therefore, a diagnosis of NC CAH was confirmed, and consequently, we discontinued the current treatment regimen, with regular follow-up visits. Both siblings remain asymptomatic without medication, with mild, expected laboratory derangements, proband’s sister had a 17-OHP levels (9,072 ng/dL) 1 year after the cessation of medication. Follow-up testing could not be performed on the proband.'}
|
Lymphatic-System
|
LYMPH
|
[] |
test-1923
|
6177667
|
{'Case report': 'This research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenants of the Helsinki declaration, and has been approved by the author\'s or equivalent committee. Informed consent was obtained from the parents of the patients. The proband was a male born to consanguineous parents ( Fig. 1 ). He had an acute viral fever at 4 years of age, and was found to have mild hyponatremia and hyperkalemia (sodium 131 mEq/L and potassium 6.1 mEq/L, respectively). Further investigation revealed increased 17-hydroxyprogesterone (17-OHP) and adrenocorticotropic hormone (ACTH) levels ( Table 1 ), and a suboptimal rise in cortisol levels following ACTH1-24 stimulation (13.4 μg/dL after 60 minutes). At the time of diagnosis proband was of normal growth and stature (height=107 cm, z -score=-0.4, 32nd percentile; weight=20.8 kg, z -score=+0.8, 80th percentile; body mass index=18.2 kg/m 2 ). Treatment was thus begun for presumed salt wasting (SW) CAH using replacement doses of hydrocortisone and fludrocortisone. He had normal male genitalia, descended testes, and no evidence of precocious adrenarche or puberty. He was seen by various providers sporadically over the years, and finally was reviewed in our pediatric endocrinology clinic at 17 years of age. He was on subphysiologic hydrocortisone replacement (7.7 mg/m 2 /day) as well as fludrocortisone (0.2 mg per day), without any symptoms, no history of prostration with illness, and normally-timed pubertal changes. He was obese with normal stature (height=170 cm, z -score=-0.8, 21st percentile; weight=110 kg, z -score=+2.4, 99th percentile; BMI=38.1 kg/m 2 ), and had normal testes with Tanner stage V pubic hair. After his diagnosis, the 3-year-old sister was screened for increased 17-OHP and ACTH levels, which were found to be mildly elevated ( Table 2 ). At the time of her diagnosis she was also of normal growth and stature (height=94 cm, z -score=-0.05, 48th percentile; weight=14 kg, z -score=0.03, 51st percentile; BMI=15.8 kg/m 2 ). She was also started on physiologic doses of hydrocortisone after ACTH1-24 -stimulation showed suboptimal rise in cortisol levels (13.12 μg/dL after 60 minutes). She also presented to us in the Pediatric Endocrinology clinic at the age of 15 and 11 months, on subphysiologic hydrocortisone replacement (8.33 g/m 2 /day), with no history of virilization, precocious puberty or prostration with illness. She was obese (height=158 m, z -score=-0.7, 23rd percentile; weight=73.6 kg, z -score=1.4, 92nd percentile; BMI=29.5 kg/m 2 ), with no hirsutism and normal female genitalia (Tanner V breasts and pubic hair). We questioned the diagnosis of SW CAH, since they were both asymptomatic on subphysiologic hydrocortisone replacement. Work up revealed normal serum electrolytes, mildly increased ACTH and stimulated 17-OHP levels, which when combined with the lack of any symptoms, led us to suspect NC CAH ( Tables 1, 2 ).Thus samples were taken from the family and sent for molecular testing. Participants were tested for the presence of mutation(s) within the CYP21A2 gene and large rearrangements between CYP21A2 and the CYP21A1P pseudogene. The method used was sequencing and multiplex ligation-dependent probe amplification. Molecular testing revealed that the proband had one deleted copy of CYP21A2, whereas the other copy harbored a likely pathogenic sequence variant (c.748C>T, p.R124C). The p.R124C variant has been reported previously in an individual with a diagnosis of CAH. Previous functional studies indicated that this variant has approximately 16% residual activity. The arginine (R) at this position is highly conserved across species and there is a large physicochemical difference between arginine (R) and cysteine (C). In silico analysis, based on SIFT, PolyPhen-2, MutationTaster, and Align GVGD suggests that this variant might affect protein function based on the amino acid change. SIFT categorized these changes as damaging. PolyPhen-2 scored it as probably damaging with HumDiv and HumVar scores of 1.000 and 0.997, respectively (scale: 0.000 – not damaging – to 1.000 – damaging). MutationTaster classified it as "disease causing" with a score of 180 (scale: 0.0 – not disease causing – to 215 – disease causing). Finally, AlignGVGD gave it a GD score of 70.97, which puts it into the most "likely damaging" prediction Class C65 (scale: Class C0 – not damaging – to C65 – most likely to be damaging). Taken together, these findings suggested that p.R124C is likely pathogenic. If p.R124C is pathogenic, the most likely phenotype due to compound heterozygosity for p.R124C and a large deletion would be NC CAH. The proband’s sister had the same genotype. To our surprise, family studies indicated that the father had the same genotype as the 2 children, with one copy deleted and the other harboring the p.R124C mutation. The mother was heterozygous for the large deletion. Therefore, a diagnosis of NC CAH was confirmed, and consequently, we discontinued the current treatment regimen, with regular follow-up visits. Both siblings remain asymptomatic without medication, with mild, expected laboratory derangements, proband’s sister had a 17-OHP levels (9,072 ng/dL) 1 year after the cessation of medication. Follow-up testing could not be performed on the proband.'}
|
{'Case report': 'This research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenants of the Helsinki declaration, and has been approved by the author\'s or equivalent committee. Informed consent was obtained from the parents of the patients. The proband was a male born to consanguineous parents ( Fig. 1 ). He had an acute viral fever at 4 years of age, and was found to have mild hyponatremia and hyperkalemia (sodium 131 mEq/L and potassium 6.1 mEq/L, respectively). Further investigation revealed increased 17-hydroxyprogesterone (17-OHP) and adrenocorticotropic hormone (ACTH) levels ( Table 1 ), and a suboptimal rise in cortisol levels following ACTH1-24 stimulation (13.4 μg/dL after 60 minutes). At the time of diagnosis proband was of normal growth and stature (height=107 cm, z -score=-0.4, 32nd percentile; weight=20.8 kg, z -score=+0.8, 80th percentile; body mass index=18.2 kg/m 2 ). Treatment was thus begun for presumed salt wasting (SW) CAH using replacement doses of hydrocortisone and fludrocortisone. He had normal male genitalia, descended testes, and no evidence of precocious adrenarche or puberty. He was seen by various providers sporadically over the years, and finally was reviewed in our pediatric endocrinology clinic at 17 years of age. He was on subphysiologic hydrocortisone replacement (7.7 mg/m 2 /day) as well as fludrocortisone (0.2 mg per day), without any symptoms, no history of prostration with illness, and normally-timed pubertal changes. He was obese with normal stature (height=170 cm, z -score=-0.8, 21st percentile; weight=110 kg, z -score=+2.4, 99th percentile; BMI=38.1 kg/m 2 ), and had normal testes with Tanner stage V pubic hair. After his diagnosis, the 3-year-old sister was screened for increased 17-OHP and ACTH levels, which were found to be mildly elevated ( Table 2 ). At the time of her diagnosis she was also of normal growth and stature (height=94 cm, z -score=-0.05, 48th percentile; weight=14 kg, z -score=0.03, 51st percentile; BMI=15.8 kg/m 2 ). She was also started on physiologic doses of hydrocortisone after ACTH1-24 -stimulation showed suboptimal rise in cortisol levels (13.12 μg/dL after 60 minutes). She also presented to us in the Pediatric Endocrinology clinic at the age of 15 and 11 months, on subphysiologic hydrocortisone replacement (8.33 g/m 2 /day), with no history of virilization, precocious puberty or prostration with illness. She was obese (height=158 m, z -score=-0.7, 23rd percentile; weight=73.6 kg, z -score=1.4, 92nd percentile; BMI=29.5 kg/m 2 ), with no hirsutism and normal female genitalia (Tanner V breasts and pubic hair). We questioned the diagnosis of SW CAH, since they were both asymptomatic on subphysiologic hydrocortisone replacement. Work up revealed normal serum electrolytes, mildly increased ACTH and stimulated 17-OHP levels, which when combined with the lack of any symptoms, led us to suspect NC CAH ( Tables 1, 2 ).Thus samples were taken from the family and sent for molecular testing. Participants were tested for the presence of mutation(s) within the CYP21A2 gene and large rearrangements between CYP21A2 and the CYP21A1P pseudogene. The method used was sequencing and multiplex ligation-dependent probe amplification. Molecular testing revealed that the proband had one deleted copy of CYP21A2, whereas the other copy harbored a likely pathogenic sequence variant (c.748C>T, p.R124C). The p.R124C variant has been reported previously in an individual with a diagnosis of CAH. Previous functional studies indicated that this variant has approximately 16% residual activity. The arginine (R) at this position is highly conserved across species and there is a large physicochemical difference between arginine (R) and cysteine (C). In silico analysis, based on SIFT, PolyPhen-2, MutationTaster, and Align GVGD suggests that this variant might affect protein function based on the amino acid change. SIFT categorized these changes as damaging. PolyPhen-2 scored it as probably damaging with HumDiv and HumVar scores of 1.000 and 0.997, respectively (scale: 0.000 – not damaging – to 1.000 – damaging). MutationTaster classified it as "disease causing" with a score of 180 (scale: 0.0 – not disease causing – to 215 – disease causing). Finally, AlignGVGD gave it a GD score of 70.97, which puts it into the most "likely damaging" prediction Class C65 (scale: Class C0 – not damaging – to C65 – most likely to be damaging). Taken together, these findings suggested that p.R124C is likely pathogenic. If p.R124C is pathogenic, the most likely phenotype due to compound heterozygosity for p.R124C and a large deletion would be NC CAH. The proband’s sister had the same genotype. To our surprise, family studies indicated that the father had the same genotype as the 2 children, with one copy deleted and the other harboring the p.R124C mutation. The mother was heterozygous for the large deletion. Therefore, a diagnosis of NC CAH was confirmed, and consequently, we discontinued the current treatment regimen, with regular follow-up visits. Both siblings remain asymptomatic without medication, with mild, expected laboratory derangements, proband’s sister had a 17-OHP levels (9,072 ng/dL) 1 year after the cessation of medication. Follow-up testing could not be performed on the proband.'}
|
Age-at-Presentation
|
Age (at case presentation)
|
[
"17 years of age",
"age of 15 and 11 months"
] |
test-1924
|
6177667
|
{'Case report': 'This research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenants of the Helsinki declaration, and has been approved by the author\'s or equivalent committee. Informed consent was obtained from the parents of the patients. The proband was a male born to consanguineous parents ( Fig. 1 ). He had an acute viral fever at 4 years of age, and was found to have mild hyponatremia and hyperkalemia (sodium 131 mEq/L and potassium 6.1 mEq/L, respectively). Further investigation revealed increased 17-hydroxyprogesterone (17-OHP) and adrenocorticotropic hormone (ACTH) levels ( Table 1 ), and a suboptimal rise in cortisol levels following ACTH1-24 stimulation (13.4 μg/dL after 60 minutes). At the time of diagnosis proband was of normal growth and stature (height=107 cm, z -score=-0.4, 32nd percentile; weight=20.8 kg, z -score=+0.8, 80th percentile; body mass index=18.2 kg/m 2 ). Treatment was thus begun for presumed salt wasting (SW) CAH using replacement doses of hydrocortisone and fludrocortisone. He had normal male genitalia, descended testes, and no evidence of precocious adrenarche or puberty. He was seen by various providers sporadically over the years, and finally was reviewed in our pediatric endocrinology clinic at 17 years of age. He was on subphysiologic hydrocortisone replacement (7.7 mg/m 2 /day) as well as fludrocortisone (0.2 mg per day), without any symptoms, no history of prostration with illness, and normally-timed pubertal changes. He was obese with normal stature (height=170 cm, z -score=-0.8, 21st percentile; weight=110 kg, z -score=+2.4, 99th percentile; BMI=38.1 kg/m 2 ), and had normal testes with Tanner stage V pubic hair. After his diagnosis, the 3-year-old sister was screened for increased 17-OHP and ACTH levels, which were found to be mildly elevated ( Table 2 ). At the time of her diagnosis she was also of normal growth and stature (height=94 cm, z -score=-0.05, 48th percentile; weight=14 kg, z -score=0.03, 51st percentile; BMI=15.8 kg/m 2 ). She was also started on physiologic doses of hydrocortisone after ACTH1-24 -stimulation showed suboptimal rise in cortisol levels (13.12 μg/dL after 60 minutes). She also presented to us in the Pediatric Endocrinology clinic at the age of 15 and 11 months, on subphysiologic hydrocortisone replacement (8.33 g/m 2 /day), with no history of virilization, precocious puberty or prostration with illness. She was obese (height=158 m, z -score=-0.7, 23rd percentile; weight=73.6 kg, z -score=1.4, 92nd percentile; BMI=29.5 kg/m 2 ), with no hirsutism and normal female genitalia (Tanner V breasts and pubic hair). We questioned the diagnosis of SW CAH, since they were both asymptomatic on subphysiologic hydrocortisone replacement. Work up revealed normal serum electrolytes, mildly increased ACTH and stimulated 17-OHP levels, which when combined with the lack of any symptoms, led us to suspect NC CAH ( Tables 1, 2 ).Thus samples were taken from the family and sent for molecular testing. Participants were tested for the presence of mutation(s) within the CYP21A2 gene and large rearrangements between CYP21A2 and the CYP21A1P pseudogene. The method used was sequencing and multiplex ligation-dependent probe amplification. Molecular testing revealed that the proband had one deleted copy of CYP21A2, whereas the other copy harbored a likely pathogenic sequence variant (c.748C>T, p.R124C). The p.R124C variant has been reported previously in an individual with a diagnosis of CAH. Previous functional studies indicated that this variant has approximately 16% residual activity. The arginine (R) at this position is highly conserved across species and there is a large physicochemical difference between arginine (R) and cysteine (C). In silico analysis, based on SIFT, PolyPhen-2, MutationTaster, and Align GVGD suggests that this variant might affect protein function based on the amino acid change. SIFT categorized these changes as damaging. PolyPhen-2 scored it as probably damaging with HumDiv and HumVar scores of 1.000 and 0.997, respectively (scale: 0.000 – not damaging – to 1.000 – damaging). MutationTaster classified it as "disease causing" with a score of 180 (scale: 0.0 – not disease causing – to 215 – disease causing). Finally, AlignGVGD gave it a GD score of 70.97, which puts it into the most "likely damaging" prediction Class C65 (scale: Class C0 – not damaging – to C65 – most likely to be damaging). Taken together, these findings suggested that p.R124C is likely pathogenic. If p.R124C is pathogenic, the most likely phenotype due to compound heterozygosity for p.R124C and a large deletion would be NC CAH. The proband’s sister had the same genotype. To our surprise, family studies indicated that the father had the same genotype as the 2 children, with one copy deleted and the other harboring the p.R124C mutation. The mother was heterozygous for the large deletion. Therefore, a diagnosis of NC CAH was confirmed, and consequently, we discontinued the current treatment regimen, with regular follow-up visits. Both siblings remain asymptomatic without medication, with mild, expected laboratory derangements, proband’s sister had a 17-OHP levels (9,072 ng/dL) 1 year after the cessation of medication. Follow-up testing could not be performed on the proband.'}
|
{'Case report': 'This research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenants of the Helsinki declaration, and has been approved by the author\'s or equivalent committee. Informed consent was obtained from the parents of the patients. The proband was a male born to consanguineous parents ( Fig. 1 ). He had an acute viral fever at 4 years of age, and was found to have mild hyponatremia and hyperkalemia (sodium 131 mEq/L and potassium 6.1 mEq/L, respectively). Further investigation revealed increased 17-hydroxyprogesterone (17-OHP) and adrenocorticotropic hormone (ACTH) levels ( Table 1 ), and a suboptimal rise in cortisol levels following ACTH1-24 stimulation (13.4 μg/dL after 60 minutes). At the time of diagnosis proband was of normal growth and stature (height=107 cm, z -score=-0.4, 32nd percentile; weight=20.8 kg, z -score=+0.8, 80th percentile; body mass index=18.2 kg/m 2 ). Treatment was thus begun for presumed salt wasting (SW) CAH using replacement doses of hydrocortisone and fludrocortisone. He had normal male genitalia, descended testes, and no evidence of precocious adrenarche or puberty. He was seen by various providers sporadically over the years, and finally was reviewed in our pediatric endocrinology clinic at 17 years of age. He was on subphysiologic hydrocortisone replacement (7.7 mg/m 2 /day) as well as fludrocortisone (0.2 mg per day), without any symptoms, no history of prostration with illness, and normally-timed pubertal changes. He was obese with normal stature (height=170 cm, z -score=-0.8, 21st percentile; weight=110 kg, z -score=+2.4, 99th percentile; BMI=38.1 kg/m 2 ), and had normal testes with Tanner stage V pubic hair. After his diagnosis, the 3-year-old sister was screened for increased 17-OHP and ACTH levels, which were found to be mildly elevated ( Table 2 ). At the time of her diagnosis she was also of normal growth and stature (height=94 cm, z -score=-0.05, 48th percentile; weight=14 kg, z -score=0.03, 51st percentile; BMI=15.8 kg/m 2 ). She was also started on physiologic doses of hydrocortisone after ACTH1-24 -stimulation showed suboptimal rise in cortisol levels (13.12 μg/dL after 60 minutes). She also presented to us in the Pediatric Endocrinology clinic at the age of 15 and 11 months, on subphysiologic hydrocortisone replacement (8.33 g/m 2 /day), with no history of virilization, precocious puberty or prostration with illness. She was obese (height=158 m, z -score=-0.7, 23rd percentile; weight=73.6 kg, z -score=1.4, 92nd percentile; BMI=29.5 kg/m 2 ), with no hirsutism and normal female genitalia (Tanner V breasts and pubic hair). We questioned the diagnosis of SW CAH, since they were both asymptomatic on subphysiologic hydrocortisone replacement. Work up revealed normal serum electrolytes, mildly increased ACTH and stimulated 17-OHP levels, which when combined with the lack of any symptoms, led us to suspect NC CAH ( Tables 1, 2 ).Thus samples were taken from the family and sent for molecular testing. Participants were tested for the presence of mutation(s) within the CYP21A2 gene and large rearrangements between CYP21A2 and the CYP21A1P pseudogene. The method used was sequencing and multiplex ligation-dependent probe amplification. Molecular testing revealed that the proband had one deleted copy of CYP21A2, whereas the other copy harbored a likely pathogenic sequence variant (c.748C>T, p.R124C). The p.R124C variant has been reported previously in an individual with a diagnosis of CAH. Previous functional studies indicated that this variant has approximately 16% residual activity. The arginine (R) at this position is highly conserved across species and there is a large physicochemical difference between arginine (R) and cysteine (C). In silico analysis, based on SIFT, PolyPhen-2, MutationTaster, and Align GVGD suggests that this variant might affect protein function based on the amino acid change. SIFT categorized these changes as damaging. PolyPhen-2 scored it as probably damaging with HumDiv and HumVar scores of 1.000 and 0.997, respectively (scale: 0.000 – not damaging – to 1.000 – damaging). MutationTaster classified it as "disease causing" with a score of 180 (scale: 0.0 – not disease causing – to 215 – disease causing). Finally, AlignGVGD gave it a GD score of 70.97, which puts it into the most "likely damaging" prediction Class C65 (scale: Class C0 – not damaging – to C65 – most likely to be damaging). Taken together, these findings suggested that p.R124C is likely pathogenic. If p.R124C is pathogenic, the most likely phenotype due to compound heterozygosity for p.R124C and a large deletion would be NC CAH. The proband’s sister had the same genotype. To our surprise, family studies indicated that the father had the same genotype as the 2 children, with one copy deleted and the other harboring the p.R124C mutation. The mother was heterozygous for the large deletion. Therefore, a diagnosis of NC CAH was confirmed, and consequently, we discontinued the current treatment regimen, with regular follow-up visits. Both siblings remain asymptomatic without medication, with mild, expected laboratory derangements, proband’s sister had a 17-OHP levels (9,072 ng/dL) 1 year after the cessation of medication. Follow-up testing could not be performed on the proband.'}
|
Age-of-Onset
|
Age (of onset)
|
[
"4 years of age ,",
"3 - year - old"
] |
test-1925
|
6177667
|
{'Case report': 'This research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenants of the Helsinki declaration, and has been approved by the author\'s or equivalent committee. Informed consent was obtained from the parents of the patients. The proband was a male born to consanguineous parents ( Fig. 1 ). He had an acute viral fever at 4 years of age, and was found to have mild hyponatremia and hyperkalemia (sodium 131 mEq/L and potassium 6.1 mEq/L, respectively). Further investigation revealed increased 17-hydroxyprogesterone (17-OHP) and adrenocorticotropic hormone (ACTH) levels ( Table 1 ), and a suboptimal rise in cortisol levels following ACTH1-24 stimulation (13.4 μg/dL after 60 minutes). At the time of diagnosis proband was of normal growth and stature (height=107 cm, z -score=-0.4, 32nd percentile; weight=20.8 kg, z -score=+0.8, 80th percentile; body mass index=18.2 kg/m 2 ). Treatment was thus begun for presumed salt wasting (SW) CAH using replacement doses of hydrocortisone and fludrocortisone. He had normal male genitalia, descended testes, and no evidence of precocious adrenarche or puberty. He was seen by various providers sporadically over the years, and finally was reviewed in our pediatric endocrinology clinic at 17 years of age. He was on subphysiologic hydrocortisone replacement (7.7 mg/m 2 /day) as well as fludrocortisone (0.2 mg per day), without any symptoms, no history of prostration with illness, and normally-timed pubertal changes. He was obese with normal stature (height=170 cm, z -score=-0.8, 21st percentile; weight=110 kg, z -score=+2.4, 99th percentile; BMI=38.1 kg/m 2 ), and had normal testes with Tanner stage V pubic hair. After his diagnosis, the 3-year-old sister was screened for increased 17-OHP and ACTH levels, which were found to be mildly elevated ( Table 2 ). At the time of her diagnosis she was also of normal growth and stature (height=94 cm, z -score=-0.05, 48th percentile; weight=14 kg, z -score=0.03, 51st percentile; BMI=15.8 kg/m 2 ). She was also started on physiologic doses of hydrocortisone after ACTH1-24 -stimulation showed suboptimal rise in cortisol levels (13.12 μg/dL after 60 minutes). She also presented to us in the Pediatric Endocrinology clinic at the age of 15 and 11 months, on subphysiologic hydrocortisone replacement (8.33 g/m 2 /day), with no history of virilization, precocious puberty or prostration with illness. She was obese (height=158 m, z -score=-0.7, 23rd percentile; weight=73.6 kg, z -score=1.4, 92nd percentile; BMI=29.5 kg/m 2 ), with no hirsutism and normal female genitalia (Tanner V breasts and pubic hair). We questioned the diagnosis of SW CAH, since they were both asymptomatic on subphysiologic hydrocortisone replacement. Work up revealed normal serum electrolytes, mildly increased ACTH and stimulated 17-OHP levels, which when combined with the lack of any symptoms, led us to suspect NC CAH ( Tables 1, 2 ).Thus samples were taken from the family and sent for molecular testing. Participants were tested for the presence of mutation(s) within the CYP21A2 gene and large rearrangements between CYP21A2 and the CYP21A1P pseudogene. The method used was sequencing and multiplex ligation-dependent probe amplification. Molecular testing revealed that the proband had one deleted copy of CYP21A2, whereas the other copy harbored a likely pathogenic sequence variant (c.748C>T, p.R124C). The p.R124C variant has been reported previously in an individual with a diagnosis of CAH. Previous functional studies indicated that this variant has approximately 16% residual activity. The arginine (R) at this position is highly conserved across species and there is a large physicochemical difference between arginine (R) and cysteine (C). In silico analysis, based on SIFT, PolyPhen-2, MutationTaster, and Align GVGD suggests that this variant might affect protein function based on the amino acid change. SIFT categorized these changes as damaging. PolyPhen-2 scored it as probably damaging with HumDiv and HumVar scores of 1.000 and 0.997, respectively (scale: 0.000 – not damaging – to 1.000 – damaging). MutationTaster classified it as "disease causing" with a score of 180 (scale: 0.0 – not disease causing – to 215 – disease causing). Finally, AlignGVGD gave it a GD score of 70.97, which puts it into the most "likely damaging" prediction Class C65 (scale: Class C0 – not damaging – to C65 – most likely to be damaging). Taken together, these findings suggested that p.R124C is likely pathogenic. If p.R124C is pathogenic, the most likely phenotype due to compound heterozygosity for p.R124C and a large deletion would be NC CAH. The proband’s sister had the same genotype. To our surprise, family studies indicated that the father had the same genotype as the 2 children, with one copy deleted and the other harboring the p.R124C mutation. The mother was heterozygous for the large deletion. Therefore, a diagnosis of NC CAH was confirmed, and consequently, we discontinued the current treatment regimen, with regular follow-up visits. Both siblings remain asymptomatic without medication, with mild, expected laboratory derangements, proband’s sister had a 17-OHP levels (9,072 ng/dL) 1 year after the cessation of medication. Follow-up testing could not be performed on the proband.'}
|
{'Case report': 'This research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenants of the Helsinki declaration, and has been approved by the author\'s or equivalent committee. Informed consent was obtained from the parents of the patients. The proband was a male born to consanguineous parents ( Fig. 1 ). He had an acute viral fever at 4 years of age, and was found to have mild hyponatremia and hyperkalemia (sodium 131 mEq/L and potassium 6.1 mEq/L, respectively). Further investigation revealed increased 17-hydroxyprogesterone (17-OHP) and adrenocorticotropic hormone (ACTH) levels ( Table 1 ), and a suboptimal rise in cortisol levels following ACTH1-24 stimulation (13.4 μg/dL after 60 minutes). At the time of diagnosis proband was of normal growth and stature (height=107 cm, z -score=-0.4, 32nd percentile; weight=20.8 kg, z -score=+0.8, 80th percentile; body mass index=18.2 kg/m 2 ). Treatment was thus begun for presumed salt wasting (SW) CAH using replacement doses of hydrocortisone and fludrocortisone. He had normal male genitalia, descended testes, and no evidence of precocious adrenarche or puberty. He was seen by various providers sporadically over the years, and finally was reviewed in our pediatric endocrinology clinic at 17 years of age. He was on subphysiologic hydrocortisone replacement (7.7 mg/m 2 /day) as well as fludrocortisone (0.2 mg per day), without any symptoms, no history of prostration with illness, and normally-timed pubertal changes. He was obese with normal stature (height=170 cm, z -score=-0.8, 21st percentile; weight=110 kg, z -score=+2.4, 99th percentile; BMI=38.1 kg/m 2 ), and had normal testes with Tanner stage V pubic hair. After his diagnosis, the 3-year-old sister was screened for increased 17-OHP and ACTH levels, which were found to be mildly elevated ( Table 2 ). At the time of her diagnosis she was also of normal growth and stature (height=94 cm, z -score=-0.05, 48th percentile; weight=14 kg, z -score=0.03, 51st percentile; BMI=15.8 kg/m 2 ). She was also started on physiologic doses of hydrocortisone after ACTH1-24 -stimulation showed suboptimal rise in cortisol levels (13.12 μg/dL after 60 minutes). She also presented to us in the Pediatric Endocrinology clinic at the age of 15 and 11 months, on subphysiologic hydrocortisone replacement (8.33 g/m 2 /day), with no history of virilization, precocious puberty or prostration with illness. She was obese (height=158 m, z -score=-0.7, 23rd percentile; weight=73.6 kg, z -score=1.4, 92nd percentile; BMI=29.5 kg/m 2 ), with no hirsutism and normal female genitalia (Tanner V breasts and pubic hair). We questioned the diagnosis of SW CAH, since they were both asymptomatic on subphysiologic hydrocortisone replacement. Work up revealed normal serum electrolytes, mildly increased ACTH and stimulated 17-OHP levels, which when combined with the lack of any symptoms, led us to suspect NC CAH ( Tables 1, 2 ).Thus samples were taken from the family and sent for molecular testing. Participants were tested for the presence of mutation(s) within the CYP21A2 gene and large rearrangements between CYP21A2 and the CYP21A1P pseudogene. The method used was sequencing and multiplex ligation-dependent probe amplification. Molecular testing revealed that the proband had one deleted copy of CYP21A2, whereas the other copy harbored a likely pathogenic sequence variant (c.748C>T, p.R124C). The p.R124C variant has been reported previously in an individual with a diagnosis of CAH. Previous functional studies indicated that this variant has approximately 16% residual activity. The arginine (R) at this position is highly conserved across species and there is a large physicochemical difference between arginine (R) and cysteine (C). In silico analysis, based on SIFT, PolyPhen-2, MutationTaster, and Align GVGD suggests that this variant might affect protein function based on the amino acid change. SIFT categorized these changes as damaging. PolyPhen-2 scored it as probably damaging with HumDiv and HumVar scores of 1.000 and 0.997, respectively (scale: 0.000 – not damaging – to 1.000 – damaging). MutationTaster classified it as "disease causing" with a score of 180 (scale: 0.0 – not disease causing – to 215 – disease causing). Finally, AlignGVGD gave it a GD score of 70.97, which puts it into the most "likely damaging" prediction Class C65 (scale: Class C0 – not damaging – to C65 – most likely to be damaging). Taken together, these findings suggested that p.R124C is likely pathogenic. If p.R124C is pathogenic, the most likely phenotype due to compound heterozygosity for p.R124C and a large deletion would be NC CAH. The proband’s sister had the same genotype. To our surprise, family studies indicated that the father had the same genotype as the 2 children, with one copy deleted and the other harboring the p.R124C mutation. The mother was heterozygous for the large deletion. Therefore, a diagnosis of NC CAH was confirmed, and consequently, we discontinued the current treatment regimen, with regular follow-up visits. Both siblings remain asymptomatic without medication, with mild, expected laboratory derangements, proband’s sister had a 17-OHP levels (9,072 ng/dL) 1 year after the cessation of medication. Follow-up testing could not be performed on the proband.'}
|
Confirmed-Diagnosis-IEM
|
Confirmed_Diagnosis(IEM)
|
[
"If p. R124C is pathogenic , the most likely phenotype due to compound heterozygosity for p. R124C and a large deletion would be NC CAH",
"a diagnosis of NC CAH was confirmed"
] |
test-1926
|
6177667
|
{'Case report': 'This research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenants of the Helsinki declaration, and has been approved by the author\'s or equivalent committee. Informed consent was obtained from the parents of the patients. The proband was a male born to consanguineous parents ( Fig. 1 ). He had an acute viral fever at 4 years of age, and was found to have mild hyponatremia and hyperkalemia (sodium 131 mEq/L and potassium 6.1 mEq/L, respectively). Further investigation revealed increased 17-hydroxyprogesterone (17-OHP) and adrenocorticotropic hormone (ACTH) levels ( Table 1 ), and a suboptimal rise in cortisol levels following ACTH1-24 stimulation (13.4 μg/dL after 60 minutes). At the time of diagnosis proband was of normal growth and stature (height=107 cm, z -score=-0.4, 32nd percentile; weight=20.8 kg, z -score=+0.8, 80th percentile; body mass index=18.2 kg/m 2 ). Treatment was thus begun for presumed salt wasting (SW) CAH using replacement doses of hydrocortisone and fludrocortisone. He had normal male genitalia, descended testes, and no evidence of precocious adrenarche or puberty. He was seen by various providers sporadically over the years, and finally was reviewed in our pediatric endocrinology clinic at 17 years of age. He was on subphysiologic hydrocortisone replacement (7.7 mg/m 2 /day) as well as fludrocortisone (0.2 mg per day), without any symptoms, no history of prostration with illness, and normally-timed pubertal changes. He was obese with normal stature (height=170 cm, z -score=-0.8, 21st percentile; weight=110 kg, z -score=+2.4, 99th percentile; BMI=38.1 kg/m 2 ), and had normal testes with Tanner stage V pubic hair. After his diagnosis, the 3-year-old sister was screened for increased 17-OHP and ACTH levels, which were found to be mildly elevated ( Table 2 ). At the time of her diagnosis she was also of normal growth and stature (height=94 cm, z -score=-0.05, 48th percentile; weight=14 kg, z -score=0.03, 51st percentile; BMI=15.8 kg/m 2 ). She was also started on physiologic doses of hydrocortisone after ACTH1-24 -stimulation showed suboptimal rise in cortisol levels (13.12 μg/dL after 60 minutes). She also presented to us in the Pediatric Endocrinology clinic at the age of 15 and 11 months, on subphysiologic hydrocortisone replacement (8.33 g/m 2 /day), with no history of virilization, precocious puberty or prostration with illness. She was obese (height=158 m, z -score=-0.7, 23rd percentile; weight=73.6 kg, z -score=1.4, 92nd percentile; BMI=29.5 kg/m 2 ), with no hirsutism and normal female genitalia (Tanner V breasts and pubic hair). We questioned the diagnosis of SW CAH, since they were both asymptomatic on subphysiologic hydrocortisone replacement. Work up revealed normal serum electrolytes, mildly increased ACTH and stimulated 17-OHP levels, which when combined with the lack of any symptoms, led us to suspect NC CAH ( Tables 1, 2 ).Thus samples were taken from the family and sent for molecular testing. Participants were tested for the presence of mutation(s) within the CYP21A2 gene and large rearrangements between CYP21A2 and the CYP21A1P pseudogene. The method used was sequencing and multiplex ligation-dependent probe amplification. Molecular testing revealed that the proband had one deleted copy of CYP21A2, whereas the other copy harbored a likely pathogenic sequence variant (c.748C>T, p.R124C). The p.R124C variant has been reported previously in an individual with a diagnosis of CAH. Previous functional studies indicated that this variant has approximately 16% residual activity. The arginine (R) at this position is highly conserved across species and there is a large physicochemical difference between arginine (R) and cysteine (C). In silico analysis, based on SIFT, PolyPhen-2, MutationTaster, and Align GVGD suggests that this variant might affect protein function based on the amino acid change. SIFT categorized these changes as damaging. PolyPhen-2 scored it as probably damaging with HumDiv and HumVar scores of 1.000 and 0.997, respectively (scale: 0.000 – not damaging – to 1.000 – damaging). MutationTaster classified it as "disease causing" with a score of 180 (scale: 0.0 – not disease causing – to 215 – disease causing). Finally, AlignGVGD gave it a GD score of 70.97, which puts it into the most "likely damaging" prediction Class C65 (scale: Class C0 – not damaging – to C65 – most likely to be damaging). Taken together, these findings suggested that p.R124C is likely pathogenic. If p.R124C is pathogenic, the most likely phenotype due to compound heterozygosity for p.R124C and a large deletion would be NC CAH. The proband’s sister had the same genotype. To our surprise, family studies indicated that the father had the same genotype as the 2 children, with one copy deleted and the other harboring the p.R124C mutation. The mother was heterozygous for the large deletion. Therefore, a diagnosis of NC CAH was confirmed, and consequently, we discontinued the current treatment regimen, with regular follow-up visits. Both siblings remain asymptomatic without medication, with mild, expected laboratory derangements, proband’s sister had a 17-OHP levels (9,072 ng/dL) 1 year after the cessation of medication. Follow-up testing could not be performed on the proband.'}
|
{'Case report': 'This research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenants of the Helsinki declaration, and has been approved by the author\'s or equivalent committee. Informed consent was obtained from the parents of the patients. The proband was a male born to consanguineous parents ( Fig. 1 ). He had an acute viral fever at 4 years of age, and was found to have mild hyponatremia and hyperkalemia (sodium 131 mEq/L and potassium 6.1 mEq/L, respectively). Further investigation revealed increased 17-hydroxyprogesterone (17-OHP) and adrenocorticotropic hormone (ACTH) levels ( Table 1 ), and a suboptimal rise in cortisol levels following ACTH1-24 stimulation (13.4 μg/dL after 60 minutes). At the time of diagnosis proband was of normal growth and stature (height=107 cm, z -score=-0.4, 32nd percentile; weight=20.8 kg, z -score=+0.8, 80th percentile; body mass index=18.2 kg/m 2 ). Treatment was thus begun for presumed salt wasting (SW) CAH using replacement doses of hydrocortisone and fludrocortisone. He had normal male genitalia, descended testes, and no evidence of precocious adrenarche or puberty. He was seen by various providers sporadically over the years, and finally was reviewed in our pediatric endocrinology clinic at 17 years of age. He was on subphysiologic hydrocortisone replacement (7.7 mg/m 2 /day) as well as fludrocortisone (0.2 mg per day), without any symptoms, no history of prostration with illness, and normally-timed pubertal changes. He was obese with normal stature (height=170 cm, z -score=-0.8, 21st percentile; weight=110 kg, z -score=+2.4, 99th percentile; BMI=38.1 kg/m 2 ), and had normal testes with Tanner stage V pubic hair. After his diagnosis, the 3-year-old sister was screened for increased 17-OHP and ACTH levels, which were found to be mildly elevated ( Table 2 ). At the time of her diagnosis she was also of normal growth and stature (height=94 cm, z -score=-0.05, 48th percentile; weight=14 kg, z -score=0.03, 51st percentile; BMI=15.8 kg/m 2 ). She was also started on physiologic doses of hydrocortisone after ACTH1-24 -stimulation showed suboptimal rise in cortisol levels (13.12 μg/dL after 60 minutes). She also presented to us in the Pediatric Endocrinology clinic at the age of 15 and 11 months, on subphysiologic hydrocortisone replacement (8.33 g/m 2 /day), with no history of virilization, precocious puberty or prostration with illness. She was obese (height=158 m, z -score=-0.7, 23rd percentile; weight=73.6 kg, z -score=1.4, 92nd percentile; BMI=29.5 kg/m 2 ), with no hirsutism and normal female genitalia (Tanner V breasts and pubic hair). We questioned the diagnosis of SW CAH, since they were both asymptomatic on subphysiologic hydrocortisone replacement. Work up revealed normal serum electrolytes, mildly increased ACTH and stimulated 17-OHP levels, which when combined with the lack of any symptoms, led us to suspect NC CAH ( Tables 1, 2 ).Thus samples were taken from the family and sent for molecular testing. Participants were tested for the presence of mutation(s) within the CYP21A2 gene and large rearrangements between CYP21A2 and the CYP21A1P pseudogene. The method used was sequencing and multiplex ligation-dependent probe amplification. Molecular testing revealed that the proband had one deleted copy of CYP21A2, whereas the other copy harbored a likely pathogenic sequence variant (c.748C>T, p.R124C). The p.R124C variant has been reported previously in an individual with a diagnosis of CAH. Previous functional studies indicated that this variant has approximately 16% residual activity. The arginine (R) at this position is highly conserved across species and there is a large physicochemical difference between arginine (R) and cysteine (C). In silico analysis, based on SIFT, PolyPhen-2, MutationTaster, and Align GVGD suggests that this variant might affect protein function based on the amino acid change. SIFT categorized these changes as damaging. PolyPhen-2 scored it as probably damaging with HumDiv and HumVar scores of 1.000 and 0.997, respectively (scale: 0.000 – not damaging – to 1.000 – damaging). MutationTaster classified it as "disease causing" with a score of 180 (scale: 0.0 – not disease causing – to 215 – disease causing). Finally, AlignGVGD gave it a GD score of 70.97, which puts it into the most "likely damaging" prediction Class C65 (scale: Class C0 – not damaging – to C65 – most likely to be damaging). Taken together, these findings suggested that p.R124C is likely pathogenic. If p.R124C is pathogenic, the most likely phenotype due to compound heterozygosity for p.R124C and a large deletion would be NC CAH. The proband’s sister had the same genotype. To our surprise, family studies indicated that the father had the same genotype as the 2 children, with one copy deleted and the other harboring the p.R124C mutation. The mother was heterozygous for the large deletion. Therefore, a diagnosis of NC CAH was confirmed, and consequently, we discontinued the current treatment regimen, with regular follow-up visits. Both siblings remain asymptomatic without medication, with mild, expected laboratory derangements, proband’s sister had a 17-OHP levels (9,072 ng/dL) 1 year after the cessation of medication. Follow-up testing could not be performed on the proband.'}
|
IEM-Treatment
|
IEM_Treatment
|
[
"replacement doses of hydrocortisone and fludrocortisone"
] |
test-1927
|
6028668
|
{'Clinical, laboratory and imaging examinations': 'The patient was lean (height 149.0 cm, weight 39.2 kg, BMI 17.7 kg/m 2 ), and the findings of a physical examination were unremarkable except for confirmation of xanthomas on the bilateral Achilles tendons ( Fig. 1B ) and right triceps muscle. She had age-appropriate slight cataracts in the bilateral eyes and did not have dementia based on the Revised Hasegawa Dementia Scale (HSD-R; 26/30), Mini-Mental State Examination (MMSE; 27/30), and Frontal Assessment Battery (FAB; 16/18) scores. On a neurological examination, her gait appeared somewhat spastic, and all of her deep tendon reflexes were mildly enhanced bilaterally with positive Babinski and Chaddock reflexes, indicating impairment in the bilateral pyramidal tracts. There were no neurological findings suggesting cerebellar impairment. Regarding the laboratory findings ( Table 1 ), there was no elevation in the levels of serum cholesterol or triglycerides or deficiencies in apolipoproteins or thyroid hormones. As the clinical findings suggested CTX, we studied the bile acids and sterols in her serum and urine ( Table 2 ). The primary bile acids were extremely low in the serum and urine when measured by both high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometer (GC/MS). The urinary levels of bile alcohols, especially 5β-cholestane-3α,7α,12α,24,25-pentol, were markedly elevated. Norcholic acid, which is mainly derived from 5β-cholestane-3α,7α,12α,23,25-pentol, was highly elevated and accounted for 78.4% of all bile acids in the urine. The serum level of cholestanol was extremely elevated, while those of sitosterol and campesterol were not elevated. T2-weighted and fluid-attenuated inversion recovery (FLAIR) MRI of the brain showed bilateral low-intensity areas in the dentate nuclei and high-intensity areas in the peripheral white matter the cerebellum ( Fig. 1C ). We also found bilateral high-intensity areas along the pyramidal tracts from the pons to the cerebral crus. Brain atrophy was not remarkable. Based on these clinical, laboratory and radiological findings, the patient was diagnosed with CTX. Ultrasound of the carotid arteries showed a slightly thickened intima-media complex at the left common carotid artery (maximum intima-media thickness, 1.2 mm). However, there was no evidence of cardiovascular disease on electrocardiogram, echocardiography and MR angiography of the brain and lower extremities. Despite being premenopausal ( Table 1 ), she had osteoporosis as determined by dual-energy X-ray absorptiometry, which showed a bone density of 61% and 75% the young-adult-mean in the lumbar vertebra and femoral neck, respectively.', 'Case presentation': 'The patient was a 50-year-old Japanese woman from non-consanguineous parents. She has no siblings but had a child. There was no apparent family history (parents, child and parent’s siblings) of neurological disorders, cardiovascular diseases or any lipid storage diseases inducing xanthomas, including CTX. She had no history of neonatal jaundice or chronic infantile diarrhea. She had been diagnosed with idiopathic epilepsy and medicated from 7 to 10 years of age. Thereafter, she had no remarkable medical developments until middle age. She insidiously developed painless tendon thickness of the bilateral Achilles tendons and right triceps muscle at 47 years of age. The gradual enlargement of the Achilles tendons caused gait disturbance when she was 49 years of age. T1- and T2-weighted magnetic resonance imaging (MRI) revealed low-intensity lesions in the thickened bilateral Achilles tendons ( Fig. 1A ) and right triceps muscle, suggestive of xanthomas. She was admitted to Nagasaki University Hospital for further investigation at 50 years of age.'}
|
{'Clinical, laboratory and imaging examinations': 'The patient was lean (height 149.0 cm, weight 39.2 kg, BMI 17.7 kg/m 2 ), and the findings of a physical examination were unremarkable except for confirmation of xanthomas on the bilateral Achilles tendons ( Fig. 1B ) and right triceps muscle. She had age-appropriate slight cataracts in the bilateral eyes and did not have dementia based on the Revised Hasegawa Dementia Scale (HSD-R; 26/30), Mini-Mental State Examination (MMSE; 27/30), and Frontal Assessment Battery (FAB; 16/18) scores. On a neurological examination, her gait appeared somewhat spastic, and all of her deep tendon reflexes were mildly enhanced bilaterally with positive Babinski and Chaddock reflexes, indicating impairment in the bilateral pyramidal tracts. There were no neurological findings suggesting cerebellar impairment. Regarding the laboratory findings ( Table 1 ), there was no elevation in the levels of serum cholesterol or triglycerides or deficiencies in apolipoproteins or thyroid hormones. As the clinical findings suggested CTX, we studied the bile acids and sterols in her serum and urine ( Table 2 ). The primary bile acids were extremely low in the serum and urine when measured by both high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometer (GC/MS). The urinary levels of bile alcohols, especially 5β-cholestane-3α,7α,12α,24,25-pentol, were markedly elevated. Norcholic acid, which is mainly derived from 5β-cholestane-3α,7α,12α,23,25-pentol, was highly elevated and accounted for 78.4% of all bile acids in the urine. The serum level of cholestanol was extremely elevated, while those of sitosterol and campesterol were not elevated. T2-weighted and fluid-attenuated inversion recovery (FLAIR) MRI of the brain showed bilateral low-intensity areas in the dentate nuclei and high-intensity areas in the peripheral white matter the cerebellum ( Fig. 1C ). We also found bilateral high-intensity areas along the pyramidal tracts from the pons to the cerebral crus. Brain atrophy was not remarkable. Based on these clinical, laboratory and radiological findings, the patient was diagnosed with CTX. Ultrasound of the carotid arteries showed a slightly thickened intima-media complex at the left common carotid artery (maximum intima-media thickness, 1.2 mm). However, there was no evidence of cardiovascular disease on electrocardiogram, echocardiography and MR angiography of the brain and lower extremities. Despite being premenopausal ( Table 1 ), she had osteoporosis as determined by dual-energy X-ray absorptiometry, which showed a bone density of 61% and 75% the young-adult-mean in the lumbar vertebra and femoral neck, respectively.', 'Case presentation': 'The patient was a 50-year-old Japanese woman from non-consanguineous parents. She has no siblings but had a child. There was no apparent family history (parents, child and parent’s siblings) of neurological disorders, cardiovascular diseases or any lipid storage diseases inducing xanthomas, including CTX. She had no history of neonatal jaundice or chronic infantile diarrhea. She had been diagnosed with idiopathic epilepsy and medicated from 7 to 10 years of age. Thereafter, she had no remarkable medical developments until middle age. She insidiously developed painless tendon thickness of the bilateral Achilles tendons and right triceps muscle at 47 years of age. The gradual enlargement of the Achilles tendons caused gait disturbance when she was 49 years of age. T1- and T2-weighted magnetic resonance imaging (MRI) revealed low-intensity lesions in the thickened bilateral Achilles tendons ( Fig. 1A ) and right triceps muscle, suggestive of xanthomas. She was admitted to Nagasaki University Hospital for further investigation at 50 years of age.'}
|
Vitals-and-Hematology
|
Vitals_Hema
|
[
"height 149.0 cm, weight 39.2 kg, BMI 17.7 kg / m 2"
] |
test-1928
|
6028668
|
{'Clinical, laboratory and imaging examinations': 'The patient was lean (height 149.0 cm, weight 39.2 kg, BMI 17.7 kg/m 2 ), and the findings of a physical examination were unremarkable except for confirmation of xanthomas on the bilateral Achilles tendons ( Fig. 1B ) and right triceps muscle. She had age-appropriate slight cataracts in the bilateral eyes and did not have dementia based on the Revised Hasegawa Dementia Scale (HSD-R; 26/30), Mini-Mental State Examination (MMSE; 27/30), and Frontal Assessment Battery (FAB; 16/18) scores. On a neurological examination, her gait appeared somewhat spastic, and all of her deep tendon reflexes were mildly enhanced bilaterally with positive Babinski and Chaddock reflexes, indicating impairment in the bilateral pyramidal tracts. There were no neurological findings suggesting cerebellar impairment. Regarding the laboratory findings ( Table 1 ), there was no elevation in the levels of serum cholesterol or triglycerides or deficiencies in apolipoproteins or thyroid hormones. As the clinical findings suggested CTX, we studied the bile acids and sterols in her serum and urine ( Table 2 ). The primary bile acids were extremely low in the serum and urine when measured by both high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometer (GC/MS). The urinary levels of bile alcohols, especially 5β-cholestane-3α,7α,12α,24,25-pentol, were markedly elevated. Norcholic acid, which is mainly derived from 5β-cholestane-3α,7α,12α,23,25-pentol, was highly elevated and accounted for 78.4% of all bile acids in the urine. The serum level of cholestanol was extremely elevated, while those of sitosterol and campesterol were not elevated. T2-weighted and fluid-attenuated inversion recovery (FLAIR) MRI of the brain showed bilateral low-intensity areas in the dentate nuclei and high-intensity areas in the peripheral white matter the cerebellum ( Fig. 1C ). We also found bilateral high-intensity areas along the pyramidal tracts from the pons to the cerebral crus. Brain atrophy was not remarkable. Based on these clinical, laboratory and radiological findings, the patient was diagnosed with CTX. Ultrasound of the carotid arteries showed a slightly thickened intima-media complex at the left common carotid artery (maximum intima-media thickness, 1.2 mm). However, there was no evidence of cardiovascular disease on electrocardiogram, echocardiography and MR angiography of the brain and lower extremities. Despite being premenopausal ( Table 1 ), she had osteoporosis as determined by dual-energy X-ray absorptiometry, which showed a bone density of 61% and 75% the young-adult-mean in the lumbar vertebra and femoral neck, respectively.', 'Case presentation': 'The patient was a 50-year-old Japanese woman from non-consanguineous parents. She has no siblings but had a child. There was no apparent family history (parents, child and parent’s siblings) of neurological disorders, cardiovascular diseases or any lipid storage diseases inducing xanthomas, including CTX. She had no history of neonatal jaundice or chronic infantile diarrhea. She had been diagnosed with idiopathic epilepsy and medicated from 7 to 10 years of age. Thereafter, she had no remarkable medical developments until middle age. She insidiously developed painless tendon thickness of the bilateral Achilles tendons and right triceps muscle at 47 years of age. The gradual enlargement of the Achilles tendons caused gait disturbance when she was 49 years of age. T1- and T2-weighted magnetic resonance imaging (MRI) revealed low-intensity lesions in the thickened bilateral Achilles tendons ( Fig. 1A ) and right triceps muscle, suggestive of xanthomas. She was admitted to Nagasaki University Hospital for further investigation at 50 years of age.'}
|
{'Clinical, laboratory and imaging examinations': 'The patient was lean (height 149.0 cm, weight 39.2 kg, BMI 17.7 kg/m 2 ), and the findings of a physical examination were unremarkable except for confirmation of xanthomas on the bilateral Achilles tendons ( Fig. 1B ) and right triceps muscle. She had age-appropriate slight cataracts in the bilateral eyes and did not have dementia based on the Revised Hasegawa Dementia Scale (HSD-R; 26/30), Mini-Mental State Examination (MMSE; 27/30), and Frontal Assessment Battery (FAB; 16/18) scores. On a neurological examination, her gait appeared somewhat spastic, and all of her deep tendon reflexes were mildly enhanced bilaterally with positive Babinski and Chaddock reflexes, indicating impairment in the bilateral pyramidal tracts. There were no neurological findings suggesting cerebellar impairment. Regarding the laboratory findings ( Table 1 ), there was no elevation in the levels of serum cholesterol or triglycerides or deficiencies in apolipoproteins or thyroid hormones. As the clinical findings suggested CTX, we studied the bile acids and sterols in her serum and urine ( Table 2 ). The primary bile acids were extremely low in the serum and urine when measured by both high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometer (GC/MS). The urinary levels of bile alcohols, especially 5β-cholestane-3α,7α,12α,24,25-pentol, were markedly elevated. Norcholic acid, which is mainly derived from 5β-cholestane-3α,7α,12α,23,25-pentol, was highly elevated and accounted for 78.4% of all bile acids in the urine. The serum level of cholestanol was extremely elevated, while those of sitosterol and campesterol were not elevated. T2-weighted and fluid-attenuated inversion recovery (FLAIR) MRI of the brain showed bilateral low-intensity areas in the dentate nuclei and high-intensity areas in the peripheral white matter the cerebellum ( Fig. 1C ). We also found bilateral high-intensity areas along the pyramidal tracts from the pons to the cerebral crus. Brain atrophy was not remarkable. Based on these clinical, laboratory and radiological findings, the patient was diagnosed with CTX. Ultrasound of the carotid arteries showed a slightly thickened intima-media complex at the left common carotid artery (maximum intima-media thickness, 1.2 mm). However, there was no evidence of cardiovascular disease on electrocardiogram, echocardiography and MR angiography of the brain and lower extremities. Despite being premenopausal ( Table 1 ), she had osteoporosis as determined by dual-energy X-ray absorptiometry, which showed a bone density of 61% and 75% the young-adult-mean in the lumbar vertebra and femoral neck, respectively.', 'Case presentation': 'The patient was a 50-year-old Japanese woman from non-consanguineous parents. She has no siblings but had a child. There was no apparent family history (parents, child and parent’s siblings) of neurological disorders, cardiovascular diseases or any lipid storage diseases inducing xanthomas, including CTX. She had no history of neonatal jaundice or chronic infantile diarrhea. She had been diagnosed with idiopathic epilepsy and medicated from 7 to 10 years of age. Thereafter, she had no remarkable medical developments until middle age. She insidiously developed painless tendon thickness of the bilateral Achilles tendons and right triceps muscle at 47 years of age. The gradual enlargement of the Achilles tendons caused gait disturbance when she was 49 years of age. T1- and T2-weighted magnetic resonance imaging (MRI) revealed low-intensity lesions in the thickened bilateral Achilles tendons ( Fig. 1A ) and right triceps muscle, suggestive of xanthomas. She was admitted to Nagasaki University Hospital for further investigation at 50 years of age.'}
|
Gastrointestinal-System
|
GI
|
[
"no history of neonatal jaundice or chronic infantile diarrhea"
] |
test-1929
|
6028668
|
{'Clinical, laboratory and imaging examinations': 'The patient was lean (height 149.0 cm, weight 39.2 kg, BMI 17.7 kg/m 2 ), and the findings of a physical examination were unremarkable except for confirmation of xanthomas on the bilateral Achilles tendons ( Fig. 1B ) and right triceps muscle. She had age-appropriate slight cataracts in the bilateral eyes and did not have dementia based on the Revised Hasegawa Dementia Scale (HSD-R; 26/30), Mini-Mental State Examination (MMSE; 27/30), and Frontal Assessment Battery (FAB; 16/18) scores. On a neurological examination, her gait appeared somewhat spastic, and all of her deep tendon reflexes were mildly enhanced bilaterally with positive Babinski and Chaddock reflexes, indicating impairment in the bilateral pyramidal tracts. There were no neurological findings suggesting cerebellar impairment. Regarding the laboratory findings ( Table 1 ), there was no elevation in the levels of serum cholesterol or triglycerides or deficiencies in apolipoproteins or thyroid hormones. As the clinical findings suggested CTX, we studied the bile acids and sterols in her serum and urine ( Table 2 ). The primary bile acids were extremely low in the serum and urine when measured by both high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometer (GC/MS). The urinary levels of bile alcohols, especially 5β-cholestane-3α,7α,12α,24,25-pentol, were markedly elevated. Norcholic acid, which is mainly derived from 5β-cholestane-3α,7α,12α,23,25-pentol, was highly elevated and accounted for 78.4% of all bile acids in the urine. The serum level of cholestanol was extremely elevated, while those of sitosterol and campesterol were not elevated. T2-weighted and fluid-attenuated inversion recovery (FLAIR) MRI of the brain showed bilateral low-intensity areas in the dentate nuclei and high-intensity areas in the peripheral white matter the cerebellum ( Fig. 1C ). We also found bilateral high-intensity areas along the pyramidal tracts from the pons to the cerebral crus. Brain atrophy was not remarkable. Based on these clinical, laboratory and radiological findings, the patient was diagnosed with CTX. Ultrasound of the carotid arteries showed a slightly thickened intima-media complex at the left common carotid artery (maximum intima-media thickness, 1.2 mm). However, there was no evidence of cardiovascular disease on electrocardiogram, echocardiography and MR angiography of the brain and lower extremities. Despite being premenopausal ( Table 1 ), she had osteoporosis as determined by dual-energy X-ray absorptiometry, which showed a bone density of 61% and 75% the young-adult-mean in the lumbar vertebra and femoral neck, respectively.', 'Case presentation': 'The patient was a 50-year-old Japanese woman from non-consanguineous parents. She has no siblings but had a child. There was no apparent family history (parents, child and parent’s siblings) of neurological disorders, cardiovascular diseases or any lipid storage diseases inducing xanthomas, including CTX. She had no history of neonatal jaundice or chronic infantile diarrhea. She had been diagnosed with idiopathic epilepsy and medicated from 7 to 10 years of age. Thereafter, she had no remarkable medical developments until middle age. She insidiously developed painless tendon thickness of the bilateral Achilles tendons and right triceps muscle at 47 years of age. The gradual enlargement of the Achilles tendons caused gait disturbance when she was 49 years of age. T1- and T2-weighted magnetic resonance imaging (MRI) revealed low-intensity lesions in the thickened bilateral Achilles tendons ( Fig. 1A ) and right triceps muscle, suggestive of xanthomas. She was admitted to Nagasaki University Hospital for further investigation at 50 years of age.'}
|
{'Clinical, laboratory and imaging examinations': 'The patient was lean (height 149.0 cm, weight 39.2 kg, BMI 17.7 kg/m 2 ), and the findings of a physical examination were unremarkable except for confirmation of xanthomas on the bilateral Achilles tendons ( Fig. 1B ) and right triceps muscle. She had age-appropriate slight cataracts in the bilateral eyes and did not have dementia based on the Revised Hasegawa Dementia Scale (HSD-R; 26/30), Mini-Mental State Examination (MMSE; 27/30), and Frontal Assessment Battery (FAB; 16/18) scores. On a neurological examination, her gait appeared somewhat spastic, and all of her deep tendon reflexes were mildly enhanced bilaterally with positive Babinski and Chaddock reflexes, indicating impairment in the bilateral pyramidal tracts. There were no neurological findings suggesting cerebellar impairment. Regarding the laboratory findings ( Table 1 ), there was no elevation in the levels of serum cholesterol or triglycerides or deficiencies in apolipoproteins or thyroid hormones. As the clinical findings suggested CTX, we studied the bile acids and sterols in her serum and urine ( Table 2 ). The primary bile acids were extremely low in the serum and urine when measured by both high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometer (GC/MS). The urinary levels of bile alcohols, especially 5β-cholestane-3α,7α,12α,24,25-pentol, were markedly elevated. Norcholic acid, which is mainly derived from 5β-cholestane-3α,7α,12α,23,25-pentol, was highly elevated and accounted for 78.4% of all bile acids in the urine. The serum level of cholestanol was extremely elevated, while those of sitosterol and campesterol were not elevated. T2-weighted and fluid-attenuated inversion recovery (FLAIR) MRI of the brain showed bilateral low-intensity areas in the dentate nuclei and high-intensity areas in the peripheral white matter the cerebellum ( Fig. 1C ). We also found bilateral high-intensity areas along the pyramidal tracts from the pons to the cerebral crus. Brain atrophy was not remarkable. Based on these clinical, laboratory and radiological findings, the patient was diagnosed with CTX. Ultrasound of the carotid arteries showed a slightly thickened intima-media complex at the left common carotid artery (maximum intima-media thickness, 1.2 mm). However, there was no evidence of cardiovascular disease on electrocardiogram, echocardiography and MR angiography of the brain and lower extremities. Despite being premenopausal ( Table 1 ), she had osteoporosis as determined by dual-energy X-ray absorptiometry, which showed a bone density of 61% and 75% the young-adult-mean in the lumbar vertebra and femoral neck, respectively.', 'Case presentation': 'The patient was a 50-year-old Japanese woman from non-consanguineous parents. She has no siblings but had a child. There was no apparent family history (parents, child and parent’s siblings) of neurological disorders, cardiovascular diseases or any lipid storage diseases inducing xanthomas, including CTX. She had no history of neonatal jaundice or chronic infantile diarrhea. She had been diagnosed with idiopathic epilepsy and medicated from 7 to 10 years of age. Thereafter, she had no remarkable medical developments until middle age. She insidiously developed painless tendon thickness of the bilateral Achilles tendons and right triceps muscle at 47 years of age. The gradual enlargement of the Achilles tendons caused gait disturbance when she was 49 years of age. T1- and T2-weighted magnetic resonance imaging (MRI) revealed low-intensity lesions in the thickened bilateral Achilles tendons ( Fig. 1A ) and right triceps muscle, suggestive of xanthomas. She was admitted to Nagasaki University Hospital for further investigation at 50 years of age.'}
|
Patient-History
|
History
|
[
"The patient was a 50 - year - old Japanese woman from non - consanguineous parents. She has no siblings but had a child. There was no apparent family history ( parents, child and parent ’s siblings ) of neurological disorders, cardiovascular diseases or any lipid storage diseases inducing xanthomas, including CTX. She had no history of neonatal jaundice or chronic infantile diarrhea. She had been diagnosed with idiopathic epilepsy and medicated from 7 to 10 years of age. Thereafter, she had no remarkable medical developments until middle age. She insidiously developed painless tendon thickness of the bilateral Achilles tendons and right triceps muscle at 47 years of age. The gradual enlargement of the Achilles tendons caused gait disturbance when she was 49 years of age"
] |
test-1930
|
6028668
|
{'Clinical, laboratory and imaging examinations': 'The patient was lean (height 149.0 cm, weight 39.2 kg, BMI 17.7 kg/m 2 ), and the findings of a physical examination were unremarkable except for confirmation of xanthomas on the bilateral Achilles tendons ( Fig. 1B ) and right triceps muscle. She had age-appropriate slight cataracts in the bilateral eyes and did not have dementia based on the Revised Hasegawa Dementia Scale (HSD-R; 26/30), Mini-Mental State Examination (MMSE; 27/30), and Frontal Assessment Battery (FAB; 16/18) scores. On a neurological examination, her gait appeared somewhat spastic, and all of her deep tendon reflexes were mildly enhanced bilaterally with positive Babinski and Chaddock reflexes, indicating impairment in the bilateral pyramidal tracts. There were no neurological findings suggesting cerebellar impairment. Regarding the laboratory findings ( Table 1 ), there was no elevation in the levels of serum cholesterol or triglycerides or deficiencies in apolipoproteins or thyroid hormones. As the clinical findings suggested CTX, we studied the bile acids and sterols in her serum and urine ( Table 2 ). The primary bile acids were extremely low in the serum and urine when measured by both high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometer (GC/MS). The urinary levels of bile alcohols, especially 5β-cholestane-3α,7α,12α,24,25-pentol, were markedly elevated. Norcholic acid, which is mainly derived from 5β-cholestane-3α,7α,12α,23,25-pentol, was highly elevated and accounted for 78.4% of all bile acids in the urine. The serum level of cholestanol was extremely elevated, while those of sitosterol and campesterol were not elevated. T2-weighted and fluid-attenuated inversion recovery (FLAIR) MRI of the brain showed bilateral low-intensity areas in the dentate nuclei and high-intensity areas in the peripheral white matter the cerebellum ( Fig. 1C ). We also found bilateral high-intensity areas along the pyramidal tracts from the pons to the cerebral crus. Brain atrophy was not remarkable. Based on these clinical, laboratory and radiological findings, the patient was diagnosed with CTX. Ultrasound of the carotid arteries showed a slightly thickened intima-media complex at the left common carotid artery (maximum intima-media thickness, 1.2 mm). However, there was no evidence of cardiovascular disease on electrocardiogram, echocardiography and MR angiography of the brain and lower extremities. Despite being premenopausal ( Table 1 ), she had osteoporosis as determined by dual-energy X-ray absorptiometry, which showed a bone density of 61% and 75% the young-adult-mean in the lumbar vertebra and femoral neck, respectively.', 'Case presentation': 'The patient was a 50-year-old Japanese woman from non-consanguineous parents. She has no siblings but had a child. There was no apparent family history (parents, child and parent’s siblings) of neurological disorders, cardiovascular diseases or any lipid storage diseases inducing xanthomas, including CTX. She had no history of neonatal jaundice or chronic infantile diarrhea. She had been diagnosed with idiopathic epilepsy and medicated from 7 to 10 years of age. Thereafter, she had no remarkable medical developments until middle age. She insidiously developed painless tendon thickness of the bilateral Achilles tendons and right triceps muscle at 47 years of age. The gradual enlargement of the Achilles tendons caused gait disturbance when she was 49 years of age. T1- and T2-weighted magnetic resonance imaging (MRI) revealed low-intensity lesions in the thickened bilateral Achilles tendons ( Fig. 1A ) and right triceps muscle, suggestive of xanthomas. She was admitted to Nagasaki University Hospital for further investigation at 50 years of age.'}
|
{'Clinical, laboratory and imaging examinations': 'The patient was lean (height 149.0 cm, weight 39.2 kg, BMI 17.7 kg/m 2 ), and the findings of a physical examination were unremarkable except for confirmation of xanthomas on the bilateral Achilles tendons ( Fig. 1B ) and right triceps muscle. She had age-appropriate slight cataracts in the bilateral eyes and did not have dementia based on the Revised Hasegawa Dementia Scale (HSD-R; 26/30), Mini-Mental State Examination (MMSE; 27/30), and Frontal Assessment Battery (FAB; 16/18) scores. On a neurological examination, her gait appeared somewhat spastic, and all of her deep tendon reflexes were mildly enhanced bilaterally with positive Babinski and Chaddock reflexes, indicating impairment in the bilateral pyramidal tracts. There were no neurological findings suggesting cerebellar impairment. Regarding the laboratory findings ( Table 1 ), there was no elevation in the levels of serum cholesterol or triglycerides or deficiencies in apolipoproteins or thyroid hormones. As the clinical findings suggested CTX, we studied the bile acids and sterols in her serum and urine ( Table 2 ). The primary bile acids were extremely low in the serum and urine when measured by both high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometer (GC/MS). The urinary levels of bile alcohols, especially 5β-cholestane-3α,7α,12α,24,25-pentol, were markedly elevated. Norcholic acid, which is mainly derived from 5β-cholestane-3α,7α,12α,23,25-pentol, was highly elevated and accounted for 78.4% of all bile acids in the urine. The serum level of cholestanol was extremely elevated, while those of sitosterol and campesterol were not elevated. T2-weighted and fluid-attenuated inversion recovery (FLAIR) MRI of the brain showed bilateral low-intensity areas in the dentate nuclei and high-intensity areas in the peripheral white matter the cerebellum ( Fig. 1C ). We also found bilateral high-intensity areas along the pyramidal tracts from the pons to the cerebral crus. Brain atrophy was not remarkable. Based on these clinical, laboratory and radiological findings, the patient was diagnosed with CTX. Ultrasound of the carotid arteries showed a slightly thickened intima-media complex at the left common carotid artery (maximum intima-media thickness, 1.2 mm). However, there was no evidence of cardiovascular disease on electrocardiogram, echocardiography and MR angiography of the brain and lower extremities. Despite being premenopausal ( Table 1 ), she had osteoporosis as determined by dual-energy X-ray absorptiometry, which showed a bone density of 61% and 75% the young-adult-mean in the lumbar vertebra and femoral neck, respectively.', 'Case presentation': 'The patient was a 50-year-old Japanese woman from non-consanguineous parents. She has no siblings but had a child. There was no apparent family history (parents, child and parent’s siblings) of neurological disorders, cardiovascular diseases or any lipid storage diseases inducing xanthomas, including CTX. She had no history of neonatal jaundice or chronic infantile diarrhea. She had been diagnosed with idiopathic epilepsy and medicated from 7 to 10 years of age. Thereafter, she had no remarkable medical developments until middle age. She insidiously developed painless tendon thickness of the bilateral Achilles tendons and right triceps muscle at 47 years of age. The gradual enlargement of the Achilles tendons caused gait disturbance when she was 49 years of age. T1- and T2-weighted magnetic resonance imaging (MRI) revealed low-intensity lesions in the thickened bilateral Achilles tendons ( Fig. 1A ) and right triceps muscle, suggestive of xanthomas. She was admitted to Nagasaki University Hospital for further investigation at 50 years of age.'}
|
Neurology
|
Neuro
|
[
"did not have dementia based on the Revised Hasegawa Dementia Scale ( HSD - R; 26/30 ), Mini - Mental State Examination ( MMSE; 27/30 ), and Frontal Assessment Battery ( FAB; 16/18 ) scores. On a neurological examination, her gait appeared somewhat spastic, and all of her deep tendon reflexes were mildly enhanced bilaterally with positive Babinski and Chaddock reflexes, indicating impairment in the bilateral pyramidal tracts. There were no neurological findings suggesting cerebellar impairment",
"T2 - weighted and fluid - attenuated inversion recovery ( FLAIR ) MRI of the brain showed bilateral low - intensity areas in the dentate nuclei and high - intensity areas in the peripheral white matter the cerebellum ( Fig. 1C ). We also found bilateral high - intensity areas along the pyramidal tracts from the pons to the cerebral crus. Brain atrophy was not remarkable.",
"idiopathic epilepsy"
] |
test-1931
|
6028668
|
{'Clinical, laboratory and imaging examinations': 'The patient was lean (height 149.0 cm, weight 39.2 kg, BMI 17.7 kg/m 2 ), and the findings of a physical examination were unremarkable except for confirmation of xanthomas on the bilateral Achilles tendons ( Fig. 1B ) and right triceps muscle. She had age-appropriate slight cataracts in the bilateral eyes and did not have dementia based on the Revised Hasegawa Dementia Scale (HSD-R; 26/30), Mini-Mental State Examination (MMSE; 27/30), and Frontal Assessment Battery (FAB; 16/18) scores. On a neurological examination, her gait appeared somewhat spastic, and all of her deep tendon reflexes were mildly enhanced bilaterally with positive Babinski and Chaddock reflexes, indicating impairment in the bilateral pyramidal tracts. There were no neurological findings suggesting cerebellar impairment. Regarding the laboratory findings ( Table 1 ), there was no elevation in the levels of serum cholesterol or triglycerides or deficiencies in apolipoproteins or thyroid hormones. As the clinical findings suggested CTX, we studied the bile acids and sterols in her serum and urine ( Table 2 ). The primary bile acids were extremely low in the serum and urine when measured by both high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometer (GC/MS). The urinary levels of bile alcohols, especially 5β-cholestane-3α,7α,12α,24,25-pentol, were markedly elevated. Norcholic acid, which is mainly derived from 5β-cholestane-3α,7α,12α,23,25-pentol, was highly elevated and accounted for 78.4% of all bile acids in the urine. The serum level of cholestanol was extremely elevated, while those of sitosterol and campesterol were not elevated. T2-weighted and fluid-attenuated inversion recovery (FLAIR) MRI of the brain showed bilateral low-intensity areas in the dentate nuclei and high-intensity areas in the peripheral white matter the cerebellum ( Fig. 1C ). We also found bilateral high-intensity areas along the pyramidal tracts from the pons to the cerebral crus. Brain atrophy was not remarkable. Based on these clinical, laboratory and radiological findings, the patient was diagnosed with CTX. Ultrasound of the carotid arteries showed a slightly thickened intima-media complex at the left common carotid artery (maximum intima-media thickness, 1.2 mm). However, there was no evidence of cardiovascular disease on electrocardiogram, echocardiography and MR angiography of the brain and lower extremities. Despite being premenopausal ( Table 1 ), she had osteoporosis as determined by dual-energy X-ray absorptiometry, which showed a bone density of 61% and 75% the young-adult-mean in the lumbar vertebra and femoral neck, respectively.', 'Case presentation': 'The patient was a 50-year-old Japanese woman from non-consanguineous parents. She has no siblings but had a child. There was no apparent family history (parents, child and parent’s siblings) of neurological disorders, cardiovascular diseases or any lipid storage diseases inducing xanthomas, including CTX. She had no history of neonatal jaundice or chronic infantile diarrhea. She had been diagnosed with idiopathic epilepsy and medicated from 7 to 10 years of age. Thereafter, she had no remarkable medical developments until middle age. She insidiously developed painless tendon thickness of the bilateral Achilles tendons and right triceps muscle at 47 years of age. The gradual enlargement of the Achilles tendons caused gait disturbance when she was 49 years of age. T1- and T2-weighted magnetic resonance imaging (MRI) revealed low-intensity lesions in the thickened bilateral Achilles tendons ( Fig. 1A ) and right triceps muscle, suggestive of xanthomas. She was admitted to Nagasaki University Hospital for further investigation at 50 years of age.'}
|
{'Clinical, laboratory and imaging examinations': 'The patient was lean (height 149.0 cm, weight 39.2 kg, BMI 17.7 kg/m 2 ), and the findings of a physical examination were unremarkable except for confirmation of xanthomas on the bilateral Achilles tendons ( Fig. 1B ) and right triceps muscle. She had age-appropriate slight cataracts in the bilateral eyes and did not have dementia based on the Revised Hasegawa Dementia Scale (HSD-R; 26/30), Mini-Mental State Examination (MMSE; 27/30), and Frontal Assessment Battery (FAB; 16/18) scores. On a neurological examination, her gait appeared somewhat spastic, and all of her deep tendon reflexes were mildly enhanced bilaterally with positive Babinski and Chaddock reflexes, indicating impairment in the bilateral pyramidal tracts. There were no neurological findings suggesting cerebellar impairment. Regarding the laboratory findings ( Table 1 ), there was no elevation in the levels of serum cholesterol or triglycerides or deficiencies in apolipoproteins or thyroid hormones. As the clinical findings suggested CTX, we studied the bile acids and sterols in her serum and urine ( Table 2 ). The primary bile acids were extremely low in the serum and urine when measured by both high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometer (GC/MS). The urinary levels of bile alcohols, especially 5β-cholestane-3α,7α,12α,24,25-pentol, were markedly elevated. Norcholic acid, which is mainly derived from 5β-cholestane-3α,7α,12α,23,25-pentol, was highly elevated and accounted for 78.4% of all bile acids in the urine. The serum level of cholestanol was extremely elevated, while those of sitosterol and campesterol were not elevated. T2-weighted and fluid-attenuated inversion recovery (FLAIR) MRI of the brain showed bilateral low-intensity areas in the dentate nuclei and high-intensity areas in the peripheral white matter the cerebellum ( Fig. 1C ). We also found bilateral high-intensity areas along the pyramidal tracts from the pons to the cerebral crus. Brain atrophy was not remarkable. Based on these clinical, laboratory and radiological findings, the patient was diagnosed with CTX. Ultrasound of the carotid arteries showed a slightly thickened intima-media complex at the left common carotid artery (maximum intima-media thickness, 1.2 mm). However, there was no evidence of cardiovascular disease on electrocardiogram, echocardiography and MR angiography of the brain and lower extremities. Despite being premenopausal ( Table 1 ), she had osteoporosis as determined by dual-energy X-ray absorptiometry, which showed a bone density of 61% and 75% the young-adult-mean in the lumbar vertebra and femoral neck, respectively.', 'Case presentation': 'The patient was a 50-year-old Japanese woman from non-consanguineous parents. She has no siblings but had a child. There was no apparent family history (parents, child and parent’s siblings) of neurological disorders, cardiovascular diseases or any lipid storage diseases inducing xanthomas, including CTX. She had no history of neonatal jaundice or chronic infantile diarrhea. She had been diagnosed with idiopathic epilepsy and medicated from 7 to 10 years of age. Thereafter, she had no remarkable medical developments until middle age. She insidiously developed painless tendon thickness of the bilateral Achilles tendons and right triceps muscle at 47 years of age. The gradual enlargement of the Achilles tendons caused gait disturbance when she was 49 years of age. T1- and T2-weighted magnetic resonance imaging (MRI) revealed low-intensity lesions in the thickened bilateral Achilles tendons ( Fig. 1A ) and right triceps muscle, suggestive of xanthomas. She was admitted to Nagasaki University Hospital for further investigation at 50 years of age.'}
|
Laboratory-and-Imaging
|
Lab_Image
|
[
"no elevation in the levels of serum cholesterol or triglycerides or deficiencies in apolipoproteins or thyroid hormones",
"The primary bile acids were extremely low in the serum and urine when measured by both high - performance liquid chromatography ( HPLC ) and gas chromatography / mass spectrometer ( GC / MS ). The urinary levels of bile alcohols, especially 5β - cholestane-3α,7α,12α,24,25 - pentol, were markedly elevated. Norcholic acid, which is mainly derived from 5β - cholestane-3α,7α,12α,23,25 - pentol, was highly elevated and accounted for 78.4 % of all bile acids in the urine. The serum level of cholestanol was extremely elevated, while those of sitosterol and campesterol were not elevated",
"T2 - weighted and fluid - attenuated inversion recovery ( FLAIR ) MRI of the brain showed bilateral low - intensity areas in the dentate nuclei and high - intensity areas in the peripheral white matter the cerebellum ( Fig. 1C ). We also found bilateral high - intensity areas along the pyramidal tracts from the pons to the cerebral crus. Brain atrophy was not remarkable",
"Ultrasound of the carotid arteries showed a slightly thickened intima - media complex at the left common carotid artery ( maximum intima - media thickness, 1.2 mm",
"However, there was no evidence of cardiovascular disease on electrocardiogram, echocardiography and MR angiography of the brain and lower extremities",
"dual - energy X - ray absorptiometry, which showed a bone density of 61 % and 75 % the young - adult - mean in the lumbar vertebra and femoral neck, respectively.",
"T1- and T2 - weighted magnetic resonance imaging ( MRI ) revealed low - intensity lesions in the thickened bilateral Achilles tendons ( Fig. 1A ) and right triceps muscle, suggestive of xanthomas"
] |
test-1932
|
6028668
|
{'Clinical, laboratory and imaging examinations': 'The patient was lean (height 149.0 cm, weight 39.2 kg, BMI 17.7 kg/m 2 ), and the findings of a physical examination were unremarkable except for confirmation of xanthomas on the bilateral Achilles tendons ( Fig. 1B ) and right triceps muscle. She had age-appropriate slight cataracts in the bilateral eyes and did not have dementia based on the Revised Hasegawa Dementia Scale (HSD-R; 26/30), Mini-Mental State Examination (MMSE; 27/30), and Frontal Assessment Battery (FAB; 16/18) scores. On a neurological examination, her gait appeared somewhat spastic, and all of her deep tendon reflexes were mildly enhanced bilaterally with positive Babinski and Chaddock reflexes, indicating impairment in the bilateral pyramidal tracts. There were no neurological findings suggesting cerebellar impairment. Regarding the laboratory findings ( Table 1 ), there was no elevation in the levels of serum cholesterol or triglycerides or deficiencies in apolipoproteins or thyroid hormones. As the clinical findings suggested CTX, we studied the bile acids and sterols in her serum and urine ( Table 2 ). The primary bile acids were extremely low in the serum and urine when measured by both high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometer (GC/MS). The urinary levels of bile alcohols, especially 5β-cholestane-3α,7α,12α,24,25-pentol, were markedly elevated. Norcholic acid, which is mainly derived from 5β-cholestane-3α,7α,12α,23,25-pentol, was highly elevated and accounted for 78.4% of all bile acids in the urine. The serum level of cholestanol was extremely elevated, while those of sitosterol and campesterol were not elevated. T2-weighted and fluid-attenuated inversion recovery (FLAIR) MRI of the brain showed bilateral low-intensity areas in the dentate nuclei and high-intensity areas in the peripheral white matter the cerebellum ( Fig. 1C ). We also found bilateral high-intensity areas along the pyramidal tracts from the pons to the cerebral crus. Brain atrophy was not remarkable. Based on these clinical, laboratory and radiological findings, the patient was diagnosed with CTX. Ultrasound of the carotid arteries showed a slightly thickened intima-media complex at the left common carotid artery (maximum intima-media thickness, 1.2 mm). However, there was no evidence of cardiovascular disease on electrocardiogram, echocardiography and MR angiography of the brain and lower extremities. Despite being premenopausal ( Table 1 ), she had osteoporosis as determined by dual-energy X-ray absorptiometry, which showed a bone density of 61% and 75% the young-adult-mean in the lumbar vertebra and femoral neck, respectively.', 'Case presentation': 'The patient was a 50-year-old Japanese woman from non-consanguineous parents. She has no siblings but had a child. There was no apparent family history (parents, child and parent’s siblings) of neurological disorders, cardiovascular diseases or any lipid storage diseases inducing xanthomas, including CTX. She had no history of neonatal jaundice or chronic infantile diarrhea. She had been diagnosed with idiopathic epilepsy and medicated from 7 to 10 years of age. Thereafter, she had no remarkable medical developments until middle age. She insidiously developed painless tendon thickness of the bilateral Achilles tendons and right triceps muscle at 47 years of age. The gradual enlargement of the Achilles tendons caused gait disturbance when she was 49 years of age. T1- and T2-weighted magnetic resonance imaging (MRI) revealed low-intensity lesions in the thickened bilateral Achilles tendons ( Fig. 1A ) and right triceps muscle, suggestive of xanthomas. She was admitted to Nagasaki University Hospital for further investigation at 50 years of age.'}
|
{'Clinical, laboratory and imaging examinations': 'The patient was lean (height 149.0 cm, weight 39.2 kg, BMI 17.7 kg/m 2 ), and the findings of a physical examination were unremarkable except for confirmation of xanthomas on the bilateral Achilles tendons ( Fig. 1B ) and right triceps muscle. She had age-appropriate slight cataracts in the bilateral eyes and did not have dementia based on the Revised Hasegawa Dementia Scale (HSD-R; 26/30), Mini-Mental State Examination (MMSE; 27/30), and Frontal Assessment Battery (FAB; 16/18) scores. On a neurological examination, her gait appeared somewhat spastic, and all of her deep tendon reflexes were mildly enhanced bilaterally with positive Babinski and Chaddock reflexes, indicating impairment in the bilateral pyramidal tracts. There were no neurological findings suggesting cerebellar impairment. Regarding the laboratory findings ( Table 1 ), there was no elevation in the levels of serum cholesterol or triglycerides or deficiencies in apolipoproteins or thyroid hormones. As the clinical findings suggested CTX, we studied the bile acids and sterols in her serum and urine ( Table 2 ). The primary bile acids were extremely low in the serum and urine when measured by both high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometer (GC/MS). The urinary levels of bile alcohols, especially 5β-cholestane-3α,7α,12α,24,25-pentol, were markedly elevated. Norcholic acid, which is mainly derived from 5β-cholestane-3α,7α,12α,23,25-pentol, was highly elevated and accounted for 78.4% of all bile acids in the urine. The serum level of cholestanol was extremely elevated, while those of sitosterol and campesterol were not elevated. T2-weighted and fluid-attenuated inversion recovery (FLAIR) MRI of the brain showed bilateral low-intensity areas in the dentate nuclei and high-intensity areas in the peripheral white matter the cerebellum ( Fig. 1C ). We also found bilateral high-intensity areas along the pyramidal tracts from the pons to the cerebral crus. Brain atrophy was not remarkable. Based on these clinical, laboratory and radiological findings, the patient was diagnosed with CTX. Ultrasound of the carotid arteries showed a slightly thickened intima-media complex at the left common carotid artery (maximum intima-media thickness, 1.2 mm). However, there was no evidence of cardiovascular disease on electrocardiogram, echocardiography and MR angiography of the brain and lower extremities. Despite being premenopausal ( Table 1 ), she had osteoporosis as determined by dual-energy X-ray absorptiometry, which showed a bone density of 61% and 75% the young-adult-mean in the lumbar vertebra and femoral neck, respectively.', 'Case presentation': 'The patient was a 50-year-old Japanese woman from non-consanguineous parents. She has no siblings but had a child. There was no apparent family history (parents, child and parent’s siblings) of neurological disorders, cardiovascular diseases or any lipid storage diseases inducing xanthomas, including CTX. She had no history of neonatal jaundice or chronic infantile diarrhea. She had been diagnosed with idiopathic epilepsy and medicated from 7 to 10 years of age. Thereafter, she had no remarkable medical developments until middle age. She insidiously developed painless tendon thickness of the bilateral Achilles tendons and right triceps muscle at 47 years of age. The gradual enlargement of the Achilles tendons caused gait disturbance when she was 49 years of age. T1- and T2-weighted magnetic resonance imaging (MRI) revealed low-intensity lesions in the thickened bilateral Achilles tendons ( Fig. 1A ) and right triceps muscle, suggestive of xanthomas. She was admitted to Nagasaki University Hospital for further investigation at 50 years of age.'}
|
Cardiovascular-System
|
CVS
|
[
"Ultrasound of the carotid arteries showed a slightly thickened intima - media complex at the left common carotid artery ( maximum intima - media thickness, 1.2 mm ). However, there was no evidence of cardiovascular disease on electrocardiogram, echocardiography and MR angiography of the brain and lower extremities"
] |
test-1933
|
6028668
|
{'Clinical, laboratory and imaging examinations': 'The patient was lean (height 149.0 cm, weight 39.2 kg, BMI 17.7 kg/m 2 ), and the findings of a physical examination were unremarkable except for confirmation of xanthomas on the bilateral Achilles tendons ( Fig. 1B ) and right triceps muscle. She had age-appropriate slight cataracts in the bilateral eyes and did not have dementia based on the Revised Hasegawa Dementia Scale (HSD-R; 26/30), Mini-Mental State Examination (MMSE; 27/30), and Frontal Assessment Battery (FAB; 16/18) scores. On a neurological examination, her gait appeared somewhat spastic, and all of her deep tendon reflexes were mildly enhanced bilaterally with positive Babinski and Chaddock reflexes, indicating impairment in the bilateral pyramidal tracts. There were no neurological findings suggesting cerebellar impairment. Regarding the laboratory findings ( Table 1 ), there was no elevation in the levels of serum cholesterol or triglycerides or deficiencies in apolipoproteins or thyroid hormones. As the clinical findings suggested CTX, we studied the bile acids and sterols in her serum and urine ( Table 2 ). The primary bile acids were extremely low in the serum and urine when measured by both high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometer (GC/MS). The urinary levels of bile alcohols, especially 5β-cholestane-3α,7α,12α,24,25-pentol, were markedly elevated. Norcholic acid, which is mainly derived from 5β-cholestane-3α,7α,12α,23,25-pentol, was highly elevated and accounted for 78.4% of all bile acids in the urine. The serum level of cholestanol was extremely elevated, while those of sitosterol and campesterol were not elevated. T2-weighted and fluid-attenuated inversion recovery (FLAIR) MRI of the brain showed bilateral low-intensity areas in the dentate nuclei and high-intensity areas in the peripheral white matter the cerebellum ( Fig. 1C ). We also found bilateral high-intensity areas along the pyramidal tracts from the pons to the cerebral crus. Brain atrophy was not remarkable. Based on these clinical, laboratory and radiological findings, the patient was diagnosed with CTX. Ultrasound of the carotid arteries showed a slightly thickened intima-media complex at the left common carotid artery (maximum intima-media thickness, 1.2 mm). However, there was no evidence of cardiovascular disease on electrocardiogram, echocardiography and MR angiography of the brain and lower extremities. Despite being premenopausal ( Table 1 ), she had osteoporosis as determined by dual-energy X-ray absorptiometry, which showed a bone density of 61% and 75% the young-adult-mean in the lumbar vertebra and femoral neck, respectively.', 'Case presentation': 'The patient was a 50-year-old Japanese woman from non-consanguineous parents. She has no siblings but had a child. There was no apparent family history (parents, child and parent’s siblings) of neurological disorders, cardiovascular diseases or any lipid storage diseases inducing xanthomas, including CTX. She had no history of neonatal jaundice or chronic infantile diarrhea. She had been diagnosed with idiopathic epilepsy and medicated from 7 to 10 years of age. Thereafter, she had no remarkable medical developments until middle age. She insidiously developed painless tendon thickness of the bilateral Achilles tendons and right triceps muscle at 47 years of age. The gradual enlargement of the Achilles tendons caused gait disturbance when she was 49 years of age. T1- and T2-weighted magnetic resonance imaging (MRI) revealed low-intensity lesions in the thickened bilateral Achilles tendons ( Fig. 1A ) and right triceps muscle, suggestive of xanthomas. She was admitted to Nagasaki University Hospital for further investigation at 50 years of age.'}
|
{'Clinical, laboratory and imaging examinations': 'The patient was lean (height 149.0 cm, weight 39.2 kg, BMI 17.7 kg/m 2 ), and the findings of a physical examination were unremarkable except for confirmation of xanthomas on the bilateral Achilles tendons ( Fig. 1B ) and right triceps muscle. She had age-appropriate slight cataracts in the bilateral eyes and did not have dementia based on the Revised Hasegawa Dementia Scale (HSD-R; 26/30), Mini-Mental State Examination (MMSE; 27/30), and Frontal Assessment Battery (FAB; 16/18) scores. On a neurological examination, her gait appeared somewhat spastic, and all of her deep tendon reflexes were mildly enhanced bilaterally with positive Babinski and Chaddock reflexes, indicating impairment in the bilateral pyramidal tracts. There were no neurological findings suggesting cerebellar impairment. Regarding the laboratory findings ( Table 1 ), there was no elevation in the levels of serum cholesterol or triglycerides or deficiencies in apolipoproteins or thyroid hormones. As the clinical findings suggested CTX, we studied the bile acids and sterols in her serum and urine ( Table 2 ). The primary bile acids were extremely low in the serum and urine when measured by both high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometer (GC/MS). The urinary levels of bile alcohols, especially 5β-cholestane-3α,7α,12α,24,25-pentol, were markedly elevated. Norcholic acid, which is mainly derived from 5β-cholestane-3α,7α,12α,23,25-pentol, was highly elevated and accounted for 78.4% of all bile acids in the urine. The serum level of cholestanol was extremely elevated, while those of sitosterol and campesterol were not elevated. T2-weighted and fluid-attenuated inversion recovery (FLAIR) MRI of the brain showed bilateral low-intensity areas in the dentate nuclei and high-intensity areas in the peripheral white matter the cerebellum ( Fig. 1C ). We also found bilateral high-intensity areas along the pyramidal tracts from the pons to the cerebral crus. Brain atrophy was not remarkable. Based on these clinical, laboratory and radiological findings, the patient was diagnosed with CTX. Ultrasound of the carotid arteries showed a slightly thickened intima-media complex at the left common carotid artery (maximum intima-media thickness, 1.2 mm). However, there was no evidence of cardiovascular disease on electrocardiogram, echocardiography and MR angiography of the brain and lower extremities. Despite being premenopausal ( Table 1 ), she had osteoporosis as determined by dual-energy X-ray absorptiometry, which showed a bone density of 61% and 75% the young-adult-mean in the lumbar vertebra and femoral neck, respectively.', 'Case presentation': 'The patient was a 50-year-old Japanese woman from non-consanguineous parents. She has no siblings but had a child. There was no apparent family history (parents, child and parent’s siblings) of neurological disorders, cardiovascular diseases or any lipid storage diseases inducing xanthomas, including CTX. She had no history of neonatal jaundice or chronic infantile diarrhea. She had been diagnosed with idiopathic epilepsy and medicated from 7 to 10 years of age. Thereafter, she had no remarkable medical developments until middle age. She insidiously developed painless tendon thickness of the bilateral Achilles tendons and right triceps muscle at 47 years of age. The gradual enlargement of the Achilles tendons caused gait disturbance when she was 49 years of age. T1- and T2-weighted magnetic resonance imaging (MRI) revealed low-intensity lesions in the thickened bilateral Achilles tendons ( Fig. 1A ) and right triceps muscle, suggestive of xanthomas. She was admitted to Nagasaki University Hospital for further investigation at 50 years of age.'}
|
Endocrinology
|
ENDO
|
[] |
test-1934
|
6028668
|
{'Clinical, laboratory and imaging examinations': 'The patient was lean (height 149.0 cm, weight 39.2 kg, BMI 17.7 kg/m 2 ), and the findings of a physical examination were unremarkable except for confirmation of xanthomas on the bilateral Achilles tendons ( Fig. 1B ) and right triceps muscle. She had age-appropriate slight cataracts in the bilateral eyes and did not have dementia based on the Revised Hasegawa Dementia Scale (HSD-R; 26/30), Mini-Mental State Examination (MMSE; 27/30), and Frontal Assessment Battery (FAB; 16/18) scores. On a neurological examination, her gait appeared somewhat spastic, and all of her deep tendon reflexes were mildly enhanced bilaterally with positive Babinski and Chaddock reflexes, indicating impairment in the bilateral pyramidal tracts. There were no neurological findings suggesting cerebellar impairment. Regarding the laboratory findings ( Table 1 ), there was no elevation in the levels of serum cholesterol or triglycerides or deficiencies in apolipoproteins or thyroid hormones. As the clinical findings suggested CTX, we studied the bile acids and sterols in her serum and urine ( Table 2 ). The primary bile acids were extremely low in the serum and urine when measured by both high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometer (GC/MS). The urinary levels of bile alcohols, especially 5β-cholestane-3α,7α,12α,24,25-pentol, were markedly elevated. Norcholic acid, which is mainly derived from 5β-cholestane-3α,7α,12α,23,25-pentol, was highly elevated and accounted for 78.4% of all bile acids in the urine. The serum level of cholestanol was extremely elevated, while those of sitosterol and campesterol were not elevated. T2-weighted and fluid-attenuated inversion recovery (FLAIR) MRI of the brain showed bilateral low-intensity areas in the dentate nuclei and high-intensity areas in the peripheral white matter the cerebellum ( Fig. 1C ). We also found bilateral high-intensity areas along the pyramidal tracts from the pons to the cerebral crus. Brain atrophy was not remarkable. Based on these clinical, laboratory and radiological findings, the patient was diagnosed with CTX. Ultrasound of the carotid arteries showed a slightly thickened intima-media complex at the left common carotid artery (maximum intima-media thickness, 1.2 mm). However, there was no evidence of cardiovascular disease on electrocardiogram, echocardiography and MR angiography of the brain and lower extremities. Despite being premenopausal ( Table 1 ), she had osteoporosis as determined by dual-energy X-ray absorptiometry, which showed a bone density of 61% and 75% the young-adult-mean in the lumbar vertebra and femoral neck, respectively.', 'Case presentation': 'The patient was a 50-year-old Japanese woman from non-consanguineous parents. She has no siblings but had a child. There was no apparent family history (parents, child and parent’s siblings) of neurological disorders, cardiovascular diseases or any lipid storage diseases inducing xanthomas, including CTX. She had no history of neonatal jaundice or chronic infantile diarrhea. She had been diagnosed with idiopathic epilepsy and medicated from 7 to 10 years of age. Thereafter, she had no remarkable medical developments until middle age. She insidiously developed painless tendon thickness of the bilateral Achilles tendons and right triceps muscle at 47 years of age. The gradual enlargement of the Achilles tendons caused gait disturbance when she was 49 years of age. T1- and T2-weighted magnetic resonance imaging (MRI) revealed low-intensity lesions in the thickened bilateral Achilles tendons ( Fig. 1A ) and right triceps muscle, suggestive of xanthomas. She was admitted to Nagasaki University Hospital for further investigation at 50 years of age.'}
|
{'Clinical, laboratory and imaging examinations': 'The patient was lean (height 149.0 cm, weight 39.2 kg, BMI 17.7 kg/m 2 ), and the findings of a physical examination were unremarkable except for confirmation of xanthomas on the bilateral Achilles tendons ( Fig. 1B ) and right triceps muscle. She had age-appropriate slight cataracts in the bilateral eyes and did not have dementia based on the Revised Hasegawa Dementia Scale (HSD-R; 26/30), Mini-Mental State Examination (MMSE; 27/30), and Frontal Assessment Battery (FAB; 16/18) scores. On a neurological examination, her gait appeared somewhat spastic, and all of her deep tendon reflexes were mildly enhanced bilaterally with positive Babinski and Chaddock reflexes, indicating impairment in the bilateral pyramidal tracts. There were no neurological findings suggesting cerebellar impairment. Regarding the laboratory findings ( Table 1 ), there was no elevation in the levels of serum cholesterol or triglycerides or deficiencies in apolipoproteins or thyroid hormones. As the clinical findings suggested CTX, we studied the bile acids and sterols in her serum and urine ( Table 2 ). The primary bile acids were extremely low in the serum and urine when measured by both high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometer (GC/MS). The urinary levels of bile alcohols, especially 5β-cholestane-3α,7α,12α,24,25-pentol, were markedly elevated. Norcholic acid, which is mainly derived from 5β-cholestane-3α,7α,12α,23,25-pentol, was highly elevated and accounted for 78.4% of all bile acids in the urine. The serum level of cholestanol was extremely elevated, while those of sitosterol and campesterol were not elevated. T2-weighted and fluid-attenuated inversion recovery (FLAIR) MRI of the brain showed bilateral low-intensity areas in the dentate nuclei and high-intensity areas in the peripheral white matter the cerebellum ( Fig. 1C ). We also found bilateral high-intensity areas along the pyramidal tracts from the pons to the cerebral crus. Brain atrophy was not remarkable. Based on these clinical, laboratory and radiological findings, the patient was diagnosed with CTX. Ultrasound of the carotid arteries showed a slightly thickened intima-media complex at the left common carotid artery (maximum intima-media thickness, 1.2 mm). However, there was no evidence of cardiovascular disease on electrocardiogram, echocardiography and MR angiography of the brain and lower extremities. Despite being premenopausal ( Table 1 ), she had osteoporosis as determined by dual-energy X-ray absorptiometry, which showed a bone density of 61% and 75% the young-adult-mean in the lumbar vertebra and femoral neck, respectively.', 'Case presentation': 'The patient was a 50-year-old Japanese woman from non-consanguineous parents. She has no siblings but had a child. There was no apparent family history (parents, child and parent’s siblings) of neurological disorders, cardiovascular diseases or any lipid storage diseases inducing xanthomas, including CTX. She had no history of neonatal jaundice or chronic infantile diarrhea. She had been diagnosed with idiopathic epilepsy and medicated from 7 to 10 years of age. Thereafter, she had no remarkable medical developments until middle age. She insidiously developed painless tendon thickness of the bilateral Achilles tendons and right triceps muscle at 47 years of age. The gradual enlargement of the Achilles tendons caused gait disturbance when she was 49 years of age. T1- and T2-weighted magnetic resonance imaging (MRI) revealed low-intensity lesions in the thickened bilateral Achilles tendons ( Fig. 1A ) and right triceps muscle, suggestive of xanthomas. She was admitted to Nagasaki University Hospital for further investigation at 50 years of age.'}
|
Genitourinary-System
|
GU
|
[] |
test-1935
|
6028668
|
{'Clinical, laboratory and imaging examinations': 'The patient was lean (height 149.0 cm, weight 39.2 kg, BMI 17.7 kg/m 2 ), and the findings of a physical examination were unremarkable except for confirmation of xanthomas on the bilateral Achilles tendons ( Fig. 1B ) and right triceps muscle. She had age-appropriate slight cataracts in the bilateral eyes and did not have dementia based on the Revised Hasegawa Dementia Scale (HSD-R; 26/30), Mini-Mental State Examination (MMSE; 27/30), and Frontal Assessment Battery (FAB; 16/18) scores. On a neurological examination, her gait appeared somewhat spastic, and all of her deep tendon reflexes were mildly enhanced bilaterally with positive Babinski and Chaddock reflexes, indicating impairment in the bilateral pyramidal tracts. There were no neurological findings suggesting cerebellar impairment. Regarding the laboratory findings ( Table 1 ), there was no elevation in the levels of serum cholesterol or triglycerides or deficiencies in apolipoproteins or thyroid hormones. As the clinical findings suggested CTX, we studied the bile acids and sterols in her serum and urine ( Table 2 ). The primary bile acids were extremely low in the serum and urine when measured by both high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometer (GC/MS). The urinary levels of bile alcohols, especially 5β-cholestane-3α,7α,12α,24,25-pentol, were markedly elevated. Norcholic acid, which is mainly derived from 5β-cholestane-3α,7α,12α,23,25-pentol, was highly elevated and accounted for 78.4% of all bile acids in the urine. The serum level of cholestanol was extremely elevated, while those of sitosterol and campesterol were not elevated. T2-weighted and fluid-attenuated inversion recovery (FLAIR) MRI of the brain showed bilateral low-intensity areas in the dentate nuclei and high-intensity areas in the peripheral white matter the cerebellum ( Fig. 1C ). We also found bilateral high-intensity areas along the pyramidal tracts from the pons to the cerebral crus. Brain atrophy was not remarkable. Based on these clinical, laboratory and radiological findings, the patient was diagnosed with CTX. Ultrasound of the carotid arteries showed a slightly thickened intima-media complex at the left common carotid artery (maximum intima-media thickness, 1.2 mm). However, there was no evidence of cardiovascular disease on electrocardiogram, echocardiography and MR angiography of the brain and lower extremities. Despite being premenopausal ( Table 1 ), she had osteoporosis as determined by dual-energy X-ray absorptiometry, which showed a bone density of 61% and 75% the young-adult-mean in the lumbar vertebra and femoral neck, respectively.', 'Case presentation': 'The patient was a 50-year-old Japanese woman from non-consanguineous parents. She has no siblings but had a child. There was no apparent family history (parents, child and parent’s siblings) of neurological disorders, cardiovascular diseases or any lipid storage diseases inducing xanthomas, including CTX. She had no history of neonatal jaundice or chronic infantile diarrhea. She had been diagnosed with idiopathic epilepsy and medicated from 7 to 10 years of age. Thereafter, she had no remarkable medical developments until middle age. She insidiously developed painless tendon thickness of the bilateral Achilles tendons and right triceps muscle at 47 years of age. The gradual enlargement of the Achilles tendons caused gait disturbance when she was 49 years of age. T1- and T2-weighted magnetic resonance imaging (MRI) revealed low-intensity lesions in the thickened bilateral Achilles tendons ( Fig. 1A ) and right triceps muscle, suggestive of xanthomas. She was admitted to Nagasaki University Hospital for further investigation at 50 years of age.'}
|
{'Clinical, laboratory and imaging examinations': 'The patient was lean (height 149.0 cm, weight 39.2 kg, BMI 17.7 kg/m 2 ), and the findings of a physical examination were unremarkable except for confirmation of xanthomas on the bilateral Achilles tendons ( Fig. 1B ) and right triceps muscle. She had age-appropriate slight cataracts in the bilateral eyes and did not have dementia based on the Revised Hasegawa Dementia Scale (HSD-R; 26/30), Mini-Mental State Examination (MMSE; 27/30), and Frontal Assessment Battery (FAB; 16/18) scores. On a neurological examination, her gait appeared somewhat spastic, and all of her deep tendon reflexes were mildly enhanced bilaterally with positive Babinski and Chaddock reflexes, indicating impairment in the bilateral pyramidal tracts. There were no neurological findings suggesting cerebellar impairment. Regarding the laboratory findings ( Table 1 ), there was no elevation in the levels of serum cholesterol or triglycerides or deficiencies in apolipoproteins or thyroid hormones. As the clinical findings suggested CTX, we studied the bile acids and sterols in her serum and urine ( Table 2 ). The primary bile acids were extremely low in the serum and urine when measured by both high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometer (GC/MS). The urinary levels of bile alcohols, especially 5β-cholestane-3α,7α,12α,24,25-pentol, were markedly elevated. Norcholic acid, which is mainly derived from 5β-cholestane-3α,7α,12α,23,25-pentol, was highly elevated and accounted for 78.4% of all bile acids in the urine. The serum level of cholestanol was extremely elevated, while those of sitosterol and campesterol were not elevated. T2-weighted and fluid-attenuated inversion recovery (FLAIR) MRI of the brain showed bilateral low-intensity areas in the dentate nuclei and high-intensity areas in the peripheral white matter the cerebellum ( Fig. 1C ). We also found bilateral high-intensity areas along the pyramidal tracts from the pons to the cerebral crus. Brain atrophy was not remarkable. Based on these clinical, laboratory and radiological findings, the patient was diagnosed with CTX. Ultrasound of the carotid arteries showed a slightly thickened intima-media complex at the left common carotid artery (maximum intima-media thickness, 1.2 mm). However, there was no evidence of cardiovascular disease on electrocardiogram, echocardiography and MR angiography of the brain and lower extremities. Despite being premenopausal ( Table 1 ), she had osteoporosis as determined by dual-energy X-ray absorptiometry, which showed a bone density of 61% and 75% the young-adult-mean in the lumbar vertebra and femoral neck, respectively.', 'Case presentation': 'The patient was a 50-year-old Japanese woman from non-consanguineous parents. She has no siblings but had a child. There was no apparent family history (parents, child and parent’s siblings) of neurological disorders, cardiovascular diseases or any lipid storage diseases inducing xanthomas, including CTX. She had no history of neonatal jaundice or chronic infantile diarrhea. She had been diagnosed with idiopathic epilepsy and medicated from 7 to 10 years of age. Thereafter, she had no remarkable medical developments until middle age. She insidiously developed painless tendon thickness of the bilateral Achilles tendons and right triceps muscle at 47 years of age. The gradual enlargement of the Achilles tendons caused gait disturbance when she was 49 years of age. T1- and T2-weighted magnetic resonance imaging (MRI) revealed low-intensity lesions in the thickened bilateral Achilles tendons ( Fig. 1A ) and right triceps muscle, suggestive of xanthomas. She was admitted to Nagasaki University Hospital for further investigation at 50 years of age.'}
|
Respiratory-System
|
RESP
|
[] |
test-1936
|
6028668
|
{'Clinical, laboratory and imaging examinations': 'The patient was lean (height 149.0 cm, weight 39.2 kg, BMI 17.7 kg/m 2 ), and the findings of a physical examination were unremarkable except for confirmation of xanthomas on the bilateral Achilles tendons ( Fig. 1B ) and right triceps muscle. She had age-appropriate slight cataracts in the bilateral eyes and did not have dementia based on the Revised Hasegawa Dementia Scale (HSD-R; 26/30), Mini-Mental State Examination (MMSE; 27/30), and Frontal Assessment Battery (FAB; 16/18) scores. On a neurological examination, her gait appeared somewhat spastic, and all of her deep tendon reflexes were mildly enhanced bilaterally with positive Babinski and Chaddock reflexes, indicating impairment in the bilateral pyramidal tracts. There were no neurological findings suggesting cerebellar impairment. Regarding the laboratory findings ( Table 1 ), there was no elevation in the levels of serum cholesterol or triglycerides or deficiencies in apolipoproteins or thyroid hormones. As the clinical findings suggested CTX, we studied the bile acids and sterols in her serum and urine ( Table 2 ). The primary bile acids were extremely low in the serum and urine when measured by both high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometer (GC/MS). The urinary levels of bile alcohols, especially 5β-cholestane-3α,7α,12α,24,25-pentol, were markedly elevated. Norcholic acid, which is mainly derived from 5β-cholestane-3α,7α,12α,23,25-pentol, was highly elevated and accounted for 78.4% of all bile acids in the urine. The serum level of cholestanol was extremely elevated, while those of sitosterol and campesterol were not elevated. T2-weighted and fluid-attenuated inversion recovery (FLAIR) MRI of the brain showed bilateral low-intensity areas in the dentate nuclei and high-intensity areas in the peripheral white matter the cerebellum ( Fig. 1C ). We also found bilateral high-intensity areas along the pyramidal tracts from the pons to the cerebral crus. Brain atrophy was not remarkable. Based on these clinical, laboratory and radiological findings, the patient was diagnosed with CTX. Ultrasound of the carotid arteries showed a slightly thickened intima-media complex at the left common carotid artery (maximum intima-media thickness, 1.2 mm). However, there was no evidence of cardiovascular disease on electrocardiogram, echocardiography and MR angiography of the brain and lower extremities. Despite being premenopausal ( Table 1 ), she had osteoporosis as determined by dual-energy X-ray absorptiometry, which showed a bone density of 61% and 75% the young-adult-mean in the lumbar vertebra and femoral neck, respectively.', 'Case presentation': 'The patient was a 50-year-old Japanese woman from non-consanguineous parents. She has no siblings but had a child. There was no apparent family history (parents, child and parent’s siblings) of neurological disorders, cardiovascular diseases or any lipid storage diseases inducing xanthomas, including CTX. She had no history of neonatal jaundice or chronic infantile diarrhea. She had been diagnosed with idiopathic epilepsy and medicated from 7 to 10 years of age. Thereafter, she had no remarkable medical developments until middle age. She insidiously developed painless tendon thickness of the bilateral Achilles tendons and right triceps muscle at 47 years of age. The gradual enlargement of the Achilles tendons caused gait disturbance when she was 49 years of age. T1- and T2-weighted magnetic resonance imaging (MRI) revealed low-intensity lesions in the thickened bilateral Achilles tendons ( Fig. 1A ) and right triceps muscle, suggestive of xanthomas. She was admitted to Nagasaki University Hospital for further investigation at 50 years of age.'}
|
{'Clinical, laboratory and imaging examinations': 'The patient was lean (height 149.0 cm, weight 39.2 kg, BMI 17.7 kg/m 2 ), and the findings of a physical examination were unremarkable except for confirmation of xanthomas on the bilateral Achilles tendons ( Fig. 1B ) and right triceps muscle. She had age-appropriate slight cataracts in the bilateral eyes and did not have dementia based on the Revised Hasegawa Dementia Scale (HSD-R; 26/30), Mini-Mental State Examination (MMSE; 27/30), and Frontal Assessment Battery (FAB; 16/18) scores. On a neurological examination, her gait appeared somewhat spastic, and all of her deep tendon reflexes were mildly enhanced bilaterally with positive Babinski and Chaddock reflexes, indicating impairment in the bilateral pyramidal tracts. There were no neurological findings suggesting cerebellar impairment. Regarding the laboratory findings ( Table 1 ), there was no elevation in the levels of serum cholesterol or triglycerides or deficiencies in apolipoproteins or thyroid hormones. As the clinical findings suggested CTX, we studied the bile acids and sterols in her serum and urine ( Table 2 ). The primary bile acids were extremely low in the serum and urine when measured by both high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometer (GC/MS). The urinary levels of bile alcohols, especially 5β-cholestane-3α,7α,12α,24,25-pentol, were markedly elevated. Norcholic acid, which is mainly derived from 5β-cholestane-3α,7α,12α,23,25-pentol, was highly elevated and accounted for 78.4% of all bile acids in the urine. The serum level of cholestanol was extremely elevated, while those of sitosterol and campesterol were not elevated. T2-weighted and fluid-attenuated inversion recovery (FLAIR) MRI of the brain showed bilateral low-intensity areas in the dentate nuclei and high-intensity areas in the peripheral white matter the cerebellum ( Fig. 1C ). We also found bilateral high-intensity areas along the pyramidal tracts from the pons to the cerebral crus. Brain atrophy was not remarkable. Based on these clinical, laboratory and radiological findings, the patient was diagnosed with CTX. Ultrasound of the carotid arteries showed a slightly thickened intima-media complex at the left common carotid artery (maximum intima-media thickness, 1.2 mm). However, there was no evidence of cardiovascular disease on electrocardiogram, echocardiography and MR angiography of the brain and lower extremities. Despite being premenopausal ( Table 1 ), she had osteoporosis as determined by dual-energy X-ray absorptiometry, which showed a bone density of 61% and 75% the young-adult-mean in the lumbar vertebra and femoral neck, respectively.', 'Case presentation': 'The patient was a 50-year-old Japanese woman from non-consanguineous parents. She has no siblings but had a child. There was no apparent family history (parents, child and parent’s siblings) of neurological disorders, cardiovascular diseases or any lipid storage diseases inducing xanthomas, including CTX. She had no history of neonatal jaundice or chronic infantile diarrhea. She had been diagnosed with idiopathic epilepsy and medicated from 7 to 10 years of age. Thereafter, she had no remarkable medical developments until middle age. She insidiously developed painless tendon thickness of the bilateral Achilles tendons and right triceps muscle at 47 years of age. The gradual enlargement of the Achilles tendons caused gait disturbance when she was 49 years of age. T1- and T2-weighted magnetic resonance imaging (MRI) revealed low-intensity lesions in the thickened bilateral Achilles tendons ( Fig. 1A ) and right triceps muscle, suggestive of xanthomas. She was admitted to Nagasaki University Hospital for further investigation at 50 years of age.'}
|
Musculoskeletal-System
|
MSK
|
[
"xanthomas on the bilateral Achilles tendons ( Fig. 1B ) and right triceps muscle",
"osteoporosis as determined by dual - energy X - ray absorptiometry, which showed a bone density of 61 % and 75 % the young - adult - mean in the lumbar vertebra and femoral neck, respectively",
"painless tendon thickness of the bilateral Achilles tendons and right triceps muscle at 47 years of age. The gradual enlargement of the Achilles tendons caused gait disturbance when she was 49 years of age. T1- and T2 - weighted magnetic resonance imaging ( MRI ) revealed low - intensity lesions in the thickened bilateral Achilles tendons ( Fig. 1A ) and right triceps muscle, suggestive of xanthomas."
] |
test-1937
|
6028668
|
{'Clinical, laboratory and imaging examinations': 'The patient was lean (height 149.0 cm, weight 39.2 kg, BMI 17.7 kg/m 2 ), and the findings of a physical examination were unremarkable except for confirmation of xanthomas on the bilateral Achilles tendons ( Fig. 1B ) and right triceps muscle. She had age-appropriate slight cataracts in the bilateral eyes and did not have dementia based on the Revised Hasegawa Dementia Scale (HSD-R; 26/30), Mini-Mental State Examination (MMSE; 27/30), and Frontal Assessment Battery (FAB; 16/18) scores. On a neurological examination, her gait appeared somewhat spastic, and all of her deep tendon reflexes were mildly enhanced bilaterally with positive Babinski and Chaddock reflexes, indicating impairment in the bilateral pyramidal tracts. There were no neurological findings suggesting cerebellar impairment. Regarding the laboratory findings ( Table 1 ), there was no elevation in the levels of serum cholesterol or triglycerides or deficiencies in apolipoproteins or thyroid hormones. As the clinical findings suggested CTX, we studied the bile acids and sterols in her serum and urine ( Table 2 ). The primary bile acids were extremely low in the serum and urine when measured by both high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometer (GC/MS). The urinary levels of bile alcohols, especially 5β-cholestane-3α,7α,12α,24,25-pentol, were markedly elevated. Norcholic acid, which is mainly derived from 5β-cholestane-3α,7α,12α,23,25-pentol, was highly elevated and accounted for 78.4% of all bile acids in the urine. The serum level of cholestanol was extremely elevated, while those of sitosterol and campesterol were not elevated. T2-weighted and fluid-attenuated inversion recovery (FLAIR) MRI of the brain showed bilateral low-intensity areas in the dentate nuclei and high-intensity areas in the peripheral white matter the cerebellum ( Fig. 1C ). We also found bilateral high-intensity areas along the pyramidal tracts from the pons to the cerebral crus. Brain atrophy was not remarkable. Based on these clinical, laboratory and radiological findings, the patient was diagnosed with CTX. Ultrasound of the carotid arteries showed a slightly thickened intima-media complex at the left common carotid artery (maximum intima-media thickness, 1.2 mm). However, there was no evidence of cardiovascular disease on electrocardiogram, echocardiography and MR angiography of the brain and lower extremities. Despite being premenopausal ( Table 1 ), she had osteoporosis as determined by dual-energy X-ray absorptiometry, which showed a bone density of 61% and 75% the young-adult-mean in the lumbar vertebra and femoral neck, respectively.', 'Case presentation': 'The patient was a 50-year-old Japanese woman from non-consanguineous parents. She has no siblings but had a child. There was no apparent family history (parents, child and parent’s siblings) of neurological disorders, cardiovascular diseases or any lipid storage diseases inducing xanthomas, including CTX. She had no history of neonatal jaundice or chronic infantile diarrhea. She had been diagnosed with idiopathic epilepsy and medicated from 7 to 10 years of age. Thereafter, she had no remarkable medical developments until middle age. She insidiously developed painless tendon thickness of the bilateral Achilles tendons and right triceps muscle at 47 years of age. The gradual enlargement of the Achilles tendons caused gait disturbance when she was 49 years of age. T1- and T2-weighted magnetic resonance imaging (MRI) revealed low-intensity lesions in the thickened bilateral Achilles tendons ( Fig. 1A ) and right triceps muscle, suggestive of xanthomas. She was admitted to Nagasaki University Hospital for further investigation at 50 years of age.'}
|
{'Clinical, laboratory and imaging examinations': 'The patient was lean (height 149.0 cm, weight 39.2 kg, BMI 17.7 kg/m 2 ), and the findings of a physical examination were unremarkable except for confirmation of xanthomas on the bilateral Achilles tendons ( Fig. 1B ) and right triceps muscle. She had age-appropriate slight cataracts in the bilateral eyes and did not have dementia based on the Revised Hasegawa Dementia Scale (HSD-R; 26/30), Mini-Mental State Examination (MMSE; 27/30), and Frontal Assessment Battery (FAB; 16/18) scores. On a neurological examination, her gait appeared somewhat spastic, and all of her deep tendon reflexes were mildly enhanced bilaterally with positive Babinski and Chaddock reflexes, indicating impairment in the bilateral pyramidal tracts. There were no neurological findings suggesting cerebellar impairment. Regarding the laboratory findings ( Table 1 ), there was no elevation in the levels of serum cholesterol or triglycerides or deficiencies in apolipoproteins or thyroid hormones. As the clinical findings suggested CTX, we studied the bile acids and sterols in her serum and urine ( Table 2 ). The primary bile acids were extremely low in the serum and urine when measured by both high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometer (GC/MS). The urinary levels of bile alcohols, especially 5β-cholestane-3α,7α,12α,24,25-pentol, were markedly elevated. Norcholic acid, which is mainly derived from 5β-cholestane-3α,7α,12α,23,25-pentol, was highly elevated and accounted for 78.4% of all bile acids in the urine. The serum level of cholestanol was extremely elevated, while those of sitosterol and campesterol were not elevated. T2-weighted and fluid-attenuated inversion recovery (FLAIR) MRI of the brain showed bilateral low-intensity areas in the dentate nuclei and high-intensity areas in the peripheral white matter the cerebellum ( Fig. 1C ). We also found bilateral high-intensity areas along the pyramidal tracts from the pons to the cerebral crus. Brain atrophy was not remarkable. Based on these clinical, laboratory and radiological findings, the patient was diagnosed with CTX. Ultrasound of the carotid arteries showed a slightly thickened intima-media complex at the left common carotid artery (maximum intima-media thickness, 1.2 mm). However, there was no evidence of cardiovascular disease on electrocardiogram, echocardiography and MR angiography of the brain and lower extremities. Despite being premenopausal ( Table 1 ), she had osteoporosis as determined by dual-energy X-ray absorptiometry, which showed a bone density of 61% and 75% the young-adult-mean in the lumbar vertebra and femoral neck, respectively.', 'Case presentation': 'The patient was a 50-year-old Japanese woman from non-consanguineous parents. She has no siblings but had a child. There was no apparent family history (parents, child and parent’s siblings) of neurological disorders, cardiovascular diseases or any lipid storage diseases inducing xanthomas, including CTX. She had no history of neonatal jaundice or chronic infantile diarrhea. She had been diagnosed with idiopathic epilepsy and medicated from 7 to 10 years of age. Thereafter, she had no remarkable medical developments until middle age. She insidiously developed painless tendon thickness of the bilateral Achilles tendons and right triceps muscle at 47 years of age. The gradual enlargement of the Achilles tendons caused gait disturbance when she was 49 years of age. T1- and T2-weighted magnetic resonance imaging (MRI) revealed low-intensity lesions in the thickened bilateral Achilles tendons ( Fig. 1A ) and right triceps muscle, suggestive of xanthomas. She was admitted to Nagasaki University Hospital for further investigation at 50 years of age.'}
|
Eyes-Ears-Nose-Throat
|
EENT
|
[
"age - appropriate slight cataracts in the bilateral eyes"
] |
test-1938
|
6028668
|
{'Clinical, laboratory and imaging examinations': 'The patient was lean (height 149.0 cm, weight 39.2 kg, BMI 17.7 kg/m 2 ), and the findings of a physical examination were unremarkable except for confirmation of xanthomas on the bilateral Achilles tendons ( Fig. 1B ) and right triceps muscle. She had age-appropriate slight cataracts in the bilateral eyes and did not have dementia based on the Revised Hasegawa Dementia Scale (HSD-R; 26/30), Mini-Mental State Examination (MMSE; 27/30), and Frontal Assessment Battery (FAB; 16/18) scores. On a neurological examination, her gait appeared somewhat spastic, and all of her deep tendon reflexes were mildly enhanced bilaterally with positive Babinski and Chaddock reflexes, indicating impairment in the bilateral pyramidal tracts. There were no neurological findings suggesting cerebellar impairment. Regarding the laboratory findings ( Table 1 ), there was no elevation in the levels of serum cholesterol or triglycerides or deficiencies in apolipoproteins or thyroid hormones. As the clinical findings suggested CTX, we studied the bile acids and sterols in her serum and urine ( Table 2 ). The primary bile acids were extremely low in the serum and urine when measured by both high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometer (GC/MS). The urinary levels of bile alcohols, especially 5β-cholestane-3α,7α,12α,24,25-pentol, were markedly elevated. Norcholic acid, which is mainly derived from 5β-cholestane-3α,7α,12α,23,25-pentol, was highly elevated and accounted for 78.4% of all bile acids in the urine. The serum level of cholestanol was extremely elevated, while those of sitosterol and campesterol were not elevated. T2-weighted and fluid-attenuated inversion recovery (FLAIR) MRI of the brain showed bilateral low-intensity areas in the dentate nuclei and high-intensity areas in the peripheral white matter the cerebellum ( Fig. 1C ). We also found bilateral high-intensity areas along the pyramidal tracts from the pons to the cerebral crus. Brain atrophy was not remarkable. Based on these clinical, laboratory and radiological findings, the patient was diagnosed with CTX. Ultrasound of the carotid arteries showed a slightly thickened intima-media complex at the left common carotid artery (maximum intima-media thickness, 1.2 mm). However, there was no evidence of cardiovascular disease on electrocardiogram, echocardiography and MR angiography of the brain and lower extremities. Despite being premenopausal ( Table 1 ), she had osteoporosis as determined by dual-energy X-ray absorptiometry, which showed a bone density of 61% and 75% the young-adult-mean in the lumbar vertebra and femoral neck, respectively.', 'Case presentation': 'The patient was a 50-year-old Japanese woman from non-consanguineous parents. She has no siblings but had a child. There was no apparent family history (parents, child and parent’s siblings) of neurological disorders, cardiovascular diseases or any lipid storage diseases inducing xanthomas, including CTX. She had no history of neonatal jaundice or chronic infantile diarrhea. She had been diagnosed with idiopathic epilepsy and medicated from 7 to 10 years of age. Thereafter, she had no remarkable medical developments until middle age. She insidiously developed painless tendon thickness of the bilateral Achilles tendons and right triceps muscle at 47 years of age. The gradual enlargement of the Achilles tendons caused gait disturbance when she was 49 years of age. T1- and T2-weighted magnetic resonance imaging (MRI) revealed low-intensity lesions in the thickened bilateral Achilles tendons ( Fig. 1A ) and right triceps muscle, suggestive of xanthomas. She was admitted to Nagasaki University Hospital for further investigation at 50 years of age.'}
|
{'Clinical, laboratory and imaging examinations': 'The patient was lean (height 149.0 cm, weight 39.2 kg, BMI 17.7 kg/m 2 ), and the findings of a physical examination were unremarkable except for confirmation of xanthomas on the bilateral Achilles tendons ( Fig. 1B ) and right triceps muscle. She had age-appropriate slight cataracts in the bilateral eyes and did not have dementia based on the Revised Hasegawa Dementia Scale (HSD-R; 26/30), Mini-Mental State Examination (MMSE; 27/30), and Frontal Assessment Battery (FAB; 16/18) scores. On a neurological examination, her gait appeared somewhat spastic, and all of her deep tendon reflexes were mildly enhanced bilaterally with positive Babinski and Chaddock reflexes, indicating impairment in the bilateral pyramidal tracts. There were no neurological findings suggesting cerebellar impairment. Regarding the laboratory findings ( Table 1 ), there was no elevation in the levels of serum cholesterol or triglycerides or deficiencies in apolipoproteins or thyroid hormones. As the clinical findings suggested CTX, we studied the bile acids and sterols in her serum and urine ( Table 2 ). The primary bile acids were extremely low in the serum and urine when measured by both high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometer (GC/MS). The urinary levels of bile alcohols, especially 5β-cholestane-3α,7α,12α,24,25-pentol, were markedly elevated. Norcholic acid, which is mainly derived from 5β-cholestane-3α,7α,12α,23,25-pentol, was highly elevated and accounted for 78.4% of all bile acids in the urine. The serum level of cholestanol was extremely elevated, while those of sitosterol and campesterol were not elevated. T2-weighted and fluid-attenuated inversion recovery (FLAIR) MRI of the brain showed bilateral low-intensity areas in the dentate nuclei and high-intensity areas in the peripheral white matter the cerebellum ( Fig. 1C ). We also found bilateral high-intensity areas along the pyramidal tracts from the pons to the cerebral crus. Brain atrophy was not remarkable. Based on these clinical, laboratory and radiological findings, the patient was diagnosed with CTX. Ultrasound of the carotid arteries showed a slightly thickened intima-media complex at the left common carotid artery (maximum intima-media thickness, 1.2 mm). However, there was no evidence of cardiovascular disease on electrocardiogram, echocardiography and MR angiography of the brain and lower extremities. Despite being premenopausal ( Table 1 ), she had osteoporosis as determined by dual-energy X-ray absorptiometry, which showed a bone density of 61% and 75% the young-adult-mean in the lumbar vertebra and femoral neck, respectively.', 'Case presentation': 'The patient was a 50-year-old Japanese woman from non-consanguineous parents. She has no siblings but had a child. There was no apparent family history (parents, child and parent’s siblings) of neurological disorders, cardiovascular diseases or any lipid storage diseases inducing xanthomas, including CTX. She had no history of neonatal jaundice or chronic infantile diarrhea. She had been diagnosed with idiopathic epilepsy and medicated from 7 to 10 years of age. Thereafter, she had no remarkable medical developments until middle age. She insidiously developed painless tendon thickness of the bilateral Achilles tendons and right triceps muscle at 47 years of age. The gradual enlargement of the Achilles tendons caused gait disturbance when she was 49 years of age. T1- and T2-weighted magnetic resonance imaging (MRI) revealed low-intensity lesions in the thickened bilateral Achilles tendons ( Fig. 1A ) and right triceps muscle, suggestive of xanthomas. She was admitted to Nagasaki University Hospital for further investigation at 50 years of age.'}
|
Dermatology
|
DERM
|
[] |
test-1939
|
6028668
|
{'Clinical, laboratory and imaging examinations': 'The patient was lean (height 149.0 cm, weight 39.2 kg, BMI 17.7 kg/m 2 ), and the findings of a physical examination were unremarkable except for confirmation of xanthomas on the bilateral Achilles tendons ( Fig. 1B ) and right triceps muscle. She had age-appropriate slight cataracts in the bilateral eyes and did not have dementia based on the Revised Hasegawa Dementia Scale (HSD-R; 26/30), Mini-Mental State Examination (MMSE; 27/30), and Frontal Assessment Battery (FAB; 16/18) scores. On a neurological examination, her gait appeared somewhat spastic, and all of her deep tendon reflexes were mildly enhanced bilaterally with positive Babinski and Chaddock reflexes, indicating impairment in the bilateral pyramidal tracts. There were no neurological findings suggesting cerebellar impairment. Regarding the laboratory findings ( Table 1 ), there was no elevation in the levels of serum cholesterol or triglycerides or deficiencies in apolipoproteins or thyroid hormones. As the clinical findings suggested CTX, we studied the bile acids and sterols in her serum and urine ( Table 2 ). The primary bile acids were extremely low in the serum and urine when measured by both high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometer (GC/MS). The urinary levels of bile alcohols, especially 5β-cholestane-3α,7α,12α,24,25-pentol, were markedly elevated. Norcholic acid, which is mainly derived from 5β-cholestane-3α,7α,12α,23,25-pentol, was highly elevated and accounted for 78.4% of all bile acids in the urine. The serum level of cholestanol was extremely elevated, while those of sitosterol and campesterol were not elevated. T2-weighted and fluid-attenuated inversion recovery (FLAIR) MRI of the brain showed bilateral low-intensity areas in the dentate nuclei and high-intensity areas in the peripheral white matter the cerebellum ( Fig. 1C ). We also found bilateral high-intensity areas along the pyramidal tracts from the pons to the cerebral crus. Brain atrophy was not remarkable. Based on these clinical, laboratory and radiological findings, the patient was diagnosed with CTX. Ultrasound of the carotid arteries showed a slightly thickened intima-media complex at the left common carotid artery (maximum intima-media thickness, 1.2 mm). However, there was no evidence of cardiovascular disease on electrocardiogram, echocardiography and MR angiography of the brain and lower extremities. Despite being premenopausal ( Table 1 ), she had osteoporosis as determined by dual-energy X-ray absorptiometry, which showed a bone density of 61% and 75% the young-adult-mean in the lumbar vertebra and femoral neck, respectively.', 'Case presentation': 'The patient was a 50-year-old Japanese woman from non-consanguineous parents. She has no siblings but had a child. There was no apparent family history (parents, child and parent’s siblings) of neurological disorders, cardiovascular diseases or any lipid storage diseases inducing xanthomas, including CTX. She had no history of neonatal jaundice or chronic infantile diarrhea. She had been diagnosed with idiopathic epilepsy and medicated from 7 to 10 years of age. Thereafter, she had no remarkable medical developments until middle age. She insidiously developed painless tendon thickness of the bilateral Achilles tendons and right triceps muscle at 47 years of age. The gradual enlargement of the Achilles tendons caused gait disturbance when she was 49 years of age. T1- and T2-weighted magnetic resonance imaging (MRI) revealed low-intensity lesions in the thickened bilateral Achilles tendons ( Fig. 1A ) and right triceps muscle, suggestive of xanthomas. She was admitted to Nagasaki University Hospital for further investigation at 50 years of age.'}
|
{'Clinical, laboratory and imaging examinations': 'The patient was lean (height 149.0 cm, weight 39.2 kg, BMI 17.7 kg/m 2 ), and the findings of a physical examination were unremarkable except for confirmation of xanthomas on the bilateral Achilles tendons ( Fig. 1B ) and right triceps muscle. She had age-appropriate slight cataracts in the bilateral eyes and did not have dementia based on the Revised Hasegawa Dementia Scale (HSD-R; 26/30), Mini-Mental State Examination (MMSE; 27/30), and Frontal Assessment Battery (FAB; 16/18) scores. On a neurological examination, her gait appeared somewhat spastic, and all of her deep tendon reflexes were mildly enhanced bilaterally with positive Babinski and Chaddock reflexes, indicating impairment in the bilateral pyramidal tracts. There were no neurological findings suggesting cerebellar impairment. Regarding the laboratory findings ( Table 1 ), there was no elevation in the levels of serum cholesterol or triglycerides or deficiencies in apolipoproteins or thyroid hormones. As the clinical findings suggested CTX, we studied the bile acids and sterols in her serum and urine ( Table 2 ). The primary bile acids were extremely low in the serum and urine when measured by both high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometer (GC/MS). The urinary levels of bile alcohols, especially 5β-cholestane-3α,7α,12α,24,25-pentol, were markedly elevated. Norcholic acid, which is mainly derived from 5β-cholestane-3α,7α,12α,23,25-pentol, was highly elevated and accounted for 78.4% of all bile acids in the urine. The serum level of cholestanol was extremely elevated, while those of sitosterol and campesterol were not elevated. T2-weighted and fluid-attenuated inversion recovery (FLAIR) MRI of the brain showed bilateral low-intensity areas in the dentate nuclei and high-intensity areas in the peripheral white matter the cerebellum ( Fig. 1C ). We also found bilateral high-intensity areas along the pyramidal tracts from the pons to the cerebral crus. Brain atrophy was not remarkable. Based on these clinical, laboratory and radiological findings, the patient was diagnosed with CTX. Ultrasound of the carotid arteries showed a slightly thickened intima-media complex at the left common carotid artery (maximum intima-media thickness, 1.2 mm). However, there was no evidence of cardiovascular disease on electrocardiogram, echocardiography and MR angiography of the brain and lower extremities. Despite being premenopausal ( Table 1 ), she had osteoporosis as determined by dual-energy X-ray absorptiometry, which showed a bone density of 61% and 75% the young-adult-mean in the lumbar vertebra and femoral neck, respectively.', 'Case presentation': 'The patient was a 50-year-old Japanese woman from non-consanguineous parents. She has no siblings but had a child. There was no apparent family history (parents, child and parent’s siblings) of neurological disorders, cardiovascular diseases or any lipid storage diseases inducing xanthomas, including CTX. She had no history of neonatal jaundice or chronic infantile diarrhea. She had been diagnosed with idiopathic epilepsy and medicated from 7 to 10 years of age. Thereafter, she had no remarkable medical developments until middle age. She insidiously developed painless tendon thickness of the bilateral Achilles tendons and right triceps muscle at 47 years of age. The gradual enlargement of the Achilles tendons caused gait disturbance when she was 49 years of age. T1- and T2-weighted magnetic resonance imaging (MRI) revealed low-intensity lesions in the thickened bilateral Achilles tendons ( Fig. 1A ) and right triceps muscle, suggestive of xanthomas. She was admitted to Nagasaki University Hospital for further investigation at 50 years of age.'}
|
Pregnancy
|
Pregnancy
|
[
"no history of neonatal jaundice"
] |
test-1940
|
6028668
|
{'Clinical, laboratory and imaging examinations': 'The patient was lean (height 149.0 cm, weight 39.2 kg, BMI 17.7 kg/m 2 ), and the findings of a physical examination were unremarkable except for confirmation of xanthomas on the bilateral Achilles tendons ( Fig. 1B ) and right triceps muscle. She had age-appropriate slight cataracts in the bilateral eyes and did not have dementia based on the Revised Hasegawa Dementia Scale (HSD-R; 26/30), Mini-Mental State Examination (MMSE; 27/30), and Frontal Assessment Battery (FAB; 16/18) scores. On a neurological examination, her gait appeared somewhat spastic, and all of her deep tendon reflexes were mildly enhanced bilaterally with positive Babinski and Chaddock reflexes, indicating impairment in the bilateral pyramidal tracts. There were no neurological findings suggesting cerebellar impairment. Regarding the laboratory findings ( Table 1 ), there was no elevation in the levels of serum cholesterol or triglycerides or deficiencies in apolipoproteins or thyroid hormones. As the clinical findings suggested CTX, we studied the bile acids and sterols in her serum and urine ( Table 2 ). The primary bile acids were extremely low in the serum and urine when measured by both high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometer (GC/MS). The urinary levels of bile alcohols, especially 5β-cholestane-3α,7α,12α,24,25-pentol, were markedly elevated. Norcholic acid, which is mainly derived from 5β-cholestane-3α,7α,12α,23,25-pentol, was highly elevated and accounted for 78.4% of all bile acids in the urine. The serum level of cholestanol was extremely elevated, while those of sitosterol and campesterol were not elevated. T2-weighted and fluid-attenuated inversion recovery (FLAIR) MRI of the brain showed bilateral low-intensity areas in the dentate nuclei and high-intensity areas in the peripheral white matter the cerebellum ( Fig. 1C ). We also found bilateral high-intensity areas along the pyramidal tracts from the pons to the cerebral crus. Brain atrophy was not remarkable. Based on these clinical, laboratory and radiological findings, the patient was diagnosed with CTX. Ultrasound of the carotid arteries showed a slightly thickened intima-media complex at the left common carotid artery (maximum intima-media thickness, 1.2 mm). However, there was no evidence of cardiovascular disease on electrocardiogram, echocardiography and MR angiography of the brain and lower extremities. Despite being premenopausal ( Table 1 ), she had osteoporosis as determined by dual-energy X-ray absorptiometry, which showed a bone density of 61% and 75% the young-adult-mean in the lumbar vertebra and femoral neck, respectively.', 'Case presentation': 'The patient was a 50-year-old Japanese woman from non-consanguineous parents. She has no siblings but had a child. There was no apparent family history (parents, child and parent’s siblings) of neurological disorders, cardiovascular diseases or any lipid storage diseases inducing xanthomas, including CTX. She had no history of neonatal jaundice or chronic infantile diarrhea. She had been diagnosed with idiopathic epilepsy and medicated from 7 to 10 years of age. Thereafter, she had no remarkable medical developments until middle age. She insidiously developed painless tendon thickness of the bilateral Achilles tendons and right triceps muscle at 47 years of age. The gradual enlargement of the Achilles tendons caused gait disturbance when she was 49 years of age. T1- and T2-weighted magnetic resonance imaging (MRI) revealed low-intensity lesions in the thickened bilateral Achilles tendons ( Fig. 1A ) and right triceps muscle, suggestive of xanthomas. She was admitted to Nagasaki University Hospital for further investigation at 50 years of age.'}
|
{'Clinical, laboratory and imaging examinations': 'The patient was lean (height 149.0 cm, weight 39.2 kg, BMI 17.7 kg/m 2 ), and the findings of a physical examination were unremarkable except for confirmation of xanthomas on the bilateral Achilles tendons ( Fig. 1B ) and right triceps muscle. She had age-appropriate slight cataracts in the bilateral eyes and did not have dementia based on the Revised Hasegawa Dementia Scale (HSD-R; 26/30), Mini-Mental State Examination (MMSE; 27/30), and Frontal Assessment Battery (FAB; 16/18) scores. On a neurological examination, her gait appeared somewhat spastic, and all of her deep tendon reflexes were mildly enhanced bilaterally with positive Babinski and Chaddock reflexes, indicating impairment in the bilateral pyramidal tracts. There were no neurological findings suggesting cerebellar impairment. Regarding the laboratory findings ( Table 1 ), there was no elevation in the levels of serum cholesterol or triglycerides or deficiencies in apolipoproteins or thyroid hormones. As the clinical findings suggested CTX, we studied the bile acids and sterols in her serum and urine ( Table 2 ). The primary bile acids were extremely low in the serum and urine when measured by both high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometer (GC/MS). The urinary levels of bile alcohols, especially 5β-cholestane-3α,7α,12α,24,25-pentol, were markedly elevated. Norcholic acid, which is mainly derived from 5β-cholestane-3α,7α,12α,23,25-pentol, was highly elevated and accounted for 78.4% of all bile acids in the urine. The serum level of cholestanol was extremely elevated, while those of sitosterol and campesterol were not elevated. T2-weighted and fluid-attenuated inversion recovery (FLAIR) MRI of the brain showed bilateral low-intensity areas in the dentate nuclei and high-intensity areas in the peripheral white matter the cerebellum ( Fig. 1C ). We also found bilateral high-intensity areas along the pyramidal tracts from the pons to the cerebral crus. Brain atrophy was not remarkable. Based on these clinical, laboratory and radiological findings, the patient was diagnosed with CTX. Ultrasound of the carotid arteries showed a slightly thickened intima-media complex at the left common carotid artery (maximum intima-media thickness, 1.2 mm). However, there was no evidence of cardiovascular disease on electrocardiogram, echocardiography and MR angiography of the brain and lower extremities. Despite being premenopausal ( Table 1 ), she had osteoporosis as determined by dual-energy X-ray absorptiometry, which showed a bone density of 61% and 75% the young-adult-mean in the lumbar vertebra and femoral neck, respectively.', 'Case presentation': 'The patient was a 50-year-old Japanese woman from non-consanguineous parents. She has no siblings but had a child. There was no apparent family history (parents, child and parent’s siblings) of neurological disorders, cardiovascular diseases or any lipid storage diseases inducing xanthomas, including CTX. She had no history of neonatal jaundice or chronic infantile diarrhea. She had been diagnosed with idiopathic epilepsy and medicated from 7 to 10 years of age. Thereafter, she had no remarkable medical developments until middle age. She insidiously developed painless tendon thickness of the bilateral Achilles tendons and right triceps muscle at 47 years of age. The gradual enlargement of the Achilles tendons caused gait disturbance when she was 49 years of age. T1- and T2-weighted magnetic resonance imaging (MRI) revealed low-intensity lesions in the thickened bilateral Achilles tendons ( Fig. 1A ) and right triceps muscle, suggestive of xanthomas. She was admitted to Nagasaki University Hospital for further investigation at 50 years of age.'}
|
Lymphatic-System
|
LYMPH
|
[] |
test-1941
|
6028668
|
{'Clinical, laboratory and imaging examinations': 'The patient was lean (height 149.0 cm, weight 39.2 kg, BMI 17.7 kg/m 2 ), and the findings of a physical examination were unremarkable except for confirmation of xanthomas on the bilateral Achilles tendons ( Fig. 1B ) and right triceps muscle. She had age-appropriate slight cataracts in the bilateral eyes and did not have dementia based on the Revised Hasegawa Dementia Scale (HSD-R; 26/30), Mini-Mental State Examination (MMSE; 27/30), and Frontal Assessment Battery (FAB; 16/18) scores. On a neurological examination, her gait appeared somewhat spastic, and all of her deep tendon reflexes were mildly enhanced bilaterally with positive Babinski and Chaddock reflexes, indicating impairment in the bilateral pyramidal tracts. There were no neurological findings suggesting cerebellar impairment. Regarding the laboratory findings ( Table 1 ), there was no elevation in the levels of serum cholesterol or triglycerides or deficiencies in apolipoproteins or thyroid hormones. As the clinical findings suggested CTX, we studied the bile acids and sterols in her serum and urine ( Table 2 ). The primary bile acids were extremely low in the serum and urine when measured by both high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometer (GC/MS). The urinary levels of bile alcohols, especially 5β-cholestane-3α,7α,12α,24,25-pentol, were markedly elevated. Norcholic acid, which is mainly derived from 5β-cholestane-3α,7α,12α,23,25-pentol, was highly elevated and accounted for 78.4% of all bile acids in the urine. The serum level of cholestanol was extremely elevated, while those of sitosterol and campesterol were not elevated. T2-weighted and fluid-attenuated inversion recovery (FLAIR) MRI of the brain showed bilateral low-intensity areas in the dentate nuclei and high-intensity areas in the peripheral white matter the cerebellum ( Fig. 1C ). We also found bilateral high-intensity areas along the pyramidal tracts from the pons to the cerebral crus. Brain atrophy was not remarkable. Based on these clinical, laboratory and radiological findings, the patient was diagnosed with CTX. Ultrasound of the carotid arteries showed a slightly thickened intima-media complex at the left common carotid artery (maximum intima-media thickness, 1.2 mm). However, there was no evidence of cardiovascular disease on electrocardiogram, echocardiography and MR angiography of the brain and lower extremities. Despite being premenopausal ( Table 1 ), she had osteoporosis as determined by dual-energy X-ray absorptiometry, which showed a bone density of 61% and 75% the young-adult-mean in the lumbar vertebra and femoral neck, respectively.', 'Case presentation': 'The patient was a 50-year-old Japanese woman from non-consanguineous parents. She has no siblings but had a child. There was no apparent family history (parents, child and parent’s siblings) of neurological disorders, cardiovascular diseases or any lipid storage diseases inducing xanthomas, including CTX. She had no history of neonatal jaundice or chronic infantile diarrhea. She had been diagnosed with idiopathic epilepsy and medicated from 7 to 10 years of age. Thereafter, she had no remarkable medical developments until middle age. She insidiously developed painless tendon thickness of the bilateral Achilles tendons and right triceps muscle at 47 years of age. The gradual enlargement of the Achilles tendons caused gait disturbance when she was 49 years of age. T1- and T2-weighted magnetic resonance imaging (MRI) revealed low-intensity lesions in the thickened bilateral Achilles tendons ( Fig. 1A ) and right triceps muscle, suggestive of xanthomas. She was admitted to Nagasaki University Hospital for further investigation at 50 years of age.'}
|
{'Clinical, laboratory and imaging examinations': 'The patient was lean (height 149.0 cm, weight 39.2 kg, BMI 17.7 kg/m 2 ), and the findings of a physical examination were unremarkable except for confirmation of xanthomas on the bilateral Achilles tendons ( Fig. 1B ) and right triceps muscle. She had age-appropriate slight cataracts in the bilateral eyes and did not have dementia based on the Revised Hasegawa Dementia Scale (HSD-R; 26/30), Mini-Mental State Examination (MMSE; 27/30), and Frontal Assessment Battery (FAB; 16/18) scores. On a neurological examination, her gait appeared somewhat spastic, and all of her deep tendon reflexes were mildly enhanced bilaterally with positive Babinski and Chaddock reflexes, indicating impairment in the bilateral pyramidal tracts. There were no neurological findings suggesting cerebellar impairment. Regarding the laboratory findings ( Table 1 ), there was no elevation in the levels of serum cholesterol or triglycerides or deficiencies in apolipoproteins or thyroid hormones. As the clinical findings suggested CTX, we studied the bile acids and sterols in her serum and urine ( Table 2 ). The primary bile acids were extremely low in the serum and urine when measured by both high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometer (GC/MS). The urinary levels of bile alcohols, especially 5β-cholestane-3α,7α,12α,24,25-pentol, were markedly elevated. Norcholic acid, which is mainly derived from 5β-cholestane-3α,7α,12α,23,25-pentol, was highly elevated and accounted for 78.4% of all bile acids in the urine. The serum level of cholestanol was extremely elevated, while those of sitosterol and campesterol were not elevated. T2-weighted and fluid-attenuated inversion recovery (FLAIR) MRI of the brain showed bilateral low-intensity areas in the dentate nuclei and high-intensity areas in the peripheral white matter the cerebellum ( Fig. 1C ). We also found bilateral high-intensity areas along the pyramidal tracts from the pons to the cerebral crus. Brain atrophy was not remarkable. Based on these clinical, laboratory and radiological findings, the patient was diagnosed with CTX. Ultrasound of the carotid arteries showed a slightly thickened intima-media complex at the left common carotid artery (maximum intima-media thickness, 1.2 mm). However, there was no evidence of cardiovascular disease on electrocardiogram, echocardiography and MR angiography of the brain and lower extremities. Despite being premenopausal ( Table 1 ), she had osteoporosis as determined by dual-energy X-ray absorptiometry, which showed a bone density of 61% and 75% the young-adult-mean in the lumbar vertebra and femoral neck, respectively.', 'Case presentation': 'The patient was a 50-year-old Japanese woman from non-consanguineous parents. She has no siblings but had a child. There was no apparent family history (parents, child and parent’s siblings) of neurological disorders, cardiovascular diseases or any lipid storage diseases inducing xanthomas, including CTX. She had no history of neonatal jaundice or chronic infantile diarrhea. She had been diagnosed with idiopathic epilepsy and medicated from 7 to 10 years of age. Thereafter, she had no remarkable medical developments until middle age. She insidiously developed painless tendon thickness of the bilateral Achilles tendons and right triceps muscle at 47 years of age. The gradual enlargement of the Achilles tendons caused gait disturbance when she was 49 years of age. T1- and T2-weighted magnetic resonance imaging (MRI) revealed low-intensity lesions in the thickened bilateral Achilles tendons ( Fig. 1A ) and right triceps muscle, suggestive of xanthomas. She was admitted to Nagasaki University Hospital for further investigation at 50 years of age.'}
|
Age-at-Presentation
|
Age (at case presentation)
|
[
"50 - year - old"
] |
test-1942
|
6028668
|
{'Clinical, laboratory and imaging examinations': 'The patient was lean (height 149.0 cm, weight 39.2 kg, BMI 17.7 kg/m 2 ), and the findings of a physical examination were unremarkable except for confirmation of xanthomas on the bilateral Achilles tendons ( Fig. 1B ) and right triceps muscle. She had age-appropriate slight cataracts in the bilateral eyes and did not have dementia based on the Revised Hasegawa Dementia Scale (HSD-R; 26/30), Mini-Mental State Examination (MMSE; 27/30), and Frontal Assessment Battery (FAB; 16/18) scores. On a neurological examination, her gait appeared somewhat spastic, and all of her deep tendon reflexes were mildly enhanced bilaterally with positive Babinski and Chaddock reflexes, indicating impairment in the bilateral pyramidal tracts. There were no neurological findings suggesting cerebellar impairment. Regarding the laboratory findings ( Table 1 ), there was no elevation in the levels of serum cholesterol or triglycerides or deficiencies in apolipoproteins or thyroid hormones. As the clinical findings suggested CTX, we studied the bile acids and sterols in her serum and urine ( Table 2 ). The primary bile acids were extremely low in the serum and urine when measured by both high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometer (GC/MS). The urinary levels of bile alcohols, especially 5β-cholestane-3α,7α,12α,24,25-pentol, were markedly elevated. Norcholic acid, which is mainly derived from 5β-cholestane-3α,7α,12α,23,25-pentol, was highly elevated and accounted for 78.4% of all bile acids in the urine. The serum level of cholestanol was extremely elevated, while those of sitosterol and campesterol were not elevated. T2-weighted and fluid-attenuated inversion recovery (FLAIR) MRI of the brain showed bilateral low-intensity areas in the dentate nuclei and high-intensity areas in the peripheral white matter the cerebellum ( Fig. 1C ). We also found bilateral high-intensity areas along the pyramidal tracts from the pons to the cerebral crus. Brain atrophy was not remarkable. Based on these clinical, laboratory and radiological findings, the patient was diagnosed with CTX. Ultrasound of the carotid arteries showed a slightly thickened intima-media complex at the left common carotid artery (maximum intima-media thickness, 1.2 mm). However, there was no evidence of cardiovascular disease on electrocardiogram, echocardiography and MR angiography of the brain and lower extremities. Despite being premenopausal ( Table 1 ), she had osteoporosis as determined by dual-energy X-ray absorptiometry, which showed a bone density of 61% and 75% the young-adult-mean in the lumbar vertebra and femoral neck, respectively.', 'Case presentation': 'The patient was a 50-year-old Japanese woman from non-consanguineous parents. She has no siblings but had a child. There was no apparent family history (parents, child and parent’s siblings) of neurological disorders, cardiovascular diseases or any lipid storage diseases inducing xanthomas, including CTX. She had no history of neonatal jaundice or chronic infantile diarrhea. She had been diagnosed with idiopathic epilepsy and medicated from 7 to 10 years of age. Thereafter, she had no remarkable medical developments until middle age. She insidiously developed painless tendon thickness of the bilateral Achilles tendons and right triceps muscle at 47 years of age. The gradual enlargement of the Achilles tendons caused gait disturbance when she was 49 years of age. T1- and T2-weighted magnetic resonance imaging (MRI) revealed low-intensity lesions in the thickened bilateral Achilles tendons ( Fig. 1A ) and right triceps muscle, suggestive of xanthomas. She was admitted to Nagasaki University Hospital for further investigation at 50 years of age.'}
|
{'Clinical, laboratory and imaging examinations': 'The patient was lean (height 149.0 cm, weight 39.2 kg, BMI 17.7 kg/m 2 ), and the findings of a physical examination were unremarkable except for confirmation of xanthomas on the bilateral Achilles tendons ( Fig. 1B ) and right triceps muscle. She had age-appropriate slight cataracts in the bilateral eyes and did not have dementia based on the Revised Hasegawa Dementia Scale (HSD-R; 26/30), Mini-Mental State Examination (MMSE; 27/30), and Frontal Assessment Battery (FAB; 16/18) scores. On a neurological examination, her gait appeared somewhat spastic, and all of her deep tendon reflexes were mildly enhanced bilaterally with positive Babinski and Chaddock reflexes, indicating impairment in the bilateral pyramidal tracts. There were no neurological findings suggesting cerebellar impairment. Regarding the laboratory findings ( Table 1 ), there was no elevation in the levels of serum cholesterol or triglycerides or deficiencies in apolipoproteins or thyroid hormones. As the clinical findings suggested CTX, we studied the bile acids and sterols in her serum and urine ( Table 2 ). The primary bile acids were extremely low in the serum and urine when measured by both high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometer (GC/MS). The urinary levels of bile alcohols, especially 5β-cholestane-3α,7α,12α,24,25-pentol, were markedly elevated. Norcholic acid, which is mainly derived from 5β-cholestane-3α,7α,12α,23,25-pentol, was highly elevated and accounted for 78.4% of all bile acids in the urine. The serum level of cholestanol was extremely elevated, while those of sitosterol and campesterol were not elevated. T2-weighted and fluid-attenuated inversion recovery (FLAIR) MRI of the brain showed bilateral low-intensity areas in the dentate nuclei and high-intensity areas in the peripheral white matter the cerebellum ( Fig. 1C ). We also found bilateral high-intensity areas along the pyramidal tracts from the pons to the cerebral crus. Brain atrophy was not remarkable. Based on these clinical, laboratory and radiological findings, the patient was diagnosed with CTX. Ultrasound of the carotid arteries showed a slightly thickened intima-media complex at the left common carotid artery (maximum intima-media thickness, 1.2 mm). However, there was no evidence of cardiovascular disease on electrocardiogram, echocardiography and MR angiography of the brain and lower extremities. Despite being premenopausal ( Table 1 ), she had osteoporosis as determined by dual-energy X-ray absorptiometry, which showed a bone density of 61% and 75% the young-adult-mean in the lumbar vertebra and femoral neck, respectively.', 'Case presentation': 'The patient was a 50-year-old Japanese woman from non-consanguineous parents. She has no siblings but had a child. There was no apparent family history (parents, child and parent’s siblings) of neurological disorders, cardiovascular diseases or any lipid storage diseases inducing xanthomas, including CTX. She had no history of neonatal jaundice or chronic infantile diarrhea. She had been diagnosed with idiopathic epilepsy and medicated from 7 to 10 years of age. Thereafter, she had no remarkable medical developments until middle age. She insidiously developed painless tendon thickness of the bilateral Achilles tendons and right triceps muscle at 47 years of age. The gradual enlargement of the Achilles tendons caused gait disturbance when she was 49 years of age. T1- and T2-weighted magnetic resonance imaging (MRI) revealed low-intensity lesions in the thickened bilateral Achilles tendons ( Fig. 1A ) and right triceps muscle, suggestive of xanthomas. She was admitted to Nagasaki University Hospital for further investigation at 50 years of age.'}
|
Age-of-Onset
|
Age (of onset)
|
[
"7 to 10 years of age"
] |
test-1943
|
6028668
|
{'Clinical, laboratory and imaging examinations': 'The patient was lean (height 149.0 cm, weight 39.2 kg, BMI 17.7 kg/m 2 ), and the findings of a physical examination were unremarkable except for confirmation of xanthomas on the bilateral Achilles tendons ( Fig. 1B ) and right triceps muscle. She had age-appropriate slight cataracts in the bilateral eyes and did not have dementia based on the Revised Hasegawa Dementia Scale (HSD-R; 26/30), Mini-Mental State Examination (MMSE; 27/30), and Frontal Assessment Battery (FAB; 16/18) scores. On a neurological examination, her gait appeared somewhat spastic, and all of her deep tendon reflexes were mildly enhanced bilaterally with positive Babinski and Chaddock reflexes, indicating impairment in the bilateral pyramidal tracts. There were no neurological findings suggesting cerebellar impairment. Regarding the laboratory findings ( Table 1 ), there was no elevation in the levels of serum cholesterol or triglycerides or deficiencies in apolipoproteins or thyroid hormones. As the clinical findings suggested CTX, we studied the bile acids and sterols in her serum and urine ( Table 2 ). The primary bile acids were extremely low in the serum and urine when measured by both high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometer (GC/MS). The urinary levels of bile alcohols, especially 5β-cholestane-3α,7α,12α,24,25-pentol, were markedly elevated. Norcholic acid, which is mainly derived from 5β-cholestane-3α,7α,12α,23,25-pentol, was highly elevated and accounted for 78.4% of all bile acids in the urine. The serum level of cholestanol was extremely elevated, while those of sitosterol and campesterol were not elevated. T2-weighted and fluid-attenuated inversion recovery (FLAIR) MRI of the brain showed bilateral low-intensity areas in the dentate nuclei and high-intensity areas in the peripheral white matter the cerebellum ( Fig. 1C ). We also found bilateral high-intensity areas along the pyramidal tracts from the pons to the cerebral crus. Brain atrophy was not remarkable. Based on these clinical, laboratory and radiological findings, the patient was diagnosed with CTX. Ultrasound of the carotid arteries showed a slightly thickened intima-media complex at the left common carotid artery (maximum intima-media thickness, 1.2 mm). However, there was no evidence of cardiovascular disease on electrocardiogram, echocardiography and MR angiography of the brain and lower extremities. Despite being premenopausal ( Table 1 ), she had osteoporosis as determined by dual-energy X-ray absorptiometry, which showed a bone density of 61% and 75% the young-adult-mean in the lumbar vertebra and femoral neck, respectively.', 'Case presentation': 'The patient was a 50-year-old Japanese woman from non-consanguineous parents. She has no siblings but had a child. There was no apparent family history (parents, child and parent’s siblings) of neurological disorders, cardiovascular diseases or any lipid storage diseases inducing xanthomas, including CTX. She had no history of neonatal jaundice or chronic infantile diarrhea. She had been diagnosed with idiopathic epilepsy and medicated from 7 to 10 years of age. Thereafter, she had no remarkable medical developments until middle age. She insidiously developed painless tendon thickness of the bilateral Achilles tendons and right triceps muscle at 47 years of age. The gradual enlargement of the Achilles tendons caused gait disturbance when she was 49 years of age. T1- and T2-weighted magnetic resonance imaging (MRI) revealed low-intensity lesions in the thickened bilateral Achilles tendons ( Fig. 1A ) and right triceps muscle, suggestive of xanthomas. She was admitted to Nagasaki University Hospital for further investigation at 50 years of age.'}
|
{'Clinical, laboratory and imaging examinations': 'The patient was lean (height 149.0 cm, weight 39.2 kg, BMI 17.7 kg/m 2 ), and the findings of a physical examination were unremarkable except for confirmation of xanthomas on the bilateral Achilles tendons ( Fig. 1B ) and right triceps muscle. She had age-appropriate slight cataracts in the bilateral eyes and did not have dementia based on the Revised Hasegawa Dementia Scale (HSD-R; 26/30), Mini-Mental State Examination (MMSE; 27/30), and Frontal Assessment Battery (FAB; 16/18) scores. On a neurological examination, her gait appeared somewhat spastic, and all of her deep tendon reflexes were mildly enhanced bilaterally with positive Babinski and Chaddock reflexes, indicating impairment in the bilateral pyramidal tracts. There were no neurological findings suggesting cerebellar impairment. Regarding the laboratory findings ( Table 1 ), there was no elevation in the levels of serum cholesterol or triglycerides or deficiencies in apolipoproteins or thyroid hormones. As the clinical findings suggested CTX, we studied the bile acids and sterols in her serum and urine ( Table 2 ). The primary bile acids were extremely low in the serum and urine when measured by both high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometer (GC/MS). The urinary levels of bile alcohols, especially 5β-cholestane-3α,7α,12α,24,25-pentol, were markedly elevated. Norcholic acid, which is mainly derived from 5β-cholestane-3α,7α,12α,23,25-pentol, was highly elevated and accounted for 78.4% of all bile acids in the urine. The serum level of cholestanol was extremely elevated, while those of sitosterol and campesterol were not elevated. T2-weighted and fluid-attenuated inversion recovery (FLAIR) MRI of the brain showed bilateral low-intensity areas in the dentate nuclei and high-intensity areas in the peripheral white matter the cerebellum ( Fig. 1C ). We also found bilateral high-intensity areas along the pyramidal tracts from the pons to the cerebral crus. Brain atrophy was not remarkable. Based on these clinical, laboratory and radiological findings, the patient was diagnosed with CTX. Ultrasound of the carotid arteries showed a slightly thickened intima-media complex at the left common carotid artery (maximum intima-media thickness, 1.2 mm). However, there was no evidence of cardiovascular disease on electrocardiogram, echocardiography and MR angiography of the brain and lower extremities. Despite being premenopausal ( Table 1 ), she had osteoporosis as determined by dual-energy X-ray absorptiometry, which showed a bone density of 61% and 75% the young-adult-mean in the lumbar vertebra and femoral neck, respectively.', 'Case presentation': 'The patient was a 50-year-old Japanese woman from non-consanguineous parents. She has no siblings but had a child. There was no apparent family history (parents, child and parent’s siblings) of neurological disorders, cardiovascular diseases or any lipid storage diseases inducing xanthomas, including CTX. She had no history of neonatal jaundice or chronic infantile diarrhea. She had been diagnosed with idiopathic epilepsy and medicated from 7 to 10 years of age. Thereafter, she had no remarkable medical developments until middle age. She insidiously developed painless tendon thickness of the bilateral Achilles tendons and right triceps muscle at 47 years of age. The gradual enlargement of the Achilles tendons caused gait disturbance when she was 49 years of age. T1- and T2-weighted magnetic resonance imaging (MRI) revealed low-intensity lesions in the thickened bilateral Achilles tendons ( Fig. 1A ) and right triceps muscle, suggestive of xanthomas. She was admitted to Nagasaki University Hospital for further investigation at 50 years of age.'}
|
Confirmed-Diagnosis-IEM
|
Confirmed_Diagnosis(IEM)
|
[
"the patient was diagnosed with CTX"
] |
test-1944
|
6028668
|
{'Clinical, laboratory and imaging examinations': 'The patient was lean (height 149.0 cm, weight 39.2 kg, BMI 17.7 kg/m 2 ), and the findings of a physical examination were unremarkable except for confirmation of xanthomas on the bilateral Achilles tendons ( Fig. 1B ) and right triceps muscle. She had age-appropriate slight cataracts in the bilateral eyes and did not have dementia based on the Revised Hasegawa Dementia Scale (HSD-R; 26/30), Mini-Mental State Examination (MMSE; 27/30), and Frontal Assessment Battery (FAB; 16/18) scores. On a neurological examination, her gait appeared somewhat spastic, and all of her deep tendon reflexes were mildly enhanced bilaterally with positive Babinski and Chaddock reflexes, indicating impairment in the bilateral pyramidal tracts. There were no neurological findings suggesting cerebellar impairment. Regarding the laboratory findings ( Table 1 ), there was no elevation in the levels of serum cholesterol or triglycerides or deficiencies in apolipoproteins or thyroid hormones. As the clinical findings suggested CTX, we studied the bile acids and sterols in her serum and urine ( Table 2 ). The primary bile acids were extremely low in the serum and urine when measured by both high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometer (GC/MS). The urinary levels of bile alcohols, especially 5β-cholestane-3α,7α,12α,24,25-pentol, were markedly elevated. Norcholic acid, which is mainly derived from 5β-cholestane-3α,7α,12α,23,25-pentol, was highly elevated and accounted for 78.4% of all bile acids in the urine. The serum level of cholestanol was extremely elevated, while those of sitosterol and campesterol were not elevated. T2-weighted and fluid-attenuated inversion recovery (FLAIR) MRI of the brain showed bilateral low-intensity areas in the dentate nuclei and high-intensity areas in the peripheral white matter the cerebellum ( Fig. 1C ). We also found bilateral high-intensity areas along the pyramidal tracts from the pons to the cerebral crus. Brain atrophy was not remarkable. Based on these clinical, laboratory and radiological findings, the patient was diagnosed with CTX. Ultrasound of the carotid arteries showed a slightly thickened intima-media complex at the left common carotid artery (maximum intima-media thickness, 1.2 mm). However, there was no evidence of cardiovascular disease on electrocardiogram, echocardiography and MR angiography of the brain and lower extremities. Despite being premenopausal ( Table 1 ), she had osteoporosis as determined by dual-energy X-ray absorptiometry, which showed a bone density of 61% and 75% the young-adult-mean in the lumbar vertebra and femoral neck, respectively.', 'Case presentation': 'The patient was a 50-year-old Japanese woman from non-consanguineous parents. She has no siblings but had a child. There was no apparent family history (parents, child and parent’s siblings) of neurological disorders, cardiovascular diseases or any lipid storage diseases inducing xanthomas, including CTX. She had no history of neonatal jaundice or chronic infantile diarrhea. She had been diagnosed with idiopathic epilepsy and medicated from 7 to 10 years of age. Thereafter, she had no remarkable medical developments until middle age. She insidiously developed painless tendon thickness of the bilateral Achilles tendons and right triceps muscle at 47 years of age. The gradual enlargement of the Achilles tendons caused gait disturbance when she was 49 years of age. T1- and T2-weighted magnetic resonance imaging (MRI) revealed low-intensity lesions in the thickened bilateral Achilles tendons ( Fig. 1A ) and right triceps muscle, suggestive of xanthomas. She was admitted to Nagasaki University Hospital for further investigation at 50 years of age.'}
|
{'Clinical, laboratory and imaging examinations': 'The patient was lean (height 149.0 cm, weight 39.2 kg, BMI 17.7 kg/m 2 ), and the findings of a physical examination were unremarkable except for confirmation of xanthomas on the bilateral Achilles tendons ( Fig. 1B ) and right triceps muscle. She had age-appropriate slight cataracts in the bilateral eyes and did not have dementia based on the Revised Hasegawa Dementia Scale (HSD-R; 26/30), Mini-Mental State Examination (MMSE; 27/30), and Frontal Assessment Battery (FAB; 16/18) scores. On a neurological examination, her gait appeared somewhat spastic, and all of her deep tendon reflexes were mildly enhanced bilaterally with positive Babinski and Chaddock reflexes, indicating impairment in the bilateral pyramidal tracts. There were no neurological findings suggesting cerebellar impairment. Regarding the laboratory findings ( Table 1 ), there was no elevation in the levels of serum cholesterol or triglycerides or deficiencies in apolipoproteins or thyroid hormones. As the clinical findings suggested CTX, we studied the bile acids and sterols in her serum and urine ( Table 2 ). The primary bile acids were extremely low in the serum and urine when measured by both high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometer (GC/MS). The urinary levels of bile alcohols, especially 5β-cholestane-3α,7α,12α,24,25-pentol, were markedly elevated. Norcholic acid, which is mainly derived from 5β-cholestane-3α,7α,12α,23,25-pentol, was highly elevated and accounted for 78.4% of all bile acids in the urine. The serum level of cholestanol was extremely elevated, while those of sitosterol and campesterol were not elevated. T2-weighted and fluid-attenuated inversion recovery (FLAIR) MRI of the brain showed bilateral low-intensity areas in the dentate nuclei and high-intensity areas in the peripheral white matter the cerebellum ( Fig. 1C ). We also found bilateral high-intensity areas along the pyramidal tracts from the pons to the cerebral crus. Brain atrophy was not remarkable. Based on these clinical, laboratory and radiological findings, the patient was diagnosed with CTX. Ultrasound of the carotid arteries showed a slightly thickened intima-media complex at the left common carotid artery (maximum intima-media thickness, 1.2 mm). However, there was no evidence of cardiovascular disease on electrocardiogram, echocardiography and MR angiography of the brain and lower extremities. Despite being premenopausal ( Table 1 ), she had osteoporosis as determined by dual-energy X-ray absorptiometry, which showed a bone density of 61% and 75% the young-adult-mean in the lumbar vertebra and femoral neck, respectively.', 'Case presentation': 'The patient was a 50-year-old Japanese woman from non-consanguineous parents. She has no siblings but had a child. There was no apparent family history (parents, child and parent’s siblings) of neurological disorders, cardiovascular diseases or any lipid storage diseases inducing xanthomas, including CTX. She had no history of neonatal jaundice or chronic infantile diarrhea. She had been diagnosed with idiopathic epilepsy and medicated from 7 to 10 years of age. Thereafter, she had no remarkable medical developments until middle age. She insidiously developed painless tendon thickness of the bilateral Achilles tendons and right triceps muscle at 47 years of age. The gradual enlargement of the Achilles tendons caused gait disturbance when she was 49 years of age. T1- and T2-weighted magnetic resonance imaging (MRI) revealed low-intensity lesions in the thickened bilateral Achilles tendons ( Fig. 1A ) and right triceps muscle, suggestive of xanthomas. She was admitted to Nagasaki University Hospital for further investigation at 50 years of age.'}
|
IEM-Treatment
|
IEM_Treatment
|
[] |
test-1945
|
6260459
|
{'Case report': "A male child was born at term by an uncomplicated pregnancy. The patient was hypotonic, irritable, and demonstrated poor feeding by breast and bottle in the first week of life. He had a history of in utero hiccups, which persisted as a neonate. At the age of 3 months, he was admitted to the hospital with Respiratory Syncytial Virus (RSV) and seizure-like activity, which prompted an MRI. Videos obtained by family showed that the child had been having seizures since birth. MRI showed myelination confined to the brainstem, central cerebellum, and posterior limbs of the internal capsule ( Fig. 1 ). There was T2 hyperintensity of the white matter ( Fig. 2 ) and superior vermian volume loss ( Fig. 3 ). The corpus callosum was unmyelinated. MRI spectroscopy revealed a low N-acetylaspartate (NAA) peak with no lactate peak ( Fig. 4 ). Fig. 1 Axial T1-weighted images of the brain acquired at 3.0 T demonstrate myelination limited to the posterior limbs of the bilateral posterior internal capsules (white arrows). Fig. 1 –. Fig. 2 Axial T2-weighted images of the brain acquired at 3.0 T show increased T2 signal in the periventricular white matter (white arrow). There is overall low parenchymal volume with prominence of the extra-axial spaces (black arrow). Fig. 2 –. Fig. 3 Sagittal T1-weighted images reveal low parenchymal volume of the superior folia with prominence of the extra-axial spaces (white arrow). The corpus callosum is unmyelinated. Fig. 3 –. Fig. 4 Magnetic resonance spectroscopy performed at TE = 144 ms with a voxel placed in the right posterior parietal white matter demonstrates a dominant choline peak and a diminished N-acetyl aspartate peak. Fig. 4 –. The patient's hospitalization was complicated by seizures requiring prolonged video electroencephalogram (EEG) monitoring and anticonvulsant therapy. CSF analysis yielded an acellular CSF with normal protein and glucose. He was subsequently discharged with a nasogastric tube on phenobarbital therapy at a dose of 10 mg twice a day and levetiracetam at a dose of 75 mg per day. He continued to exhibit excessive hiccupping, episodes of extensor spasms, and multifocal seizures. A follow-up study of the patient's CSF was found to demonstrate abnormally high concentrations of succinyladenosine and succinylaminoimidazole carboxamide riboside. The elevation of these 2 compounds confirmed the diagnosis of adenylosuccinate lyase deficiency."}
|
{'Case report': "A male child was born at term by an uncomplicated pregnancy. The patient was hypotonic, irritable, and demonstrated poor feeding by breast and bottle in the first week of life. He had a history of in utero hiccups, which persisted as a neonate. At the age of 3 months, he was admitted to the hospital with Respiratory Syncytial Virus (RSV) and seizure-like activity, which prompted an MRI. Videos obtained by family showed that the child had been having seizures since birth. MRI showed myelination confined to the brainstem, central cerebellum, and posterior limbs of the internal capsule ( Fig. 1 ). There was T2 hyperintensity of the white matter ( Fig. 2 ) and superior vermian volume loss ( Fig. 3 ). The corpus callosum was unmyelinated. MRI spectroscopy revealed a low N-acetylaspartate (NAA) peak with no lactate peak ( Fig. 4 ). Fig. 1 Axial T1-weighted images of the brain acquired at 3.0 T demonstrate myelination limited to the posterior limbs of the bilateral posterior internal capsules (white arrows). Fig. 1 –. Fig. 2 Axial T2-weighted images of the brain acquired at 3.0 T show increased T2 signal in the periventricular white matter (white arrow). There is overall low parenchymal volume with prominence of the extra-axial spaces (black arrow). Fig. 2 –. Fig. 3 Sagittal T1-weighted images reveal low parenchymal volume of the superior folia with prominence of the extra-axial spaces (white arrow). The corpus callosum is unmyelinated. Fig. 3 –. Fig. 4 Magnetic resonance spectroscopy performed at TE = 144 ms with a voxel placed in the right posterior parietal white matter demonstrates a dominant choline peak and a diminished N-acetyl aspartate peak. Fig. 4 –. The patient's hospitalization was complicated by seizures requiring prolonged video electroencephalogram (EEG) monitoring and anticonvulsant therapy. CSF analysis yielded an acellular CSF with normal protein and glucose. He was subsequently discharged with a nasogastric tube on phenobarbital therapy at a dose of 10 mg twice a day and levetiracetam at a dose of 75 mg per day. He continued to exhibit excessive hiccupping, episodes of extensor spasms, and multifocal seizures. A follow-up study of the patient's CSF was found to demonstrate abnormally high concentrations of succinyladenosine and succinylaminoimidazole carboxamide riboside. The elevation of these 2 compounds confirmed the diagnosis of adenylosuccinate lyase deficiency."}
|
Vitals-and-Hematology
|
Vitals_Hema
|
[] |
test-1946
|
6260459
|
{'Case report': "A male child was born at term by an uncomplicated pregnancy. The patient was hypotonic, irritable, and demonstrated poor feeding by breast and bottle in the first week of life. He had a history of in utero hiccups, which persisted as a neonate. At the age of 3 months, he was admitted to the hospital with Respiratory Syncytial Virus (RSV) and seizure-like activity, which prompted an MRI. Videos obtained by family showed that the child had been having seizures since birth. MRI showed myelination confined to the brainstem, central cerebellum, and posterior limbs of the internal capsule ( Fig. 1 ). There was T2 hyperintensity of the white matter ( Fig. 2 ) and superior vermian volume loss ( Fig. 3 ). The corpus callosum was unmyelinated. MRI spectroscopy revealed a low N-acetylaspartate (NAA) peak with no lactate peak ( Fig. 4 ). Fig. 1 Axial T1-weighted images of the brain acquired at 3.0 T demonstrate myelination limited to the posterior limbs of the bilateral posterior internal capsules (white arrows). Fig. 1 –. Fig. 2 Axial T2-weighted images of the brain acquired at 3.0 T show increased T2 signal in the periventricular white matter (white arrow). There is overall low parenchymal volume with prominence of the extra-axial spaces (black arrow). Fig. 2 –. Fig. 3 Sagittal T1-weighted images reveal low parenchymal volume of the superior folia with prominence of the extra-axial spaces (white arrow). The corpus callosum is unmyelinated. Fig. 3 –. Fig. 4 Magnetic resonance spectroscopy performed at TE = 144 ms with a voxel placed in the right posterior parietal white matter demonstrates a dominant choline peak and a diminished N-acetyl aspartate peak. Fig. 4 –. The patient's hospitalization was complicated by seizures requiring prolonged video electroencephalogram (EEG) monitoring and anticonvulsant therapy. CSF analysis yielded an acellular CSF with normal protein and glucose. He was subsequently discharged with a nasogastric tube on phenobarbital therapy at a dose of 10 mg twice a day and levetiracetam at a dose of 75 mg per day. He continued to exhibit excessive hiccupping, episodes of extensor spasms, and multifocal seizures. A follow-up study of the patient's CSF was found to demonstrate abnormally high concentrations of succinyladenosine and succinylaminoimidazole carboxamide riboside. The elevation of these 2 compounds confirmed the diagnosis of adenylosuccinate lyase deficiency."}
|
{'Case report': "A male child was born at term by an uncomplicated pregnancy. The patient was hypotonic, irritable, and demonstrated poor feeding by breast and bottle in the first week of life. He had a history of in utero hiccups, which persisted as a neonate. At the age of 3 months, he was admitted to the hospital with Respiratory Syncytial Virus (RSV) and seizure-like activity, which prompted an MRI. Videos obtained by family showed that the child had been having seizures since birth. MRI showed myelination confined to the brainstem, central cerebellum, and posterior limbs of the internal capsule ( Fig. 1 ). There was T2 hyperintensity of the white matter ( Fig. 2 ) and superior vermian volume loss ( Fig. 3 ). The corpus callosum was unmyelinated. MRI spectroscopy revealed a low N-acetylaspartate (NAA) peak with no lactate peak ( Fig. 4 ). Fig. 1 Axial T1-weighted images of the brain acquired at 3.0 T demonstrate myelination limited to the posterior limbs of the bilateral posterior internal capsules (white arrows). Fig. 1 –. Fig. 2 Axial T2-weighted images of the brain acquired at 3.0 T show increased T2 signal in the periventricular white matter (white arrow). There is overall low parenchymal volume with prominence of the extra-axial spaces (black arrow). Fig. 2 –. Fig. 3 Sagittal T1-weighted images reveal low parenchymal volume of the superior folia with prominence of the extra-axial spaces (white arrow). The corpus callosum is unmyelinated. Fig. 3 –. Fig. 4 Magnetic resonance spectroscopy performed at TE = 144 ms with a voxel placed in the right posterior parietal white matter demonstrates a dominant choline peak and a diminished N-acetyl aspartate peak. Fig. 4 –. The patient's hospitalization was complicated by seizures requiring prolonged video electroencephalogram (EEG) monitoring and anticonvulsant therapy. CSF analysis yielded an acellular CSF with normal protein and glucose. He was subsequently discharged with a nasogastric tube on phenobarbital therapy at a dose of 10 mg twice a day and levetiracetam at a dose of 75 mg per day. He continued to exhibit excessive hiccupping, episodes of extensor spasms, and multifocal seizures. A follow-up study of the patient's CSF was found to demonstrate abnormally high concentrations of succinyladenosine and succinylaminoimidazole carboxamide riboside. The elevation of these 2 compounds confirmed the diagnosis of adenylosuccinate lyase deficiency."}
|
Gastrointestinal-System
|
GI
|
[
"poor feeding by breast and bottle"
] |
test-1947
|
6260459
|
{'Case report': "A male child was born at term by an uncomplicated pregnancy. The patient was hypotonic, irritable, and demonstrated poor feeding by breast and bottle in the first week of life. He had a history of in utero hiccups, which persisted as a neonate. At the age of 3 months, he was admitted to the hospital with Respiratory Syncytial Virus (RSV) and seizure-like activity, which prompted an MRI. Videos obtained by family showed that the child had been having seizures since birth. MRI showed myelination confined to the brainstem, central cerebellum, and posterior limbs of the internal capsule ( Fig. 1 ). There was T2 hyperintensity of the white matter ( Fig. 2 ) and superior vermian volume loss ( Fig. 3 ). The corpus callosum was unmyelinated. MRI spectroscopy revealed a low N-acetylaspartate (NAA) peak with no lactate peak ( Fig. 4 ). Fig. 1 Axial T1-weighted images of the brain acquired at 3.0 T demonstrate myelination limited to the posterior limbs of the bilateral posterior internal capsules (white arrows). Fig. 1 –. Fig. 2 Axial T2-weighted images of the brain acquired at 3.0 T show increased T2 signal in the periventricular white matter (white arrow). There is overall low parenchymal volume with prominence of the extra-axial spaces (black arrow). Fig. 2 –. Fig. 3 Sagittal T1-weighted images reveal low parenchymal volume of the superior folia with prominence of the extra-axial spaces (white arrow). The corpus callosum is unmyelinated. Fig. 3 –. Fig. 4 Magnetic resonance spectroscopy performed at TE = 144 ms with a voxel placed in the right posterior parietal white matter demonstrates a dominant choline peak and a diminished N-acetyl aspartate peak. Fig. 4 –. The patient's hospitalization was complicated by seizures requiring prolonged video electroencephalogram (EEG) monitoring and anticonvulsant therapy. CSF analysis yielded an acellular CSF with normal protein and glucose. He was subsequently discharged with a nasogastric tube on phenobarbital therapy at a dose of 10 mg twice a day and levetiracetam at a dose of 75 mg per day. He continued to exhibit excessive hiccupping, episodes of extensor spasms, and multifocal seizures. A follow-up study of the patient's CSF was found to demonstrate abnormally high concentrations of succinyladenosine and succinylaminoimidazole carboxamide riboside. The elevation of these 2 compounds confirmed the diagnosis of adenylosuccinate lyase deficiency."}
|
{'Case report': "A male child was born at term by an uncomplicated pregnancy. The patient was hypotonic, irritable, and demonstrated poor feeding by breast and bottle in the first week of life. He had a history of in utero hiccups, which persisted as a neonate. At the age of 3 months, he was admitted to the hospital with Respiratory Syncytial Virus (RSV) and seizure-like activity, which prompted an MRI. Videos obtained by family showed that the child had been having seizures since birth. MRI showed myelination confined to the brainstem, central cerebellum, and posterior limbs of the internal capsule ( Fig. 1 ). There was T2 hyperintensity of the white matter ( Fig. 2 ) and superior vermian volume loss ( Fig. 3 ). The corpus callosum was unmyelinated. MRI spectroscopy revealed a low N-acetylaspartate (NAA) peak with no lactate peak ( Fig. 4 ). Fig. 1 Axial T1-weighted images of the brain acquired at 3.0 T demonstrate myelination limited to the posterior limbs of the bilateral posterior internal capsules (white arrows). Fig. 1 –. Fig. 2 Axial T2-weighted images of the brain acquired at 3.0 T show increased T2 signal in the periventricular white matter (white arrow). There is overall low parenchymal volume with prominence of the extra-axial spaces (black arrow). Fig. 2 –. Fig. 3 Sagittal T1-weighted images reveal low parenchymal volume of the superior folia with prominence of the extra-axial spaces (white arrow). The corpus callosum is unmyelinated. Fig. 3 –. Fig. 4 Magnetic resonance spectroscopy performed at TE = 144 ms with a voxel placed in the right posterior parietal white matter demonstrates a dominant choline peak and a diminished N-acetyl aspartate peak. Fig. 4 –. The patient's hospitalization was complicated by seizures requiring prolonged video electroencephalogram (EEG) monitoring and anticonvulsant therapy. CSF analysis yielded an acellular CSF with normal protein and glucose. He was subsequently discharged with a nasogastric tube on phenobarbital therapy at a dose of 10 mg twice a day and levetiracetam at a dose of 75 mg per day. He continued to exhibit excessive hiccupping, episodes of extensor spasms, and multifocal seizures. A follow-up study of the patient's CSF was found to demonstrate abnormally high concentrations of succinyladenosine and succinylaminoimidazole carboxamide riboside. The elevation of these 2 compounds confirmed the diagnosis of adenylosuccinate lyase deficiency."}
|
Patient-History
|
History
|
[] |
test-1948
|
6260459
|
{'Case report': "A male child was born at term by an uncomplicated pregnancy. The patient was hypotonic, irritable, and demonstrated poor feeding by breast and bottle in the first week of life. He had a history of in utero hiccups, which persisted as a neonate. At the age of 3 months, he was admitted to the hospital with Respiratory Syncytial Virus (RSV) and seizure-like activity, which prompted an MRI. Videos obtained by family showed that the child had been having seizures since birth. MRI showed myelination confined to the brainstem, central cerebellum, and posterior limbs of the internal capsule ( Fig. 1 ). There was T2 hyperintensity of the white matter ( Fig. 2 ) and superior vermian volume loss ( Fig. 3 ). The corpus callosum was unmyelinated. MRI spectroscopy revealed a low N-acetylaspartate (NAA) peak with no lactate peak ( Fig. 4 ). Fig. 1 Axial T1-weighted images of the brain acquired at 3.0 T demonstrate myelination limited to the posterior limbs of the bilateral posterior internal capsules (white arrows). Fig. 1 –. Fig. 2 Axial T2-weighted images of the brain acquired at 3.0 T show increased T2 signal in the periventricular white matter (white arrow). There is overall low parenchymal volume with prominence of the extra-axial spaces (black arrow). Fig. 2 –. Fig. 3 Sagittal T1-weighted images reveal low parenchymal volume of the superior folia with prominence of the extra-axial spaces (white arrow). The corpus callosum is unmyelinated. Fig. 3 –. Fig. 4 Magnetic resonance spectroscopy performed at TE = 144 ms with a voxel placed in the right posterior parietal white matter demonstrates a dominant choline peak and a diminished N-acetyl aspartate peak. Fig. 4 –. The patient's hospitalization was complicated by seizures requiring prolonged video electroencephalogram (EEG) monitoring and anticonvulsant therapy. CSF analysis yielded an acellular CSF with normal protein and glucose. He was subsequently discharged with a nasogastric tube on phenobarbital therapy at a dose of 10 mg twice a day and levetiracetam at a dose of 75 mg per day. He continued to exhibit excessive hiccupping, episodes of extensor spasms, and multifocal seizures. A follow-up study of the patient's CSF was found to demonstrate abnormally high concentrations of succinyladenosine and succinylaminoimidazole carboxamide riboside. The elevation of these 2 compounds confirmed the diagnosis of adenylosuccinate lyase deficiency."}
|
{'Case report': "A male child was born at term by an uncomplicated pregnancy. The patient was hypotonic, irritable, and demonstrated poor feeding by breast and bottle in the first week of life. He had a history of in utero hiccups, which persisted as a neonate. At the age of 3 months, he was admitted to the hospital with Respiratory Syncytial Virus (RSV) and seizure-like activity, which prompted an MRI. Videos obtained by family showed that the child had been having seizures since birth. MRI showed myelination confined to the brainstem, central cerebellum, and posterior limbs of the internal capsule ( Fig. 1 ). There was T2 hyperintensity of the white matter ( Fig. 2 ) and superior vermian volume loss ( Fig. 3 ). The corpus callosum was unmyelinated. MRI spectroscopy revealed a low N-acetylaspartate (NAA) peak with no lactate peak ( Fig. 4 ). Fig. 1 Axial T1-weighted images of the brain acquired at 3.0 T demonstrate myelination limited to the posterior limbs of the bilateral posterior internal capsules (white arrows). Fig. 1 –. Fig. 2 Axial T2-weighted images of the brain acquired at 3.0 T show increased T2 signal in the periventricular white matter (white arrow). There is overall low parenchymal volume with prominence of the extra-axial spaces (black arrow). Fig. 2 –. Fig. 3 Sagittal T1-weighted images reveal low parenchymal volume of the superior folia with prominence of the extra-axial spaces (white arrow). The corpus callosum is unmyelinated. Fig. 3 –. Fig. 4 Magnetic resonance spectroscopy performed at TE = 144 ms with a voxel placed in the right posterior parietal white matter demonstrates a dominant choline peak and a diminished N-acetyl aspartate peak. Fig. 4 –. The patient's hospitalization was complicated by seizures requiring prolonged video electroencephalogram (EEG) monitoring and anticonvulsant therapy. CSF analysis yielded an acellular CSF with normal protein and glucose. He was subsequently discharged with a nasogastric tube on phenobarbital therapy at a dose of 10 mg twice a day and levetiracetam at a dose of 75 mg per day. He continued to exhibit excessive hiccupping, episodes of extensor spasms, and multifocal seizures. A follow-up study of the patient's CSF was found to demonstrate abnormally high concentrations of succinyladenosine and succinylaminoimidazole carboxamide riboside. The elevation of these 2 compounds confirmed the diagnosis of adenylosuccinate lyase deficiency."}
|
Neurology
|
Neuro
|
[
"hypotonic, irritable, and demonstrated poor feeding by breast and bottle",
"in utero hiccups",
"seizure - like activity",
"seizures since birth",
"MRI showed myelination confined to the brainstem, central cerebellum, and posterior limbs of the internal capsule ( Fig. 1 ). There was T2 hyperintensity of the white matter ( Fig. 2 ) and superior vermian volume loss ( Fig. 3 ). The corpus callosum was unmyelinated. MRI spectroscopy revealed a low N - acetylaspartate ( NAA ) peak with no lactate peak ( Fig. 4 ). Fig. 1 Axial T1 - weighted images of the brain acquired at 3.0 T demonstrate myelination limited to the posterior limbs of the bilateral posterior internal capsules ( white arrows ). Fig. 1 –. Fig. 2 Axial T2 - weighted images of the brain acquired at 3.0 T show increased T2 signal in the periventricular white matter ( white arrow ). There is overall low parenchymal volume with prominence of the extra - axial spaces ( black arrow ). Fig. 2 –. Fig. 3 Sagittal T1 - weighted images reveal low parenchymal volume of the superior folia with prominence of the extra - axial spaces ( white arrow ). The corpus callosum is unmyelinated. Fig. 3 –. Fig. 4 Magnetic resonance spectroscopy performed at TE = 144 ms with a voxel placed in the right posterior parietal white matter demonstrates a dominant choline peak and a diminished N - acetyl aspartate peak.",
"seizures requiring prolonged video electroencephalogram ( EEG ) monitoring",
"CSF analysis yielded an acellular CSF with normal protein and glucose",
"excessive hiccupping, episodes of extensor spasms, and multifocal seizures",
"follow - up study of the patient 's CSF was found to demonstrate abnormally high concentrations of succinyladenosine and succinylaminoimidazole carboxamide riboside"
] |
test-1949
|
6260459
|
{'Case report': "A male child was born at term by an uncomplicated pregnancy. The patient was hypotonic, irritable, and demonstrated poor feeding by breast and bottle in the first week of life. He had a history of in utero hiccups, which persisted as a neonate. At the age of 3 months, he was admitted to the hospital with Respiratory Syncytial Virus (RSV) and seizure-like activity, which prompted an MRI. Videos obtained by family showed that the child had been having seizures since birth. MRI showed myelination confined to the brainstem, central cerebellum, and posterior limbs of the internal capsule ( Fig. 1 ). There was T2 hyperintensity of the white matter ( Fig. 2 ) and superior vermian volume loss ( Fig. 3 ). The corpus callosum was unmyelinated. MRI spectroscopy revealed a low N-acetylaspartate (NAA) peak with no lactate peak ( Fig. 4 ). Fig. 1 Axial T1-weighted images of the brain acquired at 3.0 T demonstrate myelination limited to the posterior limbs of the bilateral posterior internal capsules (white arrows). Fig. 1 –. Fig. 2 Axial T2-weighted images of the brain acquired at 3.0 T show increased T2 signal in the periventricular white matter (white arrow). There is overall low parenchymal volume with prominence of the extra-axial spaces (black arrow). Fig. 2 –. Fig. 3 Sagittal T1-weighted images reveal low parenchymal volume of the superior folia with prominence of the extra-axial spaces (white arrow). The corpus callosum is unmyelinated. Fig. 3 –. Fig. 4 Magnetic resonance spectroscopy performed at TE = 144 ms with a voxel placed in the right posterior parietal white matter demonstrates a dominant choline peak and a diminished N-acetyl aspartate peak. Fig. 4 –. The patient's hospitalization was complicated by seizures requiring prolonged video electroencephalogram (EEG) monitoring and anticonvulsant therapy. CSF analysis yielded an acellular CSF with normal protein and glucose. He was subsequently discharged with a nasogastric tube on phenobarbital therapy at a dose of 10 mg twice a day and levetiracetam at a dose of 75 mg per day. He continued to exhibit excessive hiccupping, episodes of extensor spasms, and multifocal seizures. A follow-up study of the patient's CSF was found to demonstrate abnormally high concentrations of succinyladenosine and succinylaminoimidazole carboxamide riboside. The elevation of these 2 compounds confirmed the diagnosis of adenylosuccinate lyase deficiency."}
|
{'Case report': "A male child was born at term by an uncomplicated pregnancy. The patient was hypotonic, irritable, and demonstrated poor feeding by breast and bottle in the first week of life. He had a history of in utero hiccups, which persisted as a neonate. At the age of 3 months, he was admitted to the hospital with Respiratory Syncytial Virus (RSV) and seizure-like activity, which prompted an MRI. Videos obtained by family showed that the child had been having seizures since birth. MRI showed myelination confined to the brainstem, central cerebellum, and posterior limbs of the internal capsule ( Fig. 1 ). There was T2 hyperintensity of the white matter ( Fig. 2 ) and superior vermian volume loss ( Fig. 3 ). The corpus callosum was unmyelinated. MRI spectroscopy revealed a low N-acetylaspartate (NAA) peak with no lactate peak ( Fig. 4 ). Fig. 1 Axial T1-weighted images of the brain acquired at 3.0 T demonstrate myelination limited to the posterior limbs of the bilateral posterior internal capsules (white arrows). Fig. 1 –. Fig. 2 Axial T2-weighted images of the brain acquired at 3.0 T show increased T2 signal in the periventricular white matter (white arrow). There is overall low parenchymal volume with prominence of the extra-axial spaces (black arrow). Fig. 2 –. Fig. 3 Sagittal T1-weighted images reveal low parenchymal volume of the superior folia with prominence of the extra-axial spaces (white arrow). The corpus callosum is unmyelinated. Fig. 3 –. Fig. 4 Magnetic resonance spectroscopy performed at TE = 144 ms with a voxel placed in the right posterior parietal white matter demonstrates a dominant choline peak and a diminished N-acetyl aspartate peak. Fig. 4 –. The patient's hospitalization was complicated by seizures requiring prolonged video electroencephalogram (EEG) monitoring and anticonvulsant therapy. CSF analysis yielded an acellular CSF with normal protein and glucose. He was subsequently discharged with a nasogastric tube on phenobarbital therapy at a dose of 10 mg twice a day and levetiracetam at a dose of 75 mg per day. He continued to exhibit excessive hiccupping, episodes of extensor spasms, and multifocal seizures. A follow-up study of the patient's CSF was found to demonstrate abnormally high concentrations of succinyladenosine and succinylaminoimidazole carboxamide riboside. The elevation of these 2 compounds confirmed the diagnosis of adenylosuccinate lyase deficiency."}
|
Laboratory-and-Imaging
|
Lab_Image
|
[
"MRI showed myelination confined to the brainstem, central cerebellum, and posterior limbs of the internal capsule ( Fig. 1 ). There was T2 hyperintensity of the white matter ( Fig. 2 ) and superior vermian volume loss ( Fig. 3 ). The corpus callosum was unmyelinated. MRI spectroscopy revealed a low N - acetylaspartate ( NAA ) peak with no lactate peak ( Fig. 4 ). Fig. 1 Axial T1 - weighted images of the brain acquired at 3.0 T demonstrate myelination limited to the posterior limbs of the bilateral posterior internal capsules ( white arrows ). Fig. 1 –. Fig. 2 Axial T2 - weighted images of the brain acquired at 3.0 T show increased T2 signal in the periventricular white matter ( white arrow ). There is overall low parenchymal volume with prominence of the extra - axial spaces ( black arrow ). Fig. 2 –. Fig. 3 Sagittal T1 - weighted images reveal low parenchymal volume of the superior folia with prominence of the extra - axial spaces ( white arrow ). The corpus callosum is unmyelinated. Fig. 3 –. Fig. 4 Magnetic resonance spectroscopy performed at TE = 144 ms with a voxel placed in the right posterior parietal white matter demonstrates a dominant choline peak and a diminished N - acetyl aspartate peak.",
"CSF analysis yielded an acellular CSF with normal protein and glucose",
"follow - up study of the patient 's CSF was found to demonstrate abnormally high concentrations of succinyladenosine and succinylaminoimidazole carboxamide riboside"
] |
test-1950
|
6260459
|
{'Case report': "A male child was born at term by an uncomplicated pregnancy. The patient was hypotonic, irritable, and demonstrated poor feeding by breast and bottle in the first week of life. He had a history of in utero hiccups, which persisted as a neonate. At the age of 3 months, he was admitted to the hospital with Respiratory Syncytial Virus (RSV) and seizure-like activity, which prompted an MRI. Videos obtained by family showed that the child had been having seizures since birth. MRI showed myelination confined to the brainstem, central cerebellum, and posterior limbs of the internal capsule ( Fig. 1 ). There was T2 hyperintensity of the white matter ( Fig. 2 ) and superior vermian volume loss ( Fig. 3 ). The corpus callosum was unmyelinated. MRI spectroscopy revealed a low N-acetylaspartate (NAA) peak with no lactate peak ( Fig. 4 ). Fig. 1 Axial T1-weighted images of the brain acquired at 3.0 T demonstrate myelination limited to the posterior limbs of the bilateral posterior internal capsules (white arrows). Fig. 1 –. Fig. 2 Axial T2-weighted images of the brain acquired at 3.0 T show increased T2 signal in the periventricular white matter (white arrow). There is overall low parenchymal volume with prominence of the extra-axial spaces (black arrow). Fig. 2 –. Fig. 3 Sagittal T1-weighted images reveal low parenchymal volume of the superior folia with prominence of the extra-axial spaces (white arrow). The corpus callosum is unmyelinated. Fig. 3 –. Fig. 4 Magnetic resonance spectroscopy performed at TE = 144 ms with a voxel placed in the right posterior parietal white matter demonstrates a dominant choline peak and a diminished N-acetyl aspartate peak. Fig. 4 –. The patient's hospitalization was complicated by seizures requiring prolonged video electroencephalogram (EEG) monitoring and anticonvulsant therapy. CSF analysis yielded an acellular CSF with normal protein and glucose. He was subsequently discharged with a nasogastric tube on phenobarbital therapy at a dose of 10 mg twice a day and levetiracetam at a dose of 75 mg per day. He continued to exhibit excessive hiccupping, episodes of extensor spasms, and multifocal seizures. A follow-up study of the patient's CSF was found to demonstrate abnormally high concentrations of succinyladenosine and succinylaminoimidazole carboxamide riboside. The elevation of these 2 compounds confirmed the diagnosis of adenylosuccinate lyase deficiency."}
|
{'Case report': "A male child was born at term by an uncomplicated pregnancy. The patient was hypotonic, irritable, and demonstrated poor feeding by breast and bottle in the first week of life. He had a history of in utero hiccups, which persisted as a neonate. At the age of 3 months, he was admitted to the hospital with Respiratory Syncytial Virus (RSV) and seizure-like activity, which prompted an MRI. Videos obtained by family showed that the child had been having seizures since birth. MRI showed myelination confined to the brainstem, central cerebellum, and posterior limbs of the internal capsule ( Fig. 1 ). There was T2 hyperintensity of the white matter ( Fig. 2 ) and superior vermian volume loss ( Fig. 3 ). The corpus callosum was unmyelinated. MRI spectroscopy revealed a low N-acetylaspartate (NAA) peak with no lactate peak ( Fig. 4 ). Fig. 1 Axial T1-weighted images of the brain acquired at 3.0 T demonstrate myelination limited to the posterior limbs of the bilateral posterior internal capsules (white arrows). Fig. 1 –. Fig. 2 Axial T2-weighted images of the brain acquired at 3.0 T show increased T2 signal in the periventricular white matter (white arrow). There is overall low parenchymal volume with prominence of the extra-axial spaces (black arrow). Fig. 2 –. Fig. 3 Sagittal T1-weighted images reveal low parenchymal volume of the superior folia with prominence of the extra-axial spaces (white arrow). The corpus callosum is unmyelinated. Fig. 3 –. Fig. 4 Magnetic resonance spectroscopy performed at TE = 144 ms with a voxel placed in the right posterior parietal white matter demonstrates a dominant choline peak and a diminished N-acetyl aspartate peak. Fig. 4 –. The patient's hospitalization was complicated by seizures requiring prolonged video electroencephalogram (EEG) monitoring and anticonvulsant therapy. CSF analysis yielded an acellular CSF with normal protein and glucose. He was subsequently discharged with a nasogastric tube on phenobarbital therapy at a dose of 10 mg twice a day and levetiracetam at a dose of 75 mg per day. He continued to exhibit excessive hiccupping, episodes of extensor spasms, and multifocal seizures. A follow-up study of the patient's CSF was found to demonstrate abnormally high concentrations of succinyladenosine and succinylaminoimidazole carboxamide riboside. The elevation of these 2 compounds confirmed the diagnosis of adenylosuccinate lyase deficiency."}
|
Cardiovascular-System
|
CVS
|
[] |
test-1951
|
6260459
|
{'Case report': "A male child was born at term by an uncomplicated pregnancy. The patient was hypotonic, irritable, and demonstrated poor feeding by breast and bottle in the first week of life. He had a history of in utero hiccups, which persisted as a neonate. At the age of 3 months, he was admitted to the hospital with Respiratory Syncytial Virus (RSV) and seizure-like activity, which prompted an MRI. Videos obtained by family showed that the child had been having seizures since birth. MRI showed myelination confined to the brainstem, central cerebellum, and posterior limbs of the internal capsule ( Fig. 1 ). There was T2 hyperintensity of the white matter ( Fig. 2 ) and superior vermian volume loss ( Fig. 3 ). The corpus callosum was unmyelinated. MRI spectroscopy revealed a low N-acetylaspartate (NAA) peak with no lactate peak ( Fig. 4 ). Fig. 1 Axial T1-weighted images of the brain acquired at 3.0 T demonstrate myelination limited to the posterior limbs of the bilateral posterior internal capsules (white arrows). Fig. 1 –. Fig. 2 Axial T2-weighted images of the brain acquired at 3.0 T show increased T2 signal in the periventricular white matter (white arrow). There is overall low parenchymal volume with prominence of the extra-axial spaces (black arrow). Fig. 2 –. Fig. 3 Sagittal T1-weighted images reveal low parenchymal volume of the superior folia with prominence of the extra-axial spaces (white arrow). The corpus callosum is unmyelinated. Fig. 3 –. Fig. 4 Magnetic resonance spectroscopy performed at TE = 144 ms with a voxel placed in the right posterior parietal white matter demonstrates a dominant choline peak and a diminished N-acetyl aspartate peak. Fig. 4 –. The patient's hospitalization was complicated by seizures requiring prolonged video electroencephalogram (EEG) monitoring and anticonvulsant therapy. CSF analysis yielded an acellular CSF with normal protein and glucose. He was subsequently discharged with a nasogastric tube on phenobarbital therapy at a dose of 10 mg twice a day and levetiracetam at a dose of 75 mg per day. He continued to exhibit excessive hiccupping, episodes of extensor spasms, and multifocal seizures. A follow-up study of the patient's CSF was found to demonstrate abnormally high concentrations of succinyladenosine and succinylaminoimidazole carboxamide riboside. The elevation of these 2 compounds confirmed the diagnosis of adenylosuccinate lyase deficiency."}
|
{'Case report': "A male child was born at term by an uncomplicated pregnancy. The patient was hypotonic, irritable, and demonstrated poor feeding by breast and bottle in the first week of life. He had a history of in utero hiccups, which persisted as a neonate. At the age of 3 months, he was admitted to the hospital with Respiratory Syncytial Virus (RSV) and seizure-like activity, which prompted an MRI. Videos obtained by family showed that the child had been having seizures since birth. MRI showed myelination confined to the brainstem, central cerebellum, and posterior limbs of the internal capsule ( Fig. 1 ). There was T2 hyperintensity of the white matter ( Fig. 2 ) and superior vermian volume loss ( Fig. 3 ). The corpus callosum was unmyelinated. MRI spectroscopy revealed a low N-acetylaspartate (NAA) peak with no lactate peak ( Fig. 4 ). Fig. 1 Axial T1-weighted images of the brain acquired at 3.0 T demonstrate myelination limited to the posterior limbs of the bilateral posterior internal capsules (white arrows). Fig. 1 –. Fig. 2 Axial T2-weighted images of the brain acquired at 3.0 T show increased T2 signal in the periventricular white matter (white arrow). There is overall low parenchymal volume with prominence of the extra-axial spaces (black arrow). Fig. 2 –. Fig. 3 Sagittal T1-weighted images reveal low parenchymal volume of the superior folia with prominence of the extra-axial spaces (white arrow). The corpus callosum is unmyelinated. Fig. 3 –. Fig. 4 Magnetic resonance spectroscopy performed at TE = 144 ms with a voxel placed in the right posterior parietal white matter demonstrates a dominant choline peak and a diminished N-acetyl aspartate peak. Fig. 4 –. The patient's hospitalization was complicated by seizures requiring prolonged video electroencephalogram (EEG) monitoring and anticonvulsant therapy. CSF analysis yielded an acellular CSF with normal protein and glucose. He was subsequently discharged with a nasogastric tube on phenobarbital therapy at a dose of 10 mg twice a day and levetiracetam at a dose of 75 mg per day. He continued to exhibit excessive hiccupping, episodes of extensor spasms, and multifocal seizures. A follow-up study of the patient's CSF was found to demonstrate abnormally high concentrations of succinyladenosine and succinylaminoimidazole carboxamide riboside. The elevation of these 2 compounds confirmed the diagnosis of adenylosuccinate lyase deficiency."}
|
Endocrinology
|
ENDO
|
[] |
test-1952
|
6260459
|
{'Case report': "A male child was born at term by an uncomplicated pregnancy. The patient was hypotonic, irritable, and demonstrated poor feeding by breast and bottle in the first week of life. He had a history of in utero hiccups, which persisted as a neonate. At the age of 3 months, he was admitted to the hospital with Respiratory Syncytial Virus (RSV) and seizure-like activity, which prompted an MRI. Videos obtained by family showed that the child had been having seizures since birth. MRI showed myelination confined to the brainstem, central cerebellum, and posterior limbs of the internal capsule ( Fig. 1 ). There was T2 hyperintensity of the white matter ( Fig. 2 ) and superior vermian volume loss ( Fig. 3 ). The corpus callosum was unmyelinated. MRI spectroscopy revealed a low N-acetylaspartate (NAA) peak with no lactate peak ( Fig. 4 ). Fig. 1 Axial T1-weighted images of the brain acquired at 3.0 T demonstrate myelination limited to the posterior limbs of the bilateral posterior internal capsules (white arrows). Fig. 1 –. Fig. 2 Axial T2-weighted images of the brain acquired at 3.0 T show increased T2 signal in the periventricular white matter (white arrow). There is overall low parenchymal volume with prominence of the extra-axial spaces (black arrow). Fig. 2 –. Fig. 3 Sagittal T1-weighted images reveal low parenchymal volume of the superior folia with prominence of the extra-axial spaces (white arrow). The corpus callosum is unmyelinated. Fig. 3 –. Fig. 4 Magnetic resonance spectroscopy performed at TE = 144 ms with a voxel placed in the right posterior parietal white matter demonstrates a dominant choline peak and a diminished N-acetyl aspartate peak. Fig. 4 –. The patient's hospitalization was complicated by seizures requiring prolonged video electroencephalogram (EEG) monitoring and anticonvulsant therapy. CSF analysis yielded an acellular CSF with normal protein and glucose. He was subsequently discharged with a nasogastric tube on phenobarbital therapy at a dose of 10 mg twice a day and levetiracetam at a dose of 75 mg per day. He continued to exhibit excessive hiccupping, episodes of extensor spasms, and multifocal seizures. A follow-up study of the patient's CSF was found to demonstrate abnormally high concentrations of succinyladenosine and succinylaminoimidazole carboxamide riboside. The elevation of these 2 compounds confirmed the diagnosis of adenylosuccinate lyase deficiency."}
|
{'Case report': "A male child was born at term by an uncomplicated pregnancy. The patient was hypotonic, irritable, and demonstrated poor feeding by breast and bottle in the first week of life. He had a history of in utero hiccups, which persisted as a neonate. At the age of 3 months, he was admitted to the hospital with Respiratory Syncytial Virus (RSV) and seizure-like activity, which prompted an MRI. Videos obtained by family showed that the child had been having seizures since birth. MRI showed myelination confined to the brainstem, central cerebellum, and posterior limbs of the internal capsule ( Fig. 1 ). There was T2 hyperintensity of the white matter ( Fig. 2 ) and superior vermian volume loss ( Fig. 3 ). The corpus callosum was unmyelinated. MRI spectroscopy revealed a low N-acetylaspartate (NAA) peak with no lactate peak ( Fig. 4 ). Fig. 1 Axial T1-weighted images of the brain acquired at 3.0 T demonstrate myelination limited to the posterior limbs of the bilateral posterior internal capsules (white arrows). Fig. 1 –. Fig. 2 Axial T2-weighted images of the brain acquired at 3.0 T show increased T2 signal in the periventricular white matter (white arrow). There is overall low parenchymal volume with prominence of the extra-axial spaces (black arrow). Fig. 2 –. Fig. 3 Sagittal T1-weighted images reveal low parenchymal volume of the superior folia with prominence of the extra-axial spaces (white arrow). The corpus callosum is unmyelinated. Fig. 3 –. Fig. 4 Magnetic resonance spectroscopy performed at TE = 144 ms with a voxel placed in the right posterior parietal white matter demonstrates a dominant choline peak and a diminished N-acetyl aspartate peak. Fig. 4 –. The patient's hospitalization was complicated by seizures requiring prolonged video electroencephalogram (EEG) monitoring and anticonvulsant therapy. CSF analysis yielded an acellular CSF with normal protein and glucose. He was subsequently discharged with a nasogastric tube on phenobarbital therapy at a dose of 10 mg twice a day and levetiracetam at a dose of 75 mg per day. He continued to exhibit excessive hiccupping, episodes of extensor spasms, and multifocal seizures. A follow-up study of the patient's CSF was found to demonstrate abnormally high concentrations of succinyladenosine and succinylaminoimidazole carboxamide riboside. The elevation of these 2 compounds confirmed the diagnosis of adenylosuccinate lyase deficiency."}
|
Genitourinary-System
|
GU
|
[] |
test-1953
|
6260459
|
{'Case report': "A male child was born at term by an uncomplicated pregnancy. The patient was hypotonic, irritable, and demonstrated poor feeding by breast and bottle in the first week of life. He had a history of in utero hiccups, which persisted as a neonate. At the age of 3 months, he was admitted to the hospital with Respiratory Syncytial Virus (RSV) and seizure-like activity, which prompted an MRI. Videos obtained by family showed that the child had been having seizures since birth. MRI showed myelination confined to the brainstem, central cerebellum, and posterior limbs of the internal capsule ( Fig. 1 ). There was T2 hyperintensity of the white matter ( Fig. 2 ) and superior vermian volume loss ( Fig. 3 ). The corpus callosum was unmyelinated. MRI spectroscopy revealed a low N-acetylaspartate (NAA) peak with no lactate peak ( Fig. 4 ). Fig. 1 Axial T1-weighted images of the brain acquired at 3.0 T demonstrate myelination limited to the posterior limbs of the bilateral posterior internal capsules (white arrows). Fig. 1 –. Fig. 2 Axial T2-weighted images of the brain acquired at 3.0 T show increased T2 signal in the periventricular white matter (white arrow). There is overall low parenchymal volume with prominence of the extra-axial spaces (black arrow). Fig. 2 –. Fig. 3 Sagittal T1-weighted images reveal low parenchymal volume of the superior folia with prominence of the extra-axial spaces (white arrow). The corpus callosum is unmyelinated. Fig. 3 –. Fig. 4 Magnetic resonance spectroscopy performed at TE = 144 ms with a voxel placed in the right posterior parietal white matter demonstrates a dominant choline peak and a diminished N-acetyl aspartate peak. Fig. 4 –. The patient's hospitalization was complicated by seizures requiring prolonged video electroencephalogram (EEG) monitoring and anticonvulsant therapy. CSF analysis yielded an acellular CSF with normal protein and glucose. He was subsequently discharged with a nasogastric tube on phenobarbital therapy at a dose of 10 mg twice a day and levetiracetam at a dose of 75 mg per day. He continued to exhibit excessive hiccupping, episodes of extensor spasms, and multifocal seizures. A follow-up study of the patient's CSF was found to demonstrate abnormally high concentrations of succinyladenosine and succinylaminoimidazole carboxamide riboside. The elevation of these 2 compounds confirmed the diagnosis of adenylosuccinate lyase deficiency."}
|
{'Case report': "A male child was born at term by an uncomplicated pregnancy. The patient was hypotonic, irritable, and demonstrated poor feeding by breast and bottle in the first week of life. He had a history of in utero hiccups, which persisted as a neonate. At the age of 3 months, he was admitted to the hospital with Respiratory Syncytial Virus (RSV) and seizure-like activity, which prompted an MRI. Videos obtained by family showed that the child had been having seizures since birth. MRI showed myelination confined to the brainstem, central cerebellum, and posterior limbs of the internal capsule ( Fig. 1 ). There was T2 hyperintensity of the white matter ( Fig. 2 ) and superior vermian volume loss ( Fig. 3 ). The corpus callosum was unmyelinated. MRI spectroscopy revealed a low N-acetylaspartate (NAA) peak with no lactate peak ( Fig. 4 ). Fig. 1 Axial T1-weighted images of the brain acquired at 3.0 T demonstrate myelination limited to the posterior limbs of the bilateral posterior internal capsules (white arrows). Fig. 1 –. Fig. 2 Axial T2-weighted images of the brain acquired at 3.0 T show increased T2 signal in the periventricular white matter (white arrow). There is overall low parenchymal volume with prominence of the extra-axial spaces (black arrow). Fig. 2 –. Fig. 3 Sagittal T1-weighted images reveal low parenchymal volume of the superior folia with prominence of the extra-axial spaces (white arrow). The corpus callosum is unmyelinated. Fig. 3 –. Fig. 4 Magnetic resonance spectroscopy performed at TE = 144 ms with a voxel placed in the right posterior parietal white matter demonstrates a dominant choline peak and a diminished N-acetyl aspartate peak. Fig. 4 –. The patient's hospitalization was complicated by seizures requiring prolonged video electroencephalogram (EEG) monitoring and anticonvulsant therapy. CSF analysis yielded an acellular CSF with normal protein and glucose. He was subsequently discharged with a nasogastric tube on phenobarbital therapy at a dose of 10 mg twice a day and levetiracetam at a dose of 75 mg per day. He continued to exhibit excessive hiccupping, episodes of extensor spasms, and multifocal seizures. A follow-up study of the patient's CSF was found to demonstrate abnormally high concentrations of succinyladenosine and succinylaminoimidazole carboxamide riboside. The elevation of these 2 compounds confirmed the diagnosis of adenylosuccinate lyase deficiency."}
|
Respiratory-System
|
RESP
|
[] |
test-1954
|
6260459
|
{'Case report': "A male child was born at term by an uncomplicated pregnancy. The patient was hypotonic, irritable, and demonstrated poor feeding by breast and bottle in the first week of life. He had a history of in utero hiccups, which persisted as a neonate. At the age of 3 months, he was admitted to the hospital with Respiratory Syncytial Virus (RSV) and seizure-like activity, which prompted an MRI. Videos obtained by family showed that the child had been having seizures since birth. MRI showed myelination confined to the brainstem, central cerebellum, and posterior limbs of the internal capsule ( Fig. 1 ). There was T2 hyperintensity of the white matter ( Fig. 2 ) and superior vermian volume loss ( Fig. 3 ). The corpus callosum was unmyelinated. MRI spectroscopy revealed a low N-acetylaspartate (NAA) peak with no lactate peak ( Fig. 4 ). Fig. 1 Axial T1-weighted images of the brain acquired at 3.0 T demonstrate myelination limited to the posterior limbs of the bilateral posterior internal capsules (white arrows). Fig. 1 –. Fig. 2 Axial T2-weighted images of the brain acquired at 3.0 T show increased T2 signal in the periventricular white matter (white arrow). There is overall low parenchymal volume with prominence of the extra-axial spaces (black arrow). Fig. 2 –. Fig. 3 Sagittal T1-weighted images reveal low parenchymal volume of the superior folia with prominence of the extra-axial spaces (white arrow). The corpus callosum is unmyelinated. Fig. 3 –. Fig. 4 Magnetic resonance spectroscopy performed at TE = 144 ms with a voxel placed in the right posterior parietal white matter demonstrates a dominant choline peak and a diminished N-acetyl aspartate peak. Fig. 4 –. The patient's hospitalization was complicated by seizures requiring prolonged video electroencephalogram (EEG) monitoring and anticonvulsant therapy. CSF analysis yielded an acellular CSF with normal protein and glucose. He was subsequently discharged with a nasogastric tube on phenobarbital therapy at a dose of 10 mg twice a day and levetiracetam at a dose of 75 mg per day. He continued to exhibit excessive hiccupping, episodes of extensor spasms, and multifocal seizures. A follow-up study of the patient's CSF was found to demonstrate abnormally high concentrations of succinyladenosine and succinylaminoimidazole carboxamide riboside. The elevation of these 2 compounds confirmed the diagnosis of adenylosuccinate lyase deficiency."}
|
{'Case report': "A male child was born at term by an uncomplicated pregnancy. The patient was hypotonic, irritable, and demonstrated poor feeding by breast and bottle in the first week of life. He had a history of in utero hiccups, which persisted as a neonate. At the age of 3 months, he was admitted to the hospital with Respiratory Syncytial Virus (RSV) and seizure-like activity, which prompted an MRI. Videos obtained by family showed that the child had been having seizures since birth. MRI showed myelination confined to the brainstem, central cerebellum, and posterior limbs of the internal capsule ( Fig. 1 ). There was T2 hyperintensity of the white matter ( Fig. 2 ) and superior vermian volume loss ( Fig. 3 ). The corpus callosum was unmyelinated. MRI spectroscopy revealed a low N-acetylaspartate (NAA) peak with no lactate peak ( Fig. 4 ). Fig. 1 Axial T1-weighted images of the brain acquired at 3.0 T demonstrate myelination limited to the posterior limbs of the bilateral posterior internal capsules (white arrows). Fig. 1 –. Fig. 2 Axial T2-weighted images of the brain acquired at 3.0 T show increased T2 signal in the periventricular white matter (white arrow). There is overall low parenchymal volume with prominence of the extra-axial spaces (black arrow). Fig. 2 –. Fig. 3 Sagittal T1-weighted images reveal low parenchymal volume of the superior folia with prominence of the extra-axial spaces (white arrow). The corpus callosum is unmyelinated. Fig. 3 –. Fig. 4 Magnetic resonance spectroscopy performed at TE = 144 ms with a voxel placed in the right posterior parietal white matter demonstrates a dominant choline peak and a diminished N-acetyl aspartate peak. Fig. 4 –. The patient's hospitalization was complicated by seizures requiring prolonged video electroencephalogram (EEG) monitoring and anticonvulsant therapy. CSF analysis yielded an acellular CSF with normal protein and glucose. He was subsequently discharged with a nasogastric tube on phenobarbital therapy at a dose of 10 mg twice a day and levetiracetam at a dose of 75 mg per day. He continued to exhibit excessive hiccupping, episodes of extensor spasms, and multifocal seizures. A follow-up study of the patient's CSF was found to demonstrate abnormally high concentrations of succinyladenosine and succinylaminoimidazole carboxamide riboside. The elevation of these 2 compounds confirmed the diagnosis of adenylosuccinate lyase deficiency."}
|
Musculoskeletal-System
|
MSK
|
[] |
test-1955
|
6260459
|
{'Case report': "A male child was born at term by an uncomplicated pregnancy. The patient was hypotonic, irritable, and demonstrated poor feeding by breast and bottle in the first week of life. He had a history of in utero hiccups, which persisted as a neonate. At the age of 3 months, he was admitted to the hospital with Respiratory Syncytial Virus (RSV) and seizure-like activity, which prompted an MRI. Videos obtained by family showed that the child had been having seizures since birth. MRI showed myelination confined to the brainstem, central cerebellum, and posterior limbs of the internal capsule ( Fig. 1 ). There was T2 hyperintensity of the white matter ( Fig. 2 ) and superior vermian volume loss ( Fig. 3 ). The corpus callosum was unmyelinated. MRI spectroscopy revealed a low N-acetylaspartate (NAA) peak with no lactate peak ( Fig. 4 ). Fig. 1 Axial T1-weighted images of the brain acquired at 3.0 T demonstrate myelination limited to the posterior limbs of the bilateral posterior internal capsules (white arrows). Fig. 1 –. Fig. 2 Axial T2-weighted images of the brain acquired at 3.0 T show increased T2 signal in the periventricular white matter (white arrow). There is overall low parenchymal volume with prominence of the extra-axial spaces (black arrow). Fig. 2 –. Fig. 3 Sagittal T1-weighted images reveal low parenchymal volume of the superior folia with prominence of the extra-axial spaces (white arrow). The corpus callosum is unmyelinated. Fig. 3 –. Fig. 4 Magnetic resonance spectroscopy performed at TE = 144 ms with a voxel placed in the right posterior parietal white matter demonstrates a dominant choline peak and a diminished N-acetyl aspartate peak. Fig. 4 –. The patient's hospitalization was complicated by seizures requiring prolonged video electroencephalogram (EEG) monitoring and anticonvulsant therapy. CSF analysis yielded an acellular CSF with normal protein and glucose. He was subsequently discharged with a nasogastric tube on phenobarbital therapy at a dose of 10 mg twice a day and levetiracetam at a dose of 75 mg per day. He continued to exhibit excessive hiccupping, episodes of extensor spasms, and multifocal seizures. A follow-up study of the patient's CSF was found to demonstrate abnormally high concentrations of succinyladenosine and succinylaminoimidazole carboxamide riboside. The elevation of these 2 compounds confirmed the diagnosis of adenylosuccinate lyase deficiency."}
|
{'Case report': "A male child was born at term by an uncomplicated pregnancy. The patient was hypotonic, irritable, and demonstrated poor feeding by breast and bottle in the first week of life. He had a history of in utero hiccups, which persisted as a neonate. At the age of 3 months, he was admitted to the hospital with Respiratory Syncytial Virus (RSV) and seizure-like activity, which prompted an MRI. Videos obtained by family showed that the child had been having seizures since birth. MRI showed myelination confined to the brainstem, central cerebellum, and posterior limbs of the internal capsule ( Fig. 1 ). There was T2 hyperintensity of the white matter ( Fig. 2 ) and superior vermian volume loss ( Fig. 3 ). The corpus callosum was unmyelinated. MRI spectroscopy revealed a low N-acetylaspartate (NAA) peak with no lactate peak ( Fig. 4 ). Fig. 1 Axial T1-weighted images of the brain acquired at 3.0 T demonstrate myelination limited to the posterior limbs of the bilateral posterior internal capsules (white arrows). Fig. 1 –. Fig. 2 Axial T2-weighted images of the brain acquired at 3.0 T show increased T2 signal in the periventricular white matter (white arrow). There is overall low parenchymal volume with prominence of the extra-axial spaces (black arrow). Fig. 2 –. Fig. 3 Sagittal T1-weighted images reveal low parenchymal volume of the superior folia with prominence of the extra-axial spaces (white arrow). The corpus callosum is unmyelinated. Fig. 3 –. Fig. 4 Magnetic resonance spectroscopy performed at TE = 144 ms with a voxel placed in the right posterior parietal white matter demonstrates a dominant choline peak and a diminished N-acetyl aspartate peak. Fig. 4 –. The patient's hospitalization was complicated by seizures requiring prolonged video electroencephalogram (EEG) monitoring and anticonvulsant therapy. CSF analysis yielded an acellular CSF with normal protein and glucose. He was subsequently discharged with a nasogastric tube on phenobarbital therapy at a dose of 10 mg twice a day and levetiracetam at a dose of 75 mg per day. He continued to exhibit excessive hiccupping, episodes of extensor spasms, and multifocal seizures. A follow-up study of the patient's CSF was found to demonstrate abnormally high concentrations of succinyladenosine and succinylaminoimidazole carboxamide riboside. The elevation of these 2 compounds confirmed the diagnosis of adenylosuccinate lyase deficiency."}
|
Eyes-Ears-Nose-Throat
|
EENT
|
[] |
test-1956
|
6260459
|
{'Case report': "A male child was born at term by an uncomplicated pregnancy. The patient was hypotonic, irritable, and demonstrated poor feeding by breast and bottle in the first week of life. He had a history of in utero hiccups, which persisted as a neonate. At the age of 3 months, he was admitted to the hospital with Respiratory Syncytial Virus (RSV) and seizure-like activity, which prompted an MRI. Videos obtained by family showed that the child had been having seizures since birth. MRI showed myelination confined to the brainstem, central cerebellum, and posterior limbs of the internal capsule ( Fig. 1 ). There was T2 hyperintensity of the white matter ( Fig. 2 ) and superior vermian volume loss ( Fig. 3 ). The corpus callosum was unmyelinated. MRI spectroscopy revealed a low N-acetylaspartate (NAA) peak with no lactate peak ( Fig. 4 ). Fig. 1 Axial T1-weighted images of the brain acquired at 3.0 T demonstrate myelination limited to the posterior limbs of the bilateral posterior internal capsules (white arrows). Fig. 1 –. Fig. 2 Axial T2-weighted images of the brain acquired at 3.0 T show increased T2 signal in the periventricular white matter (white arrow). There is overall low parenchymal volume with prominence of the extra-axial spaces (black arrow). Fig. 2 –. Fig. 3 Sagittal T1-weighted images reveal low parenchymal volume of the superior folia with prominence of the extra-axial spaces (white arrow). The corpus callosum is unmyelinated. Fig. 3 –. Fig. 4 Magnetic resonance spectroscopy performed at TE = 144 ms with a voxel placed in the right posterior parietal white matter demonstrates a dominant choline peak and a diminished N-acetyl aspartate peak. Fig. 4 –. The patient's hospitalization was complicated by seizures requiring prolonged video electroencephalogram (EEG) monitoring and anticonvulsant therapy. CSF analysis yielded an acellular CSF with normal protein and glucose. He was subsequently discharged with a nasogastric tube on phenobarbital therapy at a dose of 10 mg twice a day and levetiracetam at a dose of 75 mg per day. He continued to exhibit excessive hiccupping, episodes of extensor spasms, and multifocal seizures. A follow-up study of the patient's CSF was found to demonstrate abnormally high concentrations of succinyladenosine and succinylaminoimidazole carboxamide riboside. The elevation of these 2 compounds confirmed the diagnosis of adenylosuccinate lyase deficiency."}
|
{'Case report': "A male child was born at term by an uncomplicated pregnancy. The patient was hypotonic, irritable, and demonstrated poor feeding by breast and bottle in the first week of life. He had a history of in utero hiccups, which persisted as a neonate. At the age of 3 months, he was admitted to the hospital with Respiratory Syncytial Virus (RSV) and seizure-like activity, which prompted an MRI. Videos obtained by family showed that the child had been having seizures since birth. MRI showed myelination confined to the brainstem, central cerebellum, and posterior limbs of the internal capsule ( Fig. 1 ). There was T2 hyperintensity of the white matter ( Fig. 2 ) and superior vermian volume loss ( Fig. 3 ). The corpus callosum was unmyelinated. MRI spectroscopy revealed a low N-acetylaspartate (NAA) peak with no lactate peak ( Fig. 4 ). Fig. 1 Axial T1-weighted images of the brain acquired at 3.0 T demonstrate myelination limited to the posterior limbs of the bilateral posterior internal capsules (white arrows). Fig. 1 –. Fig. 2 Axial T2-weighted images of the brain acquired at 3.0 T show increased T2 signal in the periventricular white matter (white arrow). There is overall low parenchymal volume with prominence of the extra-axial spaces (black arrow). Fig. 2 –. Fig. 3 Sagittal T1-weighted images reveal low parenchymal volume of the superior folia with prominence of the extra-axial spaces (white arrow). The corpus callosum is unmyelinated. Fig. 3 –. Fig. 4 Magnetic resonance spectroscopy performed at TE = 144 ms with a voxel placed in the right posterior parietal white matter demonstrates a dominant choline peak and a diminished N-acetyl aspartate peak. Fig. 4 –. The patient's hospitalization was complicated by seizures requiring prolonged video electroencephalogram (EEG) monitoring and anticonvulsant therapy. CSF analysis yielded an acellular CSF with normal protein and glucose. He was subsequently discharged with a nasogastric tube on phenobarbital therapy at a dose of 10 mg twice a day and levetiracetam at a dose of 75 mg per day. He continued to exhibit excessive hiccupping, episodes of extensor spasms, and multifocal seizures. A follow-up study of the patient's CSF was found to demonstrate abnormally high concentrations of succinyladenosine and succinylaminoimidazole carboxamide riboside. The elevation of these 2 compounds confirmed the diagnosis of adenylosuccinate lyase deficiency."}
|
Dermatology
|
DERM
|
[] |
test-1957
|
6260459
|
{'Case report': "A male child was born at term by an uncomplicated pregnancy. The patient was hypotonic, irritable, and demonstrated poor feeding by breast and bottle in the first week of life. He had a history of in utero hiccups, which persisted as a neonate. At the age of 3 months, he was admitted to the hospital with Respiratory Syncytial Virus (RSV) and seizure-like activity, which prompted an MRI. Videos obtained by family showed that the child had been having seizures since birth. MRI showed myelination confined to the brainstem, central cerebellum, and posterior limbs of the internal capsule ( Fig. 1 ). There was T2 hyperintensity of the white matter ( Fig. 2 ) and superior vermian volume loss ( Fig. 3 ). The corpus callosum was unmyelinated. MRI spectroscopy revealed a low N-acetylaspartate (NAA) peak with no lactate peak ( Fig. 4 ). Fig. 1 Axial T1-weighted images of the brain acquired at 3.0 T demonstrate myelination limited to the posterior limbs of the bilateral posterior internal capsules (white arrows). Fig. 1 –. Fig. 2 Axial T2-weighted images of the brain acquired at 3.0 T show increased T2 signal in the periventricular white matter (white arrow). There is overall low parenchymal volume with prominence of the extra-axial spaces (black arrow). Fig. 2 –. Fig. 3 Sagittal T1-weighted images reveal low parenchymal volume of the superior folia with prominence of the extra-axial spaces (white arrow). The corpus callosum is unmyelinated. Fig. 3 –. Fig. 4 Magnetic resonance spectroscopy performed at TE = 144 ms with a voxel placed in the right posterior parietal white matter demonstrates a dominant choline peak and a diminished N-acetyl aspartate peak. Fig. 4 –. The patient's hospitalization was complicated by seizures requiring prolonged video electroencephalogram (EEG) monitoring and anticonvulsant therapy. CSF analysis yielded an acellular CSF with normal protein and glucose. He was subsequently discharged with a nasogastric tube on phenobarbital therapy at a dose of 10 mg twice a day and levetiracetam at a dose of 75 mg per day. He continued to exhibit excessive hiccupping, episodes of extensor spasms, and multifocal seizures. A follow-up study of the patient's CSF was found to demonstrate abnormally high concentrations of succinyladenosine and succinylaminoimidazole carboxamide riboside. The elevation of these 2 compounds confirmed the diagnosis of adenylosuccinate lyase deficiency."}
|
{'Case report': "A male child was born at term by an uncomplicated pregnancy. The patient was hypotonic, irritable, and demonstrated poor feeding by breast and bottle in the first week of life. He had a history of in utero hiccups, which persisted as a neonate. At the age of 3 months, he was admitted to the hospital with Respiratory Syncytial Virus (RSV) and seizure-like activity, which prompted an MRI. Videos obtained by family showed that the child had been having seizures since birth. MRI showed myelination confined to the brainstem, central cerebellum, and posterior limbs of the internal capsule ( Fig. 1 ). There was T2 hyperintensity of the white matter ( Fig. 2 ) and superior vermian volume loss ( Fig. 3 ). The corpus callosum was unmyelinated. MRI spectroscopy revealed a low N-acetylaspartate (NAA) peak with no lactate peak ( Fig. 4 ). Fig. 1 Axial T1-weighted images of the brain acquired at 3.0 T demonstrate myelination limited to the posterior limbs of the bilateral posterior internal capsules (white arrows). Fig. 1 –. Fig. 2 Axial T2-weighted images of the brain acquired at 3.0 T show increased T2 signal in the periventricular white matter (white arrow). There is overall low parenchymal volume with prominence of the extra-axial spaces (black arrow). Fig. 2 –. Fig. 3 Sagittal T1-weighted images reveal low parenchymal volume of the superior folia with prominence of the extra-axial spaces (white arrow). The corpus callosum is unmyelinated. Fig. 3 –. Fig. 4 Magnetic resonance spectroscopy performed at TE = 144 ms with a voxel placed in the right posterior parietal white matter demonstrates a dominant choline peak and a diminished N-acetyl aspartate peak. Fig. 4 –. The patient's hospitalization was complicated by seizures requiring prolonged video electroencephalogram (EEG) monitoring and anticonvulsant therapy. CSF analysis yielded an acellular CSF with normal protein and glucose. He was subsequently discharged with a nasogastric tube on phenobarbital therapy at a dose of 10 mg twice a day and levetiracetam at a dose of 75 mg per day. He continued to exhibit excessive hiccupping, episodes of extensor spasms, and multifocal seizures. A follow-up study of the patient's CSF was found to demonstrate abnormally high concentrations of succinyladenosine and succinylaminoimidazole carboxamide riboside. The elevation of these 2 compounds confirmed the diagnosis of adenylosuccinate lyase deficiency."}
|
Pregnancy
|
Pregnancy
|
[
"born at term by an uncomplicated pregnancy. The patient was hypotonic, irritable, and demonstrated poor feeding by breast and bottle in the first week of life. He had a history of in utero hiccups, which persisted as a neonate"
] |
test-1958
|
6260459
|
{'Case report': "A male child was born at term by an uncomplicated pregnancy. The patient was hypotonic, irritable, and demonstrated poor feeding by breast and bottle in the first week of life. He had a history of in utero hiccups, which persisted as a neonate. At the age of 3 months, he was admitted to the hospital with Respiratory Syncytial Virus (RSV) and seizure-like activity, which prompted an MRI. Videos obtained by family showed that the child had been having seizures since birth. MRI showed myelination confined to the brainstem, central cerebellum, and posterior limbs of the internal capsule ( Fig. 1 ). There was T2 hyperintensity of the white matter ( Fig. 2 ) and superior vermian volume loss ( Fig. 3 ). The corpus callosum was unmyelinated. MRI spectroscopy revealed a low N-acetylaspartate (NAA) peak with no lactate peak ( Fig. 4 ). Fig. 1 Axial T1-weighted images of the brain acquired at 3.0 T demonstrate myelination limited to the posterior limbs of the bilateral posterior internal capsules (white arrows). Fig. 1 –. Fig. 2 Axial T2-weighted images of the brain acquired at 3.0 T show increased T2 signal in the periventricular white matter (white arrow). There is overall low parenchymal volume with prominence of the extra-axial spaces (black arrow). Fig. 2 –. Fig. 3 Sagittal T1-weighted images reveal low parenchymal volume of the superior folia with prominence of the extra-axial spaces (white arrow). The corpus callosum is unmyelinated. Fig. 3 –. Fig. 4 Magnetic resonance spectroscopy performed at TE = 144 ms with a voxel placed in the right posterior parietal white matter demonstrates a dominant choline peak and a diminished N-acetyl aspartate peak. Fig. 4 –. The patient's hospitalization was complicated by seizures requiring prolonged video electroencephalogram (EEG) monitoring and anticonvulsant therapy. CSF analysis yielded an acellular CSF with normal protein and glucose. He was subsequently discharged with a nasogastric tube on phenobarbital therapy at a dose of 10 mg twice a day and levetiracetam at a dose of 75 mg per day. He continued to exhibit excessive hiccupping, episodes of extensor spasms, and multifocal seizures. A follow-up study of the patient's CSF was found to demonstrate abnormally high concentrations of succinyladenosine and succinylaminoimidazole carboxamide riboside. The elevation of these 2 compounds confirmed the diagnosis of adenylosuccinate lyase deficiency."}
|
{'Case report': "A male child was born at term by an uncomplicated pregnancy. The patient was hypotonic, irritable, and demonstrated poor feeding by breast and bottle in the first week of life. He had a history of in utero hiccups, which persisted as a neonate. At the age of 3 months, he was admitted to the hospital with Respiratory Syncytial Virus (RSV) and seizure-like activity, which prompted an MRI. Videos obtained by family showed that the child had been having seizures since birth. MRI showed myelination confined to the brainstem, central cerebellum, and posterior limbs of the internal capsule ( Fig. 1 ). There was T2 hyperintensity of the white matter ( Fig. 2 ) and superior vermian volume loss ( Fig. 3 ). The corpus callosum was unmyelinated. MRI spectroscopy revealed a low N-acetylaspartate (NAA) peak with no lactate peak ( Fig. 4 ). Fig. 1 Axial T1-weighted images of the brain acquired at 3.0 T demonstrate myelination limited to the posterior limbs of the bilateral posterior internal capsules (white arrows). Fig. 1 –. Fig. 2 Axial T2-weighted images of the brain acquired at 3.0 T show increased T2 signal in the periventricular white matter (white arrow). There is overall low parenchymal volume with prominence of the extra-axial spaces (black arrow). Fig. 2 –. Fig. 3 Sagittal T1-weighted images reveal low parenchymal volume of the superior folia with prominence of the extra-axial spaces (white arrow). The corpus callosum is unmyelinated. Fig. 3 –. Fig. 4 Magnetic resonance spectroscopy performed at TE = 144 ms with a voxel placed in the right posterior parietal white matter demonstrates a dominant choline peak and a diminished N-acetyl aspartate peak. Fig. 4 –. The patient's hospitalization was complicated by seizures requiring prolonged video electroencephalogram (EEG) monitoring and anticonvulsant therapy. CSF analysis yielded an acellular CSF with normal protein and glucose. He was subsequently discharged with a nasogastric tube on phenobarbital therapy at a dose of 10 mg twice a day and levetiracetam at a dose of 75 mg per day. He continued to exhibit excessive hiccupping, episodes of extensor spasms, and multifocal seizures. A follow-up study of the patient's CSF was found to demonstrate abnormally high concentrations of succinyladenosine and succinylaminoimidazole carboxamide riboside. The elevation of these 2 compounds confirmed the diagnosis of adenylosuccinate lyase deficiency."}
|
Lymphatic-System
|
LYMPH
|
[] |
test-1959
|
6260459
|
{'Case report': "A male child was born at term by an uncomplicated pregnancy. The patient was hypotonic, irritable, and demonstrated poor feeding by breast and bottle in the first week of life. He had a history of in utero hiccups, which persisted as a neonate. At the age of 3 months, he was admitted to the hospital with Respiratory Syncytial Virus (RSV) and seizure-like activity, which prompted an MRI. Videos obtained by family showed that the child had been having seizures since birth. MRI showed myelination confined to the brainstem, central cerebellum, and posterior limbs of the internal capsule ( Fig. 1 ). There was T2 hyperintensity of the white matter ( Fig. 2 ) and superior vermian volume loss ( Fig. 3 ). The corpus callosum was unmyelinated. MRI spectroscopy revealed a low N-acetylaspartate (NAA) peak with no lactate peak ( Fig. 4 ). Fig. 1 Axial T1-weighted images of the brain acquired at 3.0 T demonstrate myelination limited to the posterior limbs of the bilateral posterior internal capsules (white arrows). Fig. 1 –. Fig. 2 Axial T2-weighted images of the brain acquired at 3.0 T show increased T2 signal in the periventricular white matter (white arrow). There is overall low parenchymal volume with prominence of the extra-axial spaces (black arrow). Fig. 2 –. Fig. 3 Sagittal T1-weighted images reveal low parenchymal volume of the superior folia with prominence of the extra-axial spaces (white arrow). The corpus callosum is unmyelinated. Fig. 3 –. Fig. 4 Magnetic resonance spectroscopy performed at TE = 144 ms with a voxel placed in the right posterior parietal white matter demonstrates a dominant choline peak and a diminished N-acetyl aspartate peak. Fig. 4 –. The patient's hospitalization was complicated by seizures requiring prolonged video electroencephalogram (EEG) monitoring and anticonvulsant therapy. CSF analysis yielded an acellular CSF with normal protein and glucose. He was subsequently discharged with a nasogastric tube on phenobarbital therapy at a dose of 10 mg twice a day and levetiracetam at a dose of 75 mg per day. He continued to exhibit excessive hiccupping, episodes of extensor spasms, and multifocal seizures. A follow-up study of the patient's CSF was found to demonstrate abnormally high concentrations of succinyladenosine and succinylaminoimidazole carboxamide riboside. The elevation of these 2 compounds confirmed the diagnosis of adenylosuccinate lyase deficiency."}
|
{'Case report': "A male child was born at term by an uncomplicated pregnancy. The patient was hypotonic, irritable, and demonstrated poor feeding by breast and bottle in the first week of life. He had a history of in utero hiccups, which persisted as a neonate. At the age of 3 months, he was admitted to the hospital with Respiratory Syncytial Virus (RSV) and seizure-like activity, which prompted an MRI. Videos obtained by family showed that the child had been having seizures since birth. MRI showed myelination confined to the brainstem, central cerebellum, and posterior limbs of the internal capsule ( Fig. 1 ). There was T2 hyperintensity of the white matter ( Fig. 2 ) and superior vermian volume loss ( Fig. 3 ). The corpus callosum was unmyelinated. MRI spectroscopy revealed a low N-acetylaspartate (NAA) peak with no lactate peak ( Fig. 4 ). Fig. 1 Axial T1-weighted images of the brain acquired at 3.0 T demonstrate myelination limited to the posterior limbs of the bilateral posterior internal capsules (white arrows). Fig. 1 –. Fig. 2 Axial T2-weighted images of the brain acquired at 3.0 T show increased T2 signal in the periventricular white matter (white arrow). There is overall low parenchymal volume with prominence of the extra-axial spaces (black arrow). Fig. 2 –. Fig. 3 Sagittal T1-weighted images reveal low parenchymal volume of the superior folia with prominence of the extra-axial spaces (white arrow). The corpus callosum is unmyelinated. Fig. 3 –. Fig. 4 Magnetic resonance spectroscopy performed at TE = 144 ms with a voxel placed in the right posterior parietal white matter demonstrates a dominant choline peak and a diminished N-acetyl aspartate peak. Fig. 4 –. The patient's hospitalization was complicated by seizures requiring prolonged video electroencephalogram (EEG) monitoring and anticonvulsant therapy. CSF analysis yielded an acellular CSF with normal protein and glucose. He was subsequently discharged with a nasogastric tube on phenobarbital therapy at a dose of 10 mg twice a day and levetiracetam at a dose of 75 mg per day. He continued to exhibit excessive hiccupping, episodes of extensor spasms, and multifocal seizures. A follow-up study of the patient's CSF was found to demonstrate abnormally high concentrations of succinyladenosine and succinylaminoimidazole carboxamide riboside. The elevation of these 2 compounds confirmed the diagnosis of adenylosuccinate lyase deficiency."}
|
Age-at-Presentation
|
Age (at case presentation)
|
[
"age of 3 months"
] |
test-1960
|
6260459
|
{'Case report': "A male child was born at term by an uncomplicated pregnancy. The patient was hypotonic, irritable, and demonstrated poor feeding by breast and bottle in the first week of life. He had a history of in utero hiccups, which persisted as a neonate. At the age of 3 months, he was admitted to the hospital with Respiratory Syncytial Virus (RSV) and seizure-like activity, which prompted an MRI. Videos obtained by family showed that the child had been having seizures since birth. MRI showed myelination confined to the brainstem, central cerebellum, and posterior limbs of the internal capsule ( Fig. 1 ). There was T2 hyperintensity of the white matter ( Fig. 2 ) and superior vermian volume loss ( Fig. 3 ). The corpus callosum was unmyelinated. MRI spectroscopy revealed a low N-acetylaspartate (NAA) peak with no lactate peak ( Fig. 4 ). Fig. 1 Axial T1-weighted images of the brain acquired at 3.0 T demonstrate myelination limited to the posterior limbs of the bilateral posterior internal capsules (white arrows). Fig. 1 –. Fig. 2 Axial T2-weighted images of the brain acquired at 3.0 T show increased T2 signal in the periventricular white matter (white arrow). There is overall low parenchymal volume with prominence of the extra-axial spaces (black arrow). Fig. 2 –. Fig. 3 Sagittal T1-weighted images reveal low parenchymal volume of the superior folia with prominence of the extra-axial spaces (white arrow). The corpus callosum is unmyelinated. Fig. 3 –. Fig. 4 Magnetic resonance spectroscopy performed at TE = 144 ms with a voxel placed in the right posterior parietal white matter demonstrates a dominant choline peak and a diminished N-acetyl aspartate peak. Fig. 4 –. The patient's hospitalization was complicated by seizures requiring prolonged video electroencephalogram (EEG) monitoring and anticonvulsant therapy. CSF analysis yielded an acellular CSF with normal protein and glucose. He was subsequently discharged with a nasogastric tube on phenobarbital therapy at a dose of 10 mg twice a day and levetiracetam at a dose of 75 mg per day. He continued to exhibit excessive hiccupping, episodes of extensor spasms, and multifocal seizures. A follow-up study of the patient's CSF was found to demonstrate abnormally high concentrations of succinyladenosine and succinylaminoimidazole carboxamide riboside. The elevation of these 2 compounds confirmed the diagnosis of adenylosuccinate lyase deficiency."}
|
{'Case report': "A male child was born at term by an uncomplicated pregnancy. The patient was hypotonic, irritable, and demonstrated poor feeding by breast and bottle in the first week of life. He had a history of in utero hiccups, which persisted as a neonate. At the age of 3 months, he was admitted to the hospital with Respiratory Syncytial Virus (RSV) and seizure-like activity, which prompted an MRI. Videos obtained by family showed that the child had been having seizures since birth. MRI showed myelination confined to the brainstem, central cerebellum, and posterior limbs of the internal capsule ( Fig. 1 ). There was T2 hyperintensity of the white matter ( Fig. 2 ) and superior vermian volume loss ( Fig. 3 ). The corpus callosum was unmyelinated. MRI spectroscopy revealed a low N-acetylaspartate (NAA) peak with no lactate peak ( Fig. 4 ). Fig. 1 Axial T1-weighted images of the brain acquired at 3.0 T demonstrate myelination limited to the posterior limbs of the bilateral posterior internal capsules (white arrows). Fig. 1 –. Fig. 2 Axial T2-weighted images of the brain acquired at 3.0 T show increased T2 signal in the periventricular white matter (white arrow). There is overall low parenchymal volume with prominence of the extra-axial spaces (black arrow). Fig. 2 –. Fig. 3 Sagittal T1-weighted images reveal low parenchymal volume of the superior folia with prominence of the extra-axial spaces (white arrow). The corpus callosum is unmyelinated. Fig. 3 –. Fig. 4 Magnetic resonance spectroscopy performed at TE = 144 ms with a voxel placed in the right posterior parietal white matter demonstrates a dominant choline peak and a diminished N-acetyl aspartate peak. Fig. 4 –. The patient's hospitalization was complicated by seizures requiring prolonged video electroencephalogram (EEG) monitoring and anticonvulsant therapy. CSF analysis yielded an acellular CSF with normal protein and glucose. He was subsequently discharged with a nasogastric tube on phenobarbital therapy at a dose of 10 mg twice a day and levetiracetam at a dose of 75 mg per day. He continued to exhibit excessive hiccupping, episodes of extensor spasms, and multifocal seizures. A follow-up study of the patient's CSF was found to demonstrate abnormally high concentrations of succinyladenosine and succinylaminoimidazole carboxamide riboside. The elevation of these 2 compounds confirmed the diagnosis of adenylosuccinate lyase deficiency."}
|
Age-of-Onset
|
Age (of onset)
|
[
"in utero"
] |
test-1961
|
6260459
|
{'Case report': "A male child was born at term by an uncomplicated pregnancy. The patient was hypotonic, irritable, and demonstrated poor feeding by breast and bottle in the first week of life. He had a history of in utero hiccups, which persisted as a neonate. At the age of 3 months, he was admitted to the hospital with Respiratory Syncytial Virus (RSV) and seizure-like activity, which prompted an MRI. Videos obtained by family showed that the child had been having seizures since birth. MRI showed myelination confined to the brainstem, central cerebellum, and posterior limbs of the internal capsule ( Fig. 1 ). There was T2 hyperintensity of the white matter ( Fig. 2 ) and superior vermian volume loss ( Fig. 3 ). The corpus callosum was unmyelinated. MRI spectroscopy revealed a low N-acetylaspartate (NAA) peak with no lactate peak ( Fig. 4 ). Fig. 1 Axial T1-weighted images of the brain acquired at 3.0 T demonstrate myelination limited to the posterior limbs of the bilateral posterior internal capsules (white arrows). Fig. 1 –. Fig. 2 Axial T2-weighted images of the brain acquired at 3.0 T show increased T2 signal in the periventricular white matter (white arrow). There is overall low parenchymal volume with prominence of the extra-axial spaces (black arrow). Fig. 2 –. Fig. 3 Sagittal T1-weighted images reveal low parenchymal volume of the superior folia with prominence of the extra-axial spaces (white arrow). The corpus callosum is unmyelinated. Fig. 3 –. Fig. 4 Magnetic resonance spectroscopy performed at TE = 144 ms with a voxel placed in the right posterior parietal white matter demonstrates a dominant choline peak and a diminished N-acetyl aspartate peak. Fig. 4 –. The patient's hospitalization was complicated by seizures requiring prolonged video electroencephalogram (EEG) monitoring and anticonvulsant therapy. CSF analysis yielded an acellular CSF with normal protein and glucose. He was subsequently discharged with a nasogastric tube on phenobarbital therapy at a dose of 10 mg twice a day and levetiracetam at a dose of 75 mg per day. He continued to exhibit excessive hiccupping, episodes of extensor spasms, and multifocal seizures. A follow-up study of the patient's CSF was found to demonstrate abnormally high concentrations of succinyladenosine and succinylaminoimidazole carboxamide riboside. The elevation of these 2 compounds confirmed the diagnosis of adenylosuccinate lyase deficiency."}
|
{'Case report': "A male child was born at term by an uncomplicated pregnancy. The patient was hypotonic, irritable, and demonstrated poor feeding by breast and bottle in the first week of life. He had a history of in utero hiccups, which persisted as a neonate. At the age of 3 months, he was admitted to the hospital with Respiratory Syncytial Virus (RSV) and seizure-like activity, which prompted an MRI. Videos obtained by family showed that the child had been having seizures since birth. MRI showed myelination confined to the brainstem, central cerebellum, and posterior limbs of the internal capsule ( Fig. 1 ). There was T2 hyperintensity of the white matter ( Fig. 2 ) and superior vermian volume loss ( Fig. 3 ). The corpus callosum was unmyelinated. MRI spectroscopy revealed a low N-acetylaspartate (NAA) peak with no lactate peak ( Fig. 4 ). Fig. 1 Axial T1-weighted images of the brain acquired at 3.0 T demonstrate myelination limited to the posterior limbs of the bilateral posterior internal capsules (white arrows). Fig. 1 –. Fig. 2 Axial T2-weighted images of the brain acquired at 3.0 T show increased T2 signal in the periventricular white matter (white arrow). There is overall low parenchymal volume with prominence of the extra-axial spaces (black arrow). Fig. 2 –. Fig. 3 Sagittal T1-weighted images reveal low parenchymal volume of the superior folia with prominence of the extra-axial spaces (white arrow). The corpus callosum is unmyelinated. Fig. 3 –. Fig. 4 Magnetic resonance spectroscopy performed at TE = 144 ms with a voxel placed in the right posterior parietal white matter demonstrates a dominant choline peak and a diminished N-acetyl aspartate peak. Fig. 4 –. The patient's hospitalization was complicated by seizures requiring prolonged video electroencephalogram (EEG) monitoring and anticonvulsant therapy. CSF analysis yielded an acellular CSF with normal protein and glucose. He was subsequently discharged with a nasogastric tube on phenobarbital therapy at a dose of 10 mg twice a day and levetiracetam at a dose of 75 mg per day. He continued to exhibit excessive hiccupping, episodes of extensor spasms, and multifocal seizures. A follow-up study of the patient's CSF was found to demonstrate abnormally high concentrations of succinyladenosine and succinylaminoimidazole carboxamide riboside. The elevation of these 2 compounds confirmed the diagnosis of adenylosuccinate lyase deficiency."}
|
Confirmed-Diagnosis-IEM
|
Confirmed_Diagnosis(IEM)
|
[
"The elevation of these 2 compounds confirmed the diagnosis of adenylosuccinate lyase deficiency ."
] |
test-1962
|
6260459
|
{'Case report': "A male child was born at term by an uncomplicated pregnancy. The patient was hypotonic, irritable, and demonstrated poor feeding by breast and bottle in the first week of life. He had a history of in utero hiccups, which persisted as a neonate. At the age of 3 months, he was admitted to the hospital with Respiratory Syncytial Virus (RSV) and seizure-like activity, which prompted an MRI. Videos obtained by family showed that the child had been having seizures since birth. MRI showed myelination confined to the brainstem, central cerebellum, and posterior limbs of the internal capsule ( Fig. 1 ). There was T2 hyperintensity of the white matter ( Fig. 2 ) and superior vermian volume loss ( Fig. 3 ). The corpus callosum was unmyelinated. MRI spectroscopy revealed a low N-acetylaspartate (NAA) peak with no lactate peak ( Fig. 4 ). Fig. 1 Axial T1-weighted images of the brain acquired at 3.0 T demonstrate myelination limited to the posterior limbs of the bilateral posterior internal capsules (white arrows). Fig. 1 –. Fig. 2 Axial T2-weighted images of the brain acquired at 3.0 T show increased T2 signal in the periventricular white matter (white arrow). There is overall low parenchymal volume with prominence of the extra-axial spaces (black arrow). Fig. 2 –. Fig. 3 Sagittal T1-weighted images reveal low parenchymal volume of the superior folia with prominence of the extra-axial spaces (white arrow). The corpus callosum is unmyelinated. Fig. 3 –. Fig. 4 Magnetic resonance spectroscopy performed at TE = 144 ms with a voxel placed in the right posterior parietal white matter demonstrates a dominant choline peak and a diminished N-acetyl aspartate peak. Fig. 4 –. The patient's hospitalization was complicated by seizures requiring prolonged video electroencephalogram (EEG) monitoring and anticonvulsant therapy. CSF analysis yielded an acellular CSF with normal protein and glucose. He was subsequently discharged with a nasogastric tube on phenobarbital therapy at a dose of 10 mg twice a day and levetiracetam at a dose of 75 mg per day. He continued to exhibit excessive hiccupping, episodes of extensor spasms, and multifocal seizures. A follow-up study of the patient's CSF was found to demonstrate abnormally high concentrations of succinyladenosine and succinylaminoimidazole carboxamide riboside. The elevation of these 2 compounds confirmed the diagnosis of adenylosuccinate lyase deficiency."}
|
{'Case report': "A male child was born at term by an uncomplicated pregnancy. The patient was hypotonic, irritable, and demonstrated poor feeding by breast and bottle in the first week of life. He had a history of in utero hiccups, which persisted as a neonate. At the age of 3 months, he was admitted to the hospital with Respiratory Syncytial Virus (RSV) and seizure-like activity, which prompted an MRI. Videos obtained by family showed that the child had been having seizures since birth. MRI showed myelination confined to the brainstem, central cerebellum, and posterior limbs of the internal capsule ( Fig. 1 ). There was T2 hyperintensity of the white matter ( Fig. 2 ) and superior vermian volume loss ( Fig. 3 ). The corpus callosum was unmyelinated. MRI spectroscopy revealed a low N-acetylaspartate (NAA) peak with no lactate peak ( Fig. 4 ). Fig. 1 Axial T1-weighted images of the brain acquired at 3.0 T demonstrate myelination limited to the posterior limbs of the bilateral posterior internal capsules (white arrows). Fig. 1 –. Fig. 2 Axial T2-weighted images of the brain acquired at 3.0 T show increased T2 signal in the periventricular white matter (white arrow). There is overall low parenchymal volume with prominence of the extra-axial spaces (black arrow). Fig. 2 –. Fig. 3 Sagittal T1-weighted images reveal low parenchymal volume of the superior folia with prominence of the extra-axial spaces (white arrow). The corpus callosum is unmyelinated. Fig. 3 –. Fig. 4 Magnetic resonance spectroscopy performed at TE = 144 ms with a voxel placed in the right posterior parietal white matter demonstrates a dominant choline peak and a diminished N-acetyl aspartate peak. Fig. 4 –. The patient's hospitalization was complicated by seizures requiring prolonged video electroencephalogram (EEG) monitoring and anticonvulsant therapy. CSF analysis yielded an acellular CSF with normal protein and glucose. He was subsequently discharged with a nasogastric tube on phenobarbital therapy at a dose of 10 mg twice a day and levetiracetam at a dose of 75 mg per day. He continued to exhibit excessive hiccupping, episodes of extensor spasms, and multifocal seizures. A follow-up study of the patient's CSF was found to demonstrate abnormally high concentrations of succinyladenosine and succinylaminoimidazole carboxamide riboside. The elevation of these 2 compounds confirmed the diagnosis of adenylosuccinate lyase deficiency."}
|
IEM-Treatment
|
IEM_Treatment
|
[] |
test-1963
|
6944811
|
{'1 st case': 'This patient was a 4-year old girl, second child of related parents, delivered by cesarean section without any insult. This child developed wrist swelling at 6 months of age. Swelling of other joints were gradually added. On examination, swelling and limitation in range of motion was detected in PIP, MCP, wrist, elbow and shoulder joints of upper limbs and PIP, MTP, tarsal joints and ankle in lower limbs. Multiple firm subcutaneous nodules were found on joints –mainly on extensor surfaces- which led to deformation of joint, tenderness and inability to walk. Contracture in joints was evident in physical examination. Progressive hoarseness was present. Reports of head drop attacks were found in the history. In neurologic examination, deep tendon reflexes were diminished or absent. Although cognitive function of this patient was normal, motor and speech development was delayed. Two years later, development of seizure and tremor was reported. Tremor was evident in all limbs on physical examination. Laboratory serologic tests were normal. Radiography of both hands showed reduction in density of bones, swelling of both wrists, deformity of wrist bones, marginal erosion of wrist bones and distal phalanges in PIP and DIP joints which all were suggestive of advanced juvenile idiopathic arthritis (JIA). Chest X-ray also showed alveolar opacities with air bronchogram in the upper lobe of right lung which were in favor of pneumonia. Bronchoscopy showed a circular contraction in subglottic region of larynx. After development of neurologic involvements, Farber disease was suspected. To confirm the diagnostic suspicion, genetic analysis was performed. ASAH1 gene analysis –gene related to Farber syndrome- revealed a homozygous variant which confirmed the presence of Farber disease in this patient. This variant was a novel mutation in exon 8 of ASAH1 gene (c.553T>C p.Trp185Arg). Patient had not received treatment till the age of 2.5 years. After she was diagnosed with JIA, methotrexate, hydroxychloroquine, prednisolone and infliximab medications were initiated. After genetic testing and establishment of the diagnosis of Farber disease, patient’s treatment was switched to cyclosporine and prednisolone. With the development of neurologic involvements, Topiramate, valproate sodium and clobazam was prescribed for relieving debilitating neurologic symptoms. Bone marrow transplantation was suggested as a treatment strategy for the patient but the suggestion was declined by the family. She has under follow up after 2.5 years with neurological deficit.', '2 nd case': 'This patient was a 4 year-old girl, first child of a non-related couple, delivered by NVD who was term on birth. The patient developed swelling of joints at 7 months of age. Particularly in PIP and MCP joints, wrists and ankles ( Figure 1a ). On examination at the age of 2 years, she had multiple subcutaneous nodules on head, hands and chest ( Figure 1b ). Progressive hoarseness was also present. Extensive mucosal lesions were detected in the oral cavity. Limitation in knee’s range of motion was severe leading to difficulty in walking. Cutaneous lesions were also seen on abdomen. In the follow-up after two years, patient had developed nasal swelling. On examination, three relatively soft masses were found within lumbar to coccygeal regions of the spine with diameters of up to 5 centimeters ( Figure 1c ). Muscular atrophy of all four limbs and gluteal region was evident. In the auscultation of the lungs, wheezing was detected. Joints’ examination showed nodules and range of motion limitation in both elbows, shoulders, MCPs, PIPs and DIPs in upper limbs. In lower limbs, knees and ankles were affected with contracture, nodules and range of motion limitation. In radiography, bilateral destruction of proximal humerus and severe osteopenia were seen. After a while, progression of hoarseness and development of multiple percutaneous nodules put the diagnosis of JIA under question. Biopsies were taken from nodules to rule out Farber disease. Histopathologic examination reported collection of collagen bundles and foamy macrophages which were suggestive of Farber disease. With the early diagnosis of JIA, the patient underwent treatment with folic acid, prednisolone, cyclosporine, ibuprofen, calcium supplement and nystatin. MTX was initiated for the patient but then was discontinued due to the appearance of cutaneous lesions on the body. Corticosteroid pulses and Etanercept injections were also prescribed. Subcutaneous nodules increased gradually and she was admitted 4 times due to respiratory distress. Finally she died from respiratory failure in one episode at 4 years old.', '3 rd case': 'This patient was a 9-month old boy, the first child of related parents who was delivered by NVD without any insult. Rheumatoid arthritis history was positive for patient’s father. The patient was presented to the clinic at 9 months of age with one month history of left wrist swelling and tenderness. Within one week prior to the presentation, swelling had extended to the dorsal surfaces of the hands. Patient had been misdiagnosed with JIA and treatment with Prednisolone, MTX and ibuprofen was started. Hoarseness had developed 6 months earlier. Weight loss was also reported. On examination, lower limbs were normal but in upper limbs, limitations in flexion and extension of wrist and swelling of fingers were noted. Patient was presented to the clinic again at 18 months of age with delayed motor development, multiple subcutaneous nodules in wrists and ankles, respiratory distress and hoarseness ( Figure 2 ). In bronchoscopy, large cysts on vocal cords were seen. On radiography, osteopenia was evident (bone age equal to 9 months at the age of 18 months). CXR visualized bilateral perihilar opacities and hyperinflation in both lungs. In kidney, contrast opacity resembling kidney stone was seen. HPLC was normal. Laryngeal nodules led to severe respiratory distress which his life ended after ICU admission and tracheostomy insertion.'}
|
{'1 st case': 'This patient was a 4-year old girl, second child of related parents, delivered by cesarean section without any insult. This child developed wrist swelling at 6 months of age. Swelling of other joints were gradually added. On examination, swelling and limitation in range of motion was detected in PIP, MCP, wrist, elbow and shoulder joints of upper limbs and PIP, MTP, tarsal joints and ankle in lower limbs. Multiple firm subcutaneous nodules were found on joints –mainly on extensor surfaces- which led to deformation of joint, tenderness and inability to walk. Contracture in joints was evident in physical examination. Progressive hoarseness was present. Reports of head drop attacks were found in the history. In neurologic examination, deep tendon reflexes were diminished or absent. Although cognitive function of this patient was normal, motor and speech development was delayed. Two years later, development of seizure and tremor was reported. Tremor was evident in all limbs on physical examination. Laboratory serologic tests were normal. Radiography of both hands showed reduction in density of bones, swelling of both wrists, deformity of wrist bones, marginal erosion of wrist bones and distal phalanges in PIP and DIP joints which all were suggestive of advanced juvenile idiopathic arthritis (JIA). Chest X-ray also showed alveolar opacities with air bronchogram in the upper lobe of right lung which were in favor of pneumonia. Bronchoscopy showed a circular contraction in subglottic region of larynx. After development of neurologic involvements, Farber disease was suspected. To confirm the diagnostic suspicion, genetic analysis was performed. ASAH1 gene analysis –gene related to Farber syndrome- revealed a homozygous variant which confirmed the presence of Farber disease in this patient. This variant was a novel mutation in exon 8 of ASAH1 gene (c.553T>C p.Trp185Arg). Patient had not received treatment till the age of 2.5 years. After she was diagnosed with JIA, methotrexate, hydroxychloroquine, prednisolone and infliximab medications were initiated. After genetic testing and establishment of the diagnosis of Farber disease, patient’s treatment was switched to cyclosporine and prednisolone. With the development of neurologic involvements, Topiramate, valproate sodium and clobazam was prescribed for relieving debilitating neurologic symptoms. Bone marrow transplantation was suggested as a treatment strategy for the patient but the suggestion was declined by the family. She has under follow up after 2.5 years with neurological deficit.', '2 nd case': 'This patient was a 4 year-old girl, first child of a non-related couple, delivered by NVD who was term on birth. The patient developed swelling of joints at 7 months of age. Particularly in PIP and MCP joints, wrists and ankles ( Figure 1a ). On examination at the age of 2 years, she had multiple subcutaneous nodules on head, hands and chest ( Figure 1b ). Progressive hoarseness was also present. Extensive mucosal lesions were detected in the oral cavity. Limitation in knee’s range of motion was severe leading to difficulty in walking. Cutaneous lesions were also seen on abdomen. In the follow-up after two years, patient had developed nasal swelling. On examination, three relatively soft masses were found within lumbar to coccygeal regions of the spine with diameters of up to 5 centimeters ( Figure 1c ). Muscular atrophy of all four limbs and gluteal region was evident. In the auscultation of the lungs, wheezing was detected. Joints’ examination showed nodules and range of motion limitation in both elbows, shoulders, MCPs, PIPs and DIPs in upper limbs. In lower limbs, knees and ankles were affected with contracture, nodules and range of motion limitation. In radiography, bilateral destruction of proximal humerus and severe osteopenia were seen. After a while, progression of hoarseness and development of multiple percutaneous nodules put the diagnosis of JIA under question. Biopsies were taken from nodules to rule out Farber disease. Histopathologic examination reported collection of collagen bundles and foamy macrophages which were suggestive of Farber disease. With the early diagnosis of JIA, the patient underwent treatment with folic acid, prednisolone, cyclosporine, ibuprofen, calcium supplement and nystatin. MTX was initiated for the patient but then was discontinued due to the appearance of cutaneous lesions on the body. Corticosteroid pulses and Etanercept injections were also prescribed. Subcutaneous nodules increased gradually and she was admitted 4 times due to respiratory distress. Finally she died from respiratory failure in one episode at 4 years old.', '3 rd case': 'This patient was a 9-month old boy, the first child of related parents who was delivered by NVD without any insult. Rheumatoid arthritis history was positive for patient’s father. The patient was presented to the clinic at 9 months of age with one month history of left wrist swelling and tenderness. Within one week prior to the presentation, swelling had extended to the dorsal surfaces of the hands. Patient had been misdiagnosed with JIA and treatment with Prednisolone, MTX and ibuprofen was started. Hoarseness had developed 6 months earlier. Weight loss was also reported. On examination, lower limbs were normal but in upper limbs, limitations in flexion and extension of wrist and swelling of fingers were noted. Patient was presented to the clinic again at 18 months of age with delayed motor development, multiple subcutaneous nodules in wrists and ankles, respiratory distress and hoarseness ( Figure 2 ). In bronchoscopy, large cysts on vocal cords were seen. On radiography, osteopenia was evident (bone age equal to 9 months at the age of 18 months). CXR visualized bilateral perihilar opacities and hyperinflation in both lungs. In kidney, contrast opacity resembling kidney stone was seen. HPLC was normal. Laryngeal nodules led to severe respiratory distress which his life ended after ICU admission and tracheostomy insertion.'}
|
Vitals-and-Hematology
|
Vitals_Hema
|
[] |
test-1964
|
6944811
|
{'1 st case': 'This patient was a 4-year old girl, second child of related parents, delivered by cesarean section without any insult. This child developed wrist swelling at 6 months of age. Swelling of other joints were gradually added. On examination, swelling and limitation in range of motion was detected in PIP, MCP, wrist, elbow and shoulder joints of upper limbs and PIP, MTP, tarsal joints and ankle in lower limbs. Multiple firm subcutaneous nodules were found on joints –mainly on extensor surfaces- which led to deformation of joint, tenderness and inability to walk. Contracture in joints was evident in physical examination. Progressive hoarseness was present. Reports of head drop attacks were found in the history. In neurologic examination, deep tendon reflexes were diminished or absent. Although cognitive function of this patient was normal, motor and speech development was delayed. Two years later, development of seizure and tremor was reported. Tremor was evident in all limbs on physical examination. Laboratory serologic tests were normal. Radiography of both hands showed reduction in density of bones, swelling of both wrists, deformity of wrist bones, marginal erosion of wrist bones and distal phalanges in PIP and DIP joints which all were suggestive of advanced juvenile idiopathic arthritis (JIA). Chest X-ray also showed alveolar opacities with air bronchogram in the upper lobe of right lung which were in favor of pneumonia. Bronchoscopy showed a circular contraction in subglottic region of larynx. After development of neurologic involvements, Farber disease was suspected. To confirm the diagnostic suspicion, genetic analysis was performed. ASAH1 gene analysis –gene related to Farber syndrome- revealed a homozygous variant which confirmed the presence of Farber disease in this patient. This variant was a novel mutation in exon 8 of ASAH1 gene (c.553T>C p.Trp185Arg). Patient had not received treatment till the age of 2.5 years. After she was diagnosed with JIA, methotrexate, hydroxychloroquine, prednisolone and infliximab medications were initiated. After genetic testing and establishment of the diagnosis of Farber disease, patient’s treatment was switched to cyclosporine and prednisolone. With the development of neurologic involvements, Topiramate, valproate sodium and clobazam was prescribed for relieving debilitating neurologic symptoms. Bone marrow transplantation was suggested as a treatment strategy for the patient but the suggestion was declined by the family. She has under follow up after 2.5 years with neurological deficit.', '2 nd case': 'This patient was a 4 year-old girl, first child of a non-related couple, delivered by NVD who was term on birth. The patient developed swelling of joints at 7 months of age. Particularly in PIP and MCP joints, wrists and ankles ( Figure 1a ). On examination at the age of 2 years, she had multiple subcutaneous nodules on head, hands and chest ( Figure 1b ). Progressive hoarseness was also present. Extensive mucosal lesions were detected in the oral cavity. Limitation in knee’s range of motion was severe leading to difficulty in walking. Cutaneous lesions were also seen on abdomen. In the follow-up after two years, patient had developed nasal swelling. On examination, three relatively soft masses were found within lumbar to coccygeal regions of the spine with diameters of up to 5 centimeters ( Figure 1c ). Muscular atrophy of all four limbs and gluteal region was evident. In the auscultation of the lungs, wheezing was detected. Joints’ examination showed nodules and range of motion limitation in both elbows, shoulders, MCPs, PIPs and DIPs in upper limbs. In lower limbs, knees and ankles were affected with contracture, nodules and range of motion limitation. In radiography, bilateral destruction of proximal humerus and severe osteopenia were seen. After a while, progression of hoarseness and development of multiple percutaneous nodules put the diagnosis of JIA under question. Biopsies were taken from nodules to rule out Farber disease. Histopathologic examination reported collection of collagen bundles and foamy macrophages which were suggestive of Farber disease. With the early diagnosis of JIA, the patient underwent treatment with folic acid, prednisolone, cyclosporine, ibuprofen, calcium supplement and nystatin. MTX was initiated for the patient but then was discontinued due to the appearance of cutaneous lesions on the body. Corticosteroid pulses and Etanercept injections were also prescribed. Subcutaneous nodules increased gradually and she was admitted 4 times due to respiratory distress. Finally she died from respiratory failure in one episode at 4 years old.', '3 rd case': 'This patient was a 9-month old boy, the first child of related parents who was delivered by NVD without any insult. Rheumatoid arthritis history was positive for patient’s father. The patient was presented to the clinic at 9 months of age with one month history of left wrist swelling and tenderness. Within one week prior to the presentation, swelling had extended to the dorsal surfaces of the hands. Patient had been misdiagnosed with JIA and treatment with Prednisolone, MTX and ibuprofen was started. Hoarseness had developed 6 months earlier. Weight loss was also reported. On examination, lower limbs were normal but in upper limbs, limitations in flexion and extension of wrist and swelling of fingers were noted. Patient was presented to the clinic again at 18 months of age with delayed motor development, multiple subcutaneous nodules in wrists and ankles, respiratory distress and hoarseness ( Figure 2 ). In bronchoscopy, large cysts on vocal cords were seen. On radiography, osteopenia was evident (bone age equal to 9 months at the age of 18 months). CXR visualized bilateral perihilar opacities and hyperinflation in both lungs. In kidney, contrast opacity resembling kidney stone was seen. HPLC was normal. Laryngeal nodules led to severe respiratory distress which his life ended after ICU admission and tracheostomy insertion.'}
|
{'1 st case': 'This patient was a 4-year old girl, second child of related parents, delivered by cesarean section without any insult. This child developed wrist swelling at 6 months of age. Swelling of other joints were gradually added. On examination, swelling and limitation in range of motion was detected in PIP, MCP, wrist, elbow and shoulder joints of upper limbs and PIP, MTP, tarsal joints and ankle in lower limbs. Multiple firm subcutaneous nodules were found on joints –mainly on extensor surfaces- which led to deformation of joint, tenderness and inability to walk. Contracture in joints was evident in physical examination. Progressive hoarseness was present. Reports of head drop attacks were found in the history. In neurologic examination, deep tendon reflexes were diminished or absent. Although cognitive function of this patient was normal, motor and speech development was delayed. Two years later, development of seizure and tremor was reported. Tremor was evident in all limbs on physical examination. Laboratory serologic tests were normal. Radiography of both hands showed reduction in density of bones, swelling of both wrists, deformity of wrist bones, marginal erosion of wrist bones and distal phalanges in PIP and DIP joints which all were suggestive of advanced juvenile idiopathic arthritis (JIA). Chest X-ray also showed alveolar opacities with air bronchogram in the upper lobe of right lung which were in favor of pneumonia. Bronchoscopy showed a circular contraction in subglottic region of larynx. After development of neurologic involvements, Farber disease was suspected. To confirm the diagnostic suspicion, genetic analysis was performed. ASAH1 gene analysis –gene related to Farber syndrome- revealed a homozygous variant which confirmed the presence of Farber disease in this patient. This variant was a novel mutation in exon 8 of ASAH1 gene (c.553T>C p.Trp185Arg). Patient had not received treatment till the age of 2.5 years. After she was diagnosed with JIA, methotrexate, hydroxychloroquine, prednisolone and infliximab medications were initiated. After genetic testing and establishment of the diagnosis of Farber disease, patient’s treatment was switched to cyclosporine and prednisolone. With the development of neurologic involvements, Topiramate, valproate sodium and clobazam was prescribed for relieving debilitating neurologic symptoms. Bone marrow transplantation was suggested as a treatment strategy for the patient but the suggestion was declined by the family. She has under follow up after 2.5 years with neurological deficit.', '2 nd case': 'This patient was a 4 year-old girl, first child of a non-related couple, delivered by NVD who was term on birth. The patient developed swelling of joints at 7 months of age. Particularly in PIP and MCP joints, wrists and ankles ( Figure 1a ). On examination at the age of 2 years, she had multiple subcutaneous nodules on head, hands and chest ( Figure 1b ). Progressive hoarseness was also present. Extensive mucosal lesions were detected in the oral cavity. Limitation in knee’s range of motion was severe leading to difficulty in walking. Cutaneous lesions were also seen on abdomen. In the follow-up after two years, patient had developed nasal swelling. On examination, three relatively soft masses were found within lumbar to coccygeal regions of the spine with diameters of up to 5 centimeters ( Figure 1c ). Muscular atrophy of all four limbs and gluteal region was evident. In the auscultation of the lungs, wheezing was detected. Joints’ examination showed nodules and range of motion limitation in both elbows, shoulders, MCPs, PIPs and DIPs in upper limbs. In lower limbs, knees and ankles were affected with contracture, nodules and range of motion limitation. In radiography, bilateral destruction of proximal humerus and severe osteopenia were seen. After a while, progression of hoarseness and development of multiple percutaneous nodules put the diagnosis of JIA under question. Biopsies were taken from nodules to rule out Farber disease. Histopathologic examination reported collection of collagen bundles and foamy macrophages which were suggestive of Farber disease. With the early diagnosis of JIA, the patient underwent treatment with folic acid, prednisolone, cyclosporine, ibuprofen, calcium supplement and nystatin. MTX was initiated for the patient but then was discontinued due to the appearance of cutaneous lesions on the body. Corticosteroid pulses and Etanercept injections were also prescribed. Subcutaneous nodules increased gradually and she was admitted 4 times due to respiratory distress. Finally she died from respiratory failure in one episode at 4 years old.', '3 rd case': 'This patient was a 9-month old boy, the first child of related parents who was delivered by NVD without any insult. Rheumatoid arthritis history was positive for patient’s father. The patient was presented to the clinic at 9 months of age with one month history of left wrist swelling and tenderness. Within one week prior to the presentation, swelling had extended to the dorsal surfaces of the hands. Patient had been misdiagnosed with JIA and treatment with Prednisolone, MTX and ibuprofen was started. Hoarseness had developed 6 months earlier. Weight loss was also reported. On examination, lower limbs were normal but in upper limbs, limitations in flexion and extension of wrist and swelling of fingers were noted. Patient was presented to the clinic again at 18 months of age with delayed motor development, multiple subcutaneous nodules in wrists and ankles, respiratory distress and hoarseness ( Figure 2 ). In bronchoscopy, large cysts on vocal cords were seen. On radiography, osteopenia was evident (bone age equal to 9 months at the age of 18 months). CXR visualized bilateral perihilar opacities and hyperinflation in both lungs. In kidney, contrast opacity resembling kidney stone was seen. HPLC was normal. Laryngeal nodules led to severe respiratory distress which his life ended after ICU admission and tracheostomy insertion.'}
|
Gastrointestinal-System
|
GI
|
[] |
test-1965
|
6944811
|
{'1 st case': 'This patient was a 4-year old girl, second child of related parents, delivered by cesarean section without any insult. This child developed wrist swelling at 6 months of age. Swelling of other joints were gradually added. On examination, swelling and limitation in range of motion was detected in PIP, MCP, wrist, elbow and shoulder joints of upper limbs and PIP, MTP, tarsal joints and ankle in lower limbs. Multiple firm subcutaneous nodules were found on joints –mainly on extensor surfaces- which led to deformation of joint, tenderness and inability to walk. Contracture in joints was evident in physical examination. Progressive hoarseness was present. Reports of head drop attacks were found in the history. In neurologic examination, deep tendon reflexes were diminished or absent. Although cognitive function of this patient was normal, motor and speech development was delayed. Two years later, development of seizure and tremor was reported. Tremor was evident in all limbs on physical examination. Laboratory serologic tests were normal. Radiography of both hands showed reduction in density of bones, swelling of both wrists, deformity of wrist bones, marginal erosion of wrist bones and distal phalanges in PIP and DIP joints which all were suggestive of advanced juvenile idiopathic arthritis (JIA). Chest X-ray also showed alveolar opacities with air bronchogram in the upper lobe of right lung which were in favor of pneumonia. Bronchoscopy showed a circular contraction in subglottic region of larynx. After development of neurologic involvements, Farber disease was suspected. To confirm the diagnostic suspicion, genetic analysis was performed. ASAH1 gene analysis –gene related to Farber syndrome- revealed a homozygous variant which confirmed the presence of Farber disease in this patient. This variant was a novel mutation in exon 8 of ASAH1 gene (c.553T>C p.Trp185Arg). Patient had not received treatment till the age of 2.5 years. After she was diagnosed with JIA, methotrexate, hydroxychloroquine, prednisolone and infliximab medications were initiated. After genetic testing and establishment of the diagnosis of Farber disease, patient’s treatment was switched to cyclosporine and prednisolone. With the development of neurologic involvements, Topiramate, valproate sodium and clobazam was prescribed for relieving debilitating neurologic symptoms. Bone marrow transplantation was suggested as a treatment strategy for the patient but the suggestion was declined by the family. She has under follow up after 2.5 years with neurological deficit.', '2 nd case': 'This patient was a 4 year-old girl, first child of a non-related couple, delivered by NVD who was term on birth. The patient developed swelling of joints at 7 months of age. Particularly in PIP and MCP joints, wrists and ankles ( Figure 1a ). On examination at the age of 2 years, she had multiple subcutaneous nodules on head, hands and chest ( Figure 1b ). Progressive hoarseness was also present. Extensive mucosal lesions were detected in the oral cavity. Limitation in knee’s range of motion was severe leading to difficulty in walking. Cutaneous lesions were also seen on abdomen. In the follow-up after two years, patient had developed nasal swelling. On examination, three relatively soft masses were found within lumbar to coccygeal regions of the spine with diameters of up to 5 centimeters ( Figure 1c ). Muscular atrophy of all four limbs and gluteal region was evident. In the auscultation of the lungs, wheezing was detected. Joints’ examination showed nodules and range of motion limitation in both elbows, shoulders, MCPs, PIPs and DIPs in upper limbs. In lower limbs, knees and ankles were affected with contracture, nodules and range of motion limitation. In radiography, bilateral destruction of proximal humerus and severe osteopenia were seen. After a while, progression of hoarseness and development of multiple percutaneous nodules put the diagnosis of JIA under question. Biopsies were taken from nodules to rule out Farber disease. Histopathologic examination reported collection of collagen bundles and foamy macrophages which were suggestive of Farber disease. With the early diagnosis of JIA, the patient underwent treatment with folic acid, prednisolone, cyclosporine, ibuprofen, calcium supplement and nystatin. MTX was initiated for the patient but then was discontinued due to the appearance of cutaneous lesions on the body. Corticosteroid pulses and Etanercept injections were also prescribed. Subcutaneous nodules increased gradually and she was admitted 4 times due to respiratory distress. Finally she died from respiratory failure in one episode at 4 years old.', '3 rd case': 'This patient was a 9-month old boy, the first child of related parents who was delivered by NVD without any insult. Rheumatoid arthritis history was positive for patient’s father. The patient was presented to the clinic at 9 months of age with one month history of left wrist swelling and tenderness. Within one week prior to the presentation, swelling had extended to the dorsal surfaces of the hands. Patient had been misdiagnosed with JIA and treatment with Prednisolone, MTX and ibuprofen was started. Hoarseness had developed 6 months earlier. Weight loss was also reported. On examination, lower limbs were normal but in upper limbs, limitations in flexion and extension of wrist and swelling of fingers were noted. Patient was presented to the clinic again at 18 months of age with delayed motor development, multiple subcutaneous nodules in wrists and ankles, respiratory distress and hoarseness ( Figure 2 ). In bronchoscopy, large cysts on vocal cords were seen. On radiography, osteopenia was evident (bone age equal to 9 months at the age of 18 months). CXR visualized bilateral perihilar opacities and hyperinflation in both lungs. In kidney, contrast opacity resembling kidney stone was seen. HPLC was normal. Laryngeal nodules led to severe respiratory distress which his life ended after ICU admission and tracheostomy insertion.'}
|
{'1 st case': 'This patient was a 4-year old girl, second child of related parents, delivered by cesarean section without any insult. This child developed wrist swelling at 6 months of age. Swelling of other joints were gradually added. On examination, swelling and limitation in range of motion was detected in PIP, MCP, wrist, elbow and shoulder joints of upper limbs and PIP, MTP, tarsal joints and ankle in lower limbs. Multiple firm subcutaneous nodules were found on joints –mainly on extensor surfaces- which led to deformation of joint, tenderness and inability to walk. Contracture in joints was evident in physical examination. Progressive hoarseness was present. Reports of head drop attacks were found in the history. In neurologic examination, deep tendon reflexes were diminished or absent. Although cognitive function of this patient was normal, motor and speech development was delayed. Two years later, development of seizure and tremor was reported. Tremor was evident in all limbs on physical examination. Laboratory serologic tests were normal. Radiography of both hands showed reduction in density of bones, swelling of both wrists, deformity of wrist bones, marginal erosion of wrist bones and distal phalanges in PIP and DIP joints which all were suggestive of advanced juvenile idiopathic arthritis (JIA). Chest X-ray also showed alveolar opacities with air bronchogram in the upper lobe of right lung which were in favor of pneumonia. Bronchoscopy showed a circular contraction in subglottic region of larynx. After development of neurologic involvements, Farber disease was suspected. To confirm the diagnostic suspicion, genetic analysis was performed. ASAH1 gene analysis –gene related to Farber syndrome- revealed a homozygous variant which confirmed the presence of Farber disease in this patient. This variant was a novel mutation in exon 8 of ASAH1 gene (c.553T>C p.Trp185Arg). Patient had not received treatment till the age of 2.5 years. After she was diagnosed with JIA, methotrexate, hydroxychloroquine, prednisolone and infliximab medications were initiated. After genetic testing and establishment of the diagnosis of Farber disease, patient’s treatment was switched to cyclosporine and prednisolone. With the development of neurologic involvements, Topiramate, valproate sodium and clobazam was prescribed for relieving debilitating neurologic symptoms. Bone marrow transplantation was suggested as a treatment strategy for the patient but the suggestion was declined by the family. She has under follow up after 2.5 years with neurological deficit.', '2 nd case': 'This patient was a 4 year-old girl, first child of a non-related couple, delivered by NVD who was term on birth. The patient developed swelling of joints at 7 months of age. Particularly in PIP and MCP joints, wrists and ankles ( Figure 1a ). On examination at the age of 2 years, she had multiple subcutaneous nodules on head, hands and chest ( Figure 1b ). Progressive hoarseness was also present. Extensive mucosal lesions were detected in the oral cavity. Limitation in knee’s range of motion was severe leading to difficulty in walking. Cutaneous lesions were also seen on abdomen. In the follow-up after two years, patient had developed nasal swelling. On examination, three relatively soft masses were found within lumbar to coccygeal regions of the spine with diameters of up to 5 centimeters ( Figure 1c ). Muscular atrophy of all four limbs and gluteal region was evident. In the auscultation of the lungs, wheezing was detected. Joints’ examination showed nodules and range of motion limitation in both elbows, shoulders, MCPs, PIPs and DIPs in upper limbs. In lower limbs, knees and ankles were affected with contracture, nodules and range of motion limitation. In radiography, bilateral destruction of proximal humerus and severe osteopenia were seen. After a while, progression of hoarseness and development of multiple percutaneous nodules put the diagnosis of JIA under question. Biopsies were taken from nodules to rule out Farber disease. Histopathologic examination reported collection of collagen bundles and foamy macrophages which were suggestive of Farber disease. With the early diagnosis of JIA, the patient underwent treatment with folic acid, prednisolone, cyclosporine, ibuprofen, calcium supplement and nystatin. MTX was initiated for the patient but then was discontinued due to the appearance of cutaneous lesions on the body. Corticosteroid pulses and Etanercept injections were also prescribed. Subcutaneous nodules increased gradually and she was admitted 4 times due to respiratory distress. Finally she died from respiratory failure in one episode at 4 years old.', '3 rd case': 'This patient was a 9-month old boy, the first child of related parents who was delivered by NVD without any insult. Rheumatoid arthritis history was positive for patient’s father. The patient was presented to the clinic at 9 months of age with one month history of left wrist swelling and tenderness. Within one week prior to the presentation, swelling had extended to the dorsal surfaces of the hands. Patient had been misdiagnosed with JIA and treatment with Prednisolone, MTX and ibuprofen was started. Hoarseness had developed 6 months earlier. Weight loss was also reported. On examination, lower limbs were normal but in upper limbs, limitations in flexion and extension of wrist and swelling of fingers were noted. Patient was presented to the clinic again at 18 months of age with delayed motor development, multiple subcutaneous nodules in wrists and ankles, respiratory distress and hoarseness ( Figure 2 ). In bronchoscopy, large cysts on vocal cords were seen. On radiography, osteopenia was evident (bone age equal to 9 months at the age of 18 months). CXR visualized bilateral perihilar opacities and hyperinflation in both lungs. In kidney, contrast opacity resembling kidney stone was seen. HPLC was normal. Laryngeal nodules led to severe respiratory distress which his life ended after ICU admission and tracheostomy insertion.'}
|
Patient-History
|
History
|
[
"This patient was a 4 - year old girl, second child of related parents, delivered by cesarean section without any insult. This child developed wrist swelling at 6 months of age. Swelling of other joints were gradually added",
"Reports of head drop attacks were found in the history",
"This patient was a 4 year - old girl, first child of a non - related couple, delivered by NVD who was term on birth. The patient developed swelling of joints at 7 months of age. Particularly in PIP and MCP joints, wrists and ankles",
"admitted 4 times due to respiratory distress. Finally she died from respiratory failure in one episode at 4 years old",
"This patient was a 9 - month old boy, the first child of related parents who was delivered by NVD without any insult. Rheumatoid arthritis history was positive for patient ’s father. The patient was presented to the clinic at 9 months of age with one month history of left wrist swelling and tenderness. Within one week prior to the presentation, swelling had extended to the dorsal surfaces of the hands"
] |
test-1966
|
6944811
|
{'1 st case': 'This patient was a 4-year old girl, second child of related parents, delivered by cesarean section without any insult. This child developed wrist swelling at 6 months of age. Swelling of other joints were gradually added. On examination, swelling and limitation in range of motion was detected in PIP, MCP, wrist, elbow and shoulder joints of upper limbs and PIP, MTP, tarsal joints and ankle in lower limbs. Multiple firm subcutaneous nodules were found on joints –mainly on extensor surfaces- which led to deformation of joint, tenderness and inability to walk. Contracture in joints was evident in physical examination. Progressive hoarseness was present. Reports of head drop attacks were found in the history. In neurologic examination, deep tendon reflexes were diminished or absent. Although cognitive function of this patient was normal, motor and speech development was delayed. Two years later, development of seizure and tremor was reported. Tremor was evident in all limbs on physical examination. Laboratory serologic tests were normal. Radiography of both hands showed reduction in density of bones, swelling of both wrists, deformity of wrist bones, marginal erosion of wrist bones and distal phalanges in PIP and DIP joints which all were suggestive of advanced juvenile idiopathic arthritis (JIA). Chest X-ray also showed alveolar opacities with air bronchogram in the upper lobe of right lung which were in favor of pneumonia. Bronchoscopy showed a circular contraction in subglottic region of larynx. After development of neurologic involvements, Farber disease was suspected. To confirm the diagnostic suspicion, genetic analysis was performed. ASAH1 gene analysis –gene related to Farber syndrome- revealed a homozygous variant which confirmed the presence of Farber disease in this patient. This variant was a novel mutation in exon 8 of ASAH1 gene (c.553T>C p.Trp185Arg). Patient had not received treatment till the age of 2.5 years. After she was diagnosed with JIA, methotrexate, hydroxychloroquine, prednisolone and infliximab medications were initiated. After genetic testing and establishment of the diagnosis of Farber disease, patient’s treatment was switched to cyclosporine and prednisolone. With the development of neurologic involvements, Topiramate, valproate sodium and clobazam was prescribed for relieving debilitating neurologic symptoms. Bone marrow transplantation was suggested as a treatment strategy for the patient but the suggestion was declined by the family. She has under follow up after 2.5 years with neurological deficit.', '2 nd case': 'This patient was a 4 year-old girl, first child of a non-related couple, delivered by NVD who was term on birth. The patient developed swelling of joints at 7 months of age. Particularly in PIP and MCP joints, wrists and ankles ( Figure 1a ). On examination at the age of 2 years, she had multiple subcutaneous nodules on head, hands and chest ( Figure 1b ). Progressive hoarseness was also present. Extensive mucosal lesions were detected in the oral cavity. Limitation in knee’s range of motion was severe leading to difficulty in walking. Cutaneous lesions were also seen on abdomen. In the follow-up after two years, patient had developed nasal swelling. On examination, three relatively soft masses were found within lumbar to coccygeal regions of the spine with diameters of up to 5 centimeters ( Figure 1c ). Muscular atrophy of all four limbs and gluteal region was evident. In the auscultation of the lungs, wheezing was detected. Joints’ examination showed nodules and range of motion limitation in both elbows, shoulders, MCPs, PIPs and DIPs in upper limbs. In lower limbs, knees and ankles were affected with contracture, nodules and range of motion limitation. In radiography, bilateral destruction of proximal humerus and severe osteopenia were seen. After a while, progression of hoarseness and development of multiple percutaneous nodules put the diagnosis of JIA under question. Biopsies were taken from nodules to rule out Farber disease. Histopathologic examination reported collection of collagen bundles and foamy macrophages which were suggestive of Farber disease. With the early diagnosis of JIA, the patient underwent treatment with folic acid, prednisolone, cyclosporine, ibuprofen, calcium supplement and nystatin. MTX was initiated for the patient but then was discontinued due to the appearance of cutaneous lesions on the body. Corticosteroid pulses and Etanercept injections were also prescribed. Subcutaneous nodules increased gradually and she was admitted 4 times due to respiratory distress. Finally she died from respiratory failure in one episode at 4 years old.', '3 rd case': 'This patient was a 9-month old boy, the first child of related parents who was delivered by NVD without any insult. Rheumatoid arthritis history was positive for patient’s father. The patient was presented to the clinic at 9 months of age with one month history of left wrist swelling and tenderness. Within one week prior to the presentation, swelling had extended to the dorsal surfaces of the hands. Patient had been misdiagnosed with JIA and treatment with Prednisolone, MTX and ibuprofen was started. Hoarseness had developed 6 months earlier. Weight loss was also reported. On examination, lower limbs were normal but in upper limbs, limitations in flexion and extension of wrist and swelling of fingers were noted. Patient was presented to the clinic again at 18 months of age with delayed motor development, multiple subcutaneous nodules in wrists and ankles, respiratory distress and hoarseness ( Figure 2 ). In bronchoscopy, large cysts on vocal cords were seen. On radiography, osteopenia was evident (bone age equal to 9 months at the age of 18 months). CXR visualized bilateral perihilar opacities and hyperinflation in both lungs. In kidney, contrast opacity resembling kidney stone was seen. HPLC was normal. Laryngeal nodules led to severe respiratory distress which his life ended after ICU admission and tracheostomy insertion.'}
|
{'1 st case': 'This patient was a 4-year old girl, second child of related parents, delivered by cesarean section without any insult. This child developed wrist swelling at 6 months of age. Swelling of other joints were gradually added. On examination, swelling and limitation in range of motion was detected in PIP, MCP, wrist, elbow and shoulder joints of upper limbs and PIP, MTP, tarsal joints and ankle in lower limbs. Multiple firm subcutaneous nodules were found on joints –mainly on extensor surfaces- which led to deformation of joint, tenderness and inability to walk. Contracture in joints was evident in physical examination. Progressive hoarseness was present. Reports of head drop attacks were found in the history. In neurologic examination, deep tendon reflexes were diminished or absent. Although cognitive function of this patient was normal, motor and speech development was delayed. Two years later, development of seizure and tremor was reported. Tremor was evident in all limbs on physical examination. Laboratory serologic tests were normal. Radiography of both hands showed reduction in density of bones, swelling of both wrists, deformity of wrist bones, marginal erosion of wrist bones and distal phalanges in PIP and DIP joints which all were suggestive of advanced juvenile idiopathic arthritis (JIA). Chest X-ray also showed alveolar opacities with air bronchogram in the upper lobe of right lung which were in favor of pneumonia. Bronchoscopy showed a circular contraction in subglottic region of larynx. After development of neurologic involvements, Farber disease was suspected. To confirm the diagnostic suspicion, genetic analysis was performed. ASAH1 gene analysis –gene related to Farber syndrome- revealed a homozygous variant which confirmed the presence of Farber disease in this patient. This variant was a novel mutation in exon 8 of ASAH1 gene (c.553T>C p.Trp185Arg). Patient had not received treatment till the age of 2.5 years. After she was diagnosed with JIA, methotrexate, hydroxychloroquine, prednisolone and infliximab medications were initiated. After genetic testing and establishment of the diagnosis of Farber disease, patient’s treatment was switched to cyclosporine and prednisolone. With the development of neurologic involvements, Topiramate, valproate sodium and clobazam was prescribed for relieving debilitating neurologic symptoms. Bone marrow transplantation was suggested as a treatment strategy for the patient but the suggestion was declined by the family. She has under follow up after 2.5 years with neurological deficit.', '2 nd case': 'This patient was a 4 year-old girl, first child of a non-related couple, delivered by NVD who was term on birth. The patient developed swelling of joints at 7 months of age. Particularly in PIP and MCP joints, wrists and ankles ( Figure 1a ). On examination at the age of 2 years, she had multiple subcutaneous nodules on head, hands and chest ( Figure 1b ). Progressive hoarseness was also present. Extensive mucosal lesions were detected in the oral cavity. Limitation in knee’s range of motion was severe leading to difficulty in walking. Cutaneous lesions were also seen on abdomen. In the follow-up after two years, patient had developed nasal swelling. On examination, three relatively soft masses were found within lumbar to coccygeal regions of the spine with diameters of up to 5 centimeters ( Figure 1c ). Muscular atrophy of all four limbs and gluteal region was evident. In the auscultation of the lungs, wheezing was detected. Joints’ examination showed nodules and range of motion limitation in both elbows, shoulders, MCPs, PIPs and DIPs in upper limbs. In lower limbs, knees and ankles were affected with contracture, nodules and range of motion limitation. In radiography, bilateral destruction of proximal humerus and severe osteopenia were seen. After a while, progression of hoarseness and development of multiple percutaneous nodules put the diagnosis of JIA under question. Biopsies were taken from nodules to rule out Farber disease. Histopathologic examination reported collection of collagen bundles and foamy macrophages which were suggestive of Farber disease. With the early diagnosis of JIA, the patient underwent treatment with folic acid, prednisolone, cyclosporine, ibuprofen, calcium supplement and nystatin. MTX was initiated for the patient but then was discontinued due to the appearance of cutaneous lesions on the body. Corticosteroid pulses and Etanercept injections were also prescribed. Subcutaneous nodules increased gradually and she was admitted 4 times due to respiratory distress. Finally she died from respiratory failure in one episode at 4 years old.', '3 rd case': 'This patient was a 9-month old boy, the first child of related parents who was delivered by NVD without any insult. Rheumatoid arthritis history was positive for patient’s father. The patient was presented to the clinic at 9 months of age with one month history of left wrist swelling and tenderness. Within one week prior to the presentation, swelling had extended to the dorsal surfaces of the hands. Patient had been misdiagnosed with JIA and treatment with Prednisolone, MTX and ibuprofen was started. Hoarseness had developed 6 months earlier. Weight loss was also reported. On examination, lower limbs were normal but in upper limbs, limitations in flexion and extension of wrist and swelling of fingers were noted. Patient was presented to the clinic again at 18 months of age with delayed motor development, multiple subcutaneous nodules in wrists and ankles, respiratory distress and hoarseness ( Figure 2 ). In bronchoscopy, large cysts on vocal cords were seen. On radiography, osteopenia was evident (bone age equal to 9 months at the age of 18 months). CXR visualized bilateral perihilar opacities and hyperinflation in both lungs. In kidney, contrast opacity resembling kidney stone was seen. HPLC was normal. Laryngeal nodules led to severe respiratory distress which his life ended after ICU admission and tracheostomy insertion.'}
|
Neurology
|
Neuro
|
[
"head drop attacks",
"deep tendon reflexes were diminished or absent. Although cognitive function of this patient was normal, motor and speech development was delayed. Two years later, development of seizure and tremor was reported. Tremor was evident in all limbs on physical examination",
"development of neurologic involvements",
"with neurological deficit",
"delayed motor development"
] |
test-1967
|
6944811
|
{'1 st case': 'This patient was a 4-year old girl, second child of related parents, delivered by cesarean section without any insult. This child developed wrist swelling at 6 months of age. Swelling of other joints were gradually added. On examination, swelling and limitation in range of motion was detected in PIP, MCP, wrist, elbow and shoulder joints of upper limbs and PIP, MTP, tarsal joints and ankle in lower limbs. Multiple firm subcutaneous nodules were found on joints –mainly on extensor surfaces- which led to deformation of joint, tenderness and inability to walk. Contracture in joints was evident in physical examination. Progressive hoarseness was present. Reports of head drop attacks were found in the history. In neurologic examination, deep tendon reflexes were diminished or absent. Although cognitive function of this patient was normal, motor and speech development was delayed. Two years later, development of seizure and tremor was reported. Tremor was evident in all limbs on physical examination. Laboratory serologic tests were normal. Radiography of both hands showed reduction in density of bones, swelling of both wrists, deformity of wrist bones, marginal erosion of wrist bones and distal phalanges in PIP and DIP joints which all were suggestive of advanced juvenile idiopathic arthritis (JIA). Chest X-ray also showed alveolar opacities with air bronchogram in the upper lobe of right lung which were in favor of pneumonia. Bronchoscopy showed a circular contraction in subglottic region of larynx. After development of neurologic involvements, Farber disease was suspected. To confirm the diagnostic suspicion, genetic analysis was performed. ASAH1 gene analysis –gene related to Farber syndrome- revealed a homozygous variant which confirmed the presence of Farber disease in this patient. This variant was a novel mutation in exon 8 of ASAH1 gene (c.553T>C p.Trp185Arg). Patient had not received treatment till the age of 2.5 years. After she was diagnosed with JIA, methotrexate, hydroxychloroquine, prednisolone and infliximab medications were initiated. After genetic testing and establishment of the diagnosis of Farber disease, patient’s treatment was switched to cyclosporine and prednisolone. With the development of neurologic involvements, Topiramate, valproate sodium and clobazam was prescribed for relieving debilitating neurologic symptoms. Bone marrow transplantation was suggested as a treatment strategy for the patient but the suggestion was declined by the family. She has under follow up after 2.5 years with neurological deficit.', '2 nd case': 'This patient was a 4 year-old girl, first child of a non-related couple, delivered by NVD who was term on birth. The patient developed swelling of joints at 7 months of age. Particularly in PIP and MCP joints, wrists and ankles ( Figure 1a ). On examination at the age of 2 years, she had multiple subcutaneous nodules on head, hands and chest ( Figure 1b ). Progressive hoarseness was also present. Extensive mucosal lesions were detected in the oral cavity. Limitation in knee’s range of motion was severe leading to difficulty in walking. Cutaneous lesions were also seen on abdomen. In the follow-up after two years, patient had developed nasal swelling. On examination, three relatively soft masses were found within lumbar to coccygeal regions of the spine with diameters of up to 5 centimeters ( Figure 1c ). Muscular atrophy of all four limbs and gluteal region was evident. In the auscultation of the lungs, wheezing was detected. Joints’ examination showed nodules and range of motion limitation in both elbows, shoulders, MCPs, PIPs and DIPs in upper limbs. In lower limbs, knees and ankles were affected with contracture, nodules and range of motion limitation. In radiography, bilateral destruction of proximal humerus and severe osteopenia were seen. After a while, progression of hoarseness and development of multiple percutaneous nodules put the diagnosis of JIA under question. Biopsies were taken from nodules to rule out Farber disease. Histopathologic examination reported collection of collagen bundles and foamy macrophages which were suggestive of Farber disease. With the early diagnosis of JIA, the patient underwent treatment with folic acid, prednisolone, cyclosporine, ibuprofen, calcium supplement and nystatin. MTX was initiated for the patient but then was discontinued due to the appearance of cutaneous lesions on the body. Corticosteroid pulses and Etanercept injections were also prescribed. Subcutaneous nodules increased gradually and she was admitted 4 times due to respiratory distress. Finally she died from respiratory failure in one episode at 4 years old.', '3 rd case': 'This patient was a 9-month old boy, the first child of related parents who was delivered by NVD without any insult. Rheumatoid arthritis history was positive for patient’s father. The patient was presented to the clinic at 9 months of age with one month history of left wrist swelling and tenderness. Within one week prior to the presentation, swelling had extended to the dorsal surfaces of the hands. Patient had been misdiagnosed with JIA and treatment with Prednisolone, MTX and ibuprofen was started. Hoarseness had developed 6 months earlier. Weight loss was also reported. On examination, lower limbs were normal but in upper limbs, limitations in flexion and extension of wrist and swelling of fingers were noted. Patient was presented to the clinic again at 18 months of age with delayed motor development, multiple subcutaneous nodules in wrists and ankles, respiratory distress and hoarseness ( Figure 2 ). In bronchoscopy, large cysts on vocal cords were seen. On radiography, osteopenia was evident (bone age equal to 9 months at the age of 18 months). CXR visualized bilateral perihilar opacities and hyperinflation in both lungs. In kidney, contrast opacity resembling kidney stone was seen. HPLC was normal. Laryngeal nodules led to severe respiratory distress which his life ended after ICU admission and tracheostomy insertion.'}
|
{'1 st case': 'This patient was a 4-year old girl, second child of related parents, delivered by cesarean section without any insult. This child developed wrist swelling at 6 months of age. Swelling of other joints were gradually added. On examination, swelling and limitation in range of motion was detected in PIP, MCP, wrist, elbow and shoulder joints of upper limbs and PIP, MTP, tarsal joints and ankle in lower limbs. Multiple firm subcutaneous nodules were found on joints –mainly on extensor surfaces- which led to deformation of joint, tenderness and inability to walk. Contracture in joints was evident in physical examination. Progressive hoarseness was present. Reports of head drop attacks were found in the history. In neurologic examination, deep tendon reflexes were diminished or absent. Although cognitive function of this patient was normal, motor and speech development was delayed. Two years later, development of seizure and tremor was reported. Tremor was evident in all limbs on physical examination. Laboratory serologic tests were normal. Radiography of both hands showed reduction in density of bones, swelling of both wrists, deformity of wrist bones, marginal erosion of wrist bones and distal phalanges in PIP and DIP joints which all were suggestive of advanced juvenile idiopathic arthritis (JIA). Chest X-ray also showed alveolar opacities with air bronchogram in the upper lobe of right lung which were in favor of pneumonia. Bronchoscopy showed a circular contraction in subglottic region of larynx. After development of neurologic involvements, Farber disease was suspected. To confirm the diagnostic suspicion, genetic analysis was performed. ASAH1 gene analysis –gene related to Farber syndrome- revealed a homozygous variant which confirmed the presence of Farber disease in this patient. This variant was a novel mutation in exon 8 of ASAH1 gene (c.553T>C p.Trp185Arg). Patient had not received treatment till the age of 2.5 years. After she was diagnosed with JIA, methotrexate, hydroxychloroquine, prednisolone and infliximab medications were initiated. After genetic testing and establishment of the diagnosis of Farber disease, patient’s treatment was switched to cyclosporine and prednisolone. With the development of neurologic involvements, Topiramate, valproate sodium and clobazam was prescribed for relieving debilitating neurologic symptoms. Bone marrow transplantation was suggested as a treatment strategy for the patient but the suggestion was declined by the family. She has under follow up after 2.5 years with neurological deficit.', '2 nd case': 'This patient was a 4 year-old girl, first child of a non-related couple, delivered by NVD who was term on birth. The patient developed swelling of joints at 7 months of age. Particularly in PIP and MCP joints, wrists and ankles ( Figure 1a ). On examination at the age of 2 years, she had multiple subcutaneous nodules on head, hands and chest ( Figure 1b ). Progressive hoarseness was also present. Extensive mucosal lesions were detected in the oral cavity. Limitation in knee’s range of motion was severe leading to difficulty in walking. Cutaneous lesions were also seen on abdomen. In the follow-up after two years, patient had developed nasal swelling. On examination, three relatively soft masses were found within lumbar to coccygeal regions of the spine with diameters of up to 5 centimeters ( Figure 1c ). Muscular atrophy of all four limbs and gluteal region was evident. In the auscultation of the lungs, wheezing was detected. Joints’ examination showed nodules and range of motion limitation in both elbows, shoulders, MCPs, PIPs and DIPs in upper limbs. In lower limbs, knees and ankles were affected with contracture, nodules and range of motion limitation. In radiography, bilateral destruction of proximal humerus and severe osteopenia were seen. After a while, progression of hoarseness and development of multiple percutaneous nodules put the diagnosis of JIA under question. Biopsies were taken from nodules to rule out Farber disease. Histopathologic examination reported collection of collagen bundles and foamy macrophages which were suggestive of Farber disease. With the early diagnosis of JIA, the patient underwent treatment with folic acid, prednisolone, cyclosporine, ibuprofen, calcium supplement and nystatin. MTX was initiated for the patient but then was discontinued due to the appearance of cutaneous lesions on the body. Corticosteroid pulses and Etanercept injections were also prescribed. Subcutaneous nodules increased gradually and she was admitted 4 times due to respiratory distress. Finally she died from respiratory failure in one episode at 4 years old.', '3 rd case': 'This patient was a 9-month old boy, the first child of related parents who was delivered by NVD without any insult. Rheumatoid arthritis history was positive for patient’s father. The patient was presented to the clinic at 9 months of age with one month history of left wrist swelling and tenderness. Within one week prior to the presentation, swelling had extended to the dorsal surfaces of the hands. Patient had been misdiagnosed with JIA and treatment with Prednisolone, MTX and ibuprofen was started. Hoarseness had developed 6 months earlier. Weight loss was also reported. On examination, lower limbs were normal but in upper limbs, limitations in flexion and extension of wrist and swelling of fingers were noted. Patient was presented to the clinic again at 18 months of age with delayed motor development, multiple subcutaneous nodules in wrists and ankles, respiratory distress and hoarseness ( Figure 2 ). In bronchoscopy, large cysts on vocal cords were seen. On radiography, osteopenia was evident (bone age equal to 9 months at the age of 18 months). CXR visualized bilateral perihilar opacities and hyperinflation in both lungs. In kidney, contrast opacity resembling kidney stone was seen. HPLC was normal. Laryngeal nodules led to severe respiratory distress which his life ended after ICU admission and tracheostomy insertion.'}
|
Laboratory-and-Imaging
|
Lab_Image
|
[
"Laboratory serologic tests were normal. Radiography of both hands showed reduction in density of bones, swelling of both wrists, deformity of wrist bones, marginal erosion of wrist bones and distal phalanges in PIP and DIP joints which all were suggestive of advanced juvenile idiopathic arthritis ( JIA ). Chest X - ray also showed alveolar opacities with air bronchogram in the upper lobe of right lung which were in favor of pneumonia",
"ASAH1 gene analysis – gene related to Farber syndrome- revealed a homozygous variant which confirmed the presence of Farber disease in this patient. This variant was a novel mutation in exon 8 of ASAH1 gene ( c.553T > C p. Trp185Arg )",
"In radiography, bilateral destruction of proximal humerus and severe osteopenia were seen",
"Histopathologic examination reported collection of collagen bundles and foamy macrophages",
"On radiography, osteopenia was evident ( bone age equal to 9 months at the age of 18 months ). CXR visualized bilateral perihilar opacities and hyperinflation in both lungs. In kidney, contrast opacity resembling kidney stone was seen. HPLC was normal."
] |
test-1968
|
6944811
|
{'1 st case': 'This patient was a 4-year old girl, second child of related parents, delivered by cesarean section without any insult. This child developed wrist swelling at 6 months of age. Swelling of other joints were gradually added. On examination, swelling and limitation in range of motion was detected in PIP, MCP, wrist, elbow and shoulder joints of upper limbs and PIP, MTP, tarsal joints and ankle in lower limbs. Multiple firm subcutaneous nodules were found on joints –mainly on extensor surfaces- which led to deformation of joint, tenderness and inability to walk. Contracture in joints was evident in physical examination. Progressive hoarseness was present. Reports of head drop attacks were found in the history. In neurologic examination, deep tendon reflexes were diminished or absent. Although cognitive function of this patient was normal, motor and speech development was delayed. Two years later, development of seizure and tremor was reported. Tremor was evident in all limbs on physical examination. Laboratory serologic tests were normal. Radiography of both hands showed reduction in density of bones, swelling of both wrists, deformity of wrist bones, marginal erosion of wrist bones and distal phalanges in PIP and DIP joints which all were suggestive of advanced juvenile idiopathic arthritis (JIA). Chest X-ray also showed alveolar opacities with air bronchogram in the upper lobe of right lung which were in favor of pneumonia. Bronchoscopy showed a circular contraction in subglottic region of larynx. After development of neurologic involvements, Farber disease was suspected. To confirm the diagnostic suspicion, genetic analysis was performed. ASAH1 gene analysis –gene related to Farber syndrome- revealed a homozygous variant which confirmed the presence of Farber disease in this patient. This variant was a novel mutation in exon 8 of ASAH1 gene (c.553T>C p.Trp185Arg). Patient had not received treatment till the age of 2.5 years. After she was diagnosed with JIA, methotrexate, hydroxychloroquine, prednisolone and infliximab medications were initiated. After genetic testing and establishment of the diagnosis of Farber disease, patient’s treatment was switched to cyclosporine and prednisolone. With the development of neurologic involvements, Topiramate, valproate sodium and clobazam was prescribed for relieving debilitating neurologic symptoms. Bone marrow transplantation was suggested as a treatment strategy for the patient but the suggestion was declined by the family. She has under follow up after 2.5 years with neurological deficit.', '2 nd case': 'This patient was a 4 year-old girl, first child of a non-related couple, delivered by NVD who was term on birth. The patient developed swelling of joints at 7 months of age. Particularly in PIP and MCP joints, wrists and ankles ( Figure 1a ). On examination at the age of 2 years, she had multiple subcutaneous nodules on head, hands and chest ( Figure 1b ). Progressive hoarseness was also present. Extensive mucosal lesions were detected in the oral cavity. Limitation in knee’s range of motion was severe leading to difficulty in walking. Cutaneous lesions were also seen on abdomen. In the follow-up after two years, patient had developed nasal swelling. On examination, three relatively soft masses were found within lumbar to coccygeal regions of the spine with diameters of up to 5 centimeters ( Figure 1c ). Muscular atrophy of all four limbs and gluteal region was evident. In the auscultation of the lungs, wheezing was detected. Joints’ examination showed nodules and range of motion limitation in both elbows, shoulders, MCPs, PIPs and DIPs in upper limbs. In lower limbs, knees and ankles were affected with contracture, nodules and range of motion limitation. In radiography, bilateral destruction of proximal humerus and severe osteopenia were seen. After a while, progression of hoarseness and development of multiple percutaneous nodules put the diagnosis of JIA under question. Biopsies were taken from nodules to rule out Farber disease. Histopathologic examination reported collection of collagen bundles and foamy macrophages which were suggestive of Farber disease. With the early diagnosis of JIA, the patient underwent treatment with folic acid, prednisolone, cyclosporine, ibuprofen, calcium supplement and nystatin. MTX was initiated for the patient but then was discontinued due to the appearance of cutaneous lesions on the body. Corticosteroid pulses and Etanercept injections were also prescribed. Subcutaneous nodules increased gradually and she was admitted 4 times due to respiratory distress. Finally she died from respiratory failure in one episode at 4 years old.', '3 rd case': 'This patient was a 9-month old boy, the first child of related parents who was delivered by NVD without any insult. Rheumatoid arthritis history was positive for patient’s father. The patient was presented to the clinic at 9 months of age with one month history of left wrist swelling and tenderness. Within one week prior to the presentation, swelling had extended to the dorsal surfaces of the hands. Patient had been misdiagnosed with JIA and treatment with Prednisolone, MTX and ibuprofen was started. Hoarseness had developed 6 months earlier. Weight loss was also reported. On examination, lower limbs were normal but in upper limbs, limitations in flexion and extension of wrist and swelling of fingers were noted. Patient was presented to the clinic again at 18 months of age with delayed motor development, multiple subcutaneous nodules in wrists and ankles, respiratory distress and hoarseness ( Figure 2 ). In bronchoscopy, large cysts on vocal cords were seen. On radiography, osteopenia was evident (bone age equal to 9 months at the age of 18 months). CXR visualized bilateral perihilar opacities and hyperinflation in both lungs. In kidney, contrast opacity resembling kidney stone was seen. HPLC was normal. Laryngeal nodules led to severe respiratory distress which his life ended after ICU admission and tracheostomy insertion.'}
|
{'1 st case': 'This patient was a 4-year old girl, second child of related parents, delivered by cesarean section without any insult. This child developed wrist swelling at 6 months of age. Swelling of other joints were gradually added. On examination, swelling and limitation in range of motion was detected in PIP, MCP, wrist, elbow and shoulder joints of upper limbs and PIP, MTP, tarsal joints and ankle in lower limbs. Multiple firm subcutaneous nodules were found on joints –mainly on extensor surfaces- which led to deformation of joint, tenderness and inability to walk. Contracture in joints was evident in physical examination. Progressive hoarseness was present. Reports of head drop attacks were found in the history. In neurologic examination, deep tendon reflexes were diminished or absent. Although cognitive function of this patient was normal, motor and speech development was delayed. Two years later, development of seizure and tremor was reported. Tremor was evident in all limbs on physical examination. Laboratory serologic tests were normal. Radiography of both hands showed reduction in density of bones, swelling of both wrists, deformity of wrist bones, marginal erosion of wrist bones and distal phalanges in PIP and DIP joints which all were suggestive of advanced juvenile idiopathic arthritis (JIA). Chest X-ray also showed alveolar opacities with air bronchogram in the upper lobe of right lung which were in favor of pneumonia. Bronchoscopy showed a circular contraction in subglottic region of larynx. After development of neurologic involvements, Farber disease was suspected. To confirm the diagnostic suspicion, genetic analysis was performed. ASAH1 gene analysis –gene related to Farber syndrome- revealed a homozygous variant which confirmed the presence of Farber disease in this patient. This variant was a novel mutation in exon 8 of ASAH1 gene (c.553T>C p.Trp185Arg). Patient had not received treatment till the age of 2.5 years. After she was diagnosed with JIA, methotrexate, hydroxychloroquine, prednisolone and infliximab medications were initiated. After genetic testing and establishment of the diagnosis of Farber disease, patient’s treatment was switched to cyclosporine and prednisolone. With the development of neurologic involvements, Topiramate, valproate sodium and clobazam was prescribed for relieving debilitating neurologic symptoms. Bone marrow transplantation was suggested as a treatment strategy for the patient but the suggestion was declined by the family. She has under follow up after 2.5 years with neurological deficit.', '2 nd case': 'This patient was a 4 year-old girl, first child of a non-related couple, delivered by NVD who was term on birth. The patient developed swelling of joints at 7 months of age. Particularly in PIP and MCP joints, wrists and ankles ( Figure 1a ). On examination at the age of 2 years, she had multiple subcutaneous nodules on head, hands and chest ( Figure 1b ). Progressive hoarseness was also present. Extensive mucosal lesions were detected in the oral cavity. Limitation in knee’s range of motion was severe leading to difficulty in walking. Cutaneous lesions were also seen on abdomen. In the follow-up after two years, patient had developed nasal swelling. On examination, three relatively soft masses were found within lumbar to coccygeal regions of the spine with diameters of up to 5 centimeters ( Figure 1c ). Muscular atrophy of all four limbs and gluteal region was evident. In the auscultation of the lungs, wheezing was detected. Joints’ examination showed nodules and range of motion limitation in both elbows, shoulders, MCPs, PIPs and DIPs in upper limbs. In lower limbs, knees and ankles were affected with contracture, nodules and range of motion limitation. In radiography, bilateral destruction of proximal humerus and severe osteopenia were seen. After a while, progression of hoarseness and development of multiple percutaneous nodules put the diagnosis of JIA under question. Biopsies were taken from nodules to rule out Farber disease. Histopathologic examination reported collection of collagen bundles and foamy macrophages which were suggestive of Farber disease. With the early diagnosis of JIA, the patient underwent treatment with folic acid, prednisolone, cyclosporine, ibuprofen, calcium supplement and nystatin. MTX was initiated for the patient but then was discontinued due to the appearance of cutaneous lesions on the body. Corticosteroid pulses and Etanercept injections were also prescribed. Subcutaneous nodules increased gradually and she was admitted 4 times due to respiratory distress. Finally she died from respiratory failure in one episode at 4 years old.', '3 rd case': 'This patient was a 9-month old boy, the first child of related parents who was delivered by NVD without any insult. Rheumatoid arthritis history was positive for patient’s father. The patient was presented to the clinic at 9 months of age with one month history of left wrist swelling and tenderness. Within one week prior to the presentation, swelling had extended to the dorsal surfaces of the hands. Patient had been misdiagnosed with JIA and treatment with Prednisolone, MTX and ibuprofen was started. Hoarseness had developed 6 months earlier. Weight loss was also reported. On examination, lower limbs were normal but in upper limbs, limitations in flexion and extension of wrist and swelling of fingers were noted. Patient was presented to the clinic again at 18 months of age with delayed motor development, multiple subcutaneous nodules in wrists and ankles, respiratory distress and hoarseness ( Figure 2 ). In bronchoscopy, large cysts on vocal cords were seen. On radiography, osteopenia was evident (bone age equal to 9 months at the age of 18 months). CXR visualized bilateral perihilar opacities and hyperinflation in both lungs. In kidney, contrast opacity resembling kidney stone was seen. HPLC was normal. Laryngeal nodules led to severe respiratory distress which his life ended after ICU admission and tracheostomy insertion.'}
|
Cardiovascular-System
|
CVS
|
[] |
test-1969
|
6944811
|
{'1 st case': 'This patient was a 4-year old girl, second child of related parents, delivered by cesarean section without any insult. This child developed wrist swelling at 6 months of age. Swelling of other joints were gradually added. On examination, swelling and limitation in range of motion was detected in PIP, MCP, wrist, elbow and shoulder joints of upper limbs and PIP, MTP, tarsal joints and ankle in lower limbs. Multiple firm subcutaneous nodules were found on joints –mainly on extensor surfaces- which led to deformation of joint, tenderness and inability to walk. Contracture in joints was evident in physical examination. Progressive hoarseness was present. Reports of head drop attacks were found in the history. In neurologic examination, deep tendon reflexes were diminished or absent. Although cognitive function of this patient was normal, motor and speech development was delayed. Two years later, development of seizure and tremor was reported. Tremor was evident in all limbs on physical examination. Laboratory serologic tests were normal. Radiography of both hands showed reduction in density of bones, swelling of both wrists, deformity of wrist bones, marginal erosion of wrist bones and distal phalanges in PIP and DIP joints which all were suggestive of advanced juvenile idiopathic arthritis (JIA). Chest X-ray also showed alveolar opacities with air bronchogram in the upper lobe of right lung which were in favor of pneumonia. Bronchoscopy showed a circular contraction in subglottic region of larynx. After development of neurologic involvements, Farber disease was suspected. To confirm the diagnostic suspicion, genetic analysis was performed. ASAH1 gene analysis –gene related to Farber syndrome- revealed a homozygous variant which confirmed the presence of Farber disease in this patient. This variant was a novel mutation in exon 8 of ASAH1 gene (c.553T>C p.Trp185Arg). Patient had not received treatment till the age of 2.5 years. After she was diagnosed with JIA, methotrexate, hydroxychloroquine, prednisolone and infliximab medications were initiated. After genetic testing and establishment of the diagnosis of Farber disease, patient’s treatment was switched to cyclosporine and prednisolone. With the development of neurologic involvements, Topiramate, valproate sodium and clobazam was prescribed for relieving debilitating neurologic symptoms. Bone marrow transplantation was suggested as a treatment strategy for the patient but the suggestion was declined by the family. She has under follow up after 2.5 years with neurological deficit.', '2 nd case': 'This patient was a 4 year-old girl, first child of a non-related couple, delivered by NVD who was term on birth. The patient developed swelling of joints at 7 months of age. Particularly in PIP and MCP joints, wrists and ankles ( Figure 1a ). On examination at the age of 2 years, she had multiple subcutaneous nodules on head, hands and chest ( Figure 1b ). Progressive hoarseness was also present. Extensive mucosal lesions were detected in the oral cavity. Limitation in knee’s range of motion was severe leading to difficulty in walking. Cutaneous lesions were also seen on abdomen. In the follow-up after two years, patient had developed nasal swelling. On examination, three relatively soft masses were found within lumbar to coccygeal regions of the spine with diameters of up to 5 centimeters ( Figure 1c ). Muscular atrophy of all four limbs and gluteal region was evident. In the auscultation of the lungs, wheezing was detected. Joints’ examination showed nodules and range of motion limitation in both elbows, shoulders, MCPs, PIPs and DIPs in upper limbs. In lower limbs, knees and ankles were affected with contracture, nodules and range of motion limitation. In radiography, bilateral destruction of proximal humerus and severe osteopenia were seen. After a while, progression of hoarseness and development of multiple percutaneous nodules put the diagnosis of JIA under question. Biopsies were taken from nodules to rule out Farber disease. Histopathologic examination reported collection of collagen bundles and foamy macrophages which were suggestive of Farber disease. With the early diagnosis of JIA, the patient underwent treatment with folic acid, prednisolone, cyclosporine, ibuprofen, calcium supplement and nystatin. MTX was initiated for the patient but then was discontinued due to the appearance of cutaneous lesions on the body. Corticosteroid pulses and Etanercept injections were also prescribed. Subcutaneous nodules increased gradually and she was admitted 4 times due to respiratory distress. Finally she died from respiratory failure in one episode at 4 years old.', '3 rd case': 'This patient was a 9-month old boy, the first child of related parents who was delivered by NVD without any insult. Rheumatoid arthritis history was positive for patient’s father. The patient was presented to the clinic at 9 months of age with one month history of left wrist swelling and tenderness. Within one week prior to the presentation, swelling had extended to the dorsal surfaces of the hands. Patient had been misdiagnosed with JIA and treatment with Prednisolone, MTX and ibuprofen was started. Hoarseness had developed 6 months earlier. Weight loss was also reported. On examination, lower limbs were normal but in upper limbs, limitations in flexion and extension of wrist and swelling of fingers were noted. Patient was presented to the clinic again at 18 months of age with delayed motor development, multiple subcutaneous nodules in wrists and ankles, respiratory distress and hoarseness ( Figure 2 ). In bronchoscopy, large cysts on vocal cords were seen. On radiography, osteopenia was evident (bone age equal to 9 months at the age of 18 months). CXR visualized bilateral perihilar opacities and hyperinflation in both lungs. In kidney, contrast opacity resembling kidney stone was seen. HPLC was normal. Laryngeal nodules led to severe respiratory distress which his life ended after ICU admission and tracheostomy insertion.'}
|
{'1 st case': 'This patient was a 4-year old girl, second child of related parents, delivered by cesarean section without any insult. This child developed wrist swelling at 6 months of age. Swelling of other joints were gradually added. On examination, swelling and limitation in range of motion was detected in PIP, MCP, wrist, elbow and shoulder joints of upper limbs and PIP, MTP, tarsal joints and ankle in lower limbs. Multiple firm subcutaneous nodules were found on joints –mainly on extensor surfaces- which led to deformation of joint, tenderness and inability to walk. Contracture in joints was evident in physical examination. Progressive hoarseness was present. Reports of head drop attacks were found in the history. In neurologic examination, deep tendon reflexes were diminished or absent. Although cognitive function of this patient was normal, motor and speech development was delayed. Two years later, development of seizure and tremor was reported. Tremor was evident in all limbs on physical examination. Laboratory serologic tests were normal. Radiography of both hands showed reduction in density of bones, swelling of both wrists, deformity of wrist bones, marginal erosion of wrist bones and distal phalanges in PIP and DIP joints which all were suggestive of advanced juvenile idiopathic arthritis (JIA). Chest X-ray also showed alveolar opacities with air bronchogram in the upper lobe of right lung which were in favor of pneumonia. Bronchoscopy showed a circular contraction in subglottic region of larynx. After development of neurologic involvements, Farber disease was suspected. To confirm the diagnostic suspicion, genetic analysis was performed. ASAH1 gene analysis –gene related to Farber syndrome- revealed a homozygous variant which confirmed the presence of Farber disease in this patient. This variant was a novel mutation in exon 8 of ASAH1 gene (c.553T>C p.Trp185Arg). Patient had not received treatment till the age of 2.5 years. After she was diagnosed with JIA, methotrexate, hydroxychloroquine, prednisolone and infliximab medications were initiated. After genetic testing and establishment of the diagnosis of Farber disease, patient’s treatment was switched to cyclosporine and prednisolone. With the development of neurologic involvements, Topiramate, valproate sodium and clobazam was prescribed for relieving debilitating neurologic symptoms. Bone marrow transplantation was suggested as a treatment strategy for the patient but the suggestion was declined by the family. She has under follow up after 2.5 years with neurological deficit.', '2 nd case': 'This patient was a 4 year-old girl, first child of a non-related couple, delivered by NVD who was term on birth. The patient developed swelling of joints at 7 months of age. Particularly in PIP and MCP joints, wrists and ankles ( Figure 1a ). On examination at the age of 2 years, she had multiple subcutaneous nodules on head, hands and chest ( Figure 1b ). Progressive hoarseness was also present. Extensive mucosal lesions were detected in the oral cavity. Limitation in knee’s range of motion was severe leading to difficulty in walking. Cutaneous lesions were also seen on abdomen. In the follow-up after two years, patient had developed nasal swelling. On examination, three relatively soft masses were found within lumbar to coccygeal regions of the spine with diameters of up to 5 centimeters ( Figure 1c ). Muscular atrophy of all four limbs and gluteal region was evident. In the auscultation of the lungs, wheezing was detected. Joints’ examination showed nodules and range of motion limitation in both elbows, shoulders, MCPs, PIPs and DIPs in upper limbs. In lower limbs, knees and ankles were affected with contracture, nodules and range of motion limitation. In radiography, bilateral destruction of proximal humerus and severe osteopenia were seen. After a while, progression of hoarseness and development of multiple percutaneous nodules put the diagnosis of JIA under question. Biopsies were taken from nodules to rule out Farber disease. Histopathologic examination reported collection of collagen bundles and foamy macrophages which were suggestive of Farber disease. With the early diagnosis of JIA, the patient underwent treatment with folic acid, prednisolone, cyclosporine, ibuprofen, calcium supplement and nystatin. MTX was initiated for the patient but then was discontinued due to the appearance of cutaneous lesions on the body. Corticosteroid pulses and Etanercept injections were also prescribed. Subcutaneous nodules increased gradually and she was admitted 4 times due to respiratory distress. Finally she died from respiratory failure in one episode at 4 years old.', '3 rd case': 'This patient was a 9-month old boy, the first child of related parents who was delivered by NVD without any insult. Rheumatoid arthritis history was positive for patient’s father. The patient was presented to the clinic at 9 months of age with one month history of left wrist swelling and tenderness. Within one week prior to the presentation, swelling had extended to the dorsal surfaces of the hands. Patient had been misdiagnosed with JIA and treatment with Prednisolone, MTX and ibuprofen was started. Hoarseness had developed 6 months earlier. Weight loss was also reported. On examination, lower limbs were normal but in upper limbs, limitations in flexion and extension of wrist and swelling of fingers were noted. Patient was presented to the clinic again at 18 months of age with delayed motor development, multiple subcutaneous nodules in wrists and ankles, respiratory distress and hoarseness ( Figure 2 ). In bronchoscopy, large cysts on vocal cords were seen. On radiography, osteopenia was evident (bone age equal to 9 months at the age of 18 months). CXR visualized bilateral perihilar opacities and hyperinflation in both lungs. In kidney, contrast opacity resembling kidney stone was seen. HPLC was normal. Laryngeal nodules led to severe respiratory distress which his life ended after ICU admission and tracheostomy insertion.'}
|
Endocrinology
|
ENDO
|
[] |
test-1970
|
6944811
|
{'1 st case': 'This patient was a 4-year old girl, second child of related parents, delivered by cesarean section without any insult. This child developed wrist swelling at 6 months of age. Swelling of other joints were gradually added. On examination, swelling and limitation in range of motion was detected in PIP, MCP, wrist, elbow and shoulder joints of upper limbs and PIP, MTP, tarsal joints and ankle in lower limbs. Multiple firm subcutaneous nodules were found on joints –mainly on extensor surfaces- which led to deformation of joint, tenderness and inability to walk. Contracture in joints was evident in physical examination. Progressive hoarseness was present. Reports of head drop attacks were found in the history. In neurologic examination, deep tendon reflexes were diminished or absent. Although cognitive function of this patient was normal, motor and speech development was delayed. Two years later, development of seizure and tremor was reported. Tremor was evident in all limbs on physical examination. Laboratory serologic tests were normal. Radiography of both hands showed reduction in density of bones, swelling of both wrists, deformity of wrist bones, marginal erosion of wrist bones and distal phalanges in PIP and DIP joints which all were suggestive of advanced juvenile idiopathic arthritis (JIA). Chest X-ray also showed alveolar opacities with air bronchogram in the upper lobe of right lung which were in favor of pneumonia. Bronchoscopy showed a circular contraction in subglottic region of larynx. After development of neurologic involvements, Farber disease was suspected. To confirm the diagnostic suspicion, genetic analysis was performed. ASAH1 gene analysis –gene related to Farber syndrome- revealed a homozygous variant which confirmed the presence of Farber disease in this patient. This variant was a novel mutation in exon 8 of ASAH1 gene (c.553T>C p.Trp185Arg). Patient had not received treatment till the age of 2.5 years. After she was diagnosed with JIA, methotrexate, hydroxychloroquine, prednisolone and infliximab medications were initiated. After genetic testing and establishment of the diagnosis of Farber disease, patient’s treatment was switched to cyclosporine and prednisolone. With the development of neurologic involvements, Topiramate, valproate sodium and clobazam was prescribed for relieving debilitating neurologic symptoms. Bone marrow transplantation was suggested as a treatment strategy for the patient but the suggestion was declined by the family. She has under follow up after 2.5 years with neurological deficit.', '2 nd case': 'This patient was a 4 year-old girl, first child of a non-related couple, delivered by NVD who was term on birth. The patient developed swelling of joints at 7 months of age. Particularly in PIP and MCP joints, wrists and ankles ( Figure 1a ). On examination at the age of 2 years, she had multiple subcutaneous nodules on head, hands and chest ( Figure 1b ). Progressive hoarseness was also present. Extensive mucosal lesions were detected in the oral cavity. Limitation in knee’s range of motion was severe leading to difficulty in walking. Cutaneous lesions were also seen on abdomen. In the follow-up after two years, patient had developed nasal swelling. On examination, three relatively soft masses were found within lumbar to coccygeal regions of the spine with diameters of up to 5 centimeters ( Figure 1c ). Muscular atrophy of all four limbs and gluteal region was evident. In the auscultation of the lungs, wheezing was detected. Joints’ examination showed nodules and range of motion limitation in both elbows, shoulders, MCPs, PIPs and DIPs in upper limbs. In lower limbs, knees and ankles were affected with contracture, nodules and range of motion limitation. In radiography, bilateral destruction of proximal humerus and severe osteopenia were seen. After a while, progression of hoarseness and development of multiple percutaneous nodules put the diagnosis of JIA under question. Biopsies were taken from nodules to rule out Farber disease. Histopathologic examination reported collection of collagen bundles and foamy macrophages which were suggestive of Farber disease. With the early diagnosis of JIA, the patient underwent treatment with folic acid, prednisolone, cyclosporine, ibuprofen, calcium supplement and nystatin. MTX was initiated for the patient but then was discontinued due to the appearance of cutaneous lesions on the body. Corticosteroid pulses and Etanercept injections were also prescribed. Subcutaneous nodules increased gradually and she was admitted 4 times due to respiratory distress. Finally she died from respiratory failure in one episode at 4 years old.', '3 rd case': 'This patient was a 9-month old boy, the first child of related parents who was delivered by NVD without any insult. Rheumatoid arthritis history was positive for patient’s father. The patient was presented to the clinic at 9 months of age with one month history of left wrist swelling and tenderness. Within one week prior to the presentation, swelling had extended to the dorsal surfaces of the hands. Patient had been misdiagnosed with JIA and treatment with Prednisolone, MTX and ibuprofen was started. Hoarseness had developed 6 months earlier. Weight loss was also reported. On examination, lower limbs were normal but in upper limbs, limitations in flexion and extension of wrist and swelling of fingers were noted. Patient was presented to the clinic again at 18 months of age with delayed motor development, multiple subcutaneous nodules in wrists and ankles, respiratory distress and hoarseness ( Figure 2 ). In bronchoscopy, large cysts on vocal cords were seen. On radiography, osteopenia was evident (bone age equal to 9 months at the age of 18 months). CXR visualized bilateral perihilar opacities and hyperinflation in both lungs. In kidney, contrast opacity resembling kidney stone was seen. HPLC was normal. Laryngeal nodules led to severe respiratory distress which his life ended after ICU admission and tracheostomy insertion.'}
|
{'1 st case': 'This patient was a 4-year old girl, second child of related parents, delivered by cesarean section without any insult. This child developed wrist swelling at 6 months of age. Swelling of other joints were gradually added. On examination, swelling and limitation in range of motion was detected in PIP, MCP, wrist, elbow and shoulder joints of upper limbs and PIP, MTP, tarsal joints and ankle in lower limbs. Multiple firm subcutaneous nodules were found on joints –mainly on extensor surfaces- which led to deformation of joint, tenderness and inability to walk. Contracture in joints was evident in physical examination. Progressive hoarseness was present. Reports of head drop attacks were found in the history. In neurologic examination, deep tendon reflexes were diminished or absent. Although cognitive function of this patient was normal, motor and speech development was delayed. Two years later, development of seizure and tremor was reported. Tremor was evident in all limbs on physical examination. Laboratory serologic tests were normal. Radiography of both hands showed reduction in density of bones, swelling of both wrists, deformity of wrist bones, marginal erosion of wrist bones and distal phalanges in PIP and DIP joints which all were suggestive of advanced juvenile idiopathic arthritis (JIA). Chest X-ray also showed alveolar opacities with air bronchogram in the upper lobe of right lung which were in favor of pneumonia. Bronchoscopy showed a circular contraction in subglottic region of larynx. After development of neurologic involvements, Farber disease was suspected. To confirm the diagnostic suspicion, genetic analysis was performed. ASAH1 gene analysis –gene related to Farber syndrome- revealed a homozygous variant which confirmed the presence of Farber disease in this patient. This variant was a novel mutation in exon 8 of ASAH1 gene (c.553T>C p.Trp185Arg). Patient had not received treatment till the age of 2.5 years. After she was diagnosed with JIA, methotrexate, hydroxychloroquine, prednisolone and infliximab medications were initiated. After genetic testing and establishment of the diagnosis of Farber disease, patient’s treatment was switched to cyclosporine and prednisolone. With the development of neurologic involvements, Topiramate, valproate sodium and clobazam was prescribed for relieving debilitating neurologic symptoms. Bone marrow transplantation was suggested as a treatment strategy for the patient but the suggestion was declined by the family. She has under follow up after 2.5 years with neurological deficit.', '2 nd case': 'This patient was a 4 year-old girl, first child of a non-related couple, delivered by NVD who was term on birth. The patient developed swelling of joints at 7 months of age. Particularly in PIP and MCP joints, wrists and ankles ( Figure 1a ). On examination at the age of 2 years, she had multiple subcutaneous nodules on head, hands and chest ( Figure 1b ). Progressive hoarseness was also present. Extensive mucosal lesions were detected in the oral cavity. Limitation in knee’s range of motion was severe leading to difficulty in walking. Cutaneous lesions were also seen on abdomen. In the follow-up after two years, patient had developed nasal swelling. On examination, three relatively soft masses were found within lumbar to coccygeal regions of the spine with diameters of up to 5 centimeters ( Figure 1c ). Muscular atrophy of all four limbs and gluteal region was evident. In the auscultation of the lungs, wheezing was detected. Joints’ examination showed nodules and range of motion limitation in both elbows, shoulders, MCPs, PIPs and DIPs in upper limbs. In lower limbs, knees and ankles were affected with contracture, nodules and range of motion limitation. In radiography, bilateral destruction of proximal humerus and severe osteopenia were seen. After a while, progression of hoarseness and development of multiple percutaneous nodules put the diagnosis of JIA under question. Biopsies were taken from nodules to rule out Farber disease. Histopathologic examination reported collection of collagen bundles and foamy macrophages which were suggestive of Farber disease. With the early diagnosis of JIA, the patient underwent treatment with folic acid, prednisolone, cyclosporine, ibuprofen, calcium supplement and nystatin. MTX was initiated for the patient but then was discontinued due to the appearance of cutaneous lesions on the body. Corticosteroid pulses and Etanercept injections were also prescribed. Subcutaneous nodules increased gradually and she was admitted 4 times due to respiratory distress. Finally she died from respiratory failure in one episode at 4 years old.', '3 rd case': 'This patient was a 9-month old boy, the first child of related parents who was delivered by NVD without any insult. Rheumatoid arthritis history was positive for patient’s father. The patient was presented to the clinic at 9 months of age with one month history of left wrist swelling and tenderness. Within one week prior to the presentation, swelling had extended to the dorsal surfaces of the hands. Patient had been misdiagnosed with JIA and treatment with Prednisolone, MTX and ibuprofen was started. Hoarseness had developed 6 months earlier. Weight loss was also reported. On examination, lower limbs were normal but in upper limbs, limitations in flexion and extension of wrist and swelling of fingers were noted. Patient was presented to the clinic again at 18 months of age with delayed motor development, multiple subcutaneous nodules in wrists and ankles, respiratory distress and hoarseness ( Figure 2 ). In bronchoscopy, large cysts on vocal cords were seen. On radiography, osteopenia was evident (bone age equal to 9 months at the age of 18 months). CXR visualized bilateral perihilar opacities and hyperinflation in both lungs. In kidney, contrast opacity resembling kidney stone was seen. HPLC was normal. Laryngeal nodules led to severe respiratory distress which his life ended after ICU admission and tracheostomy insertion.'}
|
Genitourinary-System
|
GU
|
[] |
test-1971
|
6944811
|
{'1 st case': 'This patient was a 4-year old girl, second child of related parents, delivered by cesarean section without any insult. This child developed wrist swelling at 6 months of age. Swelling of other joints were gradually added. On examination, swelling and limitation in range of motion was detected in PIP, MCP, wrist, elbow and shoulder joints of upper limbs and PIP, MTP, tarsal joints and ankle in lower limbs. Multiple firm subcutaneous nodules were found on joints –mainly on extensor surfaces- which led to deformation of joint, tenderness and inability to walk. Contracture in joints was evident in physical examination. Progressive hoarseness was present. Reports of head drop attacks were found in the history. In neurologic examination, deep tendon reflexes were diminished or absent. Although cognitive function of this patient was normal, motor and speech development was delayed. Two years later, development of seizure and tremor was reported. Tremor was evident in all limbs on physical examination. Laboratory serologic tests were normal. Radiography of both hands showed reduction in density of bones, swelling of both wrists, deformity of wrist bones, marginal erosion of wrist bones and distal phalanges in PIP and DIP joints which all were suggestive of advanced juvenile idiopathic arthritis (JIA). Chest X-ray also showed alveolar opacities with air bronchogram in the upper lobe of right lung which were in favor of pneumonia. Bronchoscopy showed a circular contraction in subglottic region of larynx. After development of neurologic involvements, Farber disease was suspected. To confirm the diagnostic suspicion, genetic analysis was performed. ASAH1 gene analysis –gene related to Farber syndrome- revealed a homozygous variant which confirmed the presence of Farber disease in this patient. This variant was a novel mutation in exon 8 of ASAH1 gene (c.553T>C p.Trp185Arg). Patient had not received treatment till the age of 2.5 years. After she was diagnosed with JIA, methotrexate, hydroxychloroquine, prednisolone and infliximab medications were initiated. After genetic testing and establishment of the diagnosis of Farber disease, patient’s treatment was switched to cyclosporine and prednisolone. With the development of neurologic involvements, Topiramate, valproate sodium and clobazam was prescribed for relieving debilitating neurologic symptoms. Bone marrow transplantation was suggested as a treatment strategy for the patient but the suggestion was declined by the family. She has under follow up after 2.5 years with neurological deficit.', '2 nd case': 'This patient was a 4 year-old girl, first child of a non-related couple, delivered by NVD who was term on birth. The patient developed swelling of joints at 7 months of age. Particularly in PIP and MCP joints, wrists and ankles ( Figure 1a ). On examination at the age of 2 years, she had multiple subcutaneous nodules on head, hands and chest ( Figure 1b ). Progressive hoarseness was also present. Extensive mucosal lesions were detected in the oral cavity. Limitation in knee’s range of motion was severe leading to difficulty in walking. Cutaneous lesions were also seen on abdomen. In the follow-up after two years, patient had developed nasal swelling. On examination, three relatively soft masses were found within lumbar to coccygeal regions of the spine with diameters of up to 5 centimeters ( Figure 1c ). Muscular atrophy of all four limbs and gluteal region was evident. In the auscultation of the lungs, wheezing was detected. Joints’ examination showed nodules and range of motion limitation in both elbows, shoulders, MCPs, PIPs and DIPs in upper limbs. In lower limbs, knees and ankles were affected with contracture, nodules and range of motion limitation. In radiography, bilateral destruction of proximal humerus and severe osteopenia were seen. After a while, progression of hoarseness and development of multiple percutaneous nodules put the diagnosis of JIA under question. Biopsies were taken from nodules to rule out Farber disease. Histopathologic examination reported collection of collagen bundles and foamy macrophages which were suggestive of Farber disease. With the early diagnosis of JIA, the patient underwent treatment with folic acid, prednisolone, cyclosporine, ibuprofen, calcium supplement and nystatin. MTX was initiated for the patient but then was discontinued due to the appearance of cutaneous lesions on the body. Corticosteroid pulses and Etanercept injections were also prescribed. Subcutaneous nodules increased gradually and she was admitted 4 times due to respiratory distress. Finally she died from respiratory failure in one episode at 4 years old.', '3 rd case': 'This patient was a 9-month old boy, the first child of related parents who was delivered by NVD without any insult. Rheumatoid arthritis history was positive for patient’s father. The patient was presented to the clinic at 9 months of age with one month history of left wrist swelling and tenderness. Within one week prior to the presentation, swelling had extended to the dorsal surfaces of the hands. Patient had been misdiagnosed with JIA and treatment with Prednisolone, MTX and ibuprofen was started. Hoarseness had developed 6 months earlier. Weight loss was also reported. On examination, lower limbs were normal but in upper limbs, limitations in flexion and extension of wrist and swelling of fingers were noted. Patient was presented to the clinic again at 18 months of age with delayed motor development, multiple subcutaneous nodules in wrists and ankles, respiratory distress and hoarseness ( Figure 2 ). In bronchoscopy, large cysts on vocal cords were seen. On radiography, osteopenia was evident (bone age equal to 9 months at the age of 18 months). CXR visualized bilateral perihilar opacities and hyperinflation in both lungs. In kidney, contrast opacity resembling kidney stone was seen. HPLC was normal. Laryngeal nodules led to severe respiratory distress which his life ended after ICU admission and tracheostomy insertion.'}
|
{'1 st case': 'This patient was a 4-year old girl, second child of related parents, delivered by cesarean section without any insult. This child developed wrist swelling at 6 months of age. Swelling of other joints were gradually added. On examination, swelling and limitation in range of motion was detected in PIP, MCP, wrist, elbow and shoulder joints of upper limbs and PIP, MTP, tarsal joints and ankle in lower limbs. Multiple firm subcutaneous nodules were found on joints –mainly on extensor surfaces- which led to deformation of joint, tenderness and inability to walk. Contracture in joints was evident in physical examination. Progressive hoarseness was present. Reports of head drop attacks were found in the history. In neurologic examination, deep tendon reflexes were diminished or absent. Although cognitive function of this patient was normal, motor and speech development was delayed. Two years later, development of seizure and tremor was reported. Tremor was evident in all limbs on physical examination. Laboratory serologic tests were normal. Radiography of both hands showed reduction in density of bones, swelling of both wrists, deformity of wrist bones, marginal erosion of wrist bones and distal phalanges in PIP and DIP joints which all were suggestive of advanced juvenile idiopathic arthritis (JIA). Chest X-ray also showed alveolar opacities with air bronchogram in the upper lobe of right lung which were in favor of pneumonia. Bronchoscopy showed a circular contraction in subglottic region of larynx. After development of neurologic involvements, Farber disease was suspected. To confirm the diagnostic suspicion, genetic analysis was performed. ASAH1 gene analysis –gene related to Farber syndrome- revealed a homozygous variant which confirmed the presence of Farber disease in this patient. This variant was a novel mutation in exon 8 of ASAH1 gene (c.553T>C p.Trp185Arg). Patient had not received treatment till the age of 2.5 years. After she was diagnosed with JIA, methotrexate, hydroxychloroquine, prednisolone and infliximab medications were initiated. After genetic testing and establishment of the diagnosis of Farber disease, patient’s treatment was switched to cyclosporine and prednisolone. With the development of neurologic involvements, Topiramate, valproate sodium and clobazam was prescribed for relieving debilitating neurologic symptoms. Bone marrow transplantation was suggested as a treatment strategy for the patient but the suggestion was declined by the family. She has under follow up after 2.5 years with neurological deficit.', '2 nd case': 'This patient was a 4 year-old girl, first child of a non-related couple, delivered by NVD who was term on birth. The patient developed swelling of joints at 7 months of age. Particularly in PIP and MCP joints, wrists and ankles ( Figure 1a ). On examination at the age of 2 years, she had multiple subcutaneous nodules on head, hands and chest ( Figure 1b ). Progressive hoarseness was also present. Extensive mucosal lesions were detected in the oral cavity. Limitation in knee’s range of motion was severe leading to difficulty in walking. Cutaneous lesions were also seen on abdomen. In the follow-up after two years, patient had developed nasal swelling. On examination, three relatively soft masses were found within lumbar to coccygeal regions of the spine with diameters of up to 5 centimeters ( Figure 1c ). Muscular atrophy of all four limbs and gluteal region was evident. In the auscultation of the lungs, wheezing was detected. Joints’ examination showed nodules and range of motion limitation in both elbows, shoulders, MCPs, PIPs and DIPs in upper limbs. In lower limbs, knees and ankles were affected with contracture, nodules and range of motion limitation. In radiography, bilateral destruction of proximal humerus and severe osteopenia were seen. After a while, progression of hoarseness and development of multiple percutaneous nodules put the diagnosis of JIA under question. Biopsies were taken from nodules to rule out Farber disease. Histopathologic examination reported collection of collagen bundles and foamy macrophages which were suggestive of Farber disease. With the early diagnosis of JIA, the patient underwent treatment with folic acid, prednisolone, cyclosporine, ibuprofen, calcium supplement and nystatin. MTX was initiated for the patient but then was discontinued due to the appearance of cutaneous lesions on the body. Corticosteroid pulses and Etanercept injections were also prescribed. Subcutaneous nodules increased gradually and she was admitted 4 times due to respiratory distress. Finally she died from respiratory failure in one episode at 4 years old.', '3 rd case': 'This patient was a 9-month old boy, the first child of related parents who was delivered by NVD without any insult. Rheumatoid arthritis history was positive for patient’s father. The patient was presented to the clinic at 9 months of age with one month history of left wrist swelling and tenderness. Within one week prior to the presentation, swelling had extended to the dorsal surfaces of the hands. Patient had been misdiagnosed with JIA and treatment with Prednisolone, MTX and ibuprofen was started. Hoarseness had developed 6 months earlier. Weight loss was also reported. On examination, lower limbs were normal but in upper limbs, limitations in flexion and extension of wrist and swelling of fingers were noted. Patient was presented to the clinic again at 18 months of age with delayed motor development, multiple subcutaneous nodules in wrists and ankles, respiratory distress and hoarseness ( Figure 2 ). In bronchoscopy, large cysts on vocal cords were seen. On radiography, osteopenia was evident (bone age equal to 9 months at the age of 18 months). CXR visualized bilateral perihilar opacities and hyperinflation in both lungs. In kidney, contrast opacity resembling kidney stone was seen. HPLC was normal. Laryngeal nodules led to severe respiratory distress which his life ended after ICU admission and tracheostomy insertion.'}
|
Respiratory-System
|
RESP
|
[
"Chest X - ray also showed alveolar opacities with air bronchogram in the upper lobe of right lung which were in favor of pneumonia",
"Bronchoscopy showed a circular contraction in subglottic region of larynx",
"wheezing",
"admitted 4 times due to respiratory distress. Finally she died from respiratory failure in one episode at 4 years old.",
"respiratory distress",
"bilateral perihilar opacities and hyperinflation in both lungs",
"Laryngeal nodules led to severe respiratory distress which his life ended"
] |
test-1972
|
6944811
|
{'1 st case': 'This patient was a 4-year old girl, second child of related parents, delivered by cesarean section without any insult. This child developed wrist swelling at 6 months of age. Swelling of other joints were gradually added. On examination, swelling and limitation in range of motion was detected in PIP, MCP, wrist, elbow and shoulder joints of upper limbs and PIP, MTP, tarsal joints and ankle in lower limbs. Multiple firm subcutaneous nodules were found on joints –mainly on extensor surfaces- which led to deformation of joint, tenderness and inability to walk. Contracture in joints was evident in physical examination. Progressive hoarseness was present. Reports of head drop attacks were found in the history. In neurologic examination, deep tendon reflexes were diminished or absent. Although cognitive function of this patient was normal, motor and speech development was delayed. Two years later, development of seizure and tremor was reported. Tremor was evident in all limbs on physical examination. Laboratory serologic tests were normal. Radiography of both hands showed reduction in density of bones, swelling of both wrists, deformity of wrist bones, marginal erosion of wrist bones and distal phalanges in PIP and DIP joints which all were suggestive of advanced juvenile idiopathic arthritis (JIA). Chest X-ray also showed alveolar opacities with air bronchogram in the upper lobe of right lung which were in favor of pneumonia. Bronchoscopy showed a circular contraction in subglottic region of larynx. After development of neurologic involvements, Farber disease was suspected. To confirm the diagnostic suspicion, genetic analysis was performed. ASAH1 gene analysis –gene related to Farber syndrome- revealed a homozygous variant which confirmed the presence of Farber disease in this patient. This variant was a novel mutation in exon 8 of ASAH1 gene (c.553T>C p.Trp185Arg). Patient had not received treatment till the age of 2.5 years. After she was diagnosed with JIA, methotrexate, hydroxychloroquine, prednisolone and infliximab medications were initiated. After genetic testing and establishment of the diagnosis of Farber disease, patient’s treatment was switched to cyclosporine and prednisolone. With the development of neurologic involvements, Topiramate, valproate sodium and clobazam was prescribed for relieving debilitating neurologic symptoms. Bone marrow transplantation was suggested as a treatment strategy for the patient but the suggestion was declined by the family. She has under follow up after 2.5 years with neurological deficit.', '2 nd case': 'This patient was a 4 year-old girl, first child of a non-related couple, delivered by NVD who was term on birth. The patient developed swelling of joints at 7 months of age. Particularly in PIP and MCP joints, wrists and ankles ( Figure 1a ). On examination at the age of 2 years, she had multiple subcutaneous nodules on head, hands and chest ( Figure 1b ). Progressive hoarseness was also present. Extensive mucosal lesions were detected in the oral cavity. Limitation in knee’s range of motion was severe leading to difficulty in walking. Cutaneous lesions were also seen on abdomen. In the follow-up after two years, patient had developed nasal swelling. On examination, three relatively soft masses were found within lumbar to coccygeal regions of the spine with diameters of up to 5 centimeters ( Figure 1c ). Muscular atrophy of all four limbs and gluteal region was evident. In the auscultation of the lungs, wheezing was detected. Joints’ examination showed nodules and range of motion limitation in both elbows, shoulders, MCPs, PIPs and DIPs in upper limbs. In lower limbs, knees and ankles were affected with contracture, nodules and range of motion limitation. In radiography, bilateral destruction of proximal humerus and severe osteopenia were seen. After a while, progression of hoarseness and development of multiple percutaneous nodules put the diagnosis of JIA under question. Biopsies were taken from nodules to rule out Farber disease. Histopathologic examination reported collection of collagen bundles and foamy macrophages which were suggestive of Farber disease. With the early diagnosis of JIA, the patient underwent treatment with folic acid, prednisolone, cyclosporine, ibuprofen, calcium supplement and nystatin. MTX was initiated for the patient but then was discontinued due to the appearance of cutaneous lesions on the body. Corticosteroid pulses and Etanercept injections were also prescribed. Subcutaneous nodules increased gradually and she was admitted 4 times due to respiratory distress. Finally she died from respiratory failure in one episode at 4 years old.', '3 rd case': 'This patient was a 9-month old boy, the first child of related parents who was delivered by NVD without any insult. Rheumatoid arthritis history was positive for patient’s father. The patient was presented to the clinic at 9 months of age with one month history of left wrist swelling and tenderness. Within one week prior to the presentation, swelling had extended to the dorsal surfaces of the hands. Patient had been misdiagnosed with JIA and treatment with Prednisolone, MTX and ibuprofen was started. Hoarseness had developed 6 months earlier. Weight loss was also reported. On examination, lower limbs were normal but in upper limbs, limitations in flexion and extension of wrist and swelling of fingers were noted. Patient was presented to the clinic again at 18 months of age with delayed motor development, multiple subcutaneous nodules in wrists and ankles, respiratory distress and hoarseness ( Figure 2 ). In bronchoscopy, large cysts on vocal cords were seen. On radiography, osteopenia was evident (bone age equal to 9 months at the age of 18 months). CXR visualized bilateral perihilar opacities and hyperinflation in both lungs. In kidney, contrast opacity resembling kidney stone was seen. HPLC was normal. Laryngeal nodules led to severe respiratory distress which his life ended after ICU admission and tracheostomy insertion.'}
|
{'1 st case': 'This patient was a 4-year old girl, second child of related parents, delivered by cesarean section without any insult. This child developed wrist swelling at 6 months of age. Swelling of other joints were gradually added. On examination, swelling and limitation in range of motion was detected in PIP, MCP, wrist, elbow and shoulder joints of upper limbs and PIP, MTP, tarsal joints and ankle in lower limbs. Multiple firm subcutaneous nodules were found on joints –mainly on extensor surfaces- which led to deformation of joint, tenderness and inability to walk. Contracture in joints was evident in physical examination. Progressive hoarseness was present. Reports of head drop attacks were found in the history. In neurologic examination, deep tendon reflexes were diminished or absent. Although cognitive function of this patient was normal, motor and speech development was delayed. Two years later, development of seizure and tremor was reported. Tremor was evident in all limbs on physical examination. Laboratory serologic tests were normal. Radiography of both hands showed reduction in density of bones, swelling of both wrists, deformity of wrist bones, marginal erosion of wrist bones and distal phalanges in PIP and DIP joints which all were suggestive of advanced juvenile idiopathic arthritis (JIA). Chest X-ray also showed alveolar opacities with air bronchogram in the upper lobe of right lung which were in favor of pneumonia. Bronchoscopy showed a circular contraction in subglottic region of larynx. After development of neurologic involvements, Farber disease was suspected. To confirm the diagnostic suspicion, genetic analysis was performed. ASAH1 gene analysis –gene related to Farber syndrome- revealed a homozygous variant which confirmed the presence of Farber disease in this patient. This variant was a novel mutation in exon 8 of ASAH1 gene (c.553T>C p.Trp185Arg). Patient had not received treatment till the age of 2.5 years. After she was diagnosed with JIA, methotrexate, hydroxychloroquine, prednisolone and infliximab medications were initiated. After genetic testing and establishment of the diagnosis of Farber disease, patient’s treatment was switched to cyclosporine and prednisolone. With the development of neurologic involvements, Topiramate, valproate sodium and clobazam was prescribed for relieving debilitating neurologic symptoms. Bone marrow transplantation was suggested as a treatment strategy for the patient but the suggestion was declined by the family. She has under follow up after 2.5 years with neurological deficit.', '2 nd case': 'This patient was a 4 year-old girl, first child of a non-related couple, delivered by NVD who was term on birth. The patient developed swelling of joints at 7 months of age. Particularly in PIP and MCP joints, wrists and ankles ( Figure 1a ). On examination at the age of 2 years, she had multiple subcutaneous nodules on head, hands and chest ( Figure 1b ). Progressive hoarseness was also present. Extensive mucosal lesions were detected in the oral cavity. Limitation in knee’s range of motion was severe leading to difficulty in walking. Cutaneous lesions were also seen on abdomen. In the follow-up after two years, patient had developed nasal swelling. On examination, three relatively soft masses were found within lumbar to coccygeal regions of the spine with diameters of up to 5 centimeters ( Figure 1c ). Muscular atrophy of all four limbs and gluteal region was evident. In the auscultation of the lungs, wheezing was detected. Joints’ examination showed nodules and range of motion limitation in both elbows, shoulders, MCPs, PIPs and DIPs in upper limbs. In lower limbs, knees and ankles were affected with contracture, nodules and range of motion limitation. In radiography, bilateral destruction of proximal humerus and severe osteopenia were seen. After a while, progression of hoarseness and development of multiple percutaneous nodules put the diagnosis of JIA under question. Biopsies were taken from nodules to rule out Farber disease. Histopathologic examination reported collection of collagen bundles and foamy macrophages which were suggestive of Farber disease. With the early diagnosis of JIA, the patient underwent treatment with folic acid, prednisolone, cyclosporine, ibuprofen, calcium supplement and nystatin. MTX was initiated for the patient but then was discontinued due to the appearance of cutaneous lesions on the body. Corticosteroid pulses and Etanercept injections were also prescribed. Subcutaneous nodules increased gradually and she was admitted 4 times due to respiratory distress. Finally she died from respiratory failure in one episode at 4 years old.', '3 rd case': 'This patient was a 9-month old boy, the first child of related parents who was delivered by NVD without any insult. Rheumatoid arthritis history was positive for patient’s father. The patient was presented to the clinic at 9 months of age with one month history of left wrist swelling and tenderness. Within one week prior to the presentation, swelling had extended to the dorsal surfaces of the hands. Patient had been misdiagnosed with JIA and treatment with Prednisolone, MTX and ibuprofen was started. Hoarseness had developed 6 months earlier. Weight loss was also reported. On examination, lower limbs were normal but in upper limbs, limitations in flexion and extension of wrist and swelling of fingers were noted. Patient was presented to the clinic again at 18 months of age with delayed motor development, multiple subcutaneous nodules in wrists and ankles, respiratory distress and hoarseness ( Figure 2 ). In bronchoscopy, large cysts on vocal cords were seen. On radiography, osteopenia was evident (bone age equal to 9 months at the age of 18 months). CXR visualized bilateral perihilar opacities and hyperinflation in both lungs. In kidney, contrast opacity resembling kidney stone was seen. HPLC was normal. Laryngeal nodules led to severe respiratory distress which his life ended after ICU admission and tracheostomy insertion.'}
|
Musculoskeletal-System
|
MSK
|
[
"wrist swelling",
"Swelling of other joints were gradually added",
"swelling and limitation in range of motion was detected in PIP, MCP, wrist, elbow and shoulder joints of upper limbs and PIP, MTP, tarsal joints and ankle in lower limbs. Multiple firm subcutaneous nodules were found on joints – mainly on extensor surfaces- which led to deformation of joint, tenderness and inability to walk. Contracture in joints was evident in physical examination",
"Radiography of both hands showed reduction in density of bones, swelling of both wrists, deformity of wrist bones, marginal erosion of wrist bones and distal phalanges in PIP and DIP joints",
"swelling of joints at 7 months of age. Particularly in PIP and MCP joints, wrists and ankles",
"multiple subcutaneous nodules on head, hands and chest",
"Limitation in knee ’s range of motion was severe leading to difficulty in walking",
"three relatively soft masses were found within lumbar to coccygeal regions of the spine with diameters of up to 5 centimeters",
"Muscular atrophy of all four limbs and gluteal region was evident",
"Joints ’ examination showed nodules and range of motion limitation in both elbows, shoulders, MCPs, PIPs and DIPs in upper limbs. In lower limbs, knees and ankles were affected with contracture, nodules and range of motion limitation. In radiography, bilateral destruction of proximal humerus and severe osteopenia were seen",
"development of multiple percutaneous nodules",
"Histopathologic examination reported collection of collagen bundles and foamy macrophages",
"Subcutaneous nodules increased gradually",
"left wrist swelling and tenderness. Within one week prior to the presentation, swelling had extended to the dorsal surfaces of the hands",
"lower limbs were normal but in upper limbs, limitations in flexion and extension of wrist and swelling of fingers were noted",
"multiple subcutaneous nodules in wrists and ankles",
"osteopenia was evident ( bone age equal to 9 months at the age of 18 months"
] |
test-1973
|
6944811
|
{'1 st case': 'This patient was a 4-year old girl, second child of related parents, delivered by cesarean section without any insult. This child developed wrist swelling at 6 months of age. Swelling of other joints were gradually added. On examination, swelling and limitation in range of motion was detected in PIP, MCP, wrist, elbow and shoulder joints of upper limbs and PIP, MTP, tarsal joints and ankle in lower limbs. Multiple firm subcutaneous nodules were found on joints –mainly on extensor surfaces- which led to deformation of joint, tenderness and inability to walk. Contracture in joints was evident in physical examination. Progressive hoarseness was present. Reports of head drop attacks were found in the history. In neurologic examination, deep tendon reflexes were diminished or absent. Although cognitive function of this patient was normal, motor and speech development was delayed. Two years later, development of seizure and tremor was reported. Tremor was evident in all limbs on physical examination. Laboratory serologic tests were normal. Radiography of both hands showed reduction in density of bones, swelling of both wrists, deformity of wrist bones, marginal erosion of wrist bones and distal phalanges in PIP and DIP joints which all were suggestive of advanced juvenile idiopathic arthritis (JIA). Chest X-ray also showed alveolar opacities with air bronchogram in the upper lobe of right lung which were in favor of pneumonia. Bronchoscopy showed a circular contraction in subglottic region of larynx. After development of neurologic involvements, Farber disease was suspected. To confirm the diagnostic suspicion, genetic analysis was performed. ASAH1 gene analysis –gene related to Farber syndrome- revealed a homozygous variant which confirmed the presence of Farber disease in this patient. This variant was a novel mutation in exon 8 of ASAH1 gene (c.553T>C p.Trp185Arg). Patient had not received treatment till the age of 2.5 years. After she was diagnosed with JIA, methotrexate, hydroxychloroquine, prednisolone and infliximab medications were initiated. After genetic testing and establishment of the diagnosis of Farber disease, patient’s treatment was switched to cyclosporine and prednisolone. With the development of neurologic involvements, Topiramate, valproate sodium and clobazam was prescribed for relieving debilitating neurologic symptoms. Bone marrow transplantation was suggested as a treatment strategy for the patient but the suggestion was declined by the family. She has under follow up after 2.5 years with neurological deficit.', '2 nd case': 'This patient was a 4 year-old girl, first child of a non-related couple, delivered by NVD who was term on birth. The patient developed swelling of joints at 7 months of age. Particularly in PIP and MCP joints, wrists and ankles ( Figure 1a ). On examination at the age of 2 years, she had multiple subcutaneous nodules on head, hands and chest ( Figure 1b ). Progressive hoarseness was also present. Extensive mucosal lesions were detected in the oral cavity. Limitation in knee’s range of motion was severe leading to difficulty in walking. Cutaneous lesions were also seen on abdomen. In the follow-up after two years, patient had developed nasal swelling. On examination, three relatively soft masses were found within lumbar to coccygeal regions of the spine with diameters of up to 5 centimeters ( Figure 1c ). Muscular atrophy of all four limbs and gluteal region was evident. In the auscultation of the lungs, wheezing was detected. Joints’ examination showed nodules and range of motion limitation in both elbows, shoulders, MCPs, PIPs and DIPs in upper limbs. In lower limbs, knees and ankles were affected with contracture, nodules and range of motion limitation. In radiography, bilateral destruction of proximal humerus and severe osteopenia were seen. After a while, progression of hoarseness and development of multiple percutaneous nodules put the diagnosis of JIA under question. Biopsies were taken from nodules to rule out Farber disease. Histopathologic examination reported collection of collagen bundles and foamy macrophages which were suggestive of Farber disease. With the early diagnosis of JIA, the patient underwent treatment with folic acid, prednisolone, cyclosporine, ibuprofen, calcium supplement and nystatin. MTX was initiated for the patient but then was discontinued due to the appearance of cutaneous lesions on the body. Corticosteroid pulses and Etanercept injections were also prescribed. Subcutaneous nodules increased gradually and she was admitted 4 times due to respiratory distress. Finally she died from respiratory failure in one episode at 4 years old.', '3 rd case': 'This patient was a 9-month old boy, the first child of related parents who was delivered by NVD without any insult. Rheumatoid arthritis history was positive for patient’s father. The patient was presented to the clinic at 9 months of age with one month history of left wrist swelling and tenderness. Within one week prior to the presentation, swelling had extended to the dorsal surfaces of the hands. Patient had been misdiagnosed with JIA and treatment with Prednisolone, MTX and ibuprofen was started. Hoarseness had developed 6 months earlier. Weight loss was also reported. On examination, lower limbs were normal but in upper limbs, limitations in flexion and extension of wrist and swelling of fingers were noted. Patient was presented to the clinic again at 18 months of age with delayed motor development, multiple subcutaneous nodules in wrists and ankles, respiratory distress and hoarseness ( Figure 2 ). In bronchoscopy, large cysts on vocal cords were seen. On radiography, osteopenia was evident (bone age equal to 9 months at the age of 18 months). CXR visualized bilateral perihilar opacities and hyperinflation in both lungs. In kidney, contrast opacity resembling kidney stone was seen. HPLC was normal. Laryngeal nodules led to severe respiratory distress which his life ended after ICU admission and tracheostomy insertion.'}
|
{'1 st case': 'This patient was a 4-year old girl, second child of related parents, delivered by cesarean section without any insult. This child developed wrist swelling at 6 months of age. Swelling of other joints were gradually added. On examination, swelling and limitation in range of motion was detected in PIP, MCP, wrist, elbow and shoulder joints of upper limbs and PIP, MTP, tarsal joints and ankle in lower limbs. Multiple firm subcutaneous nodules were found on joints –mainly on extensor surfaces- which led to deformation of joint, tenderness and inability to walk. Contracture in joints was evident in physical examination. Progressive hoarseness was present. Reports of head drop attacks were found in the history. In neurologic examination, deep tendon reflexes were diminished or absent. Although cognitive function of this patient was normal, motor and speech development was delayed. Two years later, development of seizure and tremor was reported. Tremor was evident in all limbs on physical examination. Laboratory serologic tests were normal. Radiography of both hands showed reduction in density of bones, swelling of both wrists, deformity of wrist bones, marginal erosion of wrist bones and distal phalanges in PIP and DIP joints which all were suggestive of advanced juvenile idiopathic arthritis (JIA). Chest X-ray also showed alveolar opacities with air bronchogram in the upper lobe of right lung which were in favor of pneumonia. Bronchoscopy showed a circular contraction in subglottic region of larynx. After development of neurologic involvements, Farber disease was suspected. To confirm the diagnostic suspicion, genetic analysis was performed. ASAH1 gene analysis –gene related to Farber syndrome- revealed a homozygous variant which confirmed the presence of Farber disease in this patient. This variant was a novel mutation in exon 8 of ASAH1 gene (c.553T>C p.Trp185Arg). Patient had not received treatment till the age of 2.5 years. After she was diagnosed with JIA, methotrexate, hydroxychloroquine, prednisolone and infliximab medications were initiated. After genetic testing and establishment of the diagnosis of Farber disease, patient’s treatment was switched to cyclosporine and prednisolone. With the development of neurologic involvements, Topiramate, valproate sodium and clobazam was prescribed for relieving debilitating neurologic symptoms. Bone marrow transplantation was suggested as a treatment strategy for the patient but the suggestion was declined by the family. She has under follow up after 2.5 years with neurological deficit.', '2 nd case': 'This patient was a 4 year-old girl, first child of a non-related couple, delivered by NVD who was term on birth. The patient developed swelling of joints at 7 months of age. Particularly in PIP and MCP joints, wrists and ankles ( Figure 1a ). On examination at the age of 2 years, she had multiple subcutaneous nodules on head, hands and chest ( Figure 1b ). Progressive hoarseness was also present. Extensive mucosal lesions were detected in the oral cavity. Limitation in knee’s range of motion was severe leading to difficulty in walking. Cutaneous lesions were also seen on abdomen. In the follow-up after two years, patient had developed nasal swelling. On examination, three relatively soft masses were found within lumbar to coccygeal regions of the spine with diameters of up to 5 centimeters ( Figure 1c ). Muscular atrophy of all four limbs and gluteal region was evident. In the auscultation of the lungs, wheezing was detected. Joints’ examination showed nodules and range of motion limitation in both elbows, shoulders, MCPs, PIPs and DIPs in upper limbs. In lower limbs, knees and ankles were affected with contracture, nodules and range of motion limitation. In radiography, bilateral destruction of proximal humerus and severe osteopenia were seen. After a while, progression of hoarseness and development of multiple percutaneous nodules put the diagnosis of JIA under question. Biopsies were taken from nodules to rule out Farber disease. Histopathologic examination reported collection of collagen bundles and foamy macrophages which were suggestive of Farber disease. With the early diagnosis of JIA, the patient underwent treatment with folic acid, prednisolone, cyclosporine, ibuprofen, calcium supplement and nystatin. MTX was initiated for the patient but then was discontinued due to the appearance of cutaneous lesions on the body. Corticosteroid pulses and Etanercept injections were also prescribed. Subcutaneous nodules increased gradually and she was admitted 4 times due to respiratory distress. Finally she died from respiratory failure in one episode at 4 years old.', '3 rd case': 'This patient was a 9-month old boy, the first child of related parents who was delivered by NVD without any insult. Rheumatoid arthritis history was positive for patient’s father. The patient was presented to the clinic at 9 months of age with one month history of left wrist swelling and tenderness. Within one week prior to the presentation, swelling had extended to the dorsal surfaces of the hands. Patient had been misdiagnosed with JIA and treatment with Prednisolone, MTX and ibuprofen was started. Hoarseness had developed 6 months earlier. Weight loss was also reported. On examination, lower limbs were normal but in upper limbs, limitations in flexion and extension of wrist and swelling of fingers were noted. Patient was presented to the clinic again at 18 months of age with delayed motor development, multiple subcutaneous nodules in wrists and ankles, respiratory distress and hoarseness ( Figure 2 ). In bronchoscopy, large cysts on vocal cords were seen. On radiography, osteopenia was evident (bone age equal to 9 months at the age of 18 months). CXR visualized bilateral perihilar opacities and hyperinflation in both lungs. In kidney, contrast opacity resembling kidney stone was seen. HPLC was normal. Laryngeal nodules led to severe respiratory distress which his life ended after ICU admission and tracheostomy insertion.'}
|
Eyes-Ears-Nose-Throat
|
EENT
|
[
"Progressive hoarseness was present",
"Progressive hoarseness was also present. Extensive mucosal lesions were detected in the oral cavity",
"nasal swelling",
"progression of hoarseness",
"admitted 4 times due to respiratory distress. Finally she died from respiratory failure in one episode at 4 years old",
"Hoarseness had developed 6 months earlier",
"respiratory distress and hoarseness",
"large cysts on vocal cords were seen",
"Laryngeal nodules led to severe respiratory distress which his life ended"
] |
test-1974
|
6944811
|
{'1 st case': 'This patient was a 4-year old girl, second child of related parents, delivered by cesarean section without any insult. This child developed wrist swelling at 6 months of age. Swelling of other joints were gradually added. On examination, swelling and limitation in range of motion was detected in PIP, MCP, wrist, elbow and shoulder joints of upper limbs and PIP, MTP, tarsal joints and ankle in lower limbs. Multiple firm subcutaneous nodules were found on joints –mainly on extensor surfaces- which led to deformation of joint, tenderness and inability to walk. Contracture in joints was evident in physical examination. Progressive hoarseness was present. Reports of head drop attacks were found in the history. In neurologic examination, deep tendon reflexes were diminished or absent. Although cognitive function of this patient was normal, motor and speech development was delayed. Two years later, development of seizure and tremor was reported. Tremor was evident in all limbs on physical examination. Laboratory serologic tests were normal. Radiography of both hands showed reduction in density of bones, swelling of both wrists, deformity of wrist bones, marginal erosion of wrist bones and distal phalanges in PIP and DIP joints which all were suggestive of advanced juvenile idiopathic arthritis (JIA). Chest X-ray also showed alveolar opacities with air bronchogram in the upper lobe of right lung which were in favor of pneumonia. Bronchoscopy showed a circular contraction in subglottic region of larynx. After development of neurologic involvements, Farber disease was suspected. To confirm the diagnostic suspicion, genetic analysis was performed. ASAH1 gene analysis –gene related to Farber syndrome- revealed a homozygous variant which confirmed the presence of Farber disease in this patient. This variant was a novel mutation in exon 8 of ASAH1 gene (c.553T>C p.Trp185Arg). Patient had not received treatment till the age of 2.5 years. After she was diagnosed with JIA, methotrexate, hydroxychloroquine, prednisolone and infliximab medications were initiated. After genetic testing and establishment of the diagnosis of Farber disease, patient’s treatment was switched to cyclosporine and prednisolone. With the development of neurologic involvements, Topiramate, valproate sodium and clobazam was prescribed for relieving debilitating neurologic symptoms. Bone marrow transplantation was suggested as a treatment strategy for the patient but the suggestion was declined by the family. She has under follow up after 2.5 years with neurological deficit.', '2 nd case': 'This patient was a 4 year-old girl, first child of a non-related couple, delivered by NVD who was term on birth. The patient developed swelling of joints at 7 months of age. Particularly in PIP and MCP joints, wrists and ankles ( Figure 1a ). On examination at the age of 2 years, she had multiple subcutaneous nodules on head, hands and chest ( Figure 1b ). Progressive hoarseness was also present. Extensive mucosal lesions were detected in the oral cavity. Limitation in knee’s range of motion was severe leading to difficulty in walking. Cutaneous lesions were also seen on abdomen. In the follow-up after two years, patient had developed nasal swelling. On examination, three relatively soft masses were found within lumbar to coccygeal regions of the spine with diameters of up to 5 centimeters ( Figure 1c ). Muscular atrophy of all four limbs and gluteal region was evident. In the auscultation of the lungs, wheezing was detected. Joints’ examination showed nodules and range of motion limitation in both elbows, shoulders, MCPs, PIPs and DIPs in upper limbs. In lower limbs, knees and ankles were affected with contracture, nodules and range of motion limitation. In radiography, bilateral destruction of proximal humerus and severe osteopenia were seen. After a while, progression of hoarseness and development of multiple percutaneous nodules put the diagnosis of JIA under question. Biopsies were taken from nodules to rule out Farber disease. Histopathologic examination reported collection of collagen bundles and foamy macrophages which were suggestive of Farber disease. With the early diagnosis of JIA, the patient underwent treatment with folic acid, prednisolone, cyclosporine, ibuprofen, calcium supplement and nystatin. MTX was initiated for the patient but then was discontinued due to the appearance of cutaneous lesions on the body. Corticosteroid pulses and Etanercept injections were also prescribed. Subcutaneous nodules increased gradually and she was admitted 4 times due to respiratory distress. Finally she died from respiratory failure in one episode at 4 years old.', '3 rd case': 'This patient was a 9-month old boy, the first child of related parents who was delivered by NVD without any insult. Rheumatoid arthritis history was positive for patient’s father. The patient was presented to the clinic at 9 months of age with one month history of left wrist swelling and tenderness. Within one week prior to the presentation, swelling had extended to the dorsal surfaces of the hands. Patient had been misdiagnosed with JIA and treatment with Prednisolone, MTX and ibuprofen was started. Hoarseness had developed 6 months earlier. Weight loss was also reported. On examination, lower limbs were normal but in upper limbs, limitations in flexion and extension of wrist and swelling of fingers were noted. Patient was presented to the clinic again at 18 months of age with delayed motor development, multiple subcutaneous nodules in wrists and ankles, respiratory distress and hoarseness ( Figure 2 ). In bronchoscopy, large cysts on vocal cords were seen. On radiography, osteopenia was evident (bone age equal to 9 months at the age of 18 months). CXR visualized bilateral perihilar opacities and hyperinflation in both lungs. In kidney, contrast opacity resembling kidney stone was seen. HPLC was normal. Laryngeal nodules led to severe respiratory distress which his life ended after ICU admission and tracheostomy insertion.'}
|
{'1 st case': 'This patient was a 4-year old girl, second child of related parents, delivered by cesarean section without any insult. This child developed wrist swelling at 6 months of age. Swelling of other joints were gradually added. On examination, swelling and limitation in range of motion was detected in PIP, MCP, wrist, elbow and shoulder joints of upper limbs and PIP, MTP, tarsal joints and ankle in lower limbs. Multiple firm subcutaneous nodules were found on joints –mainly on extensor surfaces- which led to deformation of joint, tenderness and inability to walk. Contracture in joints was evident in physical examination. Progressive hoarseness was present. Reports of head drop attacks were found in the history. In neurologic examination, deep tendon reflexes were diminished or absent. Although cognitive function of this patient was normal, motor and speech development was delayed. Two years later, development of seizure and tremor was reported. Tremor was evident in all limbs on physical examination. Laboratory serologic tests were normal. Radiography of both hands showed reduction in density of bones, swelling of both wrists, deformity of wrist bones, marginal erosion of wrist bones and distal phalanges in PIP and DIP joints which all were suggestive of advanced juvenile idiopathic arthritis (JIA). Chest X-ray also showed alveolar opacities with air bronchogram in the upper lobe of right lung which were in favor of pneumonia. Bronchoscopy showed a circular contraction in subglottic region of larynx. After development of neurologic involvements, Farber disease was suspected. To confirm the diagnostic suspicion, genetic analysis was performed. ASAH1 gene analysis –gene related to Farber syndrome- revealed a homozygous variant which confirmed the presence of Farber disease in this patient. This variant was a novel mutation in exon 8 of ASAH1 gene (c.553T>C p.Trp185Arg). Patient had not received treatment till the age of 2.5 years. After she was diagnosed with JIA, methotrexate, hydroxychloroquine, prednisolone and infliximab medications were initiated. After genetic testing and establishment of the diagnosis of Farber disease, patient’s treatment was switched to cyclosporine and prednisolone. With the development of neurologic involvements, Topiramate, valproate sodium and clobazam was prescribed for relieving debilitating neurologic symptoms. Bone marrow transplantation was suggested as a treatment strategy for the patient but the suggestion was declined by the family. She has under follow up after 2.5 years with neurological deficit.', '2 nd case': 'This patient was a 4 year-old girl, first child of a non-related couple, delivered by NVD who was term on birth. The patient developed swelling of joints at 7 months of age. Particularly in PIP and MCP joints, wrists and ankles ( Figure 1a ). On examination at the age of 2 years, she had multiple subcutaneous nodules on head, hands and chest ( Figure 1b ). Progressive hoarseness was also present. Extensive mucosal lesions were detected in the oral cavity. Limitation in knee’s range of motion was severe leading to difficulty in walking. Cutaneous lesions were also seen on abdomen. In the follow-up after two years, patient had developed nasal swelling. On examination, three relatively soft masses were found within lumbar to coccygeal regions of the spine with diameters of up to 5 centimeters ( Figure 1c ). Muscular atrophy of all four limbs and gluteal region was evident. In the auscultation of the lungs, wheezing was detected. Joints’ examination showed nodules and range of motion limitation in both elbows, shoulders, MCPs, PIPs and DIPs in upper limbs. In lower limbs, knees and ankles were affected with contracture, nodules and range of motion limitation. In radiography, bilateral destruction of proximal humerus and severe osteopenia were seen. After a while, progression of hoarseness and development of multiple percutaneous nodules put the diagnosis of JIA under question. Biopsies were taken from nodules to rule out Farber disease. Histopathologic examination reported collection of collagen bundles and foamy macrophages which were suggestive of Farber disease. With the early diagnosis of JIA, the patient underwent treatment with folic acid, prednisolone, cyclosporine, ibuprofen, calcium supplement and nystatin. MTX was initiated for the patient but then was discontinued due to the appearance of cutaneous lesions on the body. Corticosteroid pulses and Etanercept injections were also prescribed. Subcutaneous nodules increased gradually and she was admitted 4 times due to respiratory distress. Finally she died from respiratory failure in one episode at 4 years old.', '3 rd case': 'This patient was a 9-month old boy, the first child of related parents who was delivered by NVD without any insult. Rheumatoid arthritis history was positive for patient’s father. The patient was presented to the clinic at 9 months of age with one month history of left wrist swelling and tenderness. Within one week prior to the presentation, swelling had extended to the dorsal surfaces of the hands. Patient had been misdiagnosed with JIA and treatment with Prednisolone, MTX and ibuprofen was started. Hoarseness had developed 6 months earlier. Weight loss was also reported. On examination, lower limbs were normal but in upper limbs, limitations in flexion and extension of wrist and swelling of fingers were noted. Patient was presented to the clinic again at 18 months of age with delayed motor development, multiple subcutaneous nodules in wrists and ankles, respiratory distress and hoarseness ( Figure 2 ). In bronchoscopy, large cysts on vocal cords were seen. On radiography, osteopenia was evident (bone age equal to 9 months at the age of 18 months). CXR visualized bilateral perihilar opacities and hyperinflation in both lungs. In kidney, contrast opacity resembling kidney stone was seen. HPLC was normal. Laryngeal nodules led to severe respiratory distress which his life ended after ICU admission and tracheostomy insertion.'}
|
Dermatology
|
DERM
|
[
"Cutaneous lesions were also seen on abdomen",
"appearance of cutaneous lesions on the body"
] |
test-1975
|
6944811
|
{'1 st case': 'This patient was a 4-year old girl, second child of related parents, delivered by cesarean section without any insult. This child developed wrist swelling at 6 months of age. Swelling of other joints were gradually added. On examination, swelling and limitation in range of motion was detected in PIP, MCP, wrist, elbow and shoulder joints of upper limbs and PIP, MTP, tarsal joints and ankle in lower limbs. Multiple firm subcutaneous nodules were found on joints –mainly on extensor surfaces- which led to deformation of joint, tenderness and inability to walk. Contracture in joints was evident in physical examination. Progressive hoarseness was present. Reports of head drop attacks were found in the history. In neurologic examination, deep tendon reflexes were diminished or absent. Although cognitive function of this patient was normal, motor and speech development was delayed. Two years later, development of seizure and tremor was reported. Tremor was evident in all limbs on physical examination. Laboratory serologic tests were normal. Radiography of both hands showed reduction in density of bones, swelling of both wrists, deformity of wrist bones, marginal erosion of wrist bones and distal phalanges in PIP and DIP joints which all were suggestive of advanced juvenile idiopathic arthritis (JIA). Chest X-ray also showed alveolar opacities with air bronchogram in the upper lobe of right lung which were in favor of pneumonia. Bronchoscopy showed a circular contraction in subglottic region of larynx. After development of neurologic involvements, Farber disease was suspected. To confirm the diagnostic suspicion, genetic analysis was performed. ASAH1 gene analysis –gene related to Farber syndrome- revealed a homozygous variant which confirmed the presence of Farber disease in this patient. This variant was a novel mutation in exon 8 of ASAH1 gene (c.553T>C p.Trp185Arg). Patient had not received treatment till the age of 2.5 years. After she was diagnosed with JIA, methotrexate, hydroxychloroquine, prednisolone and infliximab medications were initiated. After genetic testing and establishment of the diagnosis of Farber disease, patient’s treatment was switched to cyclosporine and prednisolone. With the development of neurologic involvements, Topiramate, valproate sodium and clobazam was prescribed for relieving debilitating neurologic symptoms. Bone marrow transplantation was suggested as a treatment strategy for the patient but the suggestion was declined by the family. She has under follow up after 2.5 years with neurological deficit.', '2 nd case': 'This patient was a 4 year-old girl, first child of a non-related couple, delivered by NVD who was term on birth. The patient developed swelling of joints at 7 months of age. Particularly in PIP and MCP joints, wrists and ankles ( Figure 1a ). On examination at the age of 2 years, she had multiple subcutaneous nodules on head, hands and chest ( Figure 1b ). Progressive hoarseness was also present. Extensive mucosal lesions were detected in the oral cavity. Limitation in knee’s range of motion was severe leading to difficulty in walking. Cutaneous lesions were also seen on abdomen. In the follow-up after two years, patient had developed nasal swelling. On examination, three relatively soft masses were found within lumbar to coccygeal regions of the spine with diameters of up to 5 centimeters ( Figure 1c ). Muscular atrophy of all four limbs and gluteal region was evident. In the auscultation of the lungs, wheezing was detected. Joints’ examination showed nodules and range of motion limitation in both elbows, shoulders, MCPs, PIPs and DIPs in upper limbs. In lower limbs, knees and ankles were affected with contracture, nodules and range of motion limitation. In radiography, bilateral destruction of proximal humerus and severe osteopenia were seen. After a while, progression of hoarseness and development of multiple percutaneous nodules put the diagnosis of JIA under question. Biopsies were taken from nodules to rule out Farber disease. Histopathologic examination reported collection of collagen bundles and foamy macrophages which were suggestive of Farber disease. With the early diagnosis of JIA, the patient underwent treatment with folic acid, prednisolone, cyclosporine, ibuprofen, calcium supplement and nystatin. MTX was initiated for the patient but then was discontinued due to the appearance of cutaneous lesions on the body. Corticosteroid pulses and Etanercept injections were also prescribed. Subcutaneous nodules increased gradually and she was admitted 4 times due to respiratory distress. Finally she died from respiratory failure in one episode at 4 years old.', '3 rd case': 'This patient was a 9-month old boy, the first child of related parents who was delivered by NVD without any insult. Rheumatoid arthritis history was positive for patient’s father. The patient was presented to the clinic at 9 months of age with one month history of left wrist swelling and tenderness. Within one week prior to the presentation, swelling had extended to the dorsal surfaces of the hands. Patient had been misdiagnosed with JIA and treatment with Prednisolone, MTX and ibuprofen was started. Hoarseness had developed 6 months earlier. Weight loss was also reported. On examination, lower limbs were normal but in upper limbs, limitations in flexion and extension of wrist and swelling of fingers were noted. Patient was presented to the clinic again at 18 months of age with delayed motor development, multiple subcutaneous nodules in wrists and ankles, respiratory distress and hoarseness ( Figure 2 ). In bronchoscopy, large cysts on vocal cords were seen. On radiography, osteopenia was evident (bone age equal to 9 months at the age of 18 months). CXR visualized bilateral perihilar opacities and hyperinflation in both lungs. In kidney, contrast opacity resembling kidney stone was seen. HPLC was normal. Laryngeal nodules led to severe respiratory distress which his life ended after ICU admission and tracheostomy insertion.'}
|
{'1 st case': 'This patient was a 4-year old girl, second child of related parents, delivered by cesarean section without any insult. This child developed wrist swelling at 6 months of age. Swelling of other joints were gradually added. On examination, swelling and limitation in range of motion was detected in PIP, MCP, wrist, elbow and shoulder joints of upper limbs and PIP, MTP, tarsal joints and ankle in lower limbs. Multiple firm subcutaneous nodules were found on joints –mainly on extensor surfaces- which led to deformation of joint, tenderness and inability to walk. Contracture in joints was evident in physical examination. Progressive hoarseness was present. Reports of head drop attacks were found in the history. In neurologic examination, deep tendon reflexes were diminished or absent. Although cognitive function of this patient was normal, motor and speech development was delayed. Two years later, development of seizure and tremor was reported. Tremor was evident in all limbs on physical examination. Laboratory serologic tests were normal. Radiography of both hands showed reduction in density of bones, swelling of both wrists, deformity of wrist bones, marginal erosion of wrist bones and distal phalanges in PIP and DIP joints which all were suggestive of advanced juvenile idiopathic arthritis (JIA). Chest X-ray also showed alveolar opacities with air bronchogram in the upper lobe of right lung which were in favor of pneumonia. Bronchoscopy showed a circular contraction in subglottic region of larynx. After development of neurologic involvements, Farber disease was suspected. To confirm the diagnostic suspicion, genetic analysis was performed. ASAH1 gene analysis –gene related to Farber syndrome- revealed a homozygous variant which confirmed the presence of Farber disease in this patient. This variant was a novel mutation in exon 8 of ASAH1 gene (c.553T>C p.Trp185Arg). Patient had not received treatment till the age of 2.5 years. After she was diagnosed with JIA, methotrexate, hydroxychloroquine, prednisolone and infliximab medications were initiated. After genetic testing and establishment of the diagnosis of Farber disease, patient’s treatment was switched to cyclosporine and prednisolone. With the development of neurologic involvements, Topiramate, valproate sodium and clobazam was prescribed for relieving debilitating neurologic symptoms. Bone marrow transplantation was suggested as a treatment strategy for the patient but the suggestion was declined by the family. She has under follow up after 2.5 years with neurological deficit.', '2 nd case': 'This patient was a 4 year-old girl, first child of a non-related couple, delivered by NVD who was term on birth. The patient developed swelling of joints at 7 months of age. Particularly in PIP and MCP joints, wrists and ankles ( Figure 1a ). On examination at the age of 2 years, she had multiple subcutaneous nodules on head, hands and chest ( Figure 1b ). Progressive hoarseness was also present. Extensive mucosal lesions were detected in the oral cavity. Limitation in knee’s range of motion was severe leading to difficulty in walking. Cutaneous lesions were also seen on abdomen. In the follow-up after two years, patient had developed nasal swelling. On examination, three relatively soft masses were found within lumbar to coccygeal regions of the spine with diameters of up to 5 centimeters ( Figure 1c ). Muscular atrophy of all four limbs and gluteal region was evident. In the auscultation of the lungs, wheezing was detected. Joints’ examination showed nodules and range of motion limitation in both elbows, shoulders, MCPs, PIPs and DIPs in upper limbs. In lower limbs, knees and ankles were affected with contracture, nodules and range of motion limitation. In radiography, bilateral destruction of proximal humerus and severe osteopenia were seen. After a while, progression of hoarseness and development of multiple percutaneous nodules put the diagnosis of JIA under question. Biopsies were taken from nodules to rule out Farber disease. Histopathologic examination reported collection of collagen bundles and foamy macrophages which were suggestive of Farber disease. With the early diagnosis of JIA, the patient underwent treatment with folic acid, prednisolone, cyclosporine, ibuprofen, calcium supplement and nystatin. MTX was initiated for the patient but then was discontinued due to the appearance of cutaneous lesions on the body. Corticosteroid pulses and Etanercept injections were also prescribed. Subcutaneous nodules increased gradually and she was admitted 4 times due to respiratory distress. Finally she died from respiratory failure in one episode at 4 years old.', '3 rd case': 'This patient was a 9-month old boy, the first child of related parents who was delivered by NVD without any insult. Rheumatoid arthritis history was positive for patient’s father. The patient was presented to the clinic at 9 months of age with one month history of left wrist swelling and tenderness. Within one week prior to the presentation, swelling had extended to the dorsal surfaces of the hands. Patient had been misdiagnosed with JIA and treatment with Prednisolone, MTX and ibuprofen was started. Hoarseness had developed 6 months earlier. Weight loss was also reported. On examination, lower limbs were normal but in upper limbs, limitations in flexion and extension of wrist and swelling of fingers were noted. Patient was presented to the clinic again at 18 months of age with delayed motor development, multiple subcutaneous nodules in wrists and ankles, respiratory distress and hoarseness ( Figure 2 ). In bronchoscopy, large cysts on vocal cords were seen. On radiography, osteopenia was evident (bone age equal to 9 months at the age of 18 months). CXR visualized bilateral perihilar opacities and hyperinflation in both lungs. In kidney, contrast opacity resembling kidney stone was seen. HPLC was normal. Laryngeal nodules led to severe respiratory distress which his life ended after ICU admission and tracheostomy insertion.'}
|
Pregnancy
|
Pregnancy
|
[
"delivered by cesarean section without any insult",
"delivered by NVD who was term on birth",
"delivered by NVD without any insult"
] |
test-1976
|
6944811
|
{'1 st case': 'This patient was a 4-year old girl, second child of related parents, delivered by cesarean section without any insult. This child developed wrist swelling at 6 months of age. Swelling of other joints were gradually added. On examination, swelling and limitation in range of motion was detected in PIP, MCP, wrist, elbow and shoulder joints of upper limbs and PIP, MTP, tarsal joints and ankle in lower limbs. Multiple firm subcutaneous nodules were found on joints –mainly on extensor surfaces- which led to deformation of joint, tenderness and inability to walk. Contracture in joints was evident in physical examination. Progressive hoarseness was present. Reports of head drop attacks were found in the history. In neurologic examination, deep tendon reflexes were diminished or absent. Although cognitive function of this patient was normal, motor and speech development was delayed. Two years later, development of seizure and tremor was reported. Tremor was evident in all limbs on physical examination. Laboratory serologic tests were normal. Radiography of both hands showed reduction in density of bones, swelling of both wrists, deformity of wrist bones, marginal erosion of wrist bones and distal phalanges in PIP and DIP joints which all were suggestive of advanced juvenile idiopathic arthritis (JIA). Chest X-ray also showed alveolar opacities with air bronchogram in the upper lobe of right lung which were in favor of pneumonia. Bronchoscopy showed a circular contraction in subglottic region of larynx. After development of neurologic involvements, Farber disease was suspected. To confirm the diagnostic suspicion, genetic analysis was performed. ASAH1 gene analysis –gene related to Farber syndrome- revealed a homozygous variant which confirmed the presence of Farber disease in this patient. This variant was a novel mutation in exon 8 of ASAH1 gene (c.553T>C p.Trp185Arg). Patient had not received treatment till the age of 2.5 years. After she was diagnosed with JIA, methotrexate, hydroxychloroquine, prednisolone and infliximab medications were initiated. After genetic testing and establishment of the diagnosis of Farber disease, patient’s treatment was switched to cyclosporine and prednisolone. With the development of neurologic involvements, Topiramate, valproate sodium and clobazam was prescribed for relieving debilitating neurologic symptoms. Bone marrow transplantation was suggested as a treatment strategy for the patient but the suggestion was declined by the family. She has under follow up after 2.5 years with neurological deficit.', '2 nd case': 'This patient was a 4 year-old girl, first child of a non-related couple, delivered by NVD who was term on birth. The patient developed swelling of joints at 7 months of age. Particularly in PIP and MCP joints, wrists and ankles ( Figure 1a ). On examination at the age of 2 years, she had multiple subcutaneous nodules on head, hands and chest ( Figure 1b ). Progressive hoarseness was also present. Extensive mucosal lesions were detected in the oral cavity. Limitation in knee’s range of motion was severe leading to difficulty in walking. Cutaneous lesions were also seen on abdomen. In the follow-up after two years, patient had developed nasal swelling. On examination, three relatively soft masses were found within lumbar to coccygeal regions of the spine with diameters of up to 5 centimeters ( Figure 1c ). Muscular atrophy of all four limbs and gluteal region was evident. In the auscultation of the lungs, wheezing was detected. Joints’ examination showed nodules and range of motion limitation in both elbows, shoulders, MCPs, PIPs and DIPs in upper limbs. In lower limbs, knees and ankles were affected with contracture, nodules and range of motion limitation. In radiography, bilateral destruction of proximal humerus and severe osteopenia were seen. After a while, progression of hoarseness and development of multiple percutaneous nodules put the diagnosis of JIA under question. Biopsies were taken from nodules to rule out Farber disease. Histopathologic examination reported collection of collagen bundles and foamy macrophages which were suggestive of Farber disease. With the early diagnosis of JIA, the patient underwent treatment with folic acid, prednisolone, cyclosporine, ibuprofen, calcium supplement and nystatin. MTX was initiated for the patient but then was discontinued due to the appearance of cutaneous lesions on the body. Corticosteroid pulses and Etanercept injections were also prescribed. Subcutaneous nodules increased gradually and she was admitted 4 times due to respiratory distress. Finally she died from respiratory failure in one episode at 4 years old.', '3 rd case': 'This patient was a 9-month old boy, the first child of related parents who was delivered by NVD without any insult. Rheumatoid arthritis history was positive for patient’s father. The patient was presented to the clinic at 9 months of age with one month history of left wrist swelling and tenderness. Within one week prior to the presentation, swelling had extended to the dorsal surfaces of the hands. Patient had been misdiagnosed with JIA and treatment with Prednisolone, MTX and ibuprofen was started. Hoarseness had developed 6 months earlier. Weight loss was also reported. On examination, lower limbs were normal but in upper limbs, limitations in flexion and extension of wrist and swelling of fingers were noted. Patient was presented to the clinic again at 18 months of age with delayed motor development, multiple subcutaneous nodules in wrists and ankles, respiratory distress and hoarseness ( Figure 2 ). In bronchoscopy, large cysts on vocal cords were seen. On radiography, osteopenia was evident (bone age equal to 9 months at the age of 18 months). CXR visualized bilateral perihilar opacities and hyperinflation in both lungs. In kidney, contrast opacity resembling kidney stone was seen. HPLC was normal. Laryngeal nodules led to severe respiratory distress which his life ended after ICU admission and tracheostomy insertion.'}
|
{'1 st case': 'This patient was a 4-year old girl, second child of related parents, delivered by cesarean section without any insult. This child developed wrist swelling at 6 months of age. Swelling of other joints were gradually added. On examination, swelling and limitation in range of motion was detected in PIP, MCP, wrist, elbow and shoulder joints of upper limbs and PIP, MTP, tarsal joints and ankle in lower limbs. Multiple firm subcutaneous nodules were found on joints –mainly on extensor surfaces- which led to deformation of joint, tenderness and inability to walk. Contracture in joints was evident in physical examination. Progressive hoarseness was present. Reports of head drop attacks were found in the history. In neurologic examination, deep tendon reflexes were diminished or absent. Although cognitive function of this patient was normal, motor and speech development was delayed. Two years later, development of seizure and tremor was reported. Tremor was evident in all limbs on physical examination. Laboratory serologic tests were normal. Radiography of both hands showed reduction in density of bones, swelling of both wrists, deformity of wrist bones, marginal erosion of wrist bones and distal phalanges in PIP and DIP joints which all were suggestive of advanced juvenile idiopathic arthritis (JIA). Chest X-ray also showed alveolar opacities with air bronchogram in the upper lobe of right lung which were in favor of pneumonia. Bronchoscopy showed a circular contraction in subglottic region of larynx. After development of neurologic involvements, Farber disease was suspected. To confirm the diagnostic suspicion, genetic analysis was performed. ASAH1 gene analysis –gene related to Farber syndrome- revealed a homozygous variant which confirmed the presence of Farber disease in this patient. This variant was a novel mutation in exon 8 of ASAH1 gene (c.553T>C p.Trp185Arg). Patient had not received treatment till the age of 2.5 years. After she was diagnosed with JIA, methotrexate, hydroxychloroquine, prednisolone and infliximab medications were initiated. After genetic testing and establishment of the diagnosis of Farber disease, patient’s treatment was switched to cyclosporine and prednisolone. With the development of neurologic involvements, Topiramate, valproate sodium and clobazam was prescribed for relieving debilitating neurologic symptoms. Bone marrow transplantation was suggested as a treatment strategy for the patient but the suggestion was declined by the family. She has under follow up after 2.5 years with neurological deficit.', '2 nd case': 'This patient was a 4 year-old girl, first child of a non-related couple, delivered by NVD who was term on birth. The patient developed swelling of joints at 7 months of age. Particularly in PIP and MCP joints, wrists and ankles ( Figure 1a ). On examination at the age of 2 years, she had multiple subcutaneous nodules on head, hands and chest ( Figure 1b ). Progressive hoarseness was also present. Extensive mucosal lesions were detected in the oral cavity. Limitation in knee’s range of motion was severe leading to difficulty in walking. Cutaneous lesions were also seen on abdomen. In the follow-up after two years, patient had developed nasal swelling. On examination, three relatively soft masses were found within lumbar to coccygeal regions of the spine with diameters of up to 5 centimeters ( Figure 1c ). Muscular atrophy of all four limbs and gluteal region was evident. In the auscultation of the lungs, wheezing was detected. Joints’ examination showed nodules and range of motion limitation in both elbows, shoulders, MCPs, PIPs and DIPs in upper limbs. In lower limbs, knees and ankles were affected with contracture, nodules and range of motion limitation. In radiography, bilateral destruction of proximal humerus and severe osteopenia were seen. After a while, progression of hoarseness and development of multiple percutaneous nodules put the diagnosis of JIA under question. Biopsies were taken from nodules to rule out Farber disease. Histopathologic examination reported collection of collagen bundles and foamy macrophages which were suggestive of Farber disease. With the early diagnosis of JIA, the patient underwent treatment with folic acid, prednisolone, cyclosporine, ibuprofen, calcium supplement and nystatin. MTX was initiated for the patient but then was discontinued due to the appearance of cutaneous lesions on the body. Corticosteroid pulses and Etanercept injections were also prescribed. Subcutaneous nodules increased gradually and she was admitted 4 times due to respiratory distress. Finally she died from respiratory failure in one episode at 4 years old.', '3 rd case': 'This patient was a 9-month old boy, the first child of related parents who was delivered by NVD without any insult. Rheumatoid arthritis history was positive for patient’s father. The patient was presented to the clinic at 9 months of age with one month history of left wrist swelling and tenderness. Within one week prior to the presentation, swelling had extended to the dorsal surfaces of the hands. Patient had been misdiagnosed with JIA and treatment with Prednisolone, MTX and ibuprofen was started. Hoarseness had developed 6 months earlier. Weight loss was also reported. On examination, lower limbs were normal but in upper limbs, limitations in flexion and extension of wrist and swelling of fingers were noted. Patient was presented to the clinic again at 18 months of age with delayed motor development, multiple subcutaneous nodules in wrists and ankles, respiratory distress and hoarseness ( Figure 2 ). In bronchoscopy, large cysts on vocal cords were seen. On radiography, osteopenia was evident (bone age equal to 9 months at the age of 18 months). CXR visualized bilateral perihilar opacities and hyperinflation in both lungs. In kidney, contrast opacity resembling kidney stone was seen. HPLC was normal. Laryngeal nodules led to severe respiratory distress which his life ended after ICU admission and tracheostomy insertion.'}
|
Lymphatic-System
|
LYMPH
|
[] |
test-1977
|
6944811
|
{'1 st case': 'This patient was a 4-year old girl, second child of related parents, delivered by cesarean section without any insult. This child developed wrist swelling at 6 months of age. Swelling of other joints were gradually added. On examination, swelling and limitation in range of motion was detected in PIP, MCP, wrist, elbow and shoulder joints of upper limbs and PIP, MTP, tarsal joints and ankle in lower limbs. Multiple firm subcutaneous nodules were found on joints –mainly on extensor surfaces- which led to deformation of joint, tenderness and inability to walk. Contracture in joints was evident in physical examination. Progressive hoarseness was present. Reports of head drop attacks were found in the history. In neurologic examination, deep tendon reflexes were diminished or absent. Although cognitive function of this patient was normal, motor and speech development was delayed. Two years later, development of seizure and tremor was reported. Tremor was evident in all limbs on physical examination. Laboratory serologic tests were normal. Radiography of both hands showed reduction in density of bones, swelling of both wrists, deformity of wrist bones, marginal erosion of wrist bones and distal phalanges in PIP and DIP joints which all were suggestive of advanced juvenile idiopathic arthritis (JIA). Chest X-ray also showed alveolar opacities with air bronchogram in the upper lobe of right lung which were in favor of pneumonia. Bronchoscopy showed a circular contraction in subglottic region of larynx. After development of neurologic involvements, Farber disease was suspected. To confirm the diagnostic suspicion, genetic analysis was performed. ASAH1 gene analysis –gene related to Farber syndrome- revealed a homozygous variant which confirmed the presence of Farber disease in this patient. This variant was a novel mutation in exon 8 of ASAH1 gene (c.553T>C p.Trp185Arg). Patient had not received treatment till the age of 2.5 years. After she was diagnosed with JIA, methotrexate, hydroxychloroquine, prednisolone and infliximab medications were initiated. After genetic testing and establishment of the diagnosis of Farber disease, patient’s treatment was switched to cyclosporine and prednisolone. With the development of neurologic involvements, Topiramate, valproate sodium and clobazam was prescribed for relieving debilitating neurologic symptoms. Bone marrow transplantation was suggested as a treatment strategy for the patient but the suggestion was declined by the family. She has under follow up after 2.5 years with neurological deficit.', '2 nd case': 'This patient was a 4 year-old girl, first child of a non-related couple, delivered by NVD who was term on birth. The patient developed swelling of joints at 7 months of age. Particularly in PIP and MCP joints, wrists and ankles ( Figure 1a ). On examination at the age of 2 years, she had multiple subcutaneous nodules on head, hands and chest ( Figure 1b ). Progressive hoarseness was also present. Extensive mucosal lesions were detected in the oral cavity. Limitation in knee’s range of motion was severe leading to difficulty in walking. Cutaneous lesions were also seen on abdomen. In the follow-up after two years, patient had developed nasal swelling. On examination, three relatively soft masses were found within lumbar to coccygeal regions of the spine with diameters of up to 5 centimeters ( Figure 1c ). Muscular atrophy of all four limbs and gluteal region was evident. In the auscultation of the lungs, wheezing was detected. Joints’ examination showed nodules and range of motion limitation in both elbows, shoulders, MCPs, PIPs and DIPs in upper limbs. In lower limbs, knees and ankles were affected with contracture, nodules and range of motion limitation. In radiography, bilateral destruction of proximal humerus and severe osteopenia were seen. After a while, progression of hoarseness and development of multiple percutaneous nodules put the diagnosis of JIA under question. Biopsies were taken from nodules to rule out Farber disease. Histopathologic examination reported collection of collagen bundles and foamy macrophages which were suggestive of Farber disease. With the early diagnosis of JIA, the patient underwent treatment with folic acid, prednisolone, cyclosporine, ibuprofen, calcium supplement and nystatin. MTX was initiated for the patient but then was discontinued due to the appearance of cutaneous lesions on the body. Corticosteroid pulses and Etanercept injections were also prescribed. Subcutaneous nodules increased gradually and she was admitted 4 times due to respiratory distress. Finally she died from respiratory failure in one episode at 4 years old.', '3 rd case': 'This patient was a 9-month old boy, the first child of related parents who was delivered by NVD without any insult. Rheumatoid arthritis history was positive for patient’s father. The patient was presented to the clinic at 9 months of age with one month history of left wrist swelling and tenderness. Within one week prior to the presentation, swelling had extended to the dorsal surfaces of the hands. Patient had been misdiagnosed with JIA and treatment with Prednisolone, MTX and ibuprofen was started. Hoarseness had developed 6 months earlier. Weight loss was also reported. On examination, lower limbs were normal but in upper limbs, limitations in flexion and extension of wrist and swelling of fingers were noted. Patient was presented to the clinic again at 18 months of age with delayed motor development, multiple subcutaneous nodules in wrists and ankles, respiratory distress and hoarseness ( Figure 2 ). In bronchoscopy, large cysts on vocal cords were seen. On radiography, osteopenia was evident (bone age equal to 9 months at the age of 18 months). CXR visualized bilateral perihilar opacities and hyperinflation in both lungs. In kidney, contrast opacity resembling kidney stone was seen. HPLC was normal. Laryngeal nodules led to severe respiratory distress which his life ended after ICU admission and tracheostomy insertion.'}
|
{'1 st case': 'This patient was a 4-year old girl, second child of related parents, delivered by cesarean section without any insult. This child developed wrist swelling at 6 months of age. Swelling of other joints were gradually added. On examination, swelling and limitation in range of motion was detected in PIP, MCP, wrist, elbow and shoulder joints of upper limbs and PIP, MTP, tarsal joints and ankle in lower limbs. Multiple firm subcutaneous nodules were found on joints –mainly on extensor surfaces- which led to deformation of joint, tenderness and inability to walk. Contracture in joints was evident in physical examination. Progressive hoarseness was present. Reports of head drop attacks were found in the history. In neurologic examination, deep tendon reflexes were diminished or absent. Although cognitive function of this patient was normal, motor and speech development was delayed. Two years later, development of seizure and tremor was reported. Tremor was evident in all limbs on physical examination. Laboratory serologic tests were normal. Radiography of both hands showed reduction in density of bones, swelling of both wrists, deformity of wrist bones, marginal erosion of wrist bones and distal phalanges in PIP and DIP joints which all were suggestive of advanced juvenile idiopathic arthritis (JIA). Chest X-ray also showed alveolar opacities with air bronchogram in the upper lobe of right lung which were in favor of pneumonia. Bronchoscopy showed a circular contraction in subglottic region of larynx. After development of neurologic involvements, Farber disease was suspected. To confirm the diagnostic suspicion, genetic analysis was performed. ASAH1 gene analysis –gene related to Farber syndrome- revealed a homozygous variant which confirmed the presence of Farber disease in this patient. This variant was a novel mutation in exon 8 of ASAH1 gene (c.553T>C p.Trp185Arg). Patient had not received treatment till the age of 2.5 years. After she was diagnosed with JIA, methotrexate, hydroxychloroquine, prednisolone and infliximab medications were initiated. After genetic testing and establishment of the diagnosis of Farber disease, patient’s treatment was switched to cyclosporine and prednisolone. With the development of neurologic involvements, Topiramate, valproate sodium and clobazam was prescribed for relieving debilitating neurologic symptoms. Bone marrow transplantation was suggested as a treatment strategy for the patient but the suggestion was declined by the family. She has under follow up after 2.5 years with neurological deficit.', '2 nd case': 'This patient was a 4 year-old girl, first child of a non-related couple, delivered by NVD who was term on birth. The patient developed swelling of joints at 7 months of age. Particularly in PIP and MCP joints, wrists and ankles ( Figure 1a ). On examination at the age of 2 years, she had multiple subcutaneous nodules on head, hands and chest ( Figure 1b ). Progressive hoarseness was also present. Extensive mucosal lesions were detected in the oral cavity. Limitation in knee’s range of motion was severe leading to difficulty in walking. Cutaneous lesions were also seen on abdomen. In the follow-up after two years, patient had developed nasal swelling. On examination, three relatively soft masses were found within lumbar to coccygeal regions of the spine with diameters of up to 5 centimeters ( Figure 1c ). Muscular atrophy of all four limbs and gluteal region was evident. In the auscultation of the lungs, wheezing was detected. Joints’ examination showed nodules and range of motion limitation in both elbows, shoulders, MCPs, PIPs and DIPs in upper limbs. In lower limbs, knees and ankles were affected with contracture, nodules and range of motion limitation. In radiography, bilateral destruction of proximal humerus and severe osteopenia were seen. After a while, progression of hoarseness and development of multiple percutaneous nodules put the diagnosis of JIA under question. Biopsies were taken from nodules to rule out Farber disease. Histopathologic examination reported collection of collagen bundles and foamy macrophages which were suggestive of Farber disease. With the early diagnosis of JIA, the patient underwent treatment with folic acid, prednisolone, cyclosporine, ibuprofen, calcium supplement and nystatin. MTX was initiated for the patient but then was discontinued due to the appearance of cutaneous lesions on the body. Corticosteroid pulses and Etanercept injections were also prescribed. Subcutaneous nodules increased gradually and she was admitted 4 times due to respiratory distress. Finally she died from respiratory failure in one episode at 4 years old.', '3 rd case': 'This patient was a 9-month old boy, the first child of related parents who was delivered by NVD without any insult. Rheumatoid arthritis history was positive for patient’s father. The patient was presented to the clinic at 9 months of age with one month history of left wrist swelling and tenderness. Within one week prior to the presentation, swelling had extended to the dorsal surfaces of the hands. Patient had been misdiagnosed with JIA and treatment with Prednisolone, MTX and ibuprofen was started. Hoarseness had developed 6 months earlier. Weight loss was also reported. On examination, lower limbs were normal but in upper limbs, limitations in flexion and extension of wrist and swelling of fingers were noted. Patient was presented to the clinic again at 18 months of age with delayed motor development, multiple subcutaneous nodules in wrists and ankles, respiratory distress and hoarseness ( Figure 2 ). In bronchoscopy, large cysts on vocal cords were seen. On radiography, osteopenia was evident (bone age equal to 9 months at the age of 18 months). CXR visualized bilateral perihilar opacities and hyperinflation in both lungs. In kidney, contrast opacity resembling kidney stone was seen. HPLC was normal. Laryngeal nodules led to severe respiratory distress which his life ended after ICU admission and tracheostomy insertion.'}
|
Age-at-Presentation
|
Age (at case presentation)
|
[
"4 - year old",
"4 year - old",
"9 - month old"
] |
test-1978
|
6944811
|
{'1 st case': 'This patient was a 4-year old girl, second child of related parents, delivered by cesarean section without any insult. This child developed wrist swelling at 6 months of age. Swelling of other joints were gradually added. On examination, swelling and limitation in range of motion was detected in PIP, MCP, wrist, elbow and shoulder joints of upper limbs and PIP, MTP, tarsal joints and ankle in lower limbs. Multiple firm subcutaneous nodules were found on joints –mainly on extensor surfaces- which led to deformation of joint, tenderness and inability to walk. Contracture in joints was evident in physical examination. Progressive hoarseness was present. Reports of head drop attacks were found in the history. In neurologic examination, deep tendon reflexes were diminished or absent. Although cognitive function of this patient was normal, motor and speech development was delayed. Two years later, development of seizure and tremor was reported. Tremor was evident in all limbs on physical examination. Laboratory serologic tests were normal. Radiography of both hands showed reduction in density of bones, swelling of both wrists, deformity of wrist bones, marginal erosion of wrist bones and distal phalanges in PIP and DIP joints which all were suggestive of advanced juvenile idiopathic arthritis (JIA). Chest X-ray also showed alveolar opacities with air bronchogram in the upper lobe of right lung which were in favor of pneumonia. Bronchoscopy showed a circular contraction in subglottic region of larynx. After development of neurologic involvements, Farber disease was suspected. To confirm the diagnostic suspicion, genetic analysis was performed. ASAH1 gene analysis –gene related to Farber syndrome- revealed a homozygous variant which confirmed the presence of Farber disease in this patient. This variant was a novel mutation in exon 8 of ASAH1 gene (c.553T>C p.Trp185Arg). Patient had not received treatment till the age of 2.5 years. After she was diagnosed with JIA, methotrexate, hydroxychloroquine, prednisolone and infliximab medications were initiated. After genetic testing and establishment of the diagnosis of Farber disease, patient’s treatment was switched to cyclosporine and prednisolone. With the development of neurologic involvements, Topiramate, valproate sodium and clobazam was prescribed for relieving debilitating neurologic symptoms. Bone marrow transplantation was suggested as a treatment strategy for the patient but the suggestion was declined by the family. She has under follow up after 2.5 years with neurological deficit.', '2 nd case': 'This patient was a 4 year-old girl, first child of a non-related couple, delivered by NVD who was term on birth. The patient developed swelling of joints at 7 months of age. Particularly in PIP and MCP joints, wrists and ankles ( Figure 1a ). On examination at the age of 2 years, she had multiple subcutaneous nodules on head, hands and chest ( Figure 1b ). Progressive hoarseness was also present. Extensive mucosal lesions were detected in the oral cavity. Limitation in knee’s range of motion was severe leading to difficulty in walking. Cutaneous lesions were also seen on abdomen. In the follow-up after two years, patient had developed nasal swelling. On examination, three relatively soft masses were found within lumbar to coccygeal regions of the spine with diameters of up to 5 centimeters ( Figure 1c ). Muscular atrophy of all four limbs and gluteal region was evident. In the auscultation of the lungs, wheezing was detected. Joints’ examination showed nodules and range of motion limitation in both elbows, shoulders, MCPs, PIPs and DIPs in upper limbs. In lower limbs, knees and ankles were affected with contracture, nodules and range of motion limitation. In radiography, bilateral destruction of proximal humerus and severe osteopenia were seen. After a while, progression of hoarseness and development of multiple percutaneous nodules put the diagnosis of JIA under question. Biopsies were taken from nodules to rule out Farber disease. Histopathologic examination reported collection of collagen bundles and foamy macrophages which were suggestive of Farber disease. With the early diagnosis of JIA, the patient underwent treatment with folic acid, prednisolone, cyclosporine, ibuprofen, calcium supplement and nystatin. MTX was initiated for the patient but then was discontinued due to the appearance of cutaneous lesions on the body. Corticosteroid pulses and Etanercept injections were also prescribed. Subcutaneous nodules increased gradually and she was admitted 4 times due to respiratory distress. Finally she died from respiratory failure in one episode at 4 years old.', '3 rd case': 'This patient was a 9-month old boy, the first child of related parents who was delivered by NVD without any insult. Rheumatoid arthritis history was positive for patient’s father. The patient was presented to the clinic at 9 months of age with one month history of left wrist swelling and tenderness. Within one week prior to the presentation, swelling had extended to the dorsal surfaces of the hands. Patient had been misdiagnosed with JIA and treatment with Prednisolone, MTX and ibuprofen was started. Hoarseness had developed 6 months earlier. Weight loss was also reported. On examination, lower limbs were normal but in upper limbs, limitations in flexion and extension of wrist and swelling of fingers were noted. Patient was presented to the clinic again at 18 months of age with delayed motor development, multiple subcutaneous nodules in wrists and ankles, respiratory distress and hoarseness ( Figure 2 ). In bronchoscopy, large cysts on vocal cords were seen. On radiography, osteopenia was evident (bone age equal to 9 months at the age of 18 months). CXR visualized bilateral perihilar opacities and hyperinflation in both lungs. In kidney, contrast opacity resembling kidney stone was seen. HPLC was normal. Laryngeal nodules led to severe respiratory distress which his life ended after ICU admission and tracheostomy insertion.'}
|
{'1 st case': 'This patient was a 4-year old girl, second child of related parents, delivered by cesarean section without any insult. This child developed wrist swelling at 6 months of age. Swelling of other joints were gradually added. On examination, swelling and limitation in range of motion was detected in PIP, MCP, wrist, elbow and shoulder joints of upper limbs and PIP, MTP, tarsal joints and ankle in lower limbs. Multiple firm subcutaneous nodules were found on joints –mainly on extensor surfaces- which led to deformation of joint, tenderness and inability to walk. Contracture in joints was evident in physical examination. Progressive hoarseness was present. Reports of head drop attacks were found in the history. In neurologic examination, deep tendon reflexes were diminished or absent. Although cognitive function of this patient was normal, motor and speech development was delayed. Two years later, development of seizure and tremor was reported. Tremor was evident in all limbs on physical examination. Laboratory serologic tests were normal. Radiography of both hands showed reduction in density of bones, swelling of both wrists, deformity of wrist bones, marginal erosion of wrist bones and distal phalanges in PIP and DIP joints which all were suggestive of advanced juvenile idiopathic arthritis (JIA). Chest X-ray also showed alveolar opacities with air bronchogram in the upper lobe of right lung which were in favor of pneumonia. Bronchoscopy showed a circular contraction in subglottic region of larynx. After development of neurologic involvements, Farber disease was suspected. To confirm the diagnostic suspicion, genetic analysis was performed. ASAH1 gene analysis –gene related to Farber syndrome- revealed a homozygous variant which confirmed the presence of Farber disease in this patient. This variant was a novel mutation in exon 8 of ASAH1 gene (c.553T>C p.Trp185Arg). Patient had not received treatment till the age of 2.5 years. After she was diagnosed with JIA, methotrexate, hydroxychloroquine, prednisolone and infliximab medications were initiated. After genetic testing and establishment of the diagnosis of Farber disease, patient’s treatment was switched to cyclosporine and prednisolone. With the development of neurologic involvements, Topiramate, valproate sodium and clobazam was prescribed for relieving debilitating neurologic symptoms. Bone marrow transplantation was suggested as a treatment strategy for the patient but the suggestion was declined by the family. She has under follow up after 2.5 years with neurological deficit.', '2 nd case': 'This patient was a 4 year-old girl, first child of a non-related couple, delivered by NVD who was term on birth. The patient developed swelling of joints at 7 months of age. Particularly in PIP and MCP joints, wrists and ankles ( Figure 1a ). On examination at the age of 2 years, she had multiple subcutaneous nodules on head, hands and chest ( Figure 1b ). Progressive hoarseness was also present. Extensive mucosal lesions were detected in the oral cavity. Limitation in knee’s range of motion was severe leading to difficulty in walking. Cutaneous lesions were also seen on abdomen. In the follow-up after two years, patient had developed nasal swelling. On examination, three relatively soft masses were found within lumbar to coccygeal regions of the spine with diameters of up to 5 centimeters ( Figure 1c ). Muscular atrophy of all four limbs and gluteal region was evident. In the auscultation of the lungs, wheezing was detected. Joints’ examination showed nodules and range of motion limitation in both elbows, shoulders, MCPs, PIPs and DIPs in upper limbs. In lower limbs, knees and ankles were affected with contracture, nodules and range of motion limitation. In radiography, bilateral destruction of proximal humerus and severe osteopenia were seen. After a while, progression of hoarseness and development of multiple percutaneous nodules put the diagnosis of JIA under question. Biopsies were taken from nodules to rule out Farber disease. Histopathologic examination reported collection of collagen bundles and foamy macrophages which were suggestive of Farber disease. With the early diagnosis of JIA, the patient underwent treatment with folic acid, prednisolone, cyclosporine, ibuprofen, calcium supplement and nystatin. MTX was initiated for the patient but then was discontinued due to the appearance of cutaneous lesions on the body. Corticosteroid pulses and Etanercept injections were also prescribed. Subcutaneous nodules increased gradually and she was admitted 4 times due to respiratory distress. Finally she died from respiratory failure in one episode at 4 years old.', '3 rd case': 'This patient was a 9-month old boy, the first child of related parents who was delivered by NVD without any insult. Rheumatoid arthritis history was positive for patient’s father. The patient was presented to the clinic at 9 months of age with one month history of left wrist swelling and tenderness. Within one week prior to the presentation, swelling had extended to the dorsal surfaces of the hands. Patient had been misdiagnosed with JIA and treatment with Prednisolone, MTX and ibuprofen was started. Hoarseness had developed 6 months earlier. Weight loss was also reported. On examination, lower limbs were normal but in upper limbs, limitations in flexion and extension of wrist and swelling of fingers were noted. Patient was presented to the clinic again at 18 months of age with delayed motor development, multiple subcutaneous nodules in wrists and ankles, respiratory distress and hoarseness ( Figure 2 ). In bronchoscopy, large cysts on vocal cords were seen. On radiography, osteopenia was evident (bone age equal to 9 months at the age of 18 months). CXR visualized bilateral perihilar opacities and hyperinflation in both lungs. In kidney, contrast opacity resembling kidney stone was seen. HPLC was normal. Laryngeal nodules led to severe respiratory distress which his life ended after ICU admission and tracheostomy insertion.'}
|
Age-of-Onset
|
Age (of onset)
|
[
"6 months of age",
"7 months of age"
] |
test-1979
|
6944811
|
{'1 st case': 'This patient was a 4-year old girl, second child of related parents, delivered by cesarean section without any insult. This child developed wrist swelling at 6 months of age. Swelling of other joints were gradually added. On examination, swelling and limitation in range of motion was detected in PIP, MCP, wrist, elbow and shoulder joints of upper limbs and PIP, MTP, tarsal joints and ankle in lower limbs. Multiple firm subcutaneous nodules were found on joints –mainly on extensor surfaces- which led to deformation of joint, tenderness and inability to walk. Contracture in joints was evident in physical examination. Progressive hoarseness was present. Reports of head drop attacks were found in the history. In neurologic examination, deep tendon reflexes were diminished or absent. Although cognitive function of this patient was normal, motor and speech development was delayed. Two years later, development of seizure and tremor was reported. Tremor was evident in all limbs on physical examination. Laboratory serologic tests were normal. Radiography of both hands showed reduction in density of bones, swelling of both wrists, deformity of wrist bones, marginal erosion of wrist bones and distal phalanges in PIP and DIP joints which all were suggestive of advanced juvenile idiopathic arthritis (JIA). Chest X-ray also showed alveolar opacities with air bronchogram in the upper lobe of right lung which were in favor of pneumonia. Bronchoscopy showed a circular contraction in subglottic region of larynx. After development of neurologic involvements, Farber disease was suspected. To confirm the diagnostic suspicion, genetic analysis was performed. ASAH1 gene analysis –gene related to Farber syndrome- revealed a homozygous variant which confirmed the presence of Farber disease in this patient. This variant was a novel mutation in exon 8 of ASAH1 gene (c.553T>C p.Trp185Arg). Patient had not received treatment till the age of 2.5 years. After she was diagnosed with JIA, methotrexate, hydroxychloroquine, prednisolone and infliximab medications were initiated. After genetic testing and establishment of the diagnosis of Farber disease, patient’s treatment was switched to cyclosporine and prednisolone. With the development of neurologic involvements, Topiramate, valproate sodium and clobazam was prescribed for relieving debilitating neurologic symptoms. Bone marrow transplantation was suggested as a treatment strategy for the patient but the suggestion was declined by the family. She has under follow up after 2.5 years with neurological deficit.', '2 nd case': 'This patient was a 4 year-old girl, first child of a non-related couple, delivered by NVD who was term on birth. The patient developed swelling of joints at 7 months of age. Particularly in PIP and MCP joints, wrists and ankles ( Figure 1a ). On examination at the age of 2 years, she had multiple subcutaneous nodules on head, hands and chest ( Figure 1b ). Progressive hoarseness was also present. Extensive mucosal lesions were detected in the oral cavity. Limitation in knee’s range of motion was severe leading to difficulty in walking. Cutaneous lesions were also seen on abdomen. In the follow-up after two years, patient had developed nasal swelling. On examination, three relatively soft masses were found within lumbar to coccygeal regions of the spine with diameters of up to 5 centimeters ( Figure 1c ). Muscular atrophy of all four limbs and gluteal region was evident. In the auscultation of the lungs, wheezing was detected. Joints’ examination showed nodules and range of motion limitation in both elbows, shoulders, MCPs, PIPs and DIPs in upper limbs. In lower limbs, knees and ankles were affected with contracture, nodules and range of motion limitation. In radiography, bilateral destruction of proximal humerus and severe osteopenia were seen. After a while, progression of hoarseness and development of multiple percutaneous nodules put the diagnosis of JIA under question. Biopsies were taken from nodules to rule out Farber disease. Histopathologic examination reported collection of collagen bundles and foamy macrophages which were suggestive of Farber disease. With the early diagnosis of JIA, the patient underwent treatment with folic acid, prednisolone, cyclosporine, ibuprofen, calcium supplement and nystatin. MTX was initiated for the patient but then was discontinued due to the appearance of cutaneous lesions on the body. Corticosteroid pulses and Etanercept injections were also prescribed. Subcutaneous nodules increased gradually and she was admitted 4 times due to respiratory distress. Finally she died from respiratory failure in one episode at 4 years old.', '3 rd case': 'This patient was a 9-month old boy, the first child of related parents who was delivered by NVD without any insult. Rheumatoid arthritis history was positive for patient’s father. The patient was presented to the clinic at 9 months of age with one month history of left wrist swelling and tenderness. Within one week prior to the presentation, swelling had extended to the dorsal surfaces of the hands. Patient had been misdiagnosed with JIA and treatment with Prednisolone, MTX and ibuprofen was started. Hoarseness had developed 6 months earlier. Weight loss was also reported. On examination, lower limbs were normal but in upper limbs, limitations in flexion and extension of wrist and swelling of fingers were noted. Patient was presented to the clinic again at 18 months of age with delayed motor development, multiple subcutaneous nodules in wrists and ankles, respiratory distress and hoarseness ( Figure 2 ). In bronchoscopy, large cysts on vocal cords were seen. On radiography, osteopenia was evident (bone age equal to 9 months at the age of 18 months). CXR visualized bilateral perihilar opacities and hyperinflation in both lungs. In kidney, contrast opacity resembling kidney stone was seen. HPLC was normal. Laryngeal nodules led to severe respiratory distress which his life ended after ICU admission and tracheostomy insertion.'}
|
{'1 st case': 'This patient was a 4-year old girl, second child of related parents, delivered by cesarean section without any insult. This child developed wrist swelling at 6 months of age. Swelling of other joints were gradually added. On examination, swelling and limitation in range of motion was detected in PIP, MCP, wrist, elbow and shoulder joints of upper limbs and PIP, MTP, tarsal joints and ankle in lower limbs. Multiple firm subcutaneous nodules were found on joints –mainly on extensor surfaces- which led to deformation of joint, tenderness and inability to walk. Contracture in joints was evident in physical examination. Progressive hoarseness was present. Reports of head drop attacks were found in the history. In neurologic examination, deep tendon reflexes were diminished or absent. Although cognitive function of this patient was normal, motor and speech development was delayed. Two years later, development of seizure and tremor was reported. Tremor was evident in all limbs on physical examination. Laboratory serologic tests were normal. Radiography of both hands showed reduction in density of bones, swelling of both wrists, deformity of wrist bones, marginal erosion of wrist bones and distal phalanges in PIP and DIP joints which all were suggestive of advanced juvenile idiopathic arthritis (JIA). Chest X-ray also showed alveolar opacities with air bronchogram in the upper lobe of right lung which were in favor of pneumonia. Bronchoscopy showed a circular contraction in subglottic region of larynx. After development of neurologic involvements, Farber disease was suspected. To confirm the diagnostic suspicion, genetic analysis was performed. ASAH1 gene analysis –gene related to Farber syndrome- revealed a homozygous variant which confirmed the presence of Farber disease in this patient. This variant was a novel mutation in exon 8 of ASAH1 gene (c.553T>C p.Trp185Arg). Patient had not received treatment till the age of 2.5 years. After she was diagnosed with JIA, methotrexate, hydroxychloroquine, prednisolone and infliximab medications were initiated. After genetic testing and establishment of the diagnosis of Farber disease, patient’s treatment was switched to cyclosporine and prednisolone. With the development of neurologic involvements, Topiramate, valproate sodium and clobazam was prescribed for relieving debilitating neurologic symptoms. Bone marrow transplantation was suggested as a treatment strategy for the patient but the suggestion was declined by the family. She has under follow up after 2.5 years with neurological deficit.', '2 nd case': 'This patient was a 4 year-old girl, first child of a non-related couple, delivered by NVD who was term on birth. The patient developed swelling of joints at 7 months of age. Particularly in PIP and MCP joints, wrists and ankles ( Figure 1a ). On examination at the age of 2 years, she had multiple subcutaneous nodules on head, hands and chest ( Figure 1b ). Progressive hoarseness was also present. Extensive mucosal lesions were detected in the oral cavity. Limitation in knee’s range of motion was severe leading to difficulty in walking. Cutaneous lesions were also seen on abdomen. In the follow-up after two years, patient had developed nasal swelling. On examination, three relatively soft masses were found within lumbar to coccygeal regions of the spine with diameters of up to 5 centimeters ( Figure 1c ). Muscular atrophy of all four limbs and gluteal region was evident. In the auscultation of the lungs, wheezing was detected. Joints’ examination showed nodules and range of motion limitation in both elbows, shoulders, MCPs, PIPs and DIPs in upper limbs. In lower limbs, knees and ankles were affected with contracture, nodules and range of motion limitation. In radiography, bilateral destruction of proximal humerus and severe osteopenia were seen. After a while, progression of hoarseness and development of multiple percutaneous nodules put the diagnosis of JIA under question. Biopsies were taken from nodules to rule out Farber disease. Histopathologic examination reported collection of collagen bundles and foamy macrophages which were suggestive of Farber disease. With the early diagnosis of JIA, the patient underwent treatment with folic acid, prednisolone, cyclosporine, ibuprofen, calcium supplement and nystatin. MTX was initiated for the patient but then was discontinued due to the appearance of cutaneous lesions on the body. Corticosteroid pulses and Etanercept injections were also prescribed. Subcutaneous nodules increased gradually and she was admitted 4 times due to respiratory distress. Finally she died from respiratory failure in one episode at 4 years old.', '3 rd case': 'This patient was a 9-month old boy, the first child of related parents who was delivered by NVD without any insult. Rheumatoid arthritis history was positive for patient’s father. The patient was presented to the clinic at 9 months of age with one month history of left wrist swelling and tenderness. Within one week prior to the presentation, swelling had extended to the dorsal surfaces of the hands. Patient had been misdiagnosed with JIA and treatment with Prednisolone, MTX and ibuprofen was started. Hoarseness had developed 6 months earlier. Weight loss was also reported. On examination, lower limbs were normal but in upper limbs, limitations in flexion and extension of wrist and swelling of fingers were noted. Patient was presented to the clinic again at 18 months of age with delayed motor development, multiple subcutaneous nodules in wrists and ankles, respiratory distress and hoarseness ( Figure 2 ). In bronchoscopy, large cysts on vocal cords were seen. On radiography, osteopenia was evident (bone age equal to 9 months at the age of 18 months). CXR visualized bilateral perihilar opacities and hyperinflation in both lungs. In kidney, contrast opacity resembling kidney stone was seen. HPLC was normal. Laryngeal nodules led to severe respiratory distress which his life ended after ICU admission and tracheostomy insertion.'}
|
Confirmed-Diagnosis-IEM
|
Confirmed_Diagnosis(IEM)
|
[
"confirmed the presence of Farber disease in this patient"
] |
test-1980
|
6944811
|
{'1 st case': 'This patient was a 4-year old girl, second child of related parents, delivered by cesarean section without any insult. This child developed wrist swelling at 6 months of age. Swelling of other joints were gradually added. On examination, swelling and limitation in range of motion was detected in PIP, MCP, wrist, elbow and shoulder joints of upper limbs and PIP, MTP, tarsal joints and ankle in lower limbs. Multiple firm subcutaneous nodules were found on joints –mainly on extensor surfaces- which led to deformation of joint, tenderness and inability to walk. Contracture in joints was evident in physical examination. Progressive hoarseness was present. Reports of head drop attacks were found in the history. In neurologic examination, deep tendon reflexes were diminished or absent. Although cognitive function of this patient was normal, motor and speech development was delayed. Two years later, development of seizure and tremor was reported. Tremor was evident in all limbs on physical examination. Laboratory serologic tests were normal. Radiography of both hands showed reduction in density of bones, swelling of both wrists, deformity of wrist bones, marginal erosion of wrist bones and distal phalanges in PIP and DIP joints which all were suggestive of advanced juvenile idiopathic arthritis (JIA). Chest X-ray also showed alveolar opacities with air bronchogram in the upper lobe of right lung which were in favor of pneumonia. Bronchoscopy showed a circular contraction in subglottic region of larynx. After development of neurologic involvements, Farber disease was suspected. To confirm the diagnostic suspicion, genetic analysis was performed. ASAH1 gene analysis –gene related to Farber syndrome- revealed a homozygous variant which confirmed the presence of Farber disease in this patient. This variant was a novel mutation in exon 8 of ASAH1 gene (c.553T>C p.Trp185Arg). Patient had not received treatment till the age of 2.5 years. After she was diagnosed with JIA, methotrexate, hydroxychloroquine, prednisolone and infliximab medications were initiated. After genetic testing and establishment of the diagnosis of Farber disease, patient’s treatment was switched to cyclosporine and prednisolone. With the development of neurologic involvements, Topiramate, valproate sodium and clobazam was prescribed for relieving debilitating neurologic symptoms. Bone marrow transplantation was suggested as a treatment strategy for the patient but the suggestion was declined by the family. She has under follow up after 2.5 years with neurological deficit.', '2 nd case': 'This patient was a 4 year-old girl, first child of a non-related couple, delivered by NVD who was term on birth. The patient developed swelling of joints at 7 months of age. Particularly in PIP and MCP joints, wrists and ankles ( Figure 1a ). On examination at the age of 2 years, she had multiple subcutaneous nodules on head, hands and chest ( Figure 1b ). Progressive hoarseness was also present. Extensive mucosal lesions were detected in the oral cavity. Limitation in knee’s range of motion was severe leading to difficulty in walking. Cutaneous lesions were also seen on abdomen. In the follow-up after two years, patient had developed nasal swelling. On examination, three relatively soft masses were found within lumbar to coccygeal regions of the spine with diameters of up to 5 centimeters ( Figure 1c ). Muscular atrophy of all four limbs and gluteal region was evident. In the auscultation of the lungs, wheezing was detected. Joints’ examination showed nodules and range of motion limitation in both elbows, shoulders, MCPs, PIPs and DIPs in upper limbs. In lower limbs, knees and ankles were affected with contracture, nodules and range of motion limitation. In radiography, bilateral destruction of proximal humerus and severe osteopenia were seen. After a while, progression of hoarseness and development of multiple percutaneous nodules put the diagnosis of JIA under question. Biopsies were taken from nodules to rule out Farber disease. Histopathologic examination reported collection of collagen bundles and foamy macrophages which were suggestive of Farber disease. With the early diagnosis of JIA, the patient underwent treatment with folic acid, prednisolone, cyclosporine, ibuprofen, calcium supplement and nystatin. MTX was initiated for the patient but then was discontinued due to the appearance of cutaneous lesions on the body. Corticosteroid pulses and Etanercept injections were also prescribed. Subcutaneous nodules increased gradually and she was admitted 4 times due to respiratory distress. Finally she died from respiratory failure in one episode at 4 years old.', '3 rd case': 'This patient was a 9-month old boy, the first child of related parents who was delivered by NVD without any insult. Rheumatoid arthritis history was positive for patient’s father. The patient was presented to the clinic at 9 months of age with one month history of left wrist swelling and tenderness. Within one week prior to the presentation, swelling had extended to the dorsal surfaces of the hands. Patient had been misdiagnosed with JIA and treatment with Prednisolone, MTX and ibuprofen was started. Hoarseness had developed 6 months earlier. Weight loss was also reported. On examination, lower limbs were normal but in upper limbs, limitations in flexion and extension of wrist and swelling of fingers were noted. Patient was presented to the clinic again at 18 months of age with delayed motor development, multiple subcutaneous nodules in wrists and ankles, respiratory distress and hoarseness ( Figure 2 ). In bronchoscopy, large cysts on vocal cords were seen. On radiography, osteopenia was evident (bone age equal to 9 months at the age of 18 months). CXR visualized bilateral perihilar opacities and hyperinflation in both lungs. In kidney, contrast opacity resembling kidney stone was seen. HPLC was normal. Laryngeal nodules led to severe respiratory distress which his life ended after ICU admission and tracheostomy insertion.'}
|
{'1 st case': 'This patient was a 4-year old girl, second child of related parents, delivered by cesarean section without any insult. This child developed wrist swelling at 6 months of age. Swelling of other joints were gradually added. On examination, swelling and limitation in range of motion was detected in PIP, MCP, wrist, elbow and shoulder joints of upper limbs and PIP, MTP, tarsal joints and ankle in lower limbs. Multiple firm subcutaneous nodules were found on joints –mainly on extensor surfaces- which led to deformation of joint, tenderness and inability to walk. Contracture in joints was evident in physical examination. Progressive hoarseness was present. Reports of head drop attacks were found in the history. In neurologic examination, deep tendon reflexes were diminished or absent. Although cognitive function of this patient was normal, motor and speech development was delayed. Two years later, development of seizure and tremor was reported. Tremor was evident in all limbs on physical examination. Laboratory serologic tests were normal. Radiography of both hands showed reduction in density of bones, swelling of both wrists, deformity of wrist bones, marginal erosion of wrist bones and distal phalanges in PIP and DIP joints which all were suggestive of advanced juvenile idiopathic arthritis (JIA). Chest X-ray also showed alveolar opacities with air bronchogram in the upper lobe of right lung which were in favor of pneumonia. Bronchoscopy showed a circular contraction in subglottic region of larynx. After development of neurologic involvements, Farber disease was suspected. To confirm the diagnostic suspicion, genetic analysis was performed. ASAH1 gene analysis –gene related to Farber syndrome- revealed a homozygous variant which confirmed the presence of Farber disease in this patient. This variant was a novel mutation in exon 8 of ASAH1 gene (c.553T>C p.Trp185Arg). Patient had not received treatment till the age of 2.5 years. After she was diagnosed with JIA, methotrexate, hydroxychloroquine, prednisolone and infliximab medications were initiated. After genetic testing and establishment of the diagnosis of Farber disease, patient’s treatment was switched to cyclosporine and prednisolone. With the development of neurologic involvements, Topiramate, valproate sodium and clobazam was prescribed for relieving debilitating neurologic symptoms. Bone marrow transplantation was suggested as a treatment strategy for the patient but the suggestion was declined by the family. She has under follow up after 2.5 years with neurological deficit.', '2 nd case': 'This patient was a 4 year-old girl, first child of a non-related couple, delivered by NVD who was term on birth. The patient developed swelling of joints at 7 months of age. Particularly in PIP and MCP joints, wrists and ankles ( Figure 1a ). On examination at the age of 2 years, she had multiple subcutaneous nodules on head, hands and chest ( Figure 1b ). Progressive hoarseness was also present. Extensive mucosal lesions were detected in the oral cavity. Limitation in knee’s range of motion was severe leading to difficulty in walking. Cutaneous lesions were also seen on abdomen. In the follow-up after two years, patient had developed nasal swelling. On examination, three relatively soft masses were found within lumbar to coccygeal regions of the spine with diameters of up to 5 centimeters ( Figure 1c ). Muscular atrophy of all four limbs and gluteal region was evident. In the auscultation of the lungs, wheezing was detected. Joints’ examination showed nodules and range of motion limitation in both elbows, shoulders, MCPs, PIPs and DIPs in upper limbs. In lower limbs, knees and ankles were affected with contracture, nodules and range of motion limitation. In radiography, bilateral destruction of proximal humerus and severe osteopenia were seen. After a while, progression of hoarseness and development of multiple percutaneous nodules put the diagnosis of JIA under question. Biopsies were taken from nodules to rule out Farber disease. Histopathologic examination reported collection of collagen bundles and foamy macrophages which were suggestive of Farber disease. With the early diagnosis of JIA, the patient underwent treatment with folic acid, prednisolone, cyclosporine, ibuprofen, calcium supplement and nystatin. MTX was initiated for the patient but then was discontinued due to the appearance of cutaneous lesions on the body. Corticosteroid pulses and Etanercept injections were also prescribed. Subcutaneous nodules increased gradually and she was admitted 4 times due to respiratory distress. Finally she died from respiratory failure in one episode at 4 years old.', '3 rd case': 'This patient was a 9-month old boy, the first child of related parents who was delivered by NVD without any insult. Rheumatoid arthritis history was positive for patient’s father. The patient was presented to the clinic at 9 months of age with one month history of left wrist swelling and tenderness. Within one week prior to the presentation, swelling had extended to the dorsal surfaces of the hands. Patient had been misdiagnosed with JIA and treatment with Prednisolone, MTX and ibuprofen was started. Hoarseness had developed 6 months earlier. Weight loss was also reported. On examination, lower limbs were normal but in upper limbs, limitations in flexion and extension of wrist and swelling of fingers were noted. Patient was presented to the clinic again at 18 months of age with delayed motor development, multiple subcutaneous nodules in wrists and ankles, respiratory distress and hoarseness ( Figure 2 ). In bronchoscopy, large cysts on vocal cords were seen. On radiography, osteopenia was evident (bone age equal to 9 months at the age of 18 months). CXR visualized bilateral perihilar opacities and hyperinflation in both lungs. In kidney, contrast opacity resembling kidney stone was seen. HPLC was normal. Laryngeal nodules led to severe respiratory distress which his life ended after ICU admission and tracheostomy insertion.'}
|
IEM-Treatment
|
IEM_Treatment
|
[
"Bone marrow transplantation was suggested as a treatment strategy for the patient"
] |
test-1981
|
7136505
|
{'Case report': "A male child was born at a gestational age of 39 weeks with no history of antenatal or perinatal problems. Apgar scores were 9 points at one minute and 10 points at 5 minutes. His birth weight and height were 3,800 g ( z -score, +1 standard deviation score) and 52.5 cm ( z -score, +1.4 SDS), respectively. There was no family history of consanguineous marriages. The patient was born with an imperforate anus and a colostomy was performed the day after birth. He had normal male genitalia, with both testes palpable, and postaxial polydactyly of the left foot. A grade 2 systolic murmur was heard in the left upper sternal border and echocardiography revealed a patent ductus arteriosus. Bilateral grade 3 vesicoureteral reflux (VUR) was revealed via voiding cystourethrography. Spine ultrasound revealed no vertebral anomalies, and tracheoesophageal fistula was not suspected clinically. Based on this clinical information, including anal atresia, renal anomalies, and limb abnormalities, he was diagnosed with VACTERL association which is defined by the presence of at least 3 of the following congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. Laboratory test results, including electrolyte levels, were normal. Neonatal screening tests for metabolic disease were also normal, including the 17-alpha-hydroxyprogesterone level. Chromosome analysis revealed a 46, XY karyotype. He was discharged from the neonatal intensive care unit at 21 days of age. At the age of 3 months, the patient was admitted to the hospital for colostomy takedown, anorectoplasty, and endoscopic dextranomer/hyaluronic acid copolymer injection for VUR. After the surgery, the patient was febrile and hypotensive and his abdomen was distended and discolored. An exploratory laparotomy revealed bowel necrosis. Bowel resection with colostomy and jejunostomy was performed 3 times, which resulted in short-bowel syndrome. He could not be discharged because parenteral nutrition was required. The remnant small bowel extended from the Treitz ligament to the jejunocolonic anastomosis and the length of the remnant bowel was only 40 cm. At the age of 7 months, a takedown of the colostomy and jejunostomy was performed. The patient’s mother observed slight bronzing of the patient’s skin after repeated surgeries At 17 months of age, the patient had an episode of sepsis and peritonitis secondary to Acinetobacter baumannii infection and an exploratory laparotomy was performed to check for bowel necrosis. At this time, generalized hyperpigmentation was noted by the doctor and the mother stated that the child's hyperpigmentation was markedly exacerbated after exploratory laparotomy for the episode of peritonitis with sepsis. The patient was referred to our department for the evaluation of the hyperpigmentation. He experienced occasional nausea and vomiting. His heart rate was 120 beats per minute and his blood pressure was 100/65 mmHg. His weight and height were 12.8 kg (1.5 SDS) and 86 cm (2 SDS), respectively. At this point, he was noted to have generalized hyperpigmentation, normal male genitalia, and postaxial polydactyly of the left foot. He was able to ascend stairs with the support of a hand grasp. He could stack 3 cubes, eat without assistance, and pronounce 10 words, meaning that the patient’s developmental status was normal for his age. Laboratory investigations revealed a slightly decreased sodium level (132 mmol/L) but normal potassium (4.8 mEq/L) and glucose (86 mg/dL) levels; complete blood count, blood gas profile, hepatic and renal function, thyroid function test and sex hormone levels were obtained. Decreased cortisol (1.0 μg/dL) and markedly elevated adrenocorticotropic hormone (ACTH) (16,064 pg/mL) levels were noted. The patient's cortisol levels did not respond to stimulation with ACTH (125 μg) ( Table 1 ). Meanwhile, he presented a normal 17-hydroxyprogesterone level (0.42 ng/mL). Plasma renin activity and aldosterone levels were 7.28 ng/mL/hr (normal range, 1.0–6.5 ng/mL/hr) and 0.1 ng/dL (normal range, 3–35 ng/dL), respectively. The abdominal ultrasound revealed no abnormalities, such as adrenal enlargement, hydronephrosis, distal ureter dilatation, or bowel wall thickening. Based on the patient’s symptoms and laboratory results, we considered several genetic causes for primary adrenal insufficiency, and the causative genes of candidate diseases were listed as STAR for NCCLAH and CYP11A1 for congenital adrenal insufficiency. Additionally, melanocortin-2 receptor (MC2R) and MC2R accessory protein for familial glucocorticoid deficiency (FGD) were listed as candidate genes with a low probability because the patient did not have elevated aldosterone. Targeted gene-panel sequencing was performed to check for pathogenic variants in those genes responsible for primary adrenal insufficiency. Genomic DNA was extracted from the peripheral blood of the patient and both parents. Library preparation was done using the TruSight One Sequencing Panel (Illumina, Inc., San Diego, CA, USA), which enriches a 12-Mb region spanning 62,000 target exons of a total of 4,813 genes. Massively parallel sequencing was performed on the Illumina NextSeq platform. Sequence reads were mapped to the UCSC hg19 standard database for comparative analysis. The average depth of the panel was 85.86X, and percentages of bases above 10X of CYP11A1 and STAR were 99.37%, and 100%, respectively. Meanwhile, no pathogenic variants were detected in CYP11A1 genes. The exome-sequencing results revealed compound heterozygous mutations for c.653C>T and c.661G>A (p.Gly221Ser) in exon 6 of the STAR gene. Sanger sequencing confirmed the presence of these variants and each of the same heterozygous variant was found in his father and mother, respectively ( Fig. 1 ). This variant has been previously reported in association with CLAH. Hydrocortisone (7.8 mg/m 2 /day) and fludrocortisone (50 μg/day) were started as therapy for primary adrenal insufficiency. The dose of hydrocortisone was gradually increased until the age of 24 months for sufficient ACTH suppression and levels of ACTH and cortisol were subsequently decreased to the optimal range ( Fig. 2 ). Finally, at 28 months of age, he was discharged and went home with the attainment of oral feeding without nausea and vomiting. He showed no symptoms of hypoglycemia and continued to show normal growth and development. Our last evaluation of the patient was when he was 36 months of age, during which point, his body weight and length were 16.7 kg (0.5 SDS) and 99.7 cm (1.5 SDS), respectively. Laboratory tests revealed normal levels of cortisol (4.6 μg/dL), sodium (139 mmol/L), potassium (4.9 mEq/L), glucose (70 mg/dL), and ACTH (53.6 pg/mL). The generalized hyperpigmentation had improved, and he continued to visit the outpatient clinic regularly without additional admission."}
|
{'Case report': "A male child was born at a gestational age of 39 weeks with no history of antenatal or perinatal problems. Apgar scores were 9 points at one minute and 10 points at 5 minutes. His birth weight and height were 3,800 g ( z -score, +1 standard deviation score) and 52.5 cm ( z -score, +1.4 SDS), respectively. There was no family history of consanguineous marriages. The patient was born with an imperforate anus and a colostomy was performed the day after birth. He had normal male genitalia, with both testes palpable, and postaxial polydactyly of the left foot. A grade 2 systolic murmur was heard in the left upper sternal border and echocardiography revealed a patent ductus arteriosus. Bilateral grade 3 vesicoureteral reflux (VUR) was revealed via voiding cystourethrography. Spine ultrasound revealed no vertebral anomalies, and tracheoesophageal fistula was not suspected clinically. Based on this clinical information, including anal atresia, renal anomalies, and limb abnormalities, he was diagnosed with VACTERL association which is defined by the presence of at least 3 of the following congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. Laboratory test results, including electrolyte levels, were normal. Neonatal screening tests for metabolic disease were also normal, including the 17-alpha-hydroxyprogesterone level. Chromosome analysis revealed a 46, XY karyotype. He was discharged from the neonatal intensive care unit at 21 days of age. At the age of 3 months, the patient was admitted to the hospital for colostomy takedown, anorectoplasty, and endoscopic dextranomer/hyaluronic acid copolymer injection for VUR. After the surgery, the patient was febrile and hypotensive and his abdomen was distended and discolored. An exploratory laparotomy revealed bowel necrosis. Bowel resection with colostomy and jejunostomy was performed 3 times, which resulted in short-bowel syndrome. He could not be discharged because parenteral nutrition was required. The remnant small bowel extended from the Treitz ligament to the jejunocolonic anastomosis and the length of the remnant bowel was only 40 cm. At the age of 7 months, a takedown of the colostomy and jejunostomy was performed. The patient’s mother observed slight bronzing of the patient’s skin after repeated surgeries At 17 months of age, the patient had an episode of sepsis and peritonitis secondary to Acinetobacter baumannii infection and an exploratory laparotomy was performed to check for bowel necrosis. At this time, generalized hyperpigmentation was noted by the doctor and the mother stated that the child's hyperpigmentation was markedly exacerbated after exploratory laparotomy for the episode of peritonitis with sepsis. The patient was referred to our department for the evaluation of the hyperpigmentation. He experienced occasional nausea and vomiting. His heart rate was 120 beats per minute and his blood pressure was 100/65 mmHg. His weight and height were 12.8 kg (1.5 SDS) and 86 cm (2 SDS), respectively. At this point, he was noted to have generalized hyperpigmentation, normal male genitalia, and postaxial polydactyly of the left foot. He was able to ascend stairs with the support of a hand grasp. He could stack 3 cubes, eat without assistance, and pronounce 10 words, meaning that the patient’s developmental status was normal for his age. Laboratory investigations revealed a slightly decreased sodium level (132 mmol/L) but normal potassium (4.8 mEq/L) and glucose (86 mg/dL) levels; complete blood count, blood gas profile, hepatic and renal function, thyroid function test and sex hormone levels were obtained. Decreased cortisol (1.0 μg/dL) and markedly elevated adrenocorticotropic hormone (ACTH) (16,064 pg/mL) levels were noted. The patient's cortisol levels did not respond to stimulation with ACTH (125 μg) ( Table 1 ). Meanwhile, he presented a normal 17-hydroxyprogesterone level (0.42 ng/mL). Plasma renin activity and aldosterone levels were 7.28 ng/mL/hr (normal range, 1.0–6.5 ng/mL/hr) and 0.1 ng/dL (normal range, 3–35 ng/dL), respectively. The abdominal ultrasound revealed no abnormalities, such as adrenal enlargement, hydronephrosis, distal ureter dilatation, or bowel wall thickening. Based on the patient’s symptoms and laboratory results, we considered several genetic causes for primary adrenal insufficiency, and the causative genes of candidate diseases were listed as STAR for NCCLAH and CYP11A1 for congenital adrenal insufficiency. Additionally, melanocortin-2 receptor (MC2R) and MC2R accessory protein for familial glucocorticoid deficiency (FGD) were listed as candidate genes with a low probability because the patient did not have elevated aldosterone. Targeted gene-panel sequencing was performed to check for pathogenic variants in those genes responsible for primary adrenal insufficiency. Genomic DNA was extracted from the peripheral blood of the patient and both parents. Library preparation was done using the TruSight One Sequencing Panel (Illumina, Inc., San Diego, CA, USA), which enriches a 12-Mb region spanning 62,000 target exons of a total of 4,813 genes. Massively parallel sequencing was performed on the Illumina NextSeq platform. Sequence reads were mapped to the UCSC hg19 standard database for comparative analysis. The average depth of the panel was 85.86X, and percentages of bases above 10X of CYP11A1 and STAR were 99.37%, and 100%, respectively. Meanwhile, no pathogenic variants were detected in CYP11A1 genes. The exome-sequencing results revealed compound heterozygous mutations for c.653C>T and c.661G>A (p.Gly221Ser) in exon 6 of the STAR gene. Sanger sequencing confirmed the presence of these variants and each of the same heterozygous variant was found in his father and mother, respectively ( Fig. 1 ). This variant has been previously reported in association with CLAH. Hydrocortisone (7.8 mg/m 2 /day) and fludrocortisone (50 μg/day) were started as therapy for primary adrenal insufficiency. The dose of hydrocortisone was gradually increased until the age of 24 months for sufficient ACTH suppression and levels of ACTH and cortisol were subsequently decreased to the optimal range ( Fig. 2 ). Finally, at 28 months of age, he was discharged and went home with the attainment of oral feeding without nausea and vomiting. He showed no symptoms of hypoglycemia and continued to show normal growth and development. Our last evaluation of the patient was when he was 36 months of age, during which point, his body weight and length were 16.7 kg (0.5 SDS) and 99.7 cm (1.5 SDS), respectively. Laboratory tests revealed normal levels of cortisol (4.6 μg/dL), sodium (139 mmol/L), potassium (4.9 mEq/L), glucose (70 mg/dL), and ACTH (53.6 pg/mL). The generalized hyperpigmentation had improved, and he continued to visit the outpatient clinic regularly without additional admission."}
|
Vitals-and-Hematology
|
Vitals_Hema
|
[
"His heart rate was 120 beats per minute and his blood pressure was 100/65 mmHg. His weight and height were 12.8 kg ( 1.5 SDS ) and 86 cm ( 2 SDS ), respectively",
"his body weight and length were 16.7 kg ( 0.5 SDS ) and 99.7 cm ( 1.5 SDS ), respectively"
] |
test-1982
|
7136505
|
{'Case report': "A male child was born at a gestational age of 39 weeks with no history of antenatal or perinatal problems. Apgar scores were 9 points at one minute and 10 points at 5 minutes. His birth weight and height were 3,800 g ( z -score, +1 standard deviation score) and 52.5 cm ( z -score, +1.4 SDS), respectively. There was no family history of consanguineous marriages. The patient was born with an imperforate anus and a colostomy was performed the day after birth. He had normal male genitalia, with both testes palpable, and postaxial polydactyly of the left foot. A grade 2 systolic murmur was heard in the left upper sternal border and echocardiography revealed a patent ductus arteriosus. Bilateral grade 3 vesicoureteral reflux (VUR) was revealed via voiding cystourethrography. Spine ultrasound revealed no vertebral anomalies, and tracheoesophageal fistula was not suspected clinically. Based on this clinical information, including anal atresia, renal anomalies, and limb abnormalities, he was diagnosed with VACTERL association which is defined by the presence of at least 3 of the following congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. Laboratory test results, including electrolyte levels, were normal. Neonatal screening tests for metabolic disease were also normal, including the 17-alpha-hydroxyprogesterone level. Chromosome analysis revealed a 46, XY karyotype. He was discharged from the neonatal intensive care unit at 21 days of age. At the age of 3 months, the patient was admitted to the hospital for colostomy takedown, anorectoplasty, and endoscopic dextranomer/hyaluronic acid copolymer injection for VUR. After the surgery, the patient was febrile and hypotensive and his abdomen was distended and discolored. An exploratory laparotomy revealed bowel necrosis. Bowel resection with colostomy and jejunostomy was performed 3 times, which resulted in short-bowel syndrome. He could not be discharged because parenteral nutrition was required. The remnant small bowel extended from the Treitz ligament to the jejunocolonic anastomosis and the length of the remnant bowel was only 40 cm. At the age of 7 months, a takedown of the colostomy and jejunostomy was performed. The patient’s mother observed slight bronzing of the patient’s skin after repeated surgeries At 17 months of age, the patient had an episode of sepsis and peritonitis secondary to Acinetobacter baumannii infection and an exploratory laparotomy was performed to check for bowel necrosis. At this time, generalized hyperpigmentation was noted by the doctor and the mother stated that the child's hyperpigmentation was markedly exacerbated after exploratory laparotomy for the episode of peritonitis with sepsis. The patient was referred to our department for the evaluation of the hyperpigmentation. He experienced occasional nausea and vomiting. His heart rate was 120 beats per minute and his blood pressure was 100/65 mmHg. His weight and height were 12.8 kg (1.5 SDS) and 86 cm (2 SDS), respectively. At this point, he was noted to have generalized hyperpigmentation, normal male genitalia, and postaxial polydactyly of the left foot. He was able to ascend stairs with the support of a hand grasp. He could stack 3 cubes, eat without assistance, and pronounce 10 words, meaning that the patient’s developmental status was normal for his age. Laboratory investigations revealed a slightly decreased sodium level (132 mmol/L) but normal potassium (4.8 mEq/L) and glucose (86 mg/dL) levels; complete blood count, blood gas profile, hepatic and renal function, thyroid function test and sex hormone levels were obtained. Decreased cortisol (1.0 μg/dL) and markedly elevated adrenocorticotropic hormone (ACTH) (16,064 pg/mL) levels were noted. The patient's cortisol levels did not respond to stimulation with ACTH (125 μg) ( Table 1 ). Meanwhile, he presented a normal 17-hydroxyprogesterone level (0.42 ng/mL). Plasma renin activity and aldosterone levels were 7.28 ng/mL/hr (normal range, 1.0–6.5 ng/mL/hr) and 0.1 ng/dL (normal range, 3–35 ng/dL), respectively. The abdominal ultrasound revealed no abnormalities, such as adrenal enlargement, hydronephrosis, distal ureter dilatation, or bowel wall thickening. Based on the patient’s symptoms and laboratory results, we considered several genetic causes for primary adrenal insufficiency, and the causative genes of candidate diseases were listed as STAR for NCCLAH and CYP11A1 for congenital adrenal insufficiency. Additionally, melanocortin-2 receptor (MC2R) and MC2R accessory protein for familial glucocorticoid deficiency (FGD) were listed as candidate genes with a low probability because the patient did not have elevated aldosterone. Targeted gene-panel sequencing was performed to check for pathogenic variants in those genes responsible for primary adrenal insufficiency. Genomic DNA was extracted from the peripheral blood of the patient and both parents. Library preparation was done using the TruSight One Sequencing Panel (Illumina, Inc., San Diego, CA, USA), which enriches a 12-Mb region spanning 62,000 target exons of a total of 4,813 genes. Massively parallel sequencing was performed on the Illumina NextSeq platform. Sequence reads were mapped to the UCSC hg19 standard database for comparative analysis. The average depth of the panel was 85.86X, and percentages of bases above 10X of CYP11A1 and STAR were 99.37%, and 100%, respectively. Meanwhile, no pathogenic variants were detected in CYP11A1 genes. The exome-sequencing results revealed compound heterozygous mutations for c.653C>T and c.661G>A (p.Gly221Ser) in exon 6 of the STAR gene. Sanger sequencing confirmed the presence of these variants and each of the same heterozygous variant was found in his father and mother, respectively ( Fig. 1 ). This variant has been previously reported in association with CLAH. Hydrocortisone (7.8 mg/m 2 /day) and fludrocortisone (50 μg/day) were started as therapy for primary adrenal insufficiency. The dose of hydrocortisone was gradually increased until the age of 24 months for sufficient ACTH suppression and levels of ACTH and cortisol were subsequently decreased to the optimal range ( Fig. 2 ). Finally, at 28 months of age, he was discharged and went home with the attainment of oral feeding without nausea and vomiting. He showed no symptoms of hypoglycemia and continued to show normal growth and development. Our last evaluation of the patient was when he was 36 months of age, during which point, his body weight and length were 16.7 kg (0.5 SDS) and 99.7 cm (1.5 SDS), respectively. Laboratory tests revealed normal levels of cortisol (4.6 μg/dL), sodium (139 mmol/L), potassium (4.9 mEq/L), glucose (70 mg/dL), and ACTH (53.6 pg/mL). The generalized hyperpigmentation had improved, and he continued to visit the outpatient clinic regularly without additional admission."}
|
{'Case report': "A male child was born at a gestational age of 39 weeks with no history of antenatal or perinatal problems. Apgar scores were 9 points at one minute and 10 points at 5 minutes. His birth weight and height were 3,800 g ( z -score, +1 standard deviation score) and 52.5 cm ( z -score, +1.4 SDS), respectively. There was no family history of consanguineous marriages. The patient was born with an imperforate anus and a colostomy was performed the day after birth. He had normal male genitalia, with both testes palpable, and postaxial polydactyly of the left foot. A grade 2 systolic murmur was heard in the left upper sternal border and echocardiography revealed a patent ductus arteriosus. Bilateral grade 3 vesicoureteral reflux (VUR) was revealed via voiding cystourethrography. Spine ultrasound revealed no vertebral anomalies, and tracheoesophageal fistula was not suspected clinically. Based on this clinical information, including anal atresia, renal anomalies, and limb abnormalities, he was diagnosed with VACTERL association which is defined by the presence of at least 3 of the following congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. Laboratory test results, including electrolyte levels, were normal. Neonatal screening tests for metabolic disease were also normal, including the 17-alpha-hydroxyprogesterone level. Chromosome analysis revealed a 46, XY karyotype. He was discharged from the neonatal intensive care unit at 21 days of age. At the age of 3 months, the patient was admitted to the hospital for colostomy takedown, anorectoplasty, and endoscopic dextranomer/hyaluronic acid copolymer injection for VUR. After the surgery, the patient was febrile and hypotensive and his abdomen was distended and discolored. An exploratory laparotomy revealed bowel necrosis. Bowel resection with colostomy and jejunostomy was performed 3 times, which resulted in short-bowel syndrome. He could not be discharged because parenteral nutrition was required. The remnant small bowel extended from the Treitz ligament to the jejunocolonic anastomosis and the length of the remnant bowel was only 40 cm. At the age of 7 months, a takedown of the colostomy and jejunostomy was performed. The patient’s mother observed slight bronzing of the patient’s skin after repeated surgeries At 17 months of age, the patient had an episode of sepsis and peritonitis secondary to Acinetobacter baumannii infection and an exploratory laparotomy was performed to check for bowel necrosis. At this time, generalized hyperpigmentation was noted by the doctor and the mother stated that the child's hyperpigmentation was markedly exacerbated after exploratory laparotomy for the episode of peritonitis with sepsis. The patient was referred to our department for the evaluation of the hyperpigmentation. He experienced occasional nausea and vomiting. His heart rate was 120 beats per minute and his blood pressure was 100/65 mmHg. His weight and height were 12.8 kg (1.5 SDS) and 86 cm (2 SDS), respectively. At this point, he was noted to have generalized hyperpigmentation, normal male genitalia, and postaxial polydactyly of the left foot. He was able to ascend stairs with the support of a hand grasp. He could stack 3 cubes, eat without assistance, and pronounce 10 words, meaning that the patient’s developmental status was normal for his age. Laboratory investigations revealed a slightly decreased sodium level (132 mmol/L) but normal potassium (4.8 mEq/L) and glucose (86 mg/dL) levels; complete blood count, blood gas profile, hepatic and renal function, thyroid function test and sex hormone levels were obtained. Decreased cortisol (1.0 μg/dL) and markedly elevated adrenocorticotropic hormone (ACTH) (16,064 pg/mL) levels were noted. The patient's cortisol levels did not respond to stimulation with ACTH (125 μg) ( Table 1 ). Meanwhile, he presented a normal 17-hydroxyprogesterone level (0.42 ng/mL). Plasma renin activity and aldosterone levels were 7.28 ng/mL/hr (normal range, 1.0–6.5 ng/mL/hr) and 0.1 ng/dL (normal range, 3–35 ng/dL), respectively. The abdominal ultrasound revealed no abnormalities, such as adrenal enlargement, hydronephrosis, distal ureter dilatation, or bowel wall thickening. Based on the patient’s symptoms and laboratory results, we considered several genetic causes for primary adrenal insufficiency, and the causative genes of candidate diseases were listed as STAR for NCCLAH and CYP11A1 for congenital adrenal insufficiency. Additionally, melanocortin-2 receptor (MC2R) and MC2R accessory protein for familial glucocorticoid deficiency (FGD) were listed as candidate genes with a low probability because the patient did not have elevated aldosterone. Targeted gene-panel sequencing was performed to check for pathogenic variants in those genes responsible for primary adrenal insufficiency. Genomic DNA was extracted from the peripheral blood of the patient and both parents. Library preparation was done using the TruSight One Sequencing Panel (Illumina, Inc., San Diego, CA, USA), which enriches a 12-Mb region spanning 62,000 target exons of a total of 4,813 genes. Massively parallel sequencing was performed on the Illumina NextSeq platform. Sequence reads were mapped to the UCSC hg19 standard database for comparative analysis. The average depth of the panel was 85.86X, and percentages of bases above 10X of CYP11A1 and STAR were 99.37%, and 100%, respectively. Meanwhile, no pathogenic variants were detected in CYP11A1 genes. The exome-sequencing results revealed compound heterozygous mutations for c.653C>T and c.661G>A (p.Gly221Ser) in exon 6 of the STAR gene. Sanger sequencing confirmed the presence of these variants and each of the same heterozygous variant was found in his father and mother, respectively ( Fig. 1 ). This variant has been previously reported in association with CLAH. Hydrocortisone (7.8 mg/m 2 /day) and fludrocortisone (50 μg/day) were started as therapy for primary adrenal insufficiency. The dose of hydrocortisone was gradually increased until the age of 24 months for sufficient ACTH suppression and levels of ACTH and cortisol were subsequently decreased to the optimal range ( Fig. 2 ). Finally, at 28 months of age, he was discharged and went home with the attainment of oral feeding without nausea and vomiting. He showed no symptoms of hypoglycemia and continued to show normal growth and development. Our last evaluation of the patient was when he was 36 months of age, during which point, his body weight and length were 16.7 kg (0.5 SDS) and 99.7 cm (1.5 SDS), respectively. Laboratory tests revealed normal levels of cortisol (4.6 μg/dL), sodium (139 mmol/L), potassium (4.9 mEq/L), glucose (70 mg/dL), and ACTH (53.6 pg/mL). The generalized hyperpigmentation had improved, and he continued to visit the outpatient clinic regularly without additional admission."}
|
Gastrointestinal-System
|
GI
|
[
"imperforate anus",
"tracheoesophageal fistula was not suspected clinically",
"anal atresia",
"abdomen was distended and discolored",
"bowel necrosis",
"peritonitis",
"peritonitis",
"occasional nausea and vomiting"
] |
test-1983
|
7136505
|
{'Case report': "A male child was born at a gestational age of 39 weeks with no history of antenatal or perinatal problems. Apgar scores were 9 points at one minute and 10 points at 5 minutes. His birth weight and height were 3,800 g ( z -score, +1 standard deviation score) and 52.5 cm ( z -score, +1.4 SDS), respectively. There was no family history of consanguineous marriages. The patient was born with an imperforate anus and a colostomy was performed the day after birth. He had normal male genitalia, with both testes palpable, and postaxial polydactyly of the left foot. A grade 2 systolic murmur was heard in the left upper sternal border and echocardiography revealed a patent ductus arteriosus. Bilateral grade 3 vesicoureteral reflux (VUR) was revealed via voiding cystourethrography. Spine ultrasound revealed no vertebral anomalies, and tracheoesophageal fistula was not suspected clinically. Based on this clinical information, including anal atresia, renal anomalies, and limb abnormalities, he was diagnosed with VACTERL association which is defined by the presence of at least 3 of the following congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. Laboratory test results, including electrolyte levels, were normal. Neonatal screening tests for metabolic disease were also normal, including the 17-alpha-hydroxyprogesterone level. Chromosome analysis revealed a 46, XY karyotype. He was discharged from the neonatal intensive care unit at 21 days of age. At the age of 3 months, the patient was admitted to the hospital for colostomy takedown, anorectoplasty, and endoscopic dextranomer/hyaluronic acid copolymer injection for VUR. After the surgery, the patient was febrile and hypotensive and his abdomen was distended and discolored. An exploratory laparotomy revealed bowel necrosis. Bowel resection with colostomy and jejunostomy was performed 3 times, which resulted in short-bowel syndrome. He could not be discharged because parenteral nutrition was required. The remnant small bowel extended from the Treitz ligament to the jejunocolonic anastomosis and the length of the remnant bowel was only 40 cm. At the age of 7 months, a takedown of the colostomy and jejunostomy was performed. The patient’s mother observed slight bronzing of the patient’s skin after repeated surgeries At 17 months of age, the patient had an episode of sepsis and peritonitis secondary to Acinetobacter baumannii infection and an exploratory laparotomy was performed to check for bowel necrosis. At this time, generalized hyperpigmentation was noted by the doctor and the mother stated that the child's hyperpigmentation was markedly exacerbated after exploratory laparotomy for the episode of peritonitis with sepsis. The patient was referred to our department for the evaluation of the hyperpigmentation. He experienced occasional nausea and vomiting. His heart rate was 120 beats per minute and his blood pressure was 100/65 mmHg. His weight and height were 12.8 kg (1.5 SDS) and 86 cm (2 SDS), respectively. At this point, he was noted to have generalized hyperpigmentation, normal male genitalia, and postaxial polydactyly of the left foot. He was able to ascend stairs with the support of a hand grasp. He could stack 3 cubes, eat without assistance, and pronounce 10 words, meaning that the patient’s developmental status was normal for his age. Laboratory investigations revealed a slightly decreased sodium level (132 mmol/L) but normal potassium (4.8 mEq/L) and glucose (86 mg/dL) levels; complete blood count, blood gas profile, hepatic and renal function, thyroid function test and sex hormone levels were obtained. Decreased cortisol (1.0 μg/dL) and markedly elevated adrenocorticotropic hormone (ACTH) (16,064 pg/mL) levels were noted. The patient's cortisol levels did not respond to stimulation with ACTH (125 μg) ( Table 1 ). Meanwhile, he presented a normal 17-hydroxyprogesterone level (0.42 ng/mL). Plasma renin activity and aldosterone levels were 7.28 ng/mL/hr (normal range, 1.0–6.5 ng/mL/hr) and 0.1 ng/dL (normal range, 3–35 ng/dL), respectively. The abdominal ultrasound revealed no abnormalities, such as adrenal enlargement, hydronephrosis, distal ureter dilatation, or bowel wall thickening. Based on the patient’s symptoms and laboratory results, we considered several genetic causes for primary adrenal insufficiency, and the causative genes of candidate diseases were listed as STAR for NCCLAH and CYP11A1 for congenital adrenal insufficiency. Additionally, melanocortin-2 receptor (MC2R) and MC2R accessory protein for familial glucocorticoid deficiency (FGD) were listed as candidate genes with a low probability because the patient did not have elevated aldosterone. Targeted gene-panel sequencing was performed to check for pathogenic variants in those genes responsible for primary adrenal insufficiency. Genomic DNA was extracted from the peripheral blood of the patient and both parents. Library preparation was done using the TruSight One Sequencing Panel (Illumina, Inc., San Diego, CA, USA), which enriches a 12-Mb region spanning 62,000 target exons of a total of 4,813 genes. Massively parallel sequencing was performed on the Illumina NextSeq platform. Sequence reads were mapped to the UCSC hg19 standard database for comparative analysis. The average depth of the panel was 85.86X, and percentages of bases above 10X of CYP11A1 and STAR were 99.37%, and 100%, respectively. Meanwhile, no pathogenic variants were detected in CYP11A1 genes. The exome-sequencing results revealed compound heterozygous mutations for c.653C>T and c.661G>A (p.Gly221Ser) in exon 6 of the STAR gene. Sanger sequencing confirmed the presence of these variants and each of the same heterozygous variant was found in his father and mother, respectively ( Fig. 1 ). This variant has been previously reported in association with CLAH. Hydrocortisone (7.8 mg/m 2 /day) and fludrocortisone (50 μg/day) were started as therapy for primary adrenal insufficiency. The dose of hydrocortisone was gradually increased until the age of 24 months for sufficient ACTH suppression and levels of ACTH and cortisol were subsequently decreased to the optimal range ( Fig. 2 ). Finally, at 28 months of age, he was discharged and went home with the attainment of oral feeding without nausea and vomiting. He showed no symptoms of hypoglycemia and continued to show normal growth and development. Our last evaluation of the patient was when he was 36 months of age, during which point, his body weight and length were 16.7 kg (0.5 SDS) and 99.7 cm (1.5 SDS), respectively. Laboratory tests revealed normal levels of cortisol (4.6 μg/dL), sodium (139 mmol/L), potassium (4.9 mEq/L), glucose (70 mg/dL), and ACTH (53.6 pg/mL). The generalized hyperpigmentation had improved, and he continued to visit the outpatient clinic regularly without additional admission."}
|
{'Case report': "A male child was born at a gestational age of 39 weeks with no history of antenatal or perinatal problems. Apgar scores were 9 points at one minute and 10 points at 5 minutes. His birth weight and height were 3,800 g ( z -score, +1 standard deviation score) and 52.5 cm ( z -score, +1.4 SDS), respectively. There was no family history of consanguineous marriages. The patient was born with an imperforate anus and a colostomy was performed the day after birth. He had normal male genitalia, with both testes palpable, and postaxial polydactyly of the left foot. A grade 2 systolic murmur was heard in the left upper sternal border and echocardiography revealed a patent ductus arteriosus. Bilateral grade 3 vesicoureteral reflux (VUR) was revealed via voiding cystourethrography. Spine ultrasound revealed no vertebral anomalies, and tracheoesophageal fistula was not suspected clinically. Based on this clinical information, including anal atresia, renal anomalies, and limb abnormalities, he was diagnosed with VACTERL association which is defined by the presence of at least 3 of the following congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. Laboratory test results, including electrolyte levels, were normal. Neonatal screening tests for metabolic disease were also normal, including the 17-alpha-hydroxyprogesterone level. Chromosome analysis revealed a 46, XY karyotype. He was discharged from the neonatal intensive care unit at 21 days of age. At the age of 3 months, the patient was admitted to the hospital for colostomy takedown, anorectoplasty, and endoscopic dextranomer/hyaluronic acid copolymer injection for VUR. After the surgery, the patient was febrile and hypotensive and his abdomen was distended and discolored. An exploratory laparotomy revealed bowel necrosis. Bowel resection with colostomy and jejunostomy was performed 3 times, which resulted in short-bowel syndrome. He could not be discharged because parenteral nutrition was required. The remnant small bowel extended from the Treitz ligament to the jejunocolonic anastomosis and the length of the remnant bowel was only 40 cm. At the age of 7 months, a takedown of the colostomy and jejunostomy was performed. The patient’s mother observed slight bronzing of the patient’s skin after repeated surgeries At 17 months of age, the patient had an episode of sepsis and peritonitis secondary to Acinetobacter baumannii infection and an exploratory laparotomy was performed to check for bowel necrosis. At this time, generalized hyperpigmentation was noted by the doctor and the mother stated that the child's hyperpigmentation was markedly exacerbated after exploratory laparotomy for the episode of peritonitis with sepsis. The patient was referred to our department for the evaluation of the hyperpigmentation. He experienced occasional nausea and vomiting. His heart rate was 120 beats per minute and his blood pressure was 100/65 mmHg. His weight and height were 12.8 kg (1.5 SDS) and 86 cm (2 SDS), respectively. At this point, he was noted to have generalized hyperpigmentation, normal male genitalia, and postaxial polydactyly of the left foot. He was able to ascend stairs with the support of a hand grasp. He could stack 3 cubes, eat without assistance, and pronounce 10 words, meaning that the patient’s developmental status was normal for his age. Laboratory investigations revealed a slightly decreased sodium level (132 mmol/L) but normal potassium (4.8 mEq/L) and glucose (86 mg/dL) levels; complete blood count, blood gas profile, hepatic and renal function, thyroid function test and sex hormone levels were obtained. Decreased cortisol (1.0 μg/dL) and markedly elevated adrenocorticotropic hormone (ACTH) (16,064 pg/mL) levels were noted. The patient's cortisol levels did not respond to stimulation with ACTH (125 μg) ( Table 1 ). Meanwhile, he presented a normal 17-hydroxyprogesterone level (0.42 ng/mL). Plasma renin activity and aldosterone levels were 7.28 ng/mL/hr (normal range, 1.0–6.5 ng/mL/hr) and 0.1 ng/dL (normal range, 3–35 ng/dL), respectively. The abdominal ultrasound revealed no abnormalities, such as adrenal enlargement, hydronephrosis, distal ureter dilatation, or bowel wall thickening. Based on the patient’s symptoms and laboratory results, we considered several genetic causes for primary adrenal insufficiency, and the causative genes of candidate diseases were listed as STAR for NCCLAH and CYP11A1 for congenital adrenal insufficiency. Additionally, melanocortin-2 receptor (MC2R) and MC2R accessory protein for familial glucocorticoid deficiency (FGD) were listed as candidate genes with a low probability because the patient did not have elevated aldosterone. Targeted gene-panel sequencing was performed to check for pathogenic variants in those genes responsible for primary adrenal insufficiency. Genomic DNA was extracted from the peripheral blood of the patient and both parents. Library preparation was done using the TruSight One Sequencing Panel (Illumina, Inc., San Diego, CA, USA), which enriches a 12-Mb region spanning 62,000 target exons of a total of 4,813 genes. Massively parallel sequencing was performed on the Illumina NextSeq platform. Sequence reads were mapped to the UCSC hg19 standard database for comparative analysis. The average depth of the panel was 85.86X, and percentages of bases above 10X of CYP11A1 and STAR were 99.37%, and 100%, respectively. Meanwhile, no pathogenic variants were detected in CYP11A1 genes. The exome-sequencing results revealed compound heterozygous mutations for c.653C>T and c.661G>A (p.Gly221Ser) in exon 6 of the STAR gene. Sanger sequencing confirmed the presence of these variants and each of the same heterozygous variant was found in his father and mother, respectively ( Fig. 1 ). This variant has been previously reported in association with CLAH. Hydrocortisone (7.8 mg/m 2 /day) and fludrocortisone (50 μg/day) were started as therapy for primary adrenal insufficiency. The dose of hydrocortisone was gradually increased until the age of 24 months for sufficient ACTH suppression and levels of ACTH and cortisol were subsequently decreased to the optimal range ( Fig. 2 ). Finally, at 28 months of age, he was discharged and went home with the attainment of oral feeding without nausea and vomiting. He showed no symptoms of hypoglycemia and continued to show normal growth and development. Our last evaluation of the patient was when he was 36 months of age, during which point, his body weight and length were 16.7 kg (0.5 SDS) and 99.7 cm (1.5 SDS), respectively. Laboratory tests revealed normal levels of cortisol (4.6 μg/dL), sodium (139 mmol/L), potassium (4.9 mEq/L), glucose (70 mg/dL), and ACTH (53.6 pg/mL). The generalized hyperpigmentation had improved, and he continued to visit the outpatient clinic regularly without additional admission."}
|
Patient-History
|
History
|
[
"A male child was born at a gestational age of 39 weeks with no history of antenatal or perinatal problems. Apgar scores were 9 points at one minute and 10 points at 5 minutes. His birth weight and height were 3,800 g ( z -score, +1 standard deviation score ) and 52.5 cm ( z -score, +1.4 SDS ), respectively. There was no family history of consanguineous marriages. The patient was born with an imperforate anus and a colostomy was performed the day after birth",
"At the age of 3 months, the patient was admitted to the hospital for colostomy takedown, anorectoplasty, and endoscopic dextranomer / hyaluronic acid copolymer injection for VUR",
"Bowel resection with colostomy and jejunostomy was performed 3 times, which resulted in short - bowel syndrome",
"At the age of 7 months, a takedown of the colostomy and jejunostomy was performed",
"At 17 months of age, the patient had an episode of sepsis and peritonitis secondary to Acinetobacter baumannii infection and an exploratory laparotomy was performed to check for bowel necrosis"
] |
test-1984
|
7136505
|
{'Case report': "A male child was born at a gestational age of 39 weeks with no history of antenatal or perinatal problems. Apgar scores were 9 points at one minute and 10 points at 5 minutes. His birth weight and height were 3,800 g ( z -score, +1 standard deviation score) and 52.5 cm ( z -score, +1.4 SDS), respectively. There was no family history of consanguineous marriages. The patient was born with an imperforate anus and a colostomy was performed the day after birth. He had normal male genitalia, with both testes palpable, and postaxial polydactyly of the left foot. A grade 2 systolic murmur was heard in the left upper sternal border and echocardiography revealed a patent ductus arteriosus. Bilateral grade 3 vesicoureteral reflux (VUR) was revealed via voiding cystourethrography. Spine ultrasound revealed no vertebral anomalies, and tracheoesophageal fistula was not suspected clinically. Based on this clinical information, including anal atresia, renal anomalies, and limb abnormalities, he was diagnosed with VACTERL association which is defined by the presence of at least 3 of the following congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. Laboratory test results, including electrolyte levels, were normal. Neonatal screening tests for metabolic disease were also normal, including the 17-alpha-hydroxyprogesterone level. Chromosome analysis revealed a 46, XY karyotype. He was discharged from the neonatal intensive care unit at 21 days of age. At the age of 3 months, the patient was admitted to the hospital for colostomy takedown, anorectoplasty, and endoscopic dextranomer/hyaluronic acid copolymer injection for VUR. After the surgery, the patient was febrile and hypotensive and his abdomen was distended and discolored. An exploratory laparotomy revealed bowel necrosis. Bowel resection with colostomy and jejunostomy was performed 3 times, which resulted in short-bowel syndrome. He could not be discharged because parenteral nutrition was required. The remnant small bowel extended from the Treitz ligament to the jejunocolonic anastomosis and the length of the remnant bowel was only 40 cm. At the age of 7 months, a takedown of the colostomy and jejunostomy was performed. The patient’s mother observed slight bronzing of the patient’s skin after repeated surgeries At 17 months of age, the patient had an episode of sepsis and peritonitis secondary to Acinetobacter baumannii infection and an exploratory laparotomy was performed to check for bowel necrosis. At this time, generalized hyperpigmentation was noted by the doctor and the mother stated that the child's hyperpigmentation was markedly exacerbated after exploratory laparotomy for the episode of peritonitis with sepsis. The patient was referred to our department for the evaluation of the hyperpigmentation. He experienced occasional nausea and vomiting. His heart rate was 120 beats per minute and his blood pressure was 100/65 mmHg. His weight and height were 12.8 kg (1.5 SDS) and 86 cm (2 SDS), respectively. At this point, he was noted to have generalized hyperpigmentation, normal male genitalia, and postaxial polydactyly of the left foot. He was able to ascend stairs with the support of a hand grasp. He could stack 3 cubes, eat without assistance, and pronounce 10 words, meaning that the patient’s developmental status was normal for his age. Laboratory investigations revealed a slightly decreased sodium level (132 mmol/L) but normal potassium (4.8 mEq/L) and glucose (86 mg/dL) levels; complete blood count, blood gas profile, hepatic and renal function, thyroid function test and sex hormone levels were obtained. Decreased cortisol (1.0 μg/dL) and markedly elevated adrenocorticotropic hormone (ACTH) (16,064 pg/mL) levels were noted. The patient's cortisol levels did not respond to stimulation with ACTH (125 μg) ( Table 1 ). Meanwhile, he presented a normal 17-hydroxyprogesterone level (0.42 ng/mL). Plasma renin activity and aldosterone levels were 7.28 ng/mL/hr (normal range, 1.0–6.5 ng/mL/hr) and 0.1 ng/dL (normal range, 3–35 ng/dL), respectively. The abdominal ultrasound revealed no abnormalities, such as adrenal enlargement, hydronephrosis, distal ureter dilatation, or bowel wall thickening. Based on the patient’s symptoms and laboratory results, we considered several genetic causes for primary adrenal insufficiency, and the causative genes of candidate diseases were listed as STAR for NCCLAH and CYP11A1 for congenital adrenal insufficiency. Additionally, melanocortin-2 receptor (MC2R) and MC2R accessory protein for familial glucocorticoid deficiency (FGD) were listed as candidate genes with a low probability because the patient did not have elevated aldosterone. Targeted gene-panel sequencing was performed to check for pathogenic variants in those genes responsible for primary adrenal insufficiency. Genomic DNA was extracted from the peripheral blood of the patient and both parents. Library preparation was done using the TruSight One Sequencing Panel (Illumina, Inc., San Diego, CA, USA), which enriches a 12-Mb region spanning 62,000 target exons of a total of 4,813 genes. Massively parallel sequencing was performed on the Illumina NextSeq platform. Sequence reads were mapped to the UCSC hg19 standard database for comparative analysis. The average depth of the panel was 85.86X, and percentages of bases above 10X of CYP11A1 and STAR were 99.37%, and 100%, respectively. Meanwhile, no pathogenic variants were detected in CYP11A1 genes. The exome-sequencing results revealed compound heterozygous mutations for c.653C>T and c.661G>A (p.Gly221Ser) in exon 6 of the STAR gene. Sanger sequencing confirmed the presence of these variants and each of the same heterozygous variant was found in his father and mother, respectively ( Fig. 1 ). This variant has been previously reported in association with CLAH. Hydrocortisone (7.8 mg/m 2 /day) and fludrocortisone (50 μg/day) were started as therapy for primary adrenal insufficiency. The dose of hydrocortisone was gradually increased until the age of 24 months for sufficient ACTH suppression and levels of ACTH and cortisol were subsequently decreased to the optimal range ( Fig. 2 ). Finally, at 28 months of age, he was discharged and went home with the attainment of oral feeding without nausea and vomiting. He showed no symptoms of hypoglycemia and continued to show normal growth and development. Our last evaluation of the patient was when he was 36 months of age, during which point, his body weight and length were 16.7 kg (0.5 SDS) and 99.7 cm (1.5 SDS), respectively. Laboratory tests revealed normal levels of cortisol (4.6 μg/dL), sodium (139 mmol/L), potassium (4.9 mEq/L), glucose (70 mg/dL), and ACTH (53.6 pg/mL). The generalized hyperpigmentation had improved, and he continued to visit the outpatient clinic regularly without additional admission."}
|
{'Case report': "A male child was born at a gestational age of 39 weeks with no history of antenatal or perinatal problems. Apgar scores were 9 points at one minute and 10 points at 5 minutes. His birth weight and height were 3,800 g ( z -score, +1 standard deviation score) and 52.5 cm ( z -score, +1.4 SDS), respectively. There was no family history of consanguineous marriages. The patient was born with an imperforate anus and a colostomy was performed the day after birth. He had normal male genitalia, with both testes palpable, and postaxial polydactyly of the left foot. A grade 2 systolic murmur was heard in the left upper sternal border and echocardiography revealed a patent ductus arteriosus. Bilateral grade 3 vesicoureteral reflux (VUR) was revealed via voiding cystourethrography. Spine ultrasound revealed no vertebral anomalies, and tracheoesophageal fistula was not suspected clinically. Based on this clinical information, including anal atresia, renal anomalies, and limb abnormalities, he was diagnosed with VACTERL association which is defined by the presence of at least 3 of the following congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. Laboratory test results, including electrolyte levels, were normal. Neonatal screening tests for metabolic disease were also normal, including the 17-alpha-hydroxyprogesterone level. Chromosome analysis revealed a 46, XY karyotype. He was discharged from the neonatal intensive care unit at 21 days of age. At the age of 3 months, the patient was admitted to the hospital for colostomy takedown, anorectoplasty, and endoscopic dextranomer/hyaluronic acid copolymer injection for VUR. After the surgery, the patient was febrile and hypotensive and his abdomen was distended and discolored. An exploratory laparotomy revealed bowel necrosis. Bowel resection with colostomy and jejunostomy was performed 3 times, which resulted in short-bowel syndrome. He could not be discharged because parenteral nutrition was required. The remnant small bowel extended from the Treitz ligament to the jejunocolonic anastomosis and the length of the remnant bowel was only 40 cm. At the age of 7 months, a takedown of the colostomy and jejunostomy was performed. The patient’s mother observed slight bronzing of the patient’s skin after repeated surgeries At 17 months of age, the patient had an episode of sepsis and peritonitis secondary to Acinetobacter baumannii infection and an exploratory laparotomy was performed to check for bowel necrosis. At this time, generalized hyperpigmentation was noted by the doctor and the mother stated that the child's hyperpigmentation was markedly exacerbated after exploratory laparotomy for the episode of peritonitis with sepsis. The patient was referred to our department for the evaluation of the hyperpigmentation. He experienced occasional nausea and vomiting. His heart rate was 120 beats per minute and his blood pressure was 100/65 mmHg. His weight and height were 12.8 kg (1.5 SDS) and 86 cm (2 SDS), respectively. At this point, he was noted to have generalized hyperpigmentation, normal male genitalia, and postaxial polydactyly of the left foot. He was able to ascend stairs with the support of a hand grasp. He could stack 3 cubes, eat without assistance, and pronounce 10 words, meaning that the patient’s developmental status was normal for his age. Laboratory investigations revealed a slightly decreased sodium level (132 mmol/L) but normal potassium (4.8 mEq/L) and glucose (86 mg/dL) levels; complete blood count, blood gas profile, hepatic and renal function, thyroid function test and sex hormone levels were obtained. Decreased cortisol (1.0 μg/dL) and markedly elevated adrenocorticotropic hormone (ACTH) (16,064 pg/mL) levels were noted. The patient's cortisol levels did not respond to stimulation with ACTH (125 μg) ( Table 1 ). Meanwhile, he presented a normal 17-hydroxyprogesterone level (0.42 ng/mL). Plasma renin activity and aldosterone levels were 7.28 ng/mL/hr (normal range, 1.0–6.5 ng/mL/hr) and 0.1 ng/dL (normal range, 3–35 ng/dL), respectively. The abdominal ultrasound revealed no abnormalities, such as adrenal enlargement, hydronephrosis, distal ureter dilatation, or bowel wall thickening. Based on the patient’s symptoms and laboratory results, we considered several genetic causes for primary adrenal insufficiency, and the causative genes of candidate diseases were listed as STAR for NCCLAH and CYP11A1 for congenital adrenal insufficiency. Additionally, melanocortin-2 receptor (MC2R) and MC2R accessory protein for familial glucocorticoid deficiency (FGD) were listed as candidate genes with a low probability because the patient did not have elevated aldosterone. Targeted gene-panel sequencing was performed to check for pathogenic variants in those genes responsible for primary adrenal insufficiency. Genomic DNA was extracted from the peripheral blood of the patient and both parents. Library preparation was done using the TruSight One Sequencing Panel (Illumina, Inc., San Diego, CA, USA), which enriches a 12-Mb region spanning 62,000 target exons of a total of 4,813 genes. Massively parallel sequencing was performed on the Illumina NextSeq platform. Sequence reads were mapped to the UCSC hg19 standard database for comparative analysis. The average depth of the panel was 85.86X, and percentages of bases above 10X of CYP11A1 and STAR were 99.37%, and 100%, respectively. Meanwhile, no pathogenic variants were detected in CYP11A1 genes. The exome-sequencing results revealed compound heterozygous mutations for c.653C>T and c.661G>A (p.Gly221Ser) in exon 6 of the STAR gene. Sanger sequencing confirmed the presence of these variants and each of the same heterozygous variant was found in his father and mother, respectively ( Fig. 1 ). This variant has been previously reported in association with CLAH. Hydrocortisone (7.8 mg/m 2 /day) and fludrocortisone (50 μg/day) were started as therapy for primary adrenal insufficiency. The dose of hydrocortisone was gradually increased until the age of 24 months for sufficient ACTH suppression and levels of ACTH and cortisol were subsequently decreased to the optimal range ( Fig. 2 ). Finally, at 28 months of age, he was discharged and went home with the attainment of oral feeding without nausea and vomiting. He showed no symptoms of hypoglycemia and continued to show normal growth and development. Our last evaluation of the patient was when he was 36 months of age, during which point, his body weight and length were 16.7 kg (0.5 SDS) and 99.7 cm (1.5 SDS), respectively. Laboratory tests revealed normal levels of cortisol (4.6 μg/dL), sodium (139 mmol/L), potassium (4.9 mEq/L), glucose (70 mg/dL), and ACTH (53.6 pg/mL). The generalized hyperpigmentation had improved, and he continued to visit the outpatient clinic regularly without additional admission."}
|
Neurology
|
Neuro
|
[
"He was able to ascend stairs with the support of a hand grasp. He could stack 3 cubes, eat without assistance, and pronounce 10 words, meaning that the patient ’s developmental status was normal for his age",
"normal growth and development"
] |
test-1985
|
7136505
|
{'Case report': "A male child was born at a gestational age of 39 weeks with no history of antenatal or perinatal problems. Apgar scores were 9 points at one minute and 10 points at 5 minutes. His birth weight and height were 3,800 g ( z -score, +1 standard deviation score) and 52.5 cm ( z -score, +1.4 SDS), respectively. There was no family history of consanguineous marriages. The patient was born with an imperforate anus and a colostomy was performed the day after birth. He had normal male genitalia, with both testes palpable, and postaxial polydactyly of the left foot. A grade 2 systolic murmur was heard in the left upper sternal border and echocardiography revealed a patent ductus arteriosus. Bilateral grade 3 vesicoureteral reflux (VUR) was revealed via voiding cystourethrography. Spine ultrasound revealed no vertebral anomalies, and tracheoesophageal fistula was not suspected clinically. Based on this clinical information, including anal atresia, renal anomalies, and limb abnormalities, he was diagnosed with VACTERL association which is defined by the presence of at least 3 of the following congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. Laboratory test results, including electrolyte levels, were normal. Neonatal screening tests for metabolic disease were also normal, including the 17-alpha-hydroxyprogesterone level. Chromosome analysis revealed a 46, XY karyotype. He was discharged from the neonatal intensive care unit at 21 days of age. At the age of 3 months, the patient was admitted to the hospital for colostomy takedown, anorectoplasty, and endoscopic dextranomer/hyaluronic acid copolymer injection for VUR. After the surgery, the patient was febrile and hypotensive and his abdomen was distended and discolored. An exploratory laparotomy revealed bowel necrosis. Bowel resection with colostomy and jejunostomy was performed 3 times, which resulted in short-bowel syndrome. He could not be discharged because parenteral nutrition was required. The remnant small bowel extended from the Treitz ligament to the jejunocolonic anastomosis and the length of the remnant bowel was only 40 cm. At the age of 7 months, a takedown of the colostomy and jejunostomy was performed. The patient’s mother observed slight bronzing of the patient’s skin after repeated surgeries At 17 months of age, the patient had an episode of sepsis and peritonitis secondary to Acinetobacter baumannii infection and an exploratory laparotomy was performed to check for bowel necrosis. At this time, generalized hyperpigmentation was noted by the doctor and the mother stated that the child's hyperpigmentation was markedly exacerbated after exploratory laparotomy for the episode of peritonitis with sepsis. The patient was referred to our department for the evaluation of the hyperpigmentation. He experienced occasional nausea and vomiting. His heart rate was 120 beats per minute and his blood pressure was 100/65 mmHg. His weight and height were 12.8 kg (1.5 SDS) and 86 cm (2 SDS), respectively. At this point, he was noted to have generalized hyperpigmentation, normal male genitalia, and postaxial polydactyly of the left foot. He was able to ascend stairs with the support of a hand grasp. He could stack 3 cubes, eat without assistance, and pronounce 10 words, meaning that the patient’s developmental status was normal for his age. Laboratory investigations revealed a slightly decreased sodium level (132 mmol/L) but normal potassium (4.8 mEq/L) and glucose (86 mg/dL) levels; complete blood count, blood gas profile, hepatic and renal function, thyroid function test and sex hormone levels were obtained. Decreased cortisol (1.0 μg/dL) and markedly elevated adrenocorticotropic hormone (ACTH) (16,064 pg/mL) levels were noted. The patient's cortisol levels did not respond to stimulation with ACTH (125 μg) ( Table 1 ). Meanwhile, he presented a normal 17-hydroxyprogesterone level (0.42 ng/mL). Plasma renin activity and aldosterone levels were 7.28 ng/mL/hr (normal range, 1.0–6.5 ng/mL/hr) and 0.1 ng/dL (normal range, 3–35 ng/dL), respectively. The abdominal ultrasound revealed no abnormalities, such as adrenal enlargement, hydronephrosis, distal ureter dilatation, or bowel wall thickening. Based on the patient’s symptoms and laboratory results, we considered several genetic causes for primary adrenal insufficiency, and the causative genes of candidate diseases were listed as STAR for NCCLAH and CYP11A1 for congenital adrenal insufficiency. Additionally, melanocortin-2 receptor (MC2R) and MC2R accessory protein for familial glucocorticoid deficiency (FGD) were listed as candidate genes with a low probability because the patient did not have elevated aldosterone. Targeted gene-panel sequencing was performed to check for pathogenic variants in those genes responsible for primary adrenal insufficiency. Genomic DNA was extracted from the peripheral blood of the patient and both parents. Library preparation was done using the TruSight One Sequencing Panel (Illumina, Inc., San Diego, CA, USA), which enriches a 12-Mb region spanning 62,000 target exons of a total of 4,813 genes. Massively parallel sequencing was performed on the Illumina NextSeq platform. Sequence reads were mapped to the UCSC hg19 standard database for comparative analysis. The average depth of the panel was 85.86X, and percentages of bases above 10X of CYP11A1 and STAR were 99.37%, and 100%, respectively. Meanwhile, no pathogenic variants were detected in CYP11A1 genes. The exome-sequencing results revealed compound heterozygous mutations for c.653C>T and c.661G>A (p.Gly221Ser) in exon 6 of the STAR gene. Sanger sequencing confirmed the presence of these variants and each of the same heterozygous variant was found in his father and mother, respectively ( Fig. 1 ). This variant has been previously reported in association with CLAH. Hydrocortisone (7.8 mg/m 2 /day) and fludrocortisone (50 μg/day) were started as therapy for primary adrenal insufficiency. The dose of hydrocortisone was gradually increased until the age of 24 months for sufficient ACTH suppression and levels of ACTH and cortisol were subsequently decreased to the optimal range ( Fig. 2 ). Finally, at 28 months of age, he was discharged and went home with the attainment of oral feeding without nausea and vomiting. He showed no symptoms of hypoglycemia and continued to show normal growth and development. Our last evaluation of the patient was when he was 36 months of age, during which point, his body weight and length were 16.7 kg (0.5 SDS) and 99.7 cm (1.5 SDS), respectively. Laboratory tests revealed normal levels of cortisol (4.6 μg/dL), sodium (139 mmol/L), potassium (4.9 mEq/L), glucose (70 mg/dL), and ACTH (53.6 pg/mL). The generalized hyperpigmentation had improved, and he continued to visit the outpatient clinic regularly without additional admission."}
|
{'Case report': "A male child was born at a gestational age of 39 weeks with no history of antenatal or perinatal problems. Apgar scores were 9 points at one minute and 10 points at 5 minutes. His birth weight and height were 3,800 g ( z -score, +1 standard deviation score) and 52.5 cm ( z -score, +1.4 SDS), respectively. There was no family history of consanguineous marriages. The patient was born with an imperforate anus and a colostomy was performed the day after birth. He had normal male genitalia, with both testes palpable, and postaxial polydactyly of the left foot. A grade 2 systolic murmur was heard in the left upper sternal border and echocardiography revealed a patent ductus arteriosus. Bilateral grade 3 vesicoureteral reflux (VUR) was revealed via voiding cystourethrography. Spine ultrasound revealed no vertebral anomalies, and tracheoesophageal fistula was not suspected clinically. Based on this clinical information, including anal atresia, renal anomalies, and limb abnormalities, he was diagnosed with VACTERL association which is defined by the presence of at least 3 of the following congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. Laboratory test results, including electrolyte levels, were normal. Neonatal screening tests for metabolic disease were also normal, including the 17-alpha-hydroxyprogesterone level. Chromosome analysis revealed a 46, XY karyotype. He was discharged from the neonatal intensive care unit at 21 days of age. At the age of 3 months, the patient was admitted to the hospital for colostomy takedown, anorectoplasty, and endoscopic dextranomer/hyaluronic acid copolymer injection for VUR. After the surgery, the patient was febrile and hypotensive and his abdomen was distended and discolored. An exploratory laparotomy revealed bowel necrosis. Bowel resection with colostomy and jejunostomy was performed 3 times, which resulted in short-bowel syndrome. He could not be discharged because parenteral nutrition was required. The remnant small bowel extended from the Treitz ligament to the jejunocolonic anastomosis and the length of the remnant bowel was only 40 cm. At the age of 7 months, a takedown of the colostomy and jejunostomy was performed. The patient’s mother observed slight bronzing of the patient’s skin after repeated surgeries At 17 months of age, the patient had an episode of sepsis and peritonitis secondary to Acinetobacter baumannii infection and an exploratory laparotomy was performed to check for bowel necrosis. At this time, generalized hyperpigmentation was noted by the doctor and the mother stated that the child's hyperpigmentation was markedly exacerbated after exploratory laparotomy for the episode of peritonitis with sepsis. The patient was referred to our department for the evaluation of the hyperpigmentation. He experienced occasional nausea and vomiting. His heart rate was 120 beats per minute and his blood pressure was 100/65 mmHg. His weight and height were 12.8 kg (1.5 SDS) and 86 cm (2 SDS), respectively. At this point, he was noted to have generalized hyperpigmentation, normal male genitalia, and postaxial polydactyly of the left foot. He was able to ascend stairs with the support of a hand grasp. He could stack 3 cubes, eat without assistance, and pronounce 10 words, meaning that the patient’s developmental status was normal for his age. Laboratory investigations revealed a slightly decreased sodium level (132 mmol/L) but normal potassium (4.8 mEq/L) and glucose (86 mg/dL) levels; complete blood count, blood gas profile, hepatic and renal function, thyroid function test and sex hormone levels were obtained. Decreased cortisol (1.0 μg/dL) and markedly elevated adrenocorticotropic hormone (ACTH) (16,064 pg/mL) levels were noted. The patient's cortisol levels did not respond to stimulation with ACTH (125 μg) ( Table 1 ). Meanwhile, he presented a normal 17-hydroxyprogesterone level (0.42 ng/mL). Plasma renin activity and aldosterone levels were 7.28 ng/mL/hr (normal range, 1.0–6.5 ng/mL/hr) and 0.1 ng/dL (normal range, 3–35 ng/dL), respectively. The abdominal ultrasound revealed no abnormalities, such as adrenal enlargement, hydronephrosis, distal ureter dilatation, or bowel wall thickening. Based on the patient’s symptoms and laboratory results, we considered several genetic causes for primary adrenal insufficiency, and the causative genes of candidate diseases were listed as STAR for NCCLAH and CYP11A1 for congenital adrenal insufficiency. Additionally, melanocortin-2 receptor (MC2R) and MC2R accessory protein for familial glucocorticoid deficiency (FGD) were listed as candidate genes with a low probability because the patient did not have elevated aldosterone. Targeted gene-panel sequencing was performed to check for pathogenic variants in those genes responsible for primary adrenal insufficiency. Genomic DNA was extracted from the peripheral blood of the patient and both parents. Library preparation was done using the TruSight One Sequencing Panel (Illumina, Inc., San Diego, CA, USA), which enriches a 12-Mb region spanning 62,000 target exons of a total of 4,813 genes. Massively parallel sequencing was performed on the Illumina NextSeq platform. Sequence reads were mapped to the UCSC hg19 standard database for comparative analysis. The average depth of the panel was 85.86X, and percentages of bases above 10X of CYP11A1 and STAR were 99.37%, and 100%, respectively. Meanwhile, no pathogenic variants were detected in CYP11A1 genes. The exome-sequencing results revealed compound heterozygous mutations for c.653C>T and c.661G>A (p.Gly221Ser) in exon 6 of the STAR gene. Sanger sequencing confirmed the presence of these variants and each of the same heterozygous variant was found in his father and mother, respectively ( Fig. 1 ). This variant has been previously reported in association with CLAH. Hydrocortisone (7.8 mg/m 2 /day) and fludrocortisone (50 μg/day) were started as therapy for primary adrenal insufficiency. The dose of hydrocortisone was gradually increased until the age of 24 months for sufficient ACTH suppression and levels of ACTH and cortisol were subsequently decreased to the optimal range ( Fig. 2 ). Finally, at 28 months of age, he was discharged and went home with the attainment of oral feeding without nausea and vomiting. He showed no symptoms of hypoglycemia and continued to show normal growth and development. Our last evaluation of the patient was when he was 36 months of age, during which point, his body weight and length were 16.7 kg (0.5 SDS) and 99.7 cm (1.5 SDS), respectively. Laboratory tests revealed normal levels of cortisol (4.6 μg/dL), sodium (139 mmol/L), potassium (4.9 mEq/L), glucose (70 mg/dL), and ACTH (53.6 pg/mL). The generalized hyperpigmentation had improved, and he continued to visit the outpatient clinic regularly without additional admission."}
|
Laboratory-and-Imaging
|
Lab_Image
|
[
"echocardiography revealed a patent ductus arteriosus",
"Bilateral grade 3 vesicoureteral reflux ( VUR ) was revealed via voiding cystourethrography. Spine ultrasound revealed no vertebral anomalies, and tracheoesophageal fistula was not suspected clinically",
"Laboratory test results, including electrolyte levels, were normal. Neonatal screening tests for metabolic disease were also normal, including the 17 - alpha - hydroxyprogesterone level. Chromosome analysis revealed a 46, XY karyotype.",
"Laboratory investigations revealed a slightly decreased sodium level ( 132 mmol / L ) but normal potassium ( 4.8 mEq / L ) and glucose ( 86 mg / dL ) levels; complete blood count, blood gas profile, hepatic and renal function, thyroid function test and sex hormone levels were obtained. Decreased cortisol ( 1.0 μg / dL ) and markedly elevated adrenocorticotropic hormone ( ACTH ) ( 16,064 pg / mL ) levels were noted. The patient 's cortisol levels did not respond to stimulation with ACTH ( 125 μg ) ( Table 1 ). Meanwhile, he presented a normal 17 - hydroxyprogesterone level ( 0.42 ng / mL ). Plasma renin activity and aldosterone levels were 7.28 ng / mL / hr ( normal range, 1.0–6.5 ng / mL / hr ) and 0.1 ng / dL ( normal range, 3–35 ng / dL ), respectively",
"The abdominal ultrasound revealed no abnormalities, such as adrenal enlargement, hydronephrosis, distal ureter dilatation, or bowel wall thickening",
"no pathogenic variants were detected in CYP11A1 genes. The exome - sequencing results revealed compound heterozygous mutations for c.653C > T and c.661G > A ( p. Gly221Ser ) in exon 6 of the STAR gene. Sanger sequencing confirmed the presence of these variants and each of the same heterozygous variant was found in his father and mother, respectively",
"Laboratory tests revealed normal levels of cortisol ( 4.6 μg / dL ), sodium ( 139 mmol / L ), potassium ( 4.9 mEq / L ), glucose ( 70 mg / dL ), and ACTH ( 53.6 pg / mL )"
] |
test-1986
|
7136505
|
{'Case report': "A male child was born at a gestational age of 39 weeks with no history of antenatal or perinatal problems. Apgar scores were 9 points at one minute and 10 points at 5 minutes. His birth weight and height were 3,800 g ( z -score, +1 standard deviation score) and 52.5 cm ( z -score, +1.4 SDS), respectively. There was no family history of consanguineous marriages. The patient was born with an imperforate anus and a colostomy was performed the day after birth. He had normal male genitalia, with both testes palpable, and postaxial polydactyly of the left foot. A grade 2 systolic murmur was heard in the left upper sternal border and echocardiography revealed a patent ductus arteriosus. Bilateral grade 3 vesicoureteral reflux (VUR) was revealed via voiding cystourethrography. Spine ultrasound revealed no vertebral anomalies, and tracheoesophageal fistula was not suspected clinically. Based on this clinical information, including anal atresia, renal anomalies, and limb abnormalities, he was diagnosed with VACTERL association which is defined by the presence of at least 3 of the following congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. Laboratory test results, including electrolyte levels, were normal. Neonatal screening tests for metabolic disease were also normal, including the 17-alpha-hydroxyprogesterone level. Chromosome analysis revealed a 46, XY karyotype. He was discharged from the neonatal intensive care unit at 21 days of age. At the age of 3 months, the patient was admitted to the hospital for colostomy takedown, anorectoplasty, and endoscopic dextranomer/hyaluronic acid copolymer injection for VUR. After the surgery, the patient was febrile and hypotensive and his abdomen was distended and discolored. An exploratory laparotomy revealed bowel necrosis. Bowel resection with colostomy and jejunostomy was performed 3 times, which resulted in short-bowel syndrome. He could not be discharged because parenteral nutrition was required. The remnant small bowel extended from the Treitz ligament to the jejunocolonic anastomosis and the length of the remnant bowel was only 40 cm. At the age of 7 months, a takedown of the colostomy and jejunostomy was performed. The patient’s mother observed slight bronzing of the patient’s skin after repeated surgeries At 17 months of age, the patient had an episode of sepsis and peritonitis secondary to Acinetobacter baumannii infection and an exploratory laparotomy was performed to check for bowel necrosis. At this time, generalized hyperpigmentation was noted by the doctor and the mother stated that the child's hyperpigmentation was markedly exacerbated after exploratory laparotomy for the episode of peritonitis with sepsis. The patient was referred to our department for the evaluation of the hyperpigmentation. He experienced occasional nausea and vomiting. His heart rate was 120 beats per minute and his blood pressure was 100/65 mmHg. His weight and height were 12.8 kg (1.5 SDS) and 86 cm (2 SDS), respectively. At this point, he was noted to have generalized hyperpigmentation, normal male genitalia, and postaxial polydactyly of the left foot. He was able to ascend stairs with the support of a hand grasp. He could stack 3 cubes, eat without assistance, and pronounce 10 words, meaning that the patient’s developmental status was normal for his age. Laboratory investigations revealed a slightly decreased sodium level (132 mmol/L) but normal potassium (4.8 mEq/L) and glucose (86 mg/dL) levels; complete blood count, blood gas profile, hepatic and renal function, thyroid function test and sex hormone levels were obtained. Decreased cortisol (1.0 μg/dL) and markedly elevated adrenocorticotropic hormone (ACTH) (16,064 pg/mL) levels were noted. The patient's cortisol levels did not respond to stimulation with ACTH (125 μg) ( Table 1 ). Meanwhile, he presented a normal 17-hydroxyprogesterone level (0.42 ng/mL). Plasma renin activity and aldosterone levels were 7.28 ng/mL/hr (normal range, 1.0–6.5 ng/mL/hr) and 0.1 ng/dL (normal range, 3–35 ng/dL), respectively. The abdominal ultrasound revealed no abnormalities, such as adrenal enlargement, hydronephrosis, distal ureter dilatation, or bowel wall thickening. Based on the patient’s symptoms and laboratory results, we considered several genetic causes for primary adrenal insufficiency, and the causative genes of candidate diseases were listed as STAR for NCCLAH and CYP11A1 for congenital adrenal insufficiency. Additionally, melanocortin-2 receptor (MC2R) and MC2R accessory protein for familial glucocorticoid deficiency (FGD) were listed as candidate genes with a low probability because the patient did not have elevated aldosterone. Targeted gene-panel sequencing was performed to check for pathogenic variants in those genes responsible for primary adrenal insufficiency. Genomic DNA was extracted from the peripheral blood of the patient and both parents. Library preparation was done using the TruSight One Sequencing Panel (Illumina, Inc., San Diego, CA, USA), which enriches a 12-Mb region spanning 62,000 target exons of a total of 4,813 genes. Massively parallel sequencing was performed on the Illumina NextSeq platform. Sequence reads were mapped to the UCSC hg19 standard database for comparative analysis. The average depth of the panel was 85.86X, and percentages of bases above 10X of CYP11A1 and STAR were 99.37%, and 100%, respectively. Meanwhile, no pathogenic variants were detected in CYP11A1 genes. The exome-sequencing results revealed compound heterozygous mutations for c.653C>T and c.661G>A (p.Gly221Ser) in exon 6 of the STAR gene. Sanger sequencing confirmed the presence of these variants and each of the same heterozygous variant was found in his father and mother, respectively ( Fig. 1 ). This variant has been previously reported in association with CLAH. Hydrocortisone (7.8 mg/m 2 /day) and fludrocortisone (50 μg/day) were started as therapy for primary adrenal insufficiency. The dose of hydrocortisone was gradually increased until the age of 24 months for sufficient ACTH suppression and levels of ACTH and cortisol were subsequently decreased to the optimal range ( Fig. 2 ). Finally, at 28 months of age, he was discharged and went home with the attainment of oral feeding without nausea and vomiting. He showed no symptoms of hypoglycemia and continued to show normal growth and development. Our last evaluation of the patient was when he was 36 months of age, during which point, his body weight and length were 16.7 kg (0.5 SDS) and 99.7 cm (1.5 SDS), respectively. Laboratory tests revealed normal levels of cortisol (4.6 μg/dL), sodium (139 mmol/L), potassium (4.9 mEq/L), glucose (70 mg/dL), and ACTH (53.6 pg/mL). The generalized hyperpigmentation had improved, and he continued to visit the outpatient clinic regularly without additional admission."}
|
{'Case report': "A male child was born at a gestational age of 39 weeks with no history of antenatal or perinatal problems. Apgar scores were 9 points at one minute and 10 points at 5 minutes. His birth weight and height were 3,800 g ( z -score, +1 standard deviation score) and 52.5 cm ( z -score, +1.4 SDS), respectively. There was no family history of consanguineous marriages. The patient was born with an imperforate anus and a colostomy was performed the day after birth. He had normal male genitalia, with both testes palpable, and postaxial polydactyly of the left foot. A grade 2 systolic murmur was heard in the left upper sternal border and echocardiography revealed a patent ductus arteriosus. Bilateral grade 3 vesicoureteral reflux (VUR) was revealed via voiding cystourethrography. Spine ultrasound revealed no vertebral anomalies, and tracheoesophageal fistula was not suspected clinically. Based on this clinical information, including anal atresia, renal anomalies, and limb abnormalities, he was diagnosed with VACTERL association which is defined by the presence of at least 3 of the following congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. Laboratory test results, including electrolyte levels, were normal. Neonatal screening tests for metabolic disease were also normal, including the 17-alpha-hydroxyprogesterone level. Chromosome analysis revealed a 46, XY karyotype. He was discharged from the neonatal intensive care unit at 21 days of age. At the age of 3 months, the patient was admitted to the hospital for colostomy takedown, anorectoplasty, and endoscopic dextranomer/hyaluronic acid copolymer injection for VUR. After the surgery, the patient was febrile and hypotensive and his abdomen was distended and discolored. An exploratory laparotomy revealed bowel necrosis. Bowel resection with colostomy and jejunostomy was performed 3 times, which resulted in short-bowel syndrome. He could not be discharged because parenteral nutrition was required. The remnant small bowel extended from the Treitz ligament to the jejunocolonic anastomosis and the length of the remnant bowel was only 40 cm. At the age of 7 months, a takedown of the colostomy and jejunostomy was performed. The patient’s mother observed slight bronzing of the patient’s skin after repeated surgeries At 17 months of age, the patient had an episode of sepsis and peritonitis secondary to Acinetobacter baumannii infection and an exploratory laparotomy was performed to check for bowel necrosis. At this time, generalized hyperpigmentation was noted by the doctor and the mother stated that the child's hyperpigmentation was markedly exacerbated after exploratory laparotomy for the episode of peritonitis with sepsis. The patient was referred to our department for the evaluation of the hyperpigmentation. He experienced occasional nausea and vomiting. His heart rate was 120 beats per minute and his blood pressure was 100/65 mmHg. His weight and height were 12.8 kg (1.5 SDS) and 86 cm (2 SDS), respectively. At this point, he was noted to have generalized hyperpigmentation, normal male genitalia, and postaxial polydactyly of the left foot. He was able to ascend stairs with the support of a hand grasp. He could stack 3 cubes, eat without assistance, and pronounce 10 words, meaning that the patient’s developmental status was normal for his age. Laboratory investigations revealed a slightly decreased sodium level (132 mmol/L) but normal potassium (4.8 mEq/L) and glucose (86 mg/dL) levels; complete blood count, blood gas profile, hepatic and renal function, thyroid function test and sex hormone levels were obtained. Decreased cortisol (1.0 μg/dL) and markedly elevated adrenocorticotropic hormone (ACTH) (16,064 pg/mL) levels were noted. The patient's cortisol levels did not respond to stimulation with ACTH (125 μg) ( Table 1 ). Meanwhile, he presented a normal 17-hydroxyprogesterone level (0.42 ng/mL). Plasma renin activity and aldosterone levels were 7.28 ng/mL/hr (normal range, 1.0–6.5 ng/mL/hr) and 0.1 ng/dL (normal range, 3–35 ng/dL), respectively. The abdominal ultrasound revealed no abnormalities, such as adrenal enlargement, hydronephrosis, distal ureter dilatation, or bowel wall thickening. Based on the patient’s symptoms and laboratory results, we considered several genetic causes for primary adrenal insufficiency, and the causative genes of candidate diseases were listed as STAR for NCCLAH and CYP11A1 for congenital adrenal insufficiency. Additionally, melanocortin-2 receptor (MC2R) and MC2R accessory protein for familial glucocorticoid deficiency (FGD) were listed as candidate genes with a low probability because the patient did not have elevated aldosterone. Targeted gene-panel sequencing was performed to check for pathogenic variants in those genes responsible for primary adrenal insufficiency. Genomic DNA was extracted from the peripheral blood of the patient and both parents. Library preparation was done using the TruSight One Sequencing Panel (Illumina, Inc., San Diego, CA, USA), which enriches a 12-Mb region spanning 62,000 target exons of a total of 4,813 genes. Massively parallel sequencing was performed on the Illumina NextSeq platform. Sequence reads were mapped to the UCSC hg19 standard database for comparative analysis. The average depth of the panel was 85.86X, and percentages of bases above 10X of CYP11A1 and STAR were 99.37%, and 100%, respectively. Meanwhile, no pathogenic variants were detected in CYP11A1 genes. The exome-sequencing results revealed compound heterozygous mutations for c.653C>T and c.661G>A (p.Gly221Ser) in exon 6 of the STAR gene. Sanger sequencing confirmed the presence of these variants and each of the same heterozygous variant was found in his father and mother, respectively ( Fig. 1 ). This variant has been previously reported in association with CLAH. Hydrocortisone (7.8 mg/m 2 /day) and fludrocortisone (50 μg/day) were started as therapy for primary adrenal insufficiency. The dose of hydrocortisone was gradually increased until the age of 24 months for sufficient ACTH suppression and levels of ACTH and cortisol were subsequently decreased to the optimal range ( Fig. 2 ). Finally, at 28 months of age, he was discharged and went home with the attainment of oral feeding without nausea and vomiting. He showed no symptoms of hypoglycemia and continued to show normal growth and development. Our last evaluation of the patient was when he was 36 months of age, during which point, his body weight and length were 16.7 kg (0.5 SDS) and 99.7 cm (1.5 SDS), respectively. Laboratory tests revealed normal levels of cortisol (4.6 μg/dL), sodium (139 mmol/L), potassium (4.9 mEq/L), glucose (70 mg/dL), and ACTH (53.6 pg/mL). The generalized hyperpigmentation had improved, and he continued to visit the outpatient clinic regularly without additional admission."}
|
Cardiovascular-System
|
CVS
|
[
"A grade 2 systolic murmur was heard in the left upper sternal border and echocardiography revealed a patent ductus arteriosus",
"hypotensive"
] |
test-1987
|
7136505
|
{'Case report': "A male child was born at a gestational age of 39 weeks with no history of antenatal or perinatal problems. Apgar scores were 9 points at one minute and 10 points at 5 minutes. His birth weight and height were 3,800 g ( z -score, +1 standard deviation score) and 52.5 cm ( z -score, +1.4 SDS), respectively. There was no family history of consanguineous marriages. The patient was born with an imperforate anus and a colostomy was performed the day after birth. He had normal male genitalia, with both testes palpable, and postaxial polydactyly of the left foot. A grade 2 systolic murmur was heard in the left upper sternal border and echocardiography revealed a patent ductus arteriosus. Bilateral grade 3 vesicoureteral reflux (VUR) was revealed via voiding cystourethrography. Spine ultrasound revealed no vertebral anomalies, and tracheoesophageal fistula was not suspected clinically. Based on this clinical information, including anal atresia, renal anomalies, and limb abnormalities, he was diagnosed with VACTERL association which is defined by the presence of at least 3 of the following congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. Laboratory test results, including electrolyte levels, were normal. Neonatal screening tests for metabolic disease were also normal, including the 17-alpha-hydroxyprogesterone level. Chromosome analysis revealed a 46, XY karyotype. He was discharged from the neonatal intensive care unit at 21 days of age. At the age of 3 months, the patient was admitted to the hospital for colostomy takedown, anorectoplasty, and endoscopic dextranomer/hyaluronic acid copolymer injection for VUR. After the surgery, the patient was febrile and hypotensive and his abdomen was distended and discolored. An exploratory laparotomy revealed bowel necrosis. Bowel resection with colostomy and jejunostomy was performed 3 times, which resulted in short-bowel syndrome. He could not be discharged because parenteral nutrition was required. The remnant small bowel extended from the Treitz ligament to the jejunocolonic anastomosis and the length of the remnant bowel was only 40 cm. At the age of 7 months, a takedown of the colostomy and jejunostomy was performed. The patient’s mother observed slight bronzing of the patient’s skin after repeated surgeries At 17 months of age, the patient had an episode of sepsis and peritonitis secondary to Acinetobacter baumannii infection and an exploratory laparotomy was performed to check for bowel necrosis. At this time, generalized hyperpigmentation was noted by the doctor and the mother stated that the child's hyperpigmentation was markedly exacerbated after exploratory laparotomy for the episode of peritonitis with sepsis. The patient was referred to our department for the evaluation of the hyperpigmentation. He experienced occasional nausea and vomiting. His heart rate was 120 beats per minute and his blood pressure was 100/65 mmHg. His weight and height were 12.8 kg (1.5 SDS) and 86 cm (2 SDS), respectively. At this point, he was noted to have generalized hyperpigmentation, normal male genitalia, and postaxial polydactyly of the left foot. He was able to ascend stairs with the support of a hand grasp. He could stack 3 cubes, eat without assistance, and pronounce 10 words, meaning that the patient’s developmental status was normal for his age. Laboratory investigations revealed a slightly decreased sodium level (132 mmol/L) but normal potassium (4.8 mEq/L) and glucose (86 mg/dL) levels; complete blood count, blood gas profile, hepatic and renal function, thyroid function test and sex hormone levels were obtained. Decreased cortisol (1.0 μg/dL) and markedly elevated adrenocorticotropic hormone (ACTH) (16,064 pg/mL) levels were noted. The patient's cortisol levels did not respond to stimulation with ACTH (125 μg) ( Table 1 ). Meanwhile, he presented a normal 17-hydroxyprogesterone level (0.42 ng/mL). Plasma renin activity and aldosterone levels were 7.28 ng/mL/hr (normal range, 1.0–6.5 ng/mL/hr) and 0.1 ng/dL (normal range, 3–35 ng/dL), respectively. The abdominal ultrasound revealed no abnormalities, such as adrenal enlargement, hydronephrosis, distal ureter dilatation, or bowel wall thickening. Based on the patient’s symptoms and laboratory results, we considered several genetic causes for primary adrenal insufficiency, and the causative genes of candidate diseases were listed as STAR for NCCLAH and CYP11A1 for congenital adrenal insufficiency. Additionally, melanocortin-2 receptor (MC2R) and MC2R accessory protein for familial glucocorticoid deficiency (FGD) were listed as candidate genes with a low probability because the patient did not have elevated aldosterone. Targeted gene-panel sequencing was performed to check for pathogenic variants in those genes responsible for primary adrenal insufficiency. Genomic DNA was extracted from the peripheral blood of the patient and both parents. Library preparation was done using the TruSight One Sequencing Panel (Illumina, Inc., San Diego, CA, USA), which enriches a 12-Mb region spanning 62,000 target exons of a total of 4,813 genes. Massively parallel sequencing was performed on the Illumina NextSeq platform. Sequence reads were mapped to the UCSC hg19 standard database for comparative analysis. The average depth of the panel was 85.86X, and percentages of bases above 10X of CYP11A1 and STAR were 99.37%, and 100%, respectively. Meanwhile, no pathogenic variants were detected in CYP11A1 genes. The exome-sequencing results revealed compound heterozygous mutations for c.653C>T and c.661G>A (p.Gly221Ser) in exon 6 of the STAR gene. Sanger sequencing confirmed the presence of these variants and each of the same heterozygous variant was found in his father and mother, respectively ( Fig. 1 ). This variant has been previously reported in association with CLAH. Hydrocortisone (7.8 mg/m 2 /day) and fludrocortisone (50 μg/day) were started as therapy for primary adrenal insufficiency. The dose of hydrocortisone was gradually increased until the age of 24 months for sufficient ACTH suppression and levels of ACTH and cortisol were subsequently decreased to the optimal range ( Fig. 2 ). Finally, at 28 months of age, he was discharged and went home with the attainment of oral feeding without nausea and vomiting. He showed no symptoms of hypoglycemia and continued to show normal growth and development. Our last evaluation of the patient was when he was 36 months of age, during which point, his body weight and length were 16.7 kg (0.5 SDS) and 99.7 cm (1.5 SDS), respectively. Laboratory tests revealed normal levels of cortisol (4.6 μg/dL), sodium (139 mmol/L), potassium (4.9 mEq/L), glucose (70 mg/dL), and ACTH (53.6 pg/mL). The generalized hyperpigmentation had improved, and he continued to visit the outpatient clinic regularly without additional admission."}
|
{'Case report': "A male child was born at a gestational age of 39 weeks with no history of antenatal or perinatal problems. Apgar scores were 9 points at one minute and 10 points at 5 minutes. His birth weight and height were 3,800 g ( z -score, +1 standard deviation score) and 52.5 cm ( z -score, +1.4 SDS), respectively. There was no family history of consanguineous marriages. The patient was born with an imperforate anus and a colostomy was performed the day after birth. He had normal male genitalia, with both testes palpable, and postaxial polydactyly of the left foot. A grade 2 systolic murmur was heard in the left upper sternal border and echocardiography revealed a patent ductus arteriosus. Bilateral grade 3 vesicoureteral reflux (VUR) was revealed via voiding cystourethrography. Spine ultrasound revealed no vertebral anomalies, and tracheoesophageal fistula was not suspected clinically. Based on this clinical information, including anal atresia, renal anomalies, and limb abnormalities, he was diagnosed with VACTERL association which is defined by the presence of at least 3 of the following congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. Laboratory test results, including electrolyte levels, were normal. Neonatal screening tests for metabolic disease were also normal, including the 17-alpha-hydroxyprogesterone level. Chromosome analysis revealed a 46, XY karyotype. He was discharged from the neonatal intensive care unit at 21 days of age. At the age of 3 months, the patient was admitted to the hospital for colostomy takedown, anorectoplasty, and endoscopic dextranomer/hyaluronic acid copolymer injection for VUR. After the surgery, the patient was febrile and hypotensive and his abdomen was distended and discolored. An exploratory laparotomy revealed bowel necrosis. Bowel resection with colostomy and jejunostomy was performed 3 times, which resulted in short-bowel syndrome. He could not be discharged because parenteral nutrition was required. The remnant small bowel extended from the Treitz ligament to the jejunocolonic anastomosis and the length of the remnant bowel was only 40 cm. At the age of 7 months, a takedown of the colostomy and jejunostomy was performed. The patient’s mother observed slight bronzing of the patient’s skin after repeated surgeries At 17 months of age, the patient had an episode of sepsis and peritonitis secondary to Acinetobacter baumannii infection and an exploratory laparotomy was performed to check for bowel necrosis. At this time, generalized hyperpigmentation was noted by the doctor and the mother stated that the child's hyperpigmentation was markedly exacerbated after exploratory laparotomy for the episode of peritonitis with sepsis. The patient was referred to our department for the evaluation of the hyperpigmentation. He experienced occasional nausea and vomiting. His heart rate was 120 beats per minute and his blood pressure was 100/65 mmHg. His weight and height were 12.8 kg (1.5 SDS) and 86 cm (2 SDS), respectively. At this point, he was noted to have generalized hyperpigmentation, normal male genitalia, and postaxial polydactyly of the left foot. He was able to ascend stairs with the support of a hand grasp. He could stack 3 cubes, eat without assistance, and pronounce 10 words, meaning that the patient’s developmental status was normal for his age. Laboratory investigations revealed a slightly decreased sodium level (132 mmol/L) but normal potassium (4.8 mEq/L) and glucose (86 mg/dL) levels; complete blood count, blood gas profile, hepatic and renal function, thyroid function test and sex hormone levels were obtained. Decreased cortisol (1.0 μg/dL) and markedly elevated adrenocorticotropic hormone (ACTH) (16,064 pg/mL) levels were noted. The patient's cortisol levels did not respond to stimulation with ACTH (125 μg) ( Table 1 ). Meanwhile, he presented a normal 17-hydroxyprogesterone level (0.42 ng/mL). Plasma renin activity and aldosterone levels were 7.28 ng/mL/hr (normal range, 1.0–6.5 ng/mL/hr) and 0.1 ng/dL (normal range, 3–35 ng/dL), respectively. The abdominal ultrasound revealed no abnormalities, such as adrenal enlargement, hydronephrosis, distal ureter dilatation, or bowel wall thickening. Based on the patient’s symptoms and laboratory results, we considered several genetic causes for primary adrenal insufficiency, and the causative genes of candidate diseases were listed as STAR for NCCLAH and CYP11A1 for congenital adrenal insufficiency. Additionally, melanocortin-2 receptor (MC2R) and MC2R accessory protein for familial glucocorticoid deficiency (FGD) were listed as candidate genes with a low probability because the patient did not have elevated aldosterone. Targeted gene-panel sequencing was performed to check for pathogenic variants in those genes responsible for primary adrenal insufficiency. Genomic DNA was extracted from the peripheral blood of the patient and both parents. Library preparation was done using the TruSight One Sequencing Panel (Illumina, Inc., San Diego, CA, USA), which enriches a 12-Mb region spanning 62,000 target exons of a total of 4,813 genes. Massively parallel sequencing was performed on the Illumina NextSeq platform. Sequence reads were mapped to the UCSC hg19 standard database for comparative analysis. The average depth of the panel was 85.86X, and percentages of bases above 10X of CYP11A1 and STAR were 99.37%, and 100%, respectively. Meanwhile, no pathogenic variants were detected in CYP11A1 genes. The exome-sequencing results revealed compound heterozygous mutations for c.653C>T and c.661G>A (p.Gly221Ser) in exon 6 of the STAR gene. Sanger sequencing confirmed the presence of these variants and each of the same heterozygous variant was found in his father and mother, respectively ( Fig. 1 ). This variant has been previously reported in association with CLAH. Hydrocortisone (7.8 mg/m 2 /day) and fludrocortisone (50 μg/day) were started as therapy for primary adrenal insufficiency. The dose of hydrocortisone was gradually increased until the age of 24 months for sufficient ACTH suppression and levels of ACTH and cortisol were subsequently decreased to the optimal range ( Fig. 2 ). Finally, at 28 months of age, he was discharged and went home with the attainment of oral feeding without nausea and vomiting. He showed no symptoms of hypoglycemia and continued to show normal growth and development. Our last evaluation of the patient was when he was 36 months of age, during which point, his body weight and length were 16.7 kg (0.5 SDS) and 99.7 cm (1.5 SDS), respectively. Laboratory tests revealed normal levels of cortisol (4.6 μg/dL), sodium (139 mmol/L), potassium (4.9 mEq/L), glucose (70 mg/dL), and ACTH (53.6 pg/mL). The generalized hyperpigmentation had improved, and he continued to visit the outpatient clinic regularly without additional admission."}
|
Endocrinology
|
ENDO
|
[] |
test-1988
|
7136505
|
{'Case report': "A male child was born at a gestational age of 39 weeks with no history of antenatal or perinatal problems. Apgar scores were 9 points at one minute and 10 points at 5 minutes. His birth weight and height were 3,800 g ( z -score, +1 standard deviation score) and 52.5 cm ( z -score, +1.4 SDS), respectively. There was no family history of consanguineous marriages. The patient was born with an imperforate anus and a colostomy was performed the day after birth. He had normal male genitalia, with both testes palpable, and postaxial polydactyly of the left foot. A grade 2 systolic murmur was heard in the left upper sternal border and echocardiography revealed a patent ductus arteriosus. Bilateral grade 3 vesicoureteral reflux (VUR) was revealed via voiding cystourethrography. Spine ultrasound revealed no vertebral anomalies, and tracheoesophageal fistula was not suspected clinically. Based on this clinical information, including anal atresia, renal anomalies, and limb abnormalities, he was diagnosed with VACTERL association which is defined by the presence of at least 3 of the following congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. Laboratory test results, including electrolyte levels, were normal. Neonatal screening tests for metabolic disease were also normal, including the 17-alpha-hydroxyprogesterone level. Chromosome analysis revealed a 46, XY karyotype. He was discharged from the neonatal intensive care unit at 21 days of age. At the age of 3 months, the patient was admitted to the hospital for colostomy takedown, anorectoplasty, and endoscopic dextranomer/hyaluronic acid copolymer injection for VUR. After the surgery, the patient was febrile and hypotensive and his abdomen was distended and discolored. An exploratory laparotomy revealed bowel necrosis. Bowel resection with colostomy and jejunostomy was performed 3 times, which resulted in short-bowel syndrome. He could not be discharged because parenteral nutrition was required. The remnant small bowel extended from the Treitz ligament to the jejunocolonic anastomosis and the length of the remnant bowel was only 40 cm. At the age of 7 months, a takedown of the colostomy and jejunostomy was performed. The patient’s mother observed slight bronzing of the patient’s skin after repeated surgeries At 17 months of age, the patient had an episode of sepsis and peritonitis secondary to Acinetobacter baumannii infection and an exploratory laparotomy was performed to check for bowel necrosis. At this time, generalized hyperpigmentation was noted by the doctor and the mother stated that the child's hyperpigmentation was markedly exacerbated after exploratory laparotomy for the episode of peritonitis with sepsis. The patient was referred to our department for the evaluation of the hyperpigmentation. He experienced occasional nausea and vomiting. His heart rate was 120 beats per minute and his blood pressure was 100/65 mmHg. His weight and height were 12.8 kg (1.5 SDS) and 86 cm (2 SDS), respectively. At this point, he was noted to have generalized hyperpigmentation, normal male genitalia, and postaxial polydactyly of the left foot. He was able to ascend stairs with the support of a hand grasp. He could stack 3 cubes, eat without assistance, and pronounce 10 words, meaning that the patient’s developmental status was normal for his age. Laboratory investigations revealed a slightly decreased sodium level (132 mmol/L) but normal potassium (4.8 mEq/L) and glucose (86 mg/dL) levels; complete blood count, blood gas profile, hepatic and renal function, thyroid function test and sex hormone levels were obtained. Decreased cortisol (1.0 μg/dL) and markedly elevated adrenocorticotropic hormone (ACTH) (16,064 pg/mL) levels were noted. The patient's cortisol levels did not respond to stimulation with ACTH (125 μg) ( Table 1 ). Meanwhile, he presented a normal 17-hydroxyprogesterone level (0.42 ng/mL). Plasma renin activity and aldosterone levels were 7.28 ng/mL/hr (normal range, 1.0–6.5 ng/mL/hr) and 0.1 ng/dL (normal range, 3–35 ng/dL), respectively. The abdominal ultrasound revealed no abnormalities, such as adrenal enlargement, hydronephrosis, distal ureter dilatation, or bowel wall thickening. Based on the patient’s symptoms and laboratory results, we considered several genetic causes for primary adrenal insufficiency, and the causative genes of candidate diseases were listed as STAR for NCCLAH and CYP11A1 for congenital adrenal insufficiency. Additionally, melanocortin-2 receptor (MC2R) and MC2R accessory protein for familial glucocorticoid deficiency (FGD) were listed as candidate genes with a low probability because the patient did not have elevated aldosterone. Targeted gene-panel sequencing was performed to check for pathogenic variants in those genes responsible for primary adrenal insufficiency. Genomic DNA was extracted from the peripheral blood of the patient and both parents. Library preparation was done using the TruSight One Sequencing Panel (Illumina, Inc., San Diego, CA, USA), which enriches a 12-Mb region spanning 62,000 target exons of a total of 4,813 genes. Massively parallel sequencing was performed on the Illumina NextSeq platform. Sequence reads were mapped to the UCSC hg19 standard database for comparative analysis. The average depth of the panel was 85.86X, and percentages of bases above 10X of CYP11A1 and STAR were 99.37%, and 100%, respectively. Meanwhile, no pathogenic variants were detected in CYP11A1 genes. The exome-sequencing results revealed compound heterozygous mutations for c.653C>T and c.661G>A (p.Gly221Ser) in exon 6 of the STAR gene. Sanger sequencing confirmed the presence of these variants and each of the same heterozygous variant was found in his father and mother, respectively ( Fig. 1 ). This variant has been previously reported in association with CLAH. Hydrocortisone (7.8 mg/m 2 /day) and fludrocortisone (50 μg/day) were started as therapy for primary adrenal insufficiency. The dose of hydrocortisone was gradually increased until the age of 24 months for sufficient ACTH suppression and levels of ACTH and cortisol were subsequently decreased to the optimal range ( Fig. 2 ). Finally, at 28 months of age, he was discharged and went home with the attainment of oral feeding without nausea and vomiting. He showed no symptoms of hypoglycemia and continued to show normal growth and development. Our last evaluation of the patient was when he was 36 months of age, during which point, his body weight and length were 16.7 kg (0.5 SDS) and 99.7 cm (1.5 SDS), respectively. Laboratory tests revealed normal levels of cortisol (4.6 μg/dL), sodium (139 mmol/L), potassium (4.9 mEq/L), glucose (70 mg/dL), and ACTH (53.6 pg/mL). The generalized hyperpigmentation had improved, and he continued to visit the outpatient clinic regularly without additional admission."}
|
{'Case report': "A male child was born at a gestational age of 39 weeks with no history of antenatal or perinatal problems. Apgar scores were 9 points at one minute and 10 points at 5 minutes. His birth weight and height were 3,800 g ( z -score, +1 standard deviation score) and 52.5 cm ( z -score, +1.4 SDS), respectively. There was no family history of consanguineous marriages. The patient was born with an imperforate anus and a colostomy was performed the day after birth. He had normal male genitalia, with both testes palpable, and postaxial polydactyly of the left foot. A grade 2 systolic murmur was heard in the left upper sternal border and echocardiography revealed a patent ductus arteriosus. Bilateral grade 3 vesicoureteral reflux (VUR) was revealed via voiding cystourethrography. Spine ultrasound revealed no vertebral anomalies, and tracheoesophageal fistula was not suspected clinically. Based on this clinical information, including anal atresia, renal anomalies, and limb abnormalities, he was diagnosed with VACTERL association which is defined by the presence of at least 3 of the following congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. Laboratory test results, including electrolyte levels, were normal. Neonatal screening tests for metabolic disease were also normal, including the 17-alpha-hydroxyprogesterone level. Chromosome analysis revealed a 46, XY karyotype. He was discharged from the neonatal intensive care unit at 21 days of age. At the age of 3 months, the patient was admitted to the hospital for colostomy takedown, anorectoplasty, and endoscopic dextranomer/hyaluronic acid copolymer injection for VUR. After the surgery, the patient was febrile and hypotensive and his abdomen was distended and discolored. An exploratory laparotomy revealed bowel necrosis. Bowel resection with colostomy and jejunostomy was performed 3 times, which resulted in short-bowel syndrome. He could not be discharged because parenteral nutrition was required. The remnant small bowel extended from the Treitz ligament to the jejunocolonic anastomosis and the length of the remnant bowel was only 40 cm. At the age of 7 months, a takedown of the colostomy and jejunostomy was performed. The patient’s mother observed slight bronzing of the patient’s skin after repeated surgeries At 17 months of age, the patient had an episode of sepsis and peritonitis secondary to Acinetobacter baumannii infection and an exploratory laparotomy was performed to check for bowel necrosis. At this time, generalized hyperpigmentation was noted by the doctor and the mother stated that the child's hyperpigmentation was markedly exacerbated after exploratory laparotomy for the episode of peritonitis with sepsis. The patient was referred to our department for the evaluation of the hyperpigmentation. He experienced occasional nausea and vomiting. His heart rate was 120 beats per minute and his blood pressure was 100/65 mmHg. His weight and height were 12.8 kg (1.5 SDS) and 86 cm (2 SDS), respectively. At this point, he was noted to have generalized hyperpigmentation, normal male genitalia, and postaxial polydactyly of the left foot. He was able to ascend stairs with the support of a hand grasp. He could stack 3 cubes, eat without assistance, and pronounce 10 words, meaning that the patient’s developmental status was normal for his age. Laboratory investigations revealed a slightly decreased sodium level (132 mmol/L) but normal potassium (4.8 mEq/L) and glucose (86 mg/dL) levels; complete blood count, blood gas profile, hepatic and renal function, thyroid function test and sex hormone levels were obtained. Decreased cortisol (1.0 μg/dL) and markedly elevated adrenocorticotropic hormone (ACTH) (16,064 pg/mL) levels were noted. The patient's cortisol levels did not respond to stimulation with ACTH (125 μg) ( Table 1 ). Meanwhile, he presented a normal 17-hydroxyprogesterone level (0.42 ng/mL). Plasma renin activity and aldosterone levels were 7.28 ng/mL/hr (normal range, 1.0–6.5 ng/mL/hr) and 0.1 ng/dL (normal range, 3–35 ng/dL), respectively. The abdominal ultrasound revealed no abnormalities, such as adrenal enlargement, hydronephrosis, distal ureter dilatation, or bowel wall thickening. Based on the patient’s symptoms and laboratory results, we considered several genetic causes for primary adrenal insufficiency, and the causative genes of candidate diseases were listed as STAR for NCCLAH and CYP11A1 for congenital adrenal insufficiency. Additionally, melanocortin-2 receptor (MC2R) and MC2R accessory protein for familial glucocorticoid deficiency (FGD) were listed as candidate genes with a low probability because the patient did not have elevated aldosterone. Targeted gene-panel sequencing was performed to check for pathogenic variants in those genes responsible for primary adrenal insufficiency. Genomic DNA was extracted from the peripheral blood of the patient and both parents. Library preparation was done using the TruSight One Sequencing Panel (Illumina, Inc., San Diego, CA, USA), which enriches a 12-Mb region spanning 62,000 target exons of a total of 4,813 genes. Massively parallel sequencing was performed on the Illumina NextSeq platform. Sequence reads were mapped to the UCSC hg19 standard database for comparative analysis. The average depth of the panel was 85.86X, and percentages of bases above 10X of CYP11A1 and STAR were 99.37%, and 100%, respectively. Meanwhile, no pathogenic variants were detected in CYP11A1 genes. The exome-sequencing results revealed compound heterozygous mutations for c.653C>T and c.661G>A (p.Gly221Ser) in exon 6 of the STAR gene. Sanger sequencing confirmed the presence of these variants and each of the same heterozygous variant was found in his father and mother, respectively ( Fig. 1 ). This variant has been previously reported in association with CLAH. Hydrocortisone (7.8 mg/m 2 /day) and fludrocortisone (50 μg/day) were started as therapy for primary adrenal insufficiency. The dose of hydrocortisone was gradually increased until the age of 24 months for sufficient ACTH suppression and levels of ACTH and cortisol were subsequently decreased to the optimal range ( Fig. 2 ). Finally, at 28 months of age, he was discharged and went home with the attainment of oral feeding without nausea and vomiting. He showed no symptoms of hypoglycemia and continued to show normal growth and development. Our last evaluation of the patient was when he was 36 months of age, during which point, his body weight and length were 16.7 kg (0.5 SDS) and 99.7 cm (1.5 SDS), respectively. Laboratory tests revealed normal levels of cortisol (4.6 μg/dL), sodium (139 mmol/L), potassium (4.9 mEq/L), glucose (70 mg/dL), and ACTH (53.6 pg/mL). The generalized hyperpigmentation had improved, and he continued to visit the outpatient clinic regularly without additional admission."}
|
Genitourinary-System
|
GU
|
[
"normal male genitalia, with both testes palpable",
"Bilateral grade 3 vesicoureteral reflux ( VUR ) was revealed via voiding cystourethrography",
"renal anomalies",
"normal male genitalia",
"slightly decreased sodium level ( 132 mmol / L ) but normal potassium ( 4.8 mEq / L )",
"no abnormalities, such as adrenal enlargement, hydronephrosis, distal ureter dilatation"
] |
test-1989
|
7136505
|
{'Case report': "A male child was born at a gestational age of 39 weeks with no history of antenatal or perinatal problems. Apgar scores were 9 points at one minute and 10 points at 5 minutes. His birth weight and height were 3,800 g ( z -score, +1 standard deviation score) and 52.5 cm ( z -score, +1.4 SDS), respectively. There was no family history of consanguineous marriages. The patient was born with an imperforate anus and a colostomy was performed the day after birth. He had normal male genitalia, with both testes palpable, and postaxial polydactyly of the left foot. A grade 2 systolic murmur was heard in the left upper sternal border and echocardiography revealed a patent ductus arteriosus. Bilateral grade 3 vesicoureteral reflux (VUR) was revealed via voiding cystourethrography. Spine ultrasound revealed no vertebral anomalies, and tracheoesophageal fistula was not suspected clinically. Based on this clinical information, including anal atresia, renal anomalies, and limb abnormalities, he was diagnosed with VACTERL association which is defined by the presence of at least 3 of the following congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. Laboratory test results, including electrolyte levels, were normal. Neonatal screening tests for metabolic disease were also normal, including the 17-alpha-hydroxyprogesterone level. Chromosome analysis revealed a 46, XY karyotype. He was discharged from the neonatal intensive care unit at 21 days of age. At the age of 3 months, the patient was admitted to the hospital for colostomy takedown, anorectoplasty, and endoscopic dextranomer/hyaluronic acid copolymer injection for VUR. After the surgery, the patient was febrile and hypotensive and his abdomen was distended and discolored. An exploratory laparotomy revealed bowel necrosis. Bowel resection with colostomy and jejunostomy was performed 3 times, which resulted in short-bowel syndrome. He could not be discharged because parenteral nutrition was required. The remnant small bowel extended from the Treitz ligament to the jejunocolonic anastomosis and the length of the remnant bowel was only 40 cm. At the age of 7 months, a takedown of the colostomy and jejunostomy was performed. The patient’s mother observed slight bronzing of the patient’s skin after repeated surgeries At 17 months of age, the patient had an episode of sepsis and peritonitis secondary to Acinetobacter baumannii infection and an exploratory laparotomy was performed to check for bowel necrosis. At this time, generalized hyperpigmentation was noted by the doctor and the mother stated that the child's hyperpigmentation was markedly exacerbated after exploratory laparotomy for the episode of peritonitis with sepsis. The patient was referred to our department for the evaluation of the hyperpigmentation. He experienced occasional nausea and vomiting. His heart rate was 120 beats per minute and his blood pressure was 100/65 mmHg. His weight and height were 12.8 kg (1.5 SDS) and 86 cm (2 SDS), respectively. At this point, he was noted to have generalized hyperpigmentation, normal male genitalia, and postaxial polydactyly of the left foot. He was able to ascend stairs with the support of a hand grasp. He could stack 3 cubes, eat without assistance, and pronounce 10 words, meaning that the patient’s developmental status was normal for his age. Laboratory investigations revealed a slightly decreased sodium level (132 mmol/L) but normal potassium (4.8 mEq/L) and glucose (86 mg/dL) levels; complete blood count, blood gas profile, hepatic and renal function, thyroid function test and sex hormone levels were obtained. Decreased cortisol (1.0 μg/dL) and markedly elevated adrenocorticotropic hormone (ACTH) (16,064 pg/mL) levels were noted. The patient's cortisol levels did not respond to stimulation with ACTH (125 μg) ( Table 1 ). Meanwhile, he presented a normal 17-hydroxyprogesterone level (0.42 ng/mL). Plasma renin activity and aldosterone levels were 7.28 ng/mL/hr (normal range, 1.0–6.5 ng/mL/hr) and 0.1 ng/dL (normal range, 3–35 ng/dL), respectively. The abdominal ultrasound revealed no abnormalities, such as adrenal enlargement, hydronephrosis, distal ureter dilatation, or bowel wall thickening. Based on the patient’s symptoms and laboratory results, we considered several genetic causes for primary adrenal insufficiency, and the causative genes of candidate diseases were listed as STAR for NCCLAH and CYP11A1 for congenital adrenal insufficiency. Additionally, melanocortin-2 receptor (MC2R) and MC2R accessory protein for familial glucocorticoid deficiency (FGD) were listed as candidate genes with a low probability because the patient did not have elevated aldosterone. Targeted gene-panel sequencing was performed to check for pathogenic variants in those genes responsible for primary adrenal insufficiency. Genomic DNA was extracted from the peripheral blood of the patient and both parents. Library preparation was done using the TruSight One Sequencing Panel (Illumina, Inc., San Diego, CA, USA), which enriches a 12-Mb region spanning 62,000 target exons of a total of 4,813 genes. Massively parallel sequencing was performed on the Illumina NextSeq platform. Sequence reads were mapped to the UCSC hg19 standard database for comparative analysis. The average depth of the panel was 85.86X, and percentages of bases above 10X of CYP11A1 and STAR were 99.37%, and 100%, respectively. Meanwhile, no pathogenic variants were detected in CYP11A1 genes. The exome-sequencing results revealed compound heterozygous mutations for c.653C>T and c.661G>A (p.Gly221Ser) in exon 6 of the STAR gene. Sanger sequencing confirmed the presence of these variants and each of the same heterozygous variant was found in his father and mother, respectively ( Fig. 1 ). This variant has been previously reported in association with CLAH. Hydrocortisone (7.8 mg/m 2 /day) and fludrocortisone (50 μg/day) were started as therapy for primary adrenal insufficiency. The dose of hydrocortisone was gradually increased until the age of 24 months for sufficient ACTH suppression and levels of ACTH and cortisol were subsequently decreased to the optimal range ( Fig. 2 ). Finally, at 28 months of age, he was discharged and went home with the attainment of oral feeding without nausea and vomiting. He showed no symptoms of hypoglycemia and continued to show normal growth and development. Our last evaluation of the patient was when he was 36 months of age, during which point, his body weight and length were 16.7 kg (0.5 SDS) and 99.7 cm (1.5 SDS), respectively. Laboratory tests revealed normal levels of cortisol (4.6 μg/dL), sodium (139 mmol/L), potassium (4.9 mEq/L), glucose (70 mg/dL), and ACTH (53.6 pg/mL). The generalized hyperpigmentation had improved, and he continued to visit the outpatient clinic regularly without additional admission."}
|
{'Case report': "A male child was born at a gestational age of 39 weeks with no history of antenatal or perinatal problems. Apgar scores were 9 points at one minute and 10 points at 5 minutes. His birth weight and height were 3,800 g ( z -score, +1 standard deviation score) and 52.5 cm ( z -score, +1.4 SDS), respectively. There was no family history of consanguineous marriages. The patient was born with an imperforate anus and a colostomy was performed the day after birth. He had normal male genitalia, with both testes palpable, and postaxial polydactyly of the left foot. A grade 2 systolic murmur was heard in the left upper sternal border and echocardiography revealed a patent ductus arteriosus. Bilateral grade 3 vesicoureteral reflux (VUR) was revealed via voiding cystourethrography. Spine ultrasound revealed no vertebral anomalies, and tracheoesophageal fistula was not suspected clinically. Based on this clinical information, including anal atresia, renal anomalies, and limb abnormalities, he was diagnosed with VACTERL association which is defined by the presence of at least 3 of the following congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. Laboratory test results, including electrolyte levels, were normal. Neonatal screening tests for metabolic disease were also normal, including the 17-alpha-hydroxyprogesterone level. Chromosome analysis revealed a 46, XY karyotype. He was discharged from the neonatal intensive care unit at 21 days of age. At the age of 3 months, the patient was admitted to the hospital for colostomy takedown, anorectoplasty, and endoscopic dextranomer/hyaluronic acid copolymer injection for VUR. After the surgery, the patient was febrile and hypotensive and his abdomen was distended and discolored. An exploratory laparotomy revealed bowel necrosis. Bowel resection with colostomy and jejunostomy was performed 3 times, which resulted in short-bowel syndrome. He could not be discharged because parenteral nutrition was required. The remnant small bowel extended from the Treitz ligament to the jejunocolonic anastomosis and the length of the remnant bowel was only 40 cm. At the age of 7 months, a takedown of the colostomy and jejunostomy was performed. The patient’s mother observed slight bronzing of the patient’s skin after repeated surgeries At 17 months of age, the patient had an episode of sepsis and peritonitis secondary to Acinetobacter baumannii infection and an exploratory laparotomy was performed to check for bowel necrosis. At this time, generalized hyperpigmentation was noted by the doctor and the mother stated that the child's hyperpigmentation was markedly exacerbated after exploratory laparotomy for the episode of peritonitis with sepsis. The patient was referred to our department for the evaluation of the hyperpigmentation. He experienced occasional nausea and vomiting. His heart rate was 120 beats per minute and his blood pressure was 100/65 mmHg. His weight and height were 12.8 kg (1.5 SDS) and 86 cm (2 SDS), respectively. At this point, he was noted to have generalized hyperpigmentation, normal male genitalia, and postaxial polydactyly of the left foot. He was able to ascend stairs with the support of a hand grasp. He could stack 3 cubes, eat without assistance, and pronounce 10 words, meaning that the patient’s developmental status was normal for his age. Laboratory investigations revealed a slightly decreased sodium level (132 mmol/L) but normal potassium (4.8 mEq/L) and glucose (86 mg/dL) levels; complete blood count, blood gas profile, hepatic and renal function, thyroid function test and sex hormone levels were obtained. Decreased cortisol (1.0 μg/dL) and markedly elevated adrenocorticotropic hormone (ACTH) (16,064 pg/mL) levels were noted. The patient's cortisol levels did not respond to stimulation with ACTH (125 μg) ( Table 1 ). Meanwhile, he presented a normal 17-hydroxyprogesterone level (0.42 ng/mL). Plasma renin activity and aldosterone levels were 7.28 ng/mL/hr (normal range, 1.0–6.5 ng/mL/hr) and 0.1 ng/dL (normal range, 3–35 ng/dL), respectively. The abdominal ultrasound revealed no abnormalities, such as adrenal enlargement, hydronephrosis, distal ureter dilatation, or bowel wall thickening. Based on the patient’s symptoms and laboratory results, we considered several genetic causes for primary adrenal insufficiency, and the causative genes of candidate diseases were listed as STAR for NCCLAH and CYP11A1 for congenital adrenal insufficiency. Additionally, melanocortin-2 receptor (MC2R) and MC2R accessory protein for familial glucocorticoid deficiency (FGD) were listed as candidate genes with a low probability because the patient did not have elevated aldosterone. Targeted gene-panel sequencing was performed to check for pathogenic variants in those genes responsible for primary adrenal insufficiency. Genomic DNA was extracted from the peripheral blood of the patient and both parents. Library preparation was done using the TruSight One Sequencing Panel (Illumina, Inc., San Diego, CA, USA), which enriches a 12-Mb region spanning 62,000 target exons of a total of 4,813 genes. Massively parallel sequencing was performed on the Illumina NextSeq platform. Sequence reads were mapped to the UCSC hg19 standard database for comparative analysis. The average depth of the panel was 85.86X, and percentages of bases above 10X of CYP11A1 and STAR were 99.37%, and 100%, respectively. Meanwhile, no pathogenic variants were detected in CYP11A1 genes. The exome-sequencing results revealed compound heterozygous mutations for c.653C>T and c.661G>A (p.Gly221Ser) in exon 6 of the STAR gene. Sanger sequencing confirmed the presence of these variants and each of the same heterozygous variant was found in his father and mother, respectively ( Fig. 1 ). This variant has been previously reported in association with CLAH. Hydrocortisone (7.8 mg/m 2 /day) and fludrocortisone (50 μg/day) were started as therapy for primary adrenal insufficiency. The dose of hydrocortisone was gradually increased until the age of 24 months for sufficient ACTH suppression and levels of ACTH and cortisol were subsequently decreased to the optimal range ( Fig. 2 ). Finally, at 28 months of age, he was discharged and went home with the attainment of oral feeding without nausea and vomiting. He showed no symptoms of hypoglycemia and continued to show normal growth and development. Our last evaluation of the patient was when he was 36 months of age, during which point, his body weight and length were 16.7 kg (0.5 SDS) and 99.7 cm (1.5 SDS), respectively. Laboratory tests revealed normal levels of cortisol (4.6 μg/dL), sodium (139 mmol/L), potassium (4.9 mEq/L), glucose (70 mg/dL), and ACTH (53.6 pg/mL). The generalized hyperpigmentation had improved, and he continued to visit the outpatient clinic regularly without additional admission."}
|
Respiratory-System
|
RESP
|
[] |
test-1990
|
7136505
|
{'Case report': "A male child was born at a gestational age of 39 weeks with no history of antenatal or perinatal problems. Apgar scores were 9 points at one minute and 10 points at 5 minutes. His birth weight and height were 3,800 g ( z -score, +1 standard deviation score) and 52.5 cm ( z -score, +1.4 SDS), respectively. There was no family history of consanguineous marriages. The patient was born with an imperforate anus and a colostomy was performed the day after birth. He had normal male genitalia, with both testes palpable, and postaxial polydactyly of the left foot. A grade 2 systolic murmur was heard in the left upper sternal border and echocardiography revealed a patent ductus arteriosus. Bilateral grade 3 vesicoureteral reflux (VUR) was revealed via voiding cystourethrography. Spine ultrasound revealed no vertebral anomalies, and tracheoesophageal fistula was not suspected clinically. Based on this clinical information, including anal atresia, renal anomalies, and limb abnormalities, he was diagnosed with VACTERL association which is defined by the presence of at least 3 of the following congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. Laboratory test results, including electrolyte levels, were normal. Neonatal screening tests for metabolic disease were also normal, including the 17-alpha-hydroxyprogesterone level. Chromosome analysis revealed a 46, XY karyotype. He was discharged from the neonatal intensive care unit at 21 days of age. At the age of 3 months, the patient was admitted to the hospital for colostomy takedown, anorectoplasty, and endoscopic dextranomer/hyaluronic acid copolymer injection for VUR. After the surgery, the patient was febrile and hypotensive and his abdomen was distended and discolored. An exploratory laparotomy revealed bowel necrosis. Bowel resection with colostomy and jejunostomy was performed 3 times, which resulted in short-bowel syndrome. He could not be discharged because parenteral nutrition was required. The remnant small bowel extended from the Treitz ligament to the jejunocolonic anastomosis and the length of the remnant bowel was only 40 cm. At the age of 7 months, a takedown of the colostomy and jejunostomy was performed. The patient’s mother observed slight bronzing of the patient’s skin after repeated surgeries At 17 months of age, the patient had an episode of sepsis and peritonitis secondary to Acinetobacter baumannii infection and an exploratory laparotomy was performed to check for bowel necrosis. At this time, generalized hyperpigmentation was noted by the doctor and the mother stated that the child's hyperpigmentation was markedly exacerbated after exploratory laparotomy for the episode of peritonitis with sepsis. The patient was referred to our department for the evaluation of the hyperpigmentation. He experienced occasional nausea and vomiting. His heart rate was 120 beats per minute and his blood pressure was 100/65 mmHg. His weight and height were 12.8 kg (1.5 SDS) and 86 cm (2 SDS), respectively. At this point, he was noted to have generalized hyperpigmentation, normal male genitalia, and postaxial polydactyly of the left foot. He was able to ascend stairs with the support of a hand grasp. He could stack 3 cubes, eat without assistance, and pronounce 10 words, meaning that the patient’s developmental status was normal for his age. Laboratory investigations revealed a slightly decreased sodium level (132 mmol/L) but normal potassium (4.8 mEq/L) and glucose (86 mg/dL) levels; complete blood count, blood gas profile, hepatic and renal function, thyroid function test and sex hormone levels were obtained. Decreased cortisol (1.0 μg/dL) and markedly elevated adrenocorticotropic hormone (ACTH) (16,064 pg/mL) levels were noted. The patient's cortisol levels did not respond to stimulation with ACTH (125 μg) ( Table 1 ). Meanwhile, he presented a normal 17-hydroxyprogesterone level (0.42 ng/mL). Plasma renin activity and aldosterone levels were 7.28 ng/mL/hr (normal range, 1.0–6.5 ng/mL/hr) and 0.1 ng/dL (normal range, 3–35 ng/dL), respectively. The abdominal ultrasound revealed no abnormalities, such as adrenal enlargement, hydronephrosis, distal ureter dilatation, or bowel wall thickening. Based on the patient’s symptoms and laboratory results, we considered several genetic causes for primary adrenal insufficiency, and the causative genes of candidate diseases were listed as STAR for NCCLAH and CYP11A1 for congenital adrenal insufficiency. Additionally, melanocortin-2 receptor (MC2R) and MC2R accessory protein for familial glucocorticoid deficiency (FGD) were listed as candidate genes with a low probability because the patient did not have elevated aldosterone. Targeted gene-panel sequencing was performed to check for pathogenic variants in those genes responsible for primary adrenal insufficiency. Genomic DNA was extracted from the peripheral blood of the patient and both parents. Library preparation was done using the TruSight One Sequencing Panel (Illumina, Inc., San Diego, CA, USA), which enriches a 12-Mb region spanning 62,000 target exons of a total of 4,813 genes. Massively parallel sequencing was performed on the Illumina NextSeq platform. Sequence reads were mapped to the UCSC hg19 standard database for comparative analysis. The average depth of the panel was 85.86X, and percentages of bases above 10X of CYP11A1 and STAR were 99.37%, and 100%, respectively. Meanwhile, no pathogenic variants were detected in CYP11A1 genes. The exome-sequencing results revealed compound heterozygous mutations for c.653C>T and c.661G>A (p.Gly221Ser) in exon 6 of the STAR gene. Sanger sequencing confirmed the presence of these variants and each of the same heterozygous variant was found in his father and mother, respectively ( Fig. 1 ). This variant has been previously reported in association with CLAH. Hydrocortisone (7.8 mg/m 2 /day) and fludrocortisone (50 μg/day) were started as therapy for primary adrenal insufficiency. The dose of hydrocortisone was gradually increased until the age of 24 months for sufficient ACTH suppression and levels of ACTH and cortisol were subsequently decreased to the optimal range ( Fig. 2 ). Finally, at 28 months of age, he was discharged and went home with the attainment of oral feeding without nausea and vomiting. He showed no symptoms of hypoglycemia and continued to show normal growth and development. Our last evaluation of the patient was when he was 36 months of age, during which point, his body weight and length were 16.7 kg (0.5 SDS) and 99.7 cm (1.5 SDS), respectively. Laboratory tests revealed normal levels of cortisol (4.6 μg/dL), sodium (139 mmol/L), potassium (4.9 mEq/L), glucose (70 mg/dL), and ACTH (53.6 pg/mL). The generalized hyperpigmentation had improved, and he continued to visit the outpatient clinic regularly without additional admission."}
|
{'Case report': "A male child was born at a gestational age of 39 weeks with no history of antenatal or perinatal problems. Apgar scores were 9 points at one minute and 10 points at 5 minutes. His birth weight and height were 3,800 g ( z -score, +1 standard deviation score) and 52.5 cm ( z -score, +1.4 SDS), respectively. There was no family history of consanguineous marriages. The patient was born with an imperforate anus and a colostomy was performed the day after birth. He had normal male genitalia, with both testes palpable, and postaxial polydactyly of the left foot. A grade 2 systolic murmur was heard in the left upper sternal border and echocardiography revealed a patent ductus arteriosus. Bilateral grade 3 vesicoureteral reflux (VUR) was revealed via voiding cystourethrography. Spine ultrasound revealed no vertebral anomalies, and tracheoesophageal fistula was not suspected clinically. Based on this clinical information, including anal atresia, renal anomalies, and limb abnormalities, he was diagnosed with VACTERL association which is defined by the presence of at least 3 of the following congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. Laboratory test results, including electrolyte levels, were normal. Neonatal screening tests for metabolic disease were also normal, including the 17-alpha-hydroxyprogesterone level. Chromosome analysis revealed a 46, XY karyotype. He was discharged from the neonatal intensive care unit at 21 days of age. At the age of 3 months, the patient was admitted to the hospital for colostomy takedown, anorectoplasty, and endoscopic dextranomer/hyaluronic acid copolymer injection for VUR. After the surgery, the patient was febrile and hypotensive and his abdomen was distended and discolored. An exploratory laparotomy revealed bowel necrosis. Bowel resection with colostomy and jejunostomy was performed 3 times, which resulted in short-bowel syndrome. He could not be discharged because parenteral nutrition was required. The remnant small bowel extended from the Treitz ligament to the jejunocolonic anastomosis and the length of the remnant bowel was only 40 cm. At the age of 7 months, a takedown of the colostomy and jejunostomy was performed. The patient’s mother observed slight bronzing of the patient’s skin after repeated surgeries At 17 months of age, the patient had an episode of sepsis and peritonitis secondary to Acinetobacter baumannii infection and an exploratory laparotomy was performed to check for bowel necrosis. At this time, generalized hyperpigmentation was noted by the doctor and the mother stated that the child's hyperpigmentation was markedly exacerbated after exploratory laparotomy for the episode of peritonitis with sepsis. The patient was referred to our department for the evaluation of the hyperpigmentation. He experienced occasional nausea and vomiting. His heart rate was 120 beats per minute and his blood pressure was 100/65 mmHg. His weight and height were 12.8 kg (1.5 SDS) and 86 cm (2 SDS), respectively. At this point, he was noted to have generalized hyperpigmentation, normal male genitalia, and postaxial polydactyly of the left foot. He was able to ascend stairs with the support of a hand grasp. He could stack 3 cubes, eat without assistance, and pronounce 10 words, meaning that the patient’s developmental status was normal for his age. Laboratory investigations revealed a slightly decreased sodium level (132 mmol/L) but normal potassium (4.8 mEq/L) and glucose (86 mg/dL) levels; complete blood count, blood gas profile, hepatic and renal function, thyroid function test and sex hormone levels were obtained. Decreased cortisol (1.0 μg/dL) and markedly elevated adrenocorticotropic hormone (ACTH) (16,064 pg/mL) levels were noted. The patient's cortisol levels did not respond to stimulation with ACTH (125 μg) ( Table 1 ). Meanwhile, he presented a normal 17-hydroxyprogesterone level (0.42 ng/mL). Plasma renin activity and aldosterone levels were 7.28 ng/mL/hr (normal range, 1.0–6.5 ng/mL/hr) and 0.1 ng/dL (normal range, 3–35 ng/dL), respectively. The abdominal ultrasound revealed no abnormalities, such as adrenal enlargement, hydronephrosis, distal ureter dilatation, or bowel wall thickening. Based on the patient’s symptoms and laboratory results, we considered several genetic causes for primary adrenal insufficiency, and the causative genes of candidate diseases were listed as STAR for NCCLAH and CYP11A1 for congenital adrenal insufficiency. Additionally, melanocortin-2 receptor (MC2R) and MC2R accessory protein for familial glucocorticoid deficiency (FGD) were listed as candidate genes with a low probability because the patient did not have elevated aldosterone. Targeted gene-panel sequencing was performed to check for pathogenic variants in those genes responsible for primary adrenal insufficiency. Genomic DNA was extracted from the peripheral blood of the patient and both parents. Library preparation was done using the TruSight One Sequencing Panel (Illumina, Inc., San Diego, CA, USA), which enriches a 12-Mb region spanning 62,000 target exons of a total of 4,813 genes. Massively parallel sequencing was performed on the Illumina NextSeq platform. Sequence reads were mapped to the UCSC hg19 standard database for comparative analysis. The average depth of the panel was 85.86X, and percentages of bases above 10X of CYP11A1 and STAR were 99.37%, and 100%, respectively. Meanwhile, no pathogenic variants were detected in CYP11A1 genes. The exome-sequencing results revealed compound heterozygous mutations for c.653C>T and c.661G>A (p.Gly221Ser) in exon 6 of the STAR gene. Sanger sequencing confirmed the presence of these variants and each of the same heterozygous variant was found in his father and mother, respectively ( Fig. 1 ). This variant has been previously reported in association with CLAH. Hydrocortisone (7.8 mg/m 2 /day) and fludrocortisone (50 μg/day) were started as therapy for primary adrenal insufficiency. The dose of hydrocortisone was gradually increased until the age of 24 months for sufficient ACTH suppression and levels of ACTH and cortisol were subsequently decreased to the optimal range ( Fig. 2 ). Finally, at 28 months of age, he was discharged and went home with the attainment of oral feeding without nausea and vomiting. He showed no symptoms of hypoglycemia and continued to show normal growth and development. Our last evaluation of the patient was when he was 36 months of age, during which point, his body weight and length were 16.7 kg (0.5 SDS) and 99.7 cm (1.5 SDS), respectively. Laboratory tests revealed normal levels of cortisol (4.6 μg/dL), sodium (139 mmol/L), potassium (4.9 mEq/L), glucose (70 mg/dL), and ACTH (53.6 pg/mL). The generalized hyperpigmentation had improved, and he continued to visit the outpatient clinic regularly without additional admission."}
|
Musculoskeletal-System
|
MSK
|
[
"postaxial polydactyly of the left foot",
"Spine ultrasound revealed no vertebral anomalies",
"limb abnormalities",
"postaxial polydactyly of the left foot"
] |
test-1991
|
7136505
|
{'Case report': "A male child was born at a gestational age of 39 weeks with no history of antenatal or perinatal problems. Apgar scores were 9 points at one minute and 10 points at 5 minutes. His birth weight and height were 3,800 g ( z -score, +1 standard deviation score) and 52.5 cm ( z -score, +1.4 SDS), respectively. There was no family history of consanguineous marriages. The patient was born with an imperforate anus and a colostomy was performed the day after birth. He had normal male genitalia, with both testes palpable, and postaxial polydactyly of the left foot. A grade 2 systolic murmur was heard in the left upper sternal border and echocardiography revealed a patent ductus arteriosus. Bilateral grade 3 vesicoureteral reflux (VUR) was revealed via voiding cystourethrography. Spine ultrasound revealed no vertebral anomalies, and tracheoesophageal fistula was not suspected clinically. Based on this clinical information, including anal atresia, renal anomalies, and limb abnormalities, he was diagnosed with VACTERL association which is defined by the presence of at least 3 of the following congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. Laboratory test results, including electrolyte levels, were normal. Neonatal screening tests for metabolic disease were also normal, including the 17-alpha-hydroxyprogesterone level. Chromosome analysis revealed a 46, XY karyotype. He was discharged from the neonatal intensive care unit at 21 days of age. At the age of 3 months, the patient was admitted to the hospital for colostomy takedown, anorectoplasty, and endoscopic dextranomer/hyaluronic acid copolymer injection for VUR. After the surgery, the patient was febrile and hypotensive and his abdomen was distended and discolored. An exploratory laparotomy revealed bowel necrosis. Bowel resection with colostomy and jejunostomy was performed 3 times, which resulted in short-bowel syndrome. He could not be discharged because parenteral nutrition was required. The remnant small bowel extended from the Treitz ligament to the jejunocolonic anastomosis and the length of the remnant bowel was only 40 cm. At the age of 7 months, a takedown of the colostomy and jejunostomy was performed. The patient’s mother observed slight bronzing of the patient’s skin after repeated surgeries At 17 months of age, the patient had an episode of sepsis and peritonitis secondary to Acinetobacter baumannii infection and an exploratory laparotomy was performed to check for bowel necrosis. At this time, generalized hyperpigmentation was noted by the doctor and the mother stated that the child's hyperpigmentation was markedly exacerbated after exploratory laparotomy for the episode of peritonitis with sepsis. The patient was referred to our department for the evaluation of the hyperpigmentation. He experienced occasional nausea and vomiting. His heart rate was 120 beats per minute and his blood pressure was 100/65 mmHg. His weight and height were 12.8 kg (1.5 SDS) and 86 cm (2 SDS), respectively. At this point, he was noted to have generalized hyperpigmentation, normal male genitalia, and postaxial polydactyly of the left foot. He was able to ascend stairs with the support of a hand grasp. He could stack 3 cubes, eat without assistance, and pronounce 10 words, meaning that the patient’s developmental status was normal for his age. Laboratory investigations revealed a slightly decreased sodium level (132 mmol/L) but normal potassium (4.8 mEq/L) and glucose (86 mg/dL) levels; complete blood count, blood gas profile, hepatic and renal function, thyroid function test and sex hormone levels were obtained. Decreased cortisol (1.0 μg/dL) and markedly elevated adrenocorticotropic hormone (ACTH) (16,064 pg/mL) levels were noted. The patient's cortisol levels did not respond to stimulation with ACTH (125 μg) ( Table 1 ). Meanwhile, he presented a normal 17-hydroxyprogesterone level (0.42 ng/mL). Plasma renin activity and aldosterone levels were 7.28 ng/mL/hr (normal range, 1.0–6.5 ng/mL/hr) and 0.1 ng/dL (normal range, 3–35 ng/dL), respectively. The abdominal ultrasound revealed no abnormalities, such as adrenal enlargement, hydronephrosis, distal ureter dilatation, or bowel wall thickening. Based on the patient’s symptoms and laboratory results, we considered several genetic causes for primary adrenal insufficiency, and the causative genes of candidate diseases were listed as STAR for NCCLAH and CYP11A1 for congenital adrenal insufficiency. Additionally, melanocortin-2 receptor (MC2R) and MC2R accessory protein for familial glucocorticoid deficiency (FGD) were listed as candidate genes with a low probability because the patient did not have elevated aldosterone. Targeted gene-panel sequencing was performed to check for pathogenic variants in those genes responsible for primary adrenal insufficiency. Genomic DNA was extracted from the peripheral blood of the patient and both parents. Library preparation was done using the TruSight One Sequencing Panel (Illumina, Inc., San Diego, CA, USA), which enriches a 12-Mb region spanning 62,000 target exons of a total of 4,813 genes. Massively parallel sequencing was performed on the Illumina NextSeq platform. Sequence reads were mapped to the UCSC hg19 standard database for comparative analysis. The average depth of the panel was 85.86X, and percentages of bases above 10X of CYP11A1 and STAR were 99.37%, and 100%, respectively. Meanwhile, no pathogenic variants were detected in CYP11A1 genes. The exome-sequencing results revealed compound heterozygous mutations for c.653C>T and c.661G>A (p.Gly221Ser) in exon 6 of the STAR gene. Sanger sequencing confirmed the presence of these variants and each of the same heterozygous variant was found in his father and mother, respectively ( Fig. 1 ). This variant has been previously reported in association with CLAH. Hydrocortisone (7.8 mg/m 2 /day) and fludrocortisone (50 μg/day) were started as therapy for primary adrenal insufficiency. The dose of hydrocortisone was gradually increased until the age of 24 months for sufficient ACTH suppression and levels of ACTH and cortisol were subsequently decreased to the optimal range ( Fig. 2 ). Finally, at 28 months of age, he was discharged and went home with the attainment of oral feeding without nausea and vomiting. He showed no symptoms of hypoglycemia and continued to show normal growth and development. Our last evaluation of the patient was when he was 36 months of age, during which point, his body weight and length were 16.7 kg (0.5 SDS) and 99.7 cm (1.5 SDS), respectively. Laboratory tests revealed normal levels of cortisol (4.6 μg/dL), sodium (139 mmol/L), potassium (4.9 mEq/L), glucose (70 mg/dL), and ACTH (53.6 pg/mL). The generalized hyperpigmentation had improved, and he continued to visit the outpatient clinic regularly without additional admission."}
|
{'Case report': "A male child was born at a gestational age of 39 weeks with no history of antenatal or perinatal problems. Apgar scores were 9 points at one minute and 10 points at 5 minutes. His birth weight and height were 3,800 g ( z -score, +1 standard deviation score) and 52.5 cm ( z -score, +1.4 SDS), respectively. There was no family history of consanguineous marriages. The patient was born with an imperforate anus and a colostomy was performed the day after birth. He had normal male genitalia, with both testes palpable, and postaxial polydactyly of the left foot. A grade 2 systolic murmur was heard in the left upper sternal border and echocardiography revealed a patent ductus arteriosus. Bilateral grade 3 vesicoureteral reflux (VUR) was revealed via voiding cystourethrography. Spine ultrasound revealed no vertebral anomalies, and tracheoesophageal fistula was not suspected clinically. Based on this clinical information, including anal atresia, renal anomalies, and limb abnormalities, he was diagnosed with VACTERL association which is defined by the presence of at least 3 of the following congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. Laboratory test results, including electrolyte levels, were normal. Neonatal screening tests for metabolic disease were also normal, including the 17-alpha-hydroxyprogesterone level. Chromosome analysis revealed a 46, XY karyotype. He was discharged from the neonatal intensive care unit at 21 days of age. At the age of 3 months, the patient was admitted to the hospital for colostomy takedown, anorectoplasty, and endoscopic dextranomer/hyaluronic acid copolymer injection for VUR. After the surgery, the patient was febrile and hypotensive and his abdomen was distended and discolored. An exploratory laparotomy revealed bowel necrosis. Bowel resection with colostomy and jejunostomy was performed 3 times, which resulted in short-bowel syndrome. He could not be discharged because parenteral nutrition was required. The remnant small bowel extended from the Treitz ligament to the jejunocolonic anastomosis and the length of the remnant bowel was only 40 cm. At the age of 7 months, a takedown of the colostomy and jejunostomy was performed. The patient’s mother observed slight bronzing of the patient’s skin after repeated surgeries At 17 months of age, the patient had an episode of sepsis and peritonitis secondary to Acinetobacter baumannii infection and an exploratory laparotomy was performed to check for bowel necrosis. At this time, generalized hyperpigmentation was noted by the doctor and the mother stated that the child's hyperpigmentation was markedly exacerbated after exploratory laparotomy for the episode of peritonitis with sepsis. The patient was referred to our department for the evaluation of the hyperpigmentation. He experienced occasional nausea and vomiting. His heart rate was 120 beats per minute and his blood pressure was 100/65 mmHg. His weight and height were 12.8 kg (1.5 SDS) and 86 cm (2 SDS), respectively. At this point, he was noted to have generalized hyperpigmentation, normal male genitalia, and postaxial polydactyly of the left foot. He was able to ascend stairs with the support of a hand grasp. He could stack 3 cubes, eat without assistance, and pronounce 10 words, meaning that the patient’s developmental status was normal for his age. Laboratory investigations revealed a slightly decreased sodium level (132 mmol/L) but normal potassium (4.8 mEq/L) and glucose (86 mg/dL) levels; complete blood count, blood gas profile, hepatic and renal function, thyroid function test and sex hormone levels were obtained. Decreased cortisol (1.0 μg/dL) and markedly elevated adrenocorticotropic hormone (ACTH) (16,064 pg/mL) levels were noted. The patient's cortisol levels did not respond to stimulation with ACTH (125 μg) ( Table 1 ). Meanwhile, he presented a normal 17-hydroxyprogesterone level (0.42 ng/mL). Plasma renin activity and aldosterone levels were 7.28 ng/mL/hr (normal range, 1.0–6.5 ng/mL/hr) and 0.1 ng/dL (normal range, 3–35 ng/dL), respectively. The abdominal ultrasound revealed no abnormalities, such as adrenal enlargement, hydronephrosis, distal ureter dilatation, or bowel wall thickening. Based on the patient’s symptoms and laboratory results, we considered several genetic causes for primary adrenal insufficiency, and the causative genes of candidate diseases were listed as STAR for NCCLAH and CYP11A1 for congenital adrenal insufficiency. Additionally, melanocortin-2 receptor (MC2R) and MC2R accessory protein for familial glucocorticoid deficiency (FGD) were listed as candidate genes with a low probability because the patient did not have elevated aldosterone. Targeted gene-panel sequencing was performed to check for pathogenic variants in those genes responsible for primary adrenal insufficiency. Genomic DNA was extracted from the peripheral blood of the patient and both parents. Library preparation was done using the TruSight One Sequencing Panel (Illumina, Inc., San Diego, CA, USA), which enriches a 12-Mb region spanning 62,000 target exons of a total of 4,813 genes. Massively parallel sequencing was performed on the Illumina NextSeq platform. Sequence reads were mapped to the UCSC hg19 standard database for comparative analysis. The average depth of the panel was 85.86X, and percentages of bases above 10X of CYP11A1 and STAR were 99.37%, and 100%, respectively. Meanwhile, no pathogenic variants were detected in CYP11A1 genes. The exome-sequencing results revealed compound heterozygous mutations for c.653C>T and c.661G>A (p.Gly221Ser) in exon 6 of the STAR gene. Sanger sequencing confirmed the presence of these variants and each of the same heterozygous variant was found in his father and mother, respectively ( Fig. 1 ). This variant has been previously reported in association with CLAH. Hydrocortisone (7.8 mg/m 2 /day) and fludrocortisone (50 μg/day) were started as therapy for primary adrenal insufficiency. The dose of hydrocortisone was gradually increased until the age of 24 months for sufficient ACTH suppression and levels of ACTH and cortisol were subsequently decreased to the optimal range ( Fig. 2 ). Finally, at 28 months of age, he was discharged and went home with the attainment of oral feeding without nausea and vomiting. He showed no symptoms of hypoglycemia and continued to show normal growth and development. Our last evaluation of the patient was when he was 36 months of age, during which point, his body weight and length were 16.7 kg (0.5 SDS) and 99.7 cm (1.5 SDS), respectively. Laboratory tests revealed normal levels of cortisol (4.6 μg/dL), sodium (139 mmol/L), potassium (4.9 mEq/L), glucose (70 mg/dL), and ACTH (53.6 pg/mL). The generalized hyperpigmentation had improved, and he continued to visit the outpatient clinic regularly without additional admission."}
|
Eyes-Ears-Nose-Throat
|
EENT
|
[] |
test-1992
|
7136505
|
{'Case report': "A male child was born at a gestational age of 39 weeks with no history of antenatal or perinatal problems. Apgar scores were 9 points at one minute and 10 points at 5 minutes. His birth weight and height were 3,800 g ( z -score, +1 standard deviation score) and 52.5 cm ( z -score, +1.4 SDS), respectively. There was no family history of consanguineous marriages. The patient was born with an imperforate anus and a colostomy was performed the day after birth. He had normal male genitalia, with both testes palpable, and postaxial polydactyly of the left foot. A grade 2 systolic murmur was heard in the left upper sternal border and echocardiography revealed a patent ductus arteriosus. Bilateral grade 3 vesicoureteral reflux (VUR) was revealed via voiding cystourethrography. Spine ultrasound revealed no vertebral anomalies, and tracheoesophageal fistula was not suspected clinically. Based on this clinical information, including anal atresia, renal anomalies, and limb abnormalities, he was diagnosed with VACTERL association which is defined by the presence of at least 3 of the following congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. Laboratory test results, including electrolyte levels, were normal. Neonatal screening tests for metabolic disease were also normal, including the 17-alpha-hydroxyprogesterone level. Chromosome analysis revealed a 46, XY karyotype. He was discharged from the neonatal intensive care unit at 21 days of age. At the age of 3 months, the patient was admitted to the hospital for colostomy takedown, anorectoplasty, and endoscopic dextranomer/hyaluronic acid copolymer injection for VUR. After the surgery, the patient was febrile and hypotensive and his abdomen was distended and discolored. An exploratory laparotomy revealed bowel necrosis. Bowel resection with colostomy and jejunostomy was performed 3 times, which resulted in short-bowel syndrome. He could not be discharged because parenteral nutrition was required. The remnant small bowel extended from the Treitz ligament to the jejunocolonic anastomosis and the length of the remnant bowel was only 40 cm. At the age of 7 months, a takedown of the colostomy and jejunostomy was performed. The patient’s mother observed slight bronzing of the patient’s skin after repeated surgeries At 17 months of age, the patient had an episode of sepsis and peritonitis secondary to Acinetobacter baumannii infection and an exploratory laparotomy was performed to check for bowel necrosis. At this time, generalized hyperpigmentation was noted by the doctor and the mother stated that the child's hyperpigmentation was markedly exacerbated after exploratory laparotomy for the episode of peritonitis with sepsis. The patient was referred to our department for the evaluation of the hyperpigmentation. He experienced occasional nausea and vomiting. His heart rate was 120 beats per minute and his blood pressure was 100/65 mmHg. His weight and height were 12.8 kg (1.5 SDS) and 86 cm (2 SDS), respectively. At this point, he was noted to have generalized hyperpigmentation, normal male genitalia, and postaxial polydactyly of the left foot. He was able to ascend stairs with the support of a hand grasp. He could stack 3 cubes, eat without assistance, and pronounce 10 words, meaning that the patient’s developmental status was normal for his age. Laboratory investigations revealed a slightly decreased sodium level (132 mmol/L) but normal potassium (4.8 mEq/L) and glucose (86 mg/dL) levels; complete blood count, blood gas profile, hepatic and renal function, thyroid function test and sex hormone levels were obtained. Decreased cortisol (1.0 μg/dL) and markedly elevated adrenocorticotropic hormone (ACTH) (16,064 pg/mL) levels were noted. The patient's cortisol levels did not respond to stimulation with ACTH (125 μg) ( Table 1 ). Meanwhile, he presented a normal 17-hydroxyprogesterone level (0.42 ng/mL). Plasma renin activity and aldosterone levels were 7.28 ng/mL/hr (normal range, 1.0–6.5 ng/mL/hr) and 0.1 ng/dL (normal range, 3–35 ng/dL), respectively. The abdominal ultrasound revealed no abnormalities, such as adrenal enlargement, hydronephrosis, distal ureter dilatation, or bowel wall thickening. Based on the patient’s symptoms and laboratory results, we considered several genetic causes for primary adrenal insufficiency, and the causative genes of candidate diseases were listed as STAR for NCCLAH and CYP11A1 for congenital adrenal insufficiency. Additionally, melanocortin-2 receptor (MC2R) and MC2R accessory protein for familial glucocorticoid deficiency (FGD) were listed as candidate genes with a low probability because the patient did not have elevated aldosterone. Targeted gene-panel sequencing was performed to check for pathogenic variants in those genes responsible for primary adrenal insufficiency. Genomic DNA was extracted from the peripheral blood of the patient and both parents. Library preparation was done using the TruSight One Sequencing Panel (Illumina, Inc., San Diego, CA, USA), which enriches a 12-Mb region spanning 62,000 target exons of a total of 4,813 genes. Massively parallel sequencing was performed on the Illumina NextSeq platform. Sequence reads were mapped to the UCSC hg19 standard database for comparative analysis. The average depth of the panel was 85.86X, and percentages of bases above 10X of CYP11A1 and STAR were 99.37%, and 100%, respectively. Meanwhile, no pathogenic variants were detected in CYP11A1 genes. The exome-sequencing results revealed compound heterozygous mutations for c.653C>T and c.661G>A (p.Gly221Ser) in exon 6 of the STAR gene. Sanger sequencing confirmed the presence of these variants and each of the same heterozygous variant was found in his father and mother, respectively ( Fig. 1 ). This variant has been previously reported in association with CLAH. Hydrocortisone (7.8 mg/m 2 /day) and fludrocortisone (50 μg/day) were started as therapy for primary adrenal insufficiency. The dose of hydrocortisone was gradually increased until the age of 24 months for sufficient ACTH suppression and levels of ACTH and cortisol were subsequently decreased to the optimal range ( Fig. 2 ). Finally, at 28 months of age, he was discharged and went home with the attainment of oral feeding without nausea and vomiting. He showed no symptoms of hypoglycemia and continued to show normal growth and development. Our last evaluation of the patient was when he was 36 months of age, during which point, his body weight and length were 16.7 kg (0.5 SDS) and 99.7 cm (1.5 SDS), respectively. Laboratory tests revealed normal levels of cortisol (4.6 μg/dL), sodium (139 mmol/L), potassium (4.9 mEq/L), glucose (70 mg/dL), and ACTH (53.6 pg/mL). The generalized hyperpigmentation had improved, and he continued to visit the outpatient clinic regularly without additional admission."}
|
{'Case report': "A male child was born at a gestational age of 39 weeks with no history of antenatal or perinatal problems. Apgar scores were 9 points at one minute and 10 points at 5 minutes. His birth weight and height were 3,800 g ( z -score, +1 standard deviation score) and 52.5 cm ( z -score, +1.4 SDS), respectively. There was no family history of consanguineous marriages. The patient was born with an imperforate anus and a colostomy was performed the day after birth. He had normal male genitalia, with both testes palpable, and postaxial polydactyly of the left foot. A grade 2 systolic murmur was heard in the left upper sternal border and echocardiography revealed a patent ductus arteriosus. Bilateral grade 3 vesicoureteral reflux (VUR) was revealed via voiding cystourethrography. Spine ultrasound revealed no vertebral anomalies, and tracheoesophageal fistula was not suspected clinically. Based on this clinical information, including anal atresia, renal anomalies, and limb abnormalities, he was diagnosed with VACTERL association which is defined by the presence of at least 3 of the following congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. Laboratory test results, including electrolyte levels, were normal. Neonatal screening tests for metabolic disease were also normal, including the 17-alpha-hydroxyprogesterone level. Chromosome analysis revealed a 46, XY karyotype. He was discharged from the neonatal intensive care unit at 21 days of age. At the age of 3 months, the patient was admitted to the hospital for colostomy takedown, anorectoplasty, and endoscopic dextranomer/hyaluronic acid copolymer injection for VUR. After the surgery, the patient was febrile and hypotensive and his abdomen was distended and discolored. An exploratory laparotomy revealed bowel necrosis. Bowel resection with colostomy and jejunostomy was performed 3 times, which resulted in short-bowel syndrome. He could not be discharged because parenteral nutrition was required. The remnant small bowel extended from the Treitz ligament to the jejunocolonic anastomosis and the length of the remnant bowel was only 40 cm. At the age of 7 months, a takedown of the colostomy and jejunostomy was performed. The patient’s mother observed slight bronzing of the patient’s skin after repeated surgeries At 17 months of age, the patient had an episode of sepsis and peritonitis secondary to Acinetobacter baumannii infection and an exploratory laparotomy was performed to check for bowel necrosis. At this time, generalized hyperpigmentation was noted by the doctor and the mother stated that the child's hyperpigmentation was markedly exacerbated after exploratory laparotomy for the episode of peritonitis with sepsis. The patient was referred to our department for the evaluation of the hyperpigmentation. He experienced occasional nausea and vomiting. His heart rate was 120 beats per minute and his blood pressure was 100/65 mmHg. His weight and height were 12.8 kg (1.5 SDS) and 86 cm (2 SDS), respectively. At this point, he was noted to have generalized hyperpigmentation, normal male genitalia, and postaxial polydactyly of the left foot. He was able to ascend stairs with the support of a hand grasp. He could stack 3 cubes, eat without assistance, and pronounce 10 words, meaning that the patient’s developmental status was normal for his age. Laboratory investigations revealed a slightly decreased sodium level (132 mmol/L) but normal potassium (4.8 mEq/L) and glucose (86 mg/dL) levels; complete blood count, blood gas profile, hepatic and renal function, thyroid function test and sex hormone levels were obtained. Decreased cortisol (1.0 μg/dL) and markedly elevated adrenocorticotropic hormone (ACTH) (16,064 pg/mL) levels were noted. The patient's cortisol levels did not respond to stimulation with ACTH (125 μg) ( Table 1 ). Meanwhile, he presented a normal 17-hydroxyprogesterone level (0.42 ng/mL). Plasma renin activity and aldosterone levels were 7.28 ng/mL/hr (normal range, 1.0–6.5 ng/mL/hr) and 0.1 ng/dL (normal range, 3–35 ng/dL), respectively. The abdominal ultrasound revealed no abnormalities, such as adrenal enlargement, hydronephrosis, distal ureter dilatation, or bowel wall thickening. Based on the patient’s symptoms and laboratory results, we considered several genetic causes for primary adrenal insufficiency, and the causative genes of candidate diseases were listed as STAR for NCCLAH and CYP11A1 for congenital adrenal insufficiency. Additionally, melanocortin-2 receptor (MC2R) and MC2R accessory protein for familial glucocorticoid deficiency (FGD) were listed as candidate genes with a low probability because the patient did not have elevated aldosterone. Targeted gene-panel sequencing was performed to check for pathogenic variants in those genes responsible for primary adrenal insufficiency. Genomic DNA was extracted from the peripheral blood of the patient and both parents. Library preparation was done using the TruSight One Sequencing Panel (Illumina, Inc., San Diego, CA, USA), which enriches a 12-Mb region spanning 62,000 target exons of a total of 4,813 genes. Massively parallel sequencing was performed on the Illumina NextSeq platform. Sequence reads were mapped to the UCSC hg19 standard database for comparative analysis. The average depth of the panel was 85.86X, and percentages of bases above 10X of CYP11A1 and STAR were 99.37%, and 100%, respectively. Meanwhile, no pathogenic variants were detected in CYP11A1 genes. The exome-sequencing results revealed compound heterozygous mutations for c.653C>T and c.661G>A (p.Gly221Ser) in exon 6 of the STAR gene. Sanger sequencing confirmed the presence of these variants and each of the same heterozygous variant was found in his father and mother, respectively ( Fig. 1 ). This variant has been previously reported in association with CLAH. Hydrocortisone (7.8 mg/m 2 /day) and fludrocortisone (50 μg/day) were started as therapy for primary adrenal insufficiency. The dose of hydrocortisone was gradually increased until the age of 24 months for sufficient ACTH suppression and levels of ACTH and cortisol were subsequently decreased to the optimal range ( Fig. 2 ). Finally, at 28 months of age, he was discharged and went home with the attainment of oral feeding without nausea and vomiting. He showed no symptoms of hypoglycemia and continued to show normal growth and development. Our last evaluation of the patient was when he was 36 months of age, during which point, his body weight and length were 16.7 kg (0.5 SDS) and 99.7 cm (1.5 SDS), respectively. Laboratory tests revealed normal levels of cortisol (4.6 μg/dL), sodium (139 mmol/L), potassium (4.9 mEq/L), glucose (70 mg/dL), and ACTH (53.6 pg/mL). The generalized hyperpigmentation had improved, and he continued to visit the outpatient clinic regularly without additional admission."}
|
Dermatology
|
DERM
|
[
"slight bronzing of the patient ’s skin after repeated surgeries",
"generalized hyperpigmentation",
"child 's hyperpigmentation was markedly exacerbated after exploratory laparotomy for the episode of peritonitis with sepsis",
"hyperpigmentation",
"generalized hyperpigmentation",
"generalized hyperpigmentation had improved"
] |
test-1993
|
7136505
|
{'Case report': "A male child was born at a gestational age of 39 weeks with no history of antenatal or perinatal problems. Apgar scores were 9 points at one minute and 10 points at 5 minutes. His birth weight and height were 3,800 g ( z -score, +1 standard deviation score) and 52.5 cm ( z -score, +1.4 SDS), respectively. There was no family history of consanguineous marriages. The patient was born with an imperforate anus and a colostomy was performed the day after birth. He had normal male genitalia, with both testes palpable, and postaxial polydactyly of the left foot. A grade 2 systolic murmur was heard in the left upper sternal border and echocardiography revealed a patent ductus arteriosus. Bilateral grade 3 vesicoureteral reflux (VUR) was revealed via voiding cystourethrography. Spine ultrasound revealed no vertebral anomalies, and tracheoesophageal fistula was not suspected clinically. Based on this clinical information, including anal atresia, renal anomalies, and limb abnormalities, he was diagnosed with VACTERL association which is defined by the presence of at least 3 of the following congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. Laboratory test results, including electrolyte levels, were normal. Neonatal screening tests for metabolic disease were also normal, including the 17-alpha-hydroxyprogesterone level. Chromosome analysis revealed a 46, XY karyotype. He was discharged from the neonatal intensive care unit at 21 days of age. At the age of 3 months, the patient was admitted to the hospital for colostomy takedown, anorectoplasty, and endoscopic dextranomer/hyaluronic acid copolymer injection for VUR. After the surgery, the patient was febrile and hypotensive and his abdomen was distended and discolored. An exploratory laparotomy revealed bowel necrosis. Bowel resection with colostomy and jejunostomy was performed 3 times, which resulted in short-bowel syndrome. He could not be discharged because parenteral nutrition was required. The remnant small bowel extended from the Treitz ligament to the jejunocolonic anastomosis and the length of the remnant bowel was only 40 cm. At the age of 7 months, a takedown of the colostomy and jejunostomy was performed. The patient’s mother observed slight bronzing of the patient’s skin after repeated surgeries At 17 months of age, the patient had an episode of sepsis and peritonitis secondary to Acinetobacter baumannii infection and an exploratory laparotomy was performed to check for bowel necrosis. At this time, generalized hyperpigmentation was noted by the doctor and the mother stated that the child's hyperpigmentation was markedly exacerbated after exploratory laparotomy for the episode of peritonitis with sepsis. The patient was referred to our department for the evaluation of the hyperpigmentation. He experienced occasional nausea and vomiting. His heart rate was 120 beats per minute and his blood pressure was 100/65 mmHg. His weight and height were 12.8 kg (1.5 SDS) and 86 cm (2 SDS), respectively. At this point, he was noted to have generalized hyperpigmentation, normal male genitalia, and postaxial polydactyly of the left foot. He was able to ascend stairs with the support of a hand grasp. He could stack 3 cubes, eat without assistance, and pronounce 10 words, meaning that the patient’s developmental status was normal for his age. Laboratory investigations revealed a slightly decreased sodium level (132 mmol/L) but normal potassium (4.8 mEq/L) and glucose (86 mg/dL) levels; complete blood count, blood gas profile, hepatic and renal function, thyroid function test and sex hormone levels were obtained. Decreased cortisol (1.0 μg/dL) and markedly elevated adrenocorticotropic hormone (ACTH) (16,064 pg/mL) levels were noted. The patient's cortisol levels did not respond to stimulation with ACTH (125 μg) ( Table 1 ). Meanwhile, he presented a normal 17-hydroxyprogesterone level (0.42 ng/mL). Plasma renin activity and aldosterone levels were 7.28 ng/mL/hr (normal range, 1.0–6.5 ng/mL/hr) and 0.1 ng/dL (normal range, 3–35 ng/dL), respectively. The abdominal ultrasound revealed no abnormalities, such as adrenal enlargement, hydronephrosis, distal ureter dilatation, or bowel wall thickening. Based on the patient’s symptoms and laboratory results, we considered several genetic causes for primary adrenal insufficiency, and the causative genes of candidate diseases were listed as STAR for NCCLAH and CYP11A1 for congenital adrenal insufficiency. Additionally, melanocortin-2 receptor (MC2R) and MC2R accessory protein for familial glucocorticoid deficiency (FGD) were listed as candidate genes with a low probability because the patient did not have elevated aldosterone. Targeted gene-panel sequencing was performed to check for pathogenic variants in those genes responsible for primary adrenal insufficiency. Genomic DNA was extracted from the peripheral blood of the patient and both parents. Library preparation was done using the TruSight One Sequencing Panel (Illumina, Inc., San Diego, CA, USA), which enriches a 12-Mb region spanning 62,000 target exons of a total of 4,813 genes. Massively parallel sequencing was performed on the Illumina NextSeq platform. Sequence reads were mapped to the UCSC hg19 standard database for comparative analysis. The average depth of the panel was 85.86X, and percentages of bases above 10X of CYP11A1 and STAR were 99.37%, and 100%, respectively. Meanwhile, no pathogenic variants were detected in CYP11A1 genes. The exome-sequencing results revealed compound heterozygous mutations for c.653C>T and c.661G>A (p.Gly221Ser) in exon 6 of the STAR gene. Sanger sequencing confirmed the presence of these variants and each of the same heterozygous variant was found in his father and mother, respectively ( Fig. 1 ). This variant has been previously reported in association with CLAH. Hydrocortisone (7.8 mg/m 2 /day) and fludrocortisone (50 μg/day) were started as therapy for primary adrenal insufficiency. The dose of hydrocortisone was gradually increased until the age of 24 months for sufficient ACTH suppression and levels of ACTH and cortisol were subsequently decreased to the optimal range ( Fig. 2 ). Finally, at 28 months of age, he was discharged and went home with the attainment of oral feeding without nausea and vomiting. He showed no symptoms of hypoglycemia and continued to show normal growth and development. Our last evaluation of the patient was when he was 36 months of age, during which point, his body weight and length were 16.7 kg (0.5 SDS) and 99.7 cm (1.5 SDS), respectively. Laboratory tests revealed normal levels of cortisol (4.6 μg/dL), sodium (139 mmol/L), potassium (4.9 mEq/L), glucose (70 mg/dL), and ACTH (53.6 pg/mL). The generalized hyperpigmentation had improved, and he continued to visit the outpatient clinic regularly without additional admission."}
|
{'Case report': "A male child was born at a gestational age of 39 weeks with no history of antenatal or perinatal problems. Apgar scores were 9 points at one minute and 10 points at 5 minutes. His birth weight and height were 3,800 g ( z -score, +1 standard deviation score) and 52.5 cm ( z -score, +1.4 SDS), respectively. There was no family history of consanguineous marriages. The patient was born with an imperforate anus and a colostomy was performed the day after birth. He had normal male genitalia, with both testes palpable, and postaxial polydactyly of the left foot. A grade 2 systolic murmur was heard in the left upper sternal border and echocardiography revealed a patent ductus arteriosus. Bilateral grade 3 vesicoureteral reflux (VUR) was revealed via voiding cystourethrography. Spine ultrasound revealed no vertebral anomalies, and tracheoesophageal fistula was not suspected clinically. Based on this clinical information, including anal atresia, renal anomalies, and limb abnormalities, he was diagnosed with VACTERL association which is defined by the presence of at least 3 of the following congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. Laboratory test results, including electrolyte levels, were normal. Neonatal screening tests for metabolic disease were also normal, including the 17-alpha-hydroxyprogesterone level. Chromosome analysis revealed a 46, XY karyotype. He was discharged from the neonatal intensive care unit at 21 days of age. At the age of 3 months, the patient was admitted to the hospital for colostomy takedown, anorectoplasty, and endoscopic dextranomer/hyaluronic acid copolymer injection for VUR. After the surgery, the patient was febrile and hypotensive and his abdomen was distended and discolored. An exploratory laparotomy revealed bowel necrosis. Bowel resection with colostomy and jejunostomy was performed 3 times, which resulted in short-bowel syndrome. He could not be discharged because parenteral nutrition was required. The remnant small bowel extended from the Treitz ligament to the jejunocolonic anastomosis and the length of the remnant bowel was only 40 cm. At the age of 7 months, a takedown of the colostomy and jejunostomy was performed. The patient’s mother observed slight bronzing of the patient’s skin after repeated surgeries At 17 months of age, the patient had an episode of sepsis and peritonitis secondary to Acinetobacter baumannii infection and an exploratory laparotomy was performed to check for bowel necrosis. At this time, generalized hyperpigmentation was noted by the doctor and the mother stated that the child's hyperpigmentation was markedly exacerbated after exploratory laparotomy for the episode of peritonitis with sepsis. The patient was referred to our department for the evaluation of the hyperpigmentation. He experienced occasional nausea and vomiting. His heart rate was 120 beats per minute and his blood pressure was 100/65 mmHg. His weight and height were 12.8 kg (1.5 SDS) and 86 cm (2 SDS), respectively. At this point, he was noted to have generalized hyperpigmentation, normal male genitalia, and postaxial polydactyly of the left foot. He was able to ascend stairs with the support of a hand grasp. He could stack 3 cubes, eat without assistance, and pronounce 10 words, meaning that the patient’s developmental status was normal for his age. Laboratory investigations revealed a slightly decreased sodium level (132 mmol/L) but normal potassium (4.8 mEq/L) and glucose (86 mg/dL) levels; complete blood count, blood gas profile, hepatic and renal function, thyroid function test and sex hormone levels were obtained. Decreased cortisol (1.0 μg/dL) and markedly elevated adrenocorticotropic hormone (ACTH) (16,064 pg/mL) levels were noted. The patient's cortisol levels did not respond to stimulation with ACTH (125 μg) ( Table 1 ). Meanwhile, he presented a normal 17-hydroxyprogesterone level (0.42 ng/mL). Plasma renin activity and aldosterone levels were 7.28 ng/mL/hr (normal range, 1.0–6.5 ng/mL/hr) and 0.1 ng/dL (normal range, 3–35 ng/dL), respectively. The abdominal ultrasound revealed no abnormalities, such as adrenal enlargement, hydronephrosis, distal ureter dilatation, or bowel wall thickening. Based on the patient’s symptoms and laboratory results, we considered several genetic causes for primary adrenal insufficiency, and the causative genes of candidate diseases were listed as STAR for NCCLAH and CYP11A1 for congenital adrenal insufficiency. Additionally, melanocortin-2 receptor (MC2R) and MC2R accessory protein for familial glucocorticoid deficiency (FGD) were listed as candidate genes with a low probability because the patient did not have elevated aldosterone. Targeted gene-panel sequencing was performed to check for pathogenic variants in those genes responsible for primary adrenal insufficiency. Genomic DNA was extracted from the peripheral blood of the patient and both parents. Library preparation was done using the TruSight One Sequencing Panel (Illumina, Inc., San Diego, CA, USA), which enriches a 12-Mb region spanning 62,000 target exons of a total of 4,813 genes. Massively parallel sequencing was performed on the Illumina NextSeq platform. Sequence reads were mapped to the UCSC hg19 standard database for comparative analysis. The average depth of the panel was 85.86X, and percentages of bases above 10X of CYP11A1 and STAR were 99.37%, and 100%, respectively. Meanwhile, no pathogenic variants were detected in CYP11A1 genes. The exome-sequencing results revealed compound heterozygous mutations for c.653C>T and c.661G>A (p.Gly221Ser) in exon 6 of the STAR gene. Sanger sequencing confirmed the presence of these variants and each of the same heterozygous variant was found in his father and mother, respectively ( Fig. 1 ). This variant has been previously reported in association with CLAH. Hydrocortisone (7.8 mg/m 2 /day) and fludrocortisone (50 μg/day) were started as therapy for primary adrenal insufficiency. The dose of hydrocortisone was gradually increased until the age of 24 months for sufficient ACTH suppression and levels of ACTH and cortisol were subsequently decreased to the optimal range ( Fig. 2 ). Finally, at 28 months of age, he was discharged and went home with the attainment of oral feeding without nausea and vomiting. He showed no symptoms of hypoglycemia and continued to show normal growth and development. Our last evaluation of the patient was when he was 36 months of age, during which point, his body weight and length were 16.7 kg (0.5 SDS) and 99.7 cm (1.5 SDS), respectively. Laboratory tests revealed normal levels of cortisol (4.6 μg/dL), sodium (139 mmol/L), potassium (4.9 mEq/L), glucose (70 mg/dL), and ACTH (53.6 pg/mL). The generalized hyperpigmentation had improved, and he continued to visit the outpatient clinic regularly without additional admission."}
|
Pregnancy
|
Pregnancy
|
[
"born at a gestational age of 39 weeks with no history of antenatal or perinatal problems. Apgar scores were 9 points at one minute and 10 points at 5 minutes. His birth weight and height were 3,800 g ( z -score, +1 standard deviation score ) and 52.5 cm ( z -score, +1.4 SDS ), respectively"
] |
test-1994
|
7136505
|
{'Case report': "A male child was born at a gestational age of 39 weeks with no history of antenatal or perinatal problems. Apgar scores were 9 points at one minute and 10 points at 5 minutes. His birth weight and height were 3,800 g ( z -score, +1 standard deviation score) and 52.5 cm ( z -score, +1.4 SDS), respectively. There was no family history of consanguineous marriages. The patient was born with an imperforate anus and a colostomy was performed the day after birth. He had normal male genitalia, with both testes palpable, and postaxial polydactyly of the left foot. A grade 2 systolic murmur was heard in the left upper sternal border and echocardiography revealed a patent ductus arteriosus. Bilateral grade 3 vesicoureteral reflux (VUR) was revealed via voiding cystourethrography. Spine ultrasound revealed no vertebral anomalies, and tracheoesophageal fistula was not suspected clinically. Based on this clinical information, including anal atresia, renal anomalies, and limb abnormalities, he was diagnosed with VACTERL association which is defined by the presence of at least 3 of the following congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. Laboratory test results, including electrolyte levels, were normal. Neonatal screening tests for metabolic disease were also normal, including the 17-alpha-hydroxyprogesterone level. Chromosome analysis revealed a 46, XY karyotype. He was discharged from the neonatal intensive care unit at 21 days of age. At the age of 3 months, the patient was admitted to the hospital for colostomy takedown, anorectoplasty, and endoscopic dextranomer/hyaluronic acid copolymer injection for VUR. After the surgery, the patient was febrile and hypotensive and his abdomen was distended and discolored. An exploratory laparotomy revealed bowel necrosis. Bowel resection with colostomy and jejunostomy was performed 3 times, which resulted in short-bowel syndrome. He could not be discharged because parenteral nutrition was required. The remnant small bowel extended from the Treitz ligament to the jejunocolonic anastomosis and the length of the remnant bowel was only 40 cm. At the age of 7 months, a takedown of the colostomy and jejunostomy was performed. The patient’s mother observed slight bronzing of the patient’s skin after repeated surgeries At 17 months of age, the patient had an episode of sepsis and peritonitis secondary to Acinetobacter baumannii infection and an exploratory laparotomy was performed to check for bowel necrosis. At this time, generalized hyperpigmentation was noted by the doctor and the mother stated that the child's hyperpigmentation was markedly exacerbated after exploratory laparotomy for the episode of peritonitis with sepsis. The patient was referred to our department for the evaluation of the hyperpigmentation. He experienced occasional nausea and vomiting. His heart rate was 120 beats per minute and his blood pressure was 100/65 mmHg. His weight and height were 12.8 kg (1.5 SDS) and 86 cm (2 SDS), respectively. At this point, he was noted to have generalized hyperpigmentation, normal male genitalia, and postaxial polydactyly of the left foot. He was able to ascend stairs with the support of a hand grasp. He could stack 3 cubes, eat without assistance, and pronounce 10 words, meaning that the patient’s developmental status was normal for his age. Laboratory investigations revealed a slightly decreased sodium level (132 mmol/L) but normal potassium (4.8 mEq/L) and glucose (86 mg/dL) levels; complete blood count, blood gas profile, hepatic and renal function, thyroid function test and sex hormone levels were obtained. Decreased cortisol (1.0 μg/dL) and markedly elevated adrenocorticotropic hormone (ACTH) (16,064 pg/mL) levels were noted. The patient's cortisol levels did not respond to stimulation with ACTH (125 μg) ( Table 1 ). Meanwhile, he presented a normal 17-hydroxyprogesterone level (0.42 ng/mL). Plasma renin activity and aldosterone levels were 7.28 ng/mL/hr (normal range, 1.0–6.5 ng/mL/hr) and 0.1 ng/dL (normal range, 3–35 ng/dL), respectively. The abdominal ultrasound revealed no abnormalities, such as adrenal enlargement, hydronephrosis, distal ureter dilatation, or bowel wall thickening. Based on the patient’s symptoms and laboratory results, we considered several genetic causes for primary adrenal insufficiency, and the causative genes of candidate diseases were listed as STAR for NCCLAH and CYP11A1 for congenital adrenal insufficiency. Additionally, melanocortin-2 receptor (MC2R) and MC2R accessory protein for familial glucocorticoid deficiency (FGD) were listed as candidate genes with a low probability because the patient did not have elevated aldosterone. Targeted gene-panel sequencing was performed to check for pathogenic variants in those genes responsible for primary adrenal insufficiency. Genomic DNA was extracted from the peripheral blood of the patient and both parents. Library preparation was done using the TruSight One Sequencing Panel (Illumina, Inc., San Diego, CA, USA), which enriches a 12-Mb region spanning 62,000 target exons of a total of 4,813 genes. Massively parallel sequencing was performed on the Illumina NextSeq platform. Sequence reads were mapped to the UCSC hg19 standard database for comparative analysis. The average depth of the panel was 85.86X, and percentages of bases above 10X of CYP11A1 and STAR were 99.37%, and 100%, respectively. Meanwhile, no pathogenic variants were detected in CYP11A1 genes. The exome-sequencing results revealed compound heterozygous mutations for c.653C>T and c.661G>A (p.Gly221Ser) in exon 6 of the STAR gene. Sanger sequencing confirmed the presence of these variants and each of the same heterozygous variant was found in his father and mother, respectively ( Fig. 1 ). This variant has been previously reported in association with CLAH. Hydrocortisone (7.8 mg/m 2 /day) and fludrocortisone (50 μg/day) were started as therapy for primary adrenal insufficiency. The dose of hydrocortisone was gradually increased until the age of 24 months for sufficient ACTH suppression and levels of ACTH and cortisol were subsequently decreased to the optimal range ( Fig. 2 ). Finally, at 28 months of age, he was discharged and went home with the attainment of oral feeding without nausea and vomiting. He showed no symptoms of hypoglycemia and continued to show normal growth and development. Our last evaluation of the patient was when he was 36 months of age, during which point, his body weight and length were 16.7 kg (0.5 SDS) and 99.7 cm (1.5 SDS), respectively. Laboratory tests revealed normal levels of cortisol (4.6 μg/dL), sodium (139 mmol/L), potassium (4.9 mEq/L), glucose (70 mg/dL), and ACTH (53.6 pg/mL). The generalized hyperpigmentation had improved, and he continued to visit the outpatient clinic regularly without additional admission."}
|
{'Case report': "A male child was born at a gestational age of 39 weeks with no history of antenatal or perinatal problems. Apgar scores were 9 points at one minute and 10 points at 5 minutes. His birth weight and height were 3,800 g ( z -score, +1 standard deviation score) and 52.5 cm ( z -score, +1.4 SDS), respectively. There was no family history of consanguineous marriages. The patient was born with an imperforate anus and a colostomy was performed the day after birth. He had normal male genitalia, with both testes palpable, and postaxial polydactyly of the left foot. A grade 2 systolic murmur was heard in the left upper sternal border and echocardiography revealed a patent ductus arteriosus. Bilateral grade 3 vesicoureteral reflux (VUR) was revealed via voiding cystourethrography. Spine ultrasound revealed no vertebral anomalies, and tracheoesophageal fistula was not suspected clinically. Based on this clinical information, including anal atresia, renal anomalies, and limb abnormalities, he was diagnosed with VACTERL association which is defined by the presence of at least 3 of the following congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. Laboratory test results, including electrolyte levels, were normal. Neonatal screening tests for metabolic disease were also normal, including the 17-alpha-hydroxyprogesterone level. Chromosome analysis revealed a 46, XY karyotype. He was discharged from the neonatal intensive care unit at 21 days of age. At the age of 3 months, the patient was admitted to the hospital for colostomy takedown, anorectoplasty, and endoscopic dextranomer/hyaluronic acid copolymer injection for VUR. After the surgery, the patient was febrile and hypotensive and his abdomen was distended and discolored. An exploratory laparotomy revealed bowel necrosis. Bowel resection with colostomy and jejunostomy was performed 3 times, which resulted in short-bowel syndrome. He could not be discharged because parenteral nutrition was required. The remnant small bowel extended from the Treitz ligament to the jejunocolonic anastomosis and the length of the remnant bowel was only 40 cm. At the age of 7 months, a takedown of the colostomy and jejunostomy was performed. The patient’s mother observed slight bronzing of the patient’s skin after repeated surgeries At 17 months of age, the patient had an episode of sepsis and peritonitis secondary to Acinetobacter baumannii infection and an exploratory laparotomy was performed to check for bowel necrosis. At this time, generalized hyperpigmentation was noted by the doctor and the mother stated that the child's hyperpigmentation was markedly exacerbated after exploratory laparotomy for the episode of peritonitis with sepsis. The patient was referred to our department for the evaluation of the hyperpigmentation. He experienced occasional nausea and vomiting. His heart rate was 120 beats per minute and his blood pressure was 100/65 mmHg. His weight and height were 12.8 kg (1.5 SDS) and 86 cm (2 SDS), respectively. At this point, he was noted to have generalized hyperpigmentation, normal male genitalia, and postaxial polydactyly of the left foot. He was able to ascend stairs with the support of a hand grasp. He could stack 3 cubes, eat without assistance, and pronounce 10 words, meaning that the patient’s developmental status was normal for his age. Laboratory investigations revealed a slightly decreased sodium level (132 mmol/L) but normal potassium (4.8 mEq/L) and glucose (86 mg/dL) levels; complete blood count, blood gas profile, hepatic and renal function, thyroid function test and sex hormone levels were obtained. Decreased cortisol (1.0 μg/dL) and markedly elevated adrenocorticotropic hormone (ACTH) (16,064 pg/mL) levels were noted. The patient's cortisol levels did not respond to stimulation with ACTH (125 μg) ( Table 1 ). Meanwhile, he presented a normal 17-hydroxyprogesterone level (0.42 ng/mL). Plasma renin activity and aldosterone levels were 7.28 ng/mL/hr (normal range, 1.0–6.5 ng/mL/hr) and 0.1 ng/dL (normal range, 3–35 ng/dL), respectively. The abdominal ultrasound revealed no abnormalities, such as adrenal enlargement, hydronephrosis, distal ureter dilatation, or bowel wall thickening. Based on the patient’s symptoms and laboratory results, we considered several genetic causes for primary adrenal insufficiency, and the causative genes of candidate diseases were listed as STAR for NCCLAH and CYP11A1 for congenital adrenal insufficiency. Additionally, melanocortin-2 receptor (MC2R) and MC2R accessory protein for familial glucocorticoid deficiency (FGD) were listed as candidate genes with a low probability because the patient did not have elevated aldosterone. Targeted gene-panel sequencing was performed to check for pathogenic variants in those genes responsible for primary adrenal insufficiency. Genomic DNA was extracted from the peripheral blood of the patient and both parents. Library preparation was done using the TruSight One Sequencing Panel (Illumina, Inc., San Diego, CA, USA), which enriches a 12-Mb region spanning 62,000 target exons of a total of 4,813 genes. Massively parallel sequencing was performed on the Illumina NextSeq platform. Sequence reads were mapped to the UCSC hg19 standard database for comparative analysis. The average depth of the panel was 85.86X, and percentages of bases above 10X of CYP11A1 and STAR were 99.37%, and 100%, respectively. Meanwhile, no pathogenic variants were detected in CYP11A1 genes. The exome-sequencing results revealed compound heterozygous mutations for c.653C>T and c.661G>A (p.Gly221Ser) in exon 6 of the STAR gene. Sanger sequencing confirmed the presence of these variants and each of the same heterozygous variant was found in his father and mother, respectively ( Fig. 1 ). This variant has been previously reported in association with CLAH. Hydrocortisone (7.8 mg/m 2 /day) and fludrocortisone (50 μg/day) were started as therapy for primary adrenal insufficiency. The dose of hydrocortisone was gradually increased until the age of 24 months for sufficient ACTH suppression and levels of ACTH and cortisol were subsequently decreased to the optimal range ( Fig. 2 ). Finally, at 28 months of age, he was discharged and went home with the attainment of oral feeding without nausea and vomiting. He showed no symptoms of hypoglycemia and continued to show normal growth and development. Our last evaluation of the patient was when he was 36 months of age, during which point, his body weight and length were 16.7 kg (0.5 SDS) and 99.7 cm (1.5 SDS), respectively. Laboratory tests revealed normal levels of cortisol (4.6 μg/dL), sodium (139 mmol/L), potassium (4.9 mEq/L), glucose (70 mg/dL), and ACTH (53.6 pg/mL). The generalized hyperpigmentation had improved, and he continued to visit the outpatient clinic regularly without additional admission."}
|
Lymphatic-System
|
LYMPH
|
[] |
test-1995
|
7136505
|
{'Case report': "A male child was born at a gestational age of 39 weeks with no history of antenatal or perinatal problems. Apgar scores were 9 points at one minute and 10 points at 5 minutes. His birth weight and height were 3,800 g ( z -score, +1 standard deviation score) and 52.5 cm ( z -score, +1.4 SDS), respectively. There was no family history of consanguineous marriages. The patient was born with an imperforate anus and a colostomy was performed the day after birth. He had normal male genitalia, with both testes palpable, and postaxial polydactyly of the left foot. A grade 2 systolic murmur was heard in the left upper sternal border and echocardiography revealed a patent ductus arteriosus. Bilateral grade 3 vesicoureteral reflux (VUR) was revealed via voiding cystourethrography. Spine ultrasound revealed no vertebral anomalies, and tracheoesophageal fistula was not suspected clinically. Based on this clinical information, including anal atresia, renal anomalies, and limb abnormalities, he was diagnosed with VACTERL association which is defined by the presence of at least 3 of the following congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. Laboratory test results, including electrolyte levels, were normal. Neonatal screening tests for metabolic disease were also normal, including the 17-alpha-hydroxyprogesterone level. Chromosome analysis revealed a 46, XY karyotype. He was discharged from the neonatal intensive care unit at 21 days of age. At the age of 3 months, the patient was admitted to the hospital for colostomy takedown, anorectoplasty, and endoscopic dextranomer/hyaluronic acid copolymer injection for VUR. After the surgery, the patient was febrile and hypotensive and his abdomen was distended and discolored. An exploratory laparotomy revealed bowel necrosis. Bowel resection with colostomy and jejunostomy was performed 3 times, which resulted in short-bowel syndrome. He could not be discharged because parenteral nutrition was required. The remnant small bowel extended from the Treitz ligament to the jejunocolonic anastomosis and the length of the remnant bowel was only 40 cm. At the age of 7 months, a takedown of the colostomy and jejunostomy was performed. The patient’s mother observed slight bronzing of the patient’s skin after repeated surgeries At 17 months of age, the patient had an episode of sepsis and peritonitis secondary to Acinetobacter baumannii infection and an exploratory laparotomy was performed to check for bowel necrosis. At this time, generalized hyperpigmentation was noted by the doctor and the mother stated that the child's hyperpigmentation was markedly exacerbated after exploratory laparotomy for the episode of peritonitis with sepsis. The patient was referred to our department for the evaluation of the hyperpigmentation. He experienced occasional nausea and vomiting. His heart rate was 120 beats per minute and his blood pressure was 100/65 mmHg. His weight and height were 12.8 kg (1.5 SDS) and 86 cm (2 SDS), respectively. At this point, he was noted to have generalized hyperpigmentation, normal male genitalia, and postaxial polydactyly of the left foot. He was able to ascend stairs with the support of a hand grasp. He could stack 3 cubes, eat without assistance, and pronounce 10 words, meaning that the patient’s developmental status was normal for his age. Laboratory investigations revealed a slightly decreased sodium level (132 mmol/L) but normal potassium (4.8 mEq/L) and glucose (86 mg/dL) levels; complete blood count, blood gas profile, hepatic and renal function, thyroid function test and sex hormone levels were obtained. Decreased cortisol (1.0 μg/dL) and markedly elevated adrenocorticotropic hormone (ACTH) (16,064 pg/mL) levels were noted. The patient's cortisol levels did not respond to stimulation with ACTH (125 μg) ( Table 1 ). Meanwhile, he presented a normal 17-hydroxyprogesterone level (0.42 ng/mL). Plasma renin activity and aldosterone levels were 7.28 ng/mL/hr (normal range, 1.0–6.5 ng/mL/hr) and 0.1 ng/dL (normal range, 3–35 ng/dL), respectively. The abdominal ultrasound revealed no abnormalities, such as adrenal enlargement, hydronephrosis, distal ureter dilatation, or bowel wall thickening. Based on the patient’s symptoms and laboratory results, we considered several genetic causes for primary adrenal insufficiency, and the causative genes of candidate diseases were listed as STAR for NCCLAH and CYP11A1 for congenital adrenal insufficiency. Additionally, melanocortin-2 receptor (MC2R) and MC2R accessory protein for familial glucocorticoid deficiency (FGD) were listed as candidate genes with a low probability because the patient did not have elevated aldosterone. Targeted gene-panel sequencing was performed to check for pathogenic variants in those genes responsible for primary adrenal insufficiency. Genomic DNA was extracted from the peripheral blood of the patient and both parents. Library preparation was done using the TruSight One Sequencing Panel (Illumina, Inc., San Diego, CA, USA), which enriches a 12-Mb region spanning 62,000 target exons of a total of 4,813 genes. Massively parallel sequencing was performed on the Illumina NextSeq platform. Sequence reads were mapped to the UCSC hg19 standard database for comparative analysis. The average depth of the panel was 85.86X, and percentages of bases above 10X of CYP11A1 and STAR were 99.37%, and 100%, respectively. Meanwhile, no pathogenic variants were detected in CYP11A1 genes. The exome-sequencing results revealed compound heterozygous mutations for c.653C>T and c.661G>A (p.Gly221Ser) in exon 6 of the STAR gene. Sanger sequencing confirmed the presence of these variants and each of the same heterozygous variant was found in his father and mother, respectively ( Fig. 1 ). This variant has been previously reported in association with CLAH. Hydrocortisone (7.8 mg/m 2 /day) and fludrocortisone (50 μg/day) were started as therapy for primary adrenal insufficiency. The dose of hydrocortisone was gradually increased until the age of 24 months for sufficient ACTH suppression and levels of ACTH and cortisol were subsequently decreased to the optimal range ( Fig. 2 ). Finally, at 28 months of age, he was discharged and went home with the attainment of oral feeding without nausea and vomiting. He showed no symptoms of hypoglycemia and continued to show normal growth and development. Our last evaluation of the patient was when he was 36 months of age, during which point, his body weight and length were 16.7 kg (0.5 SDS) and 99.7 cm (1.5 SDS), respectively. Laboratory tests revealed normal levels of cortisol (4.6 μg/dL), sodium (139 mmol/L), potassium (4.9 mEq/L), glucose (70 mg/dL), and ACTH (53.6 pg/mL). The generalized hyperpigmentation had improved, and he continued to visit the outpatient clinic regularly without additional admission."}
|
{'Case report': "A male child was born at a gestational age of 39 weeks with no history of antenatal or perinatal problems. Apgar scores were 9 points at one minute and 10 points at 5 minutes. His birth weight and height were 3,800 g ( z -score, +1 standard deviation score) and 52.5 cm ( z -score, +1.4 SDS), respectively. There was no family history of consanguineous marriages. The patient was born with an imperforate anus and a colostomy was performed the day after birth. He had normal male genitalia, with both testes palpable, and postaxial polydactyly of the left foot. A grade 2 systolic murmur was heard in the left upper sternal border and echocardiography revealed a patent ductus arteriosus. Bilateral grade 3 vesicoureteral reflux (VUR) was revealed via voiding cystourethrography. Spine ultrasound revealed no vertebral anomalies, and tracheoesophageal fistula was not suspected clinically. Based on this clinical information, including anal atresia, renal anomalies, and limb abnormalities, he was diagnosed with VACTERL association which is defined by the presence of at least 3 of the following congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. Laboratory test results, including electrolyte levels, were normal. Neonatal screening tests for metabolic disease were also normal, including the 17-alpha-hydroxyprogesterone level. Chromosome analysis revealed a 46, XY karyotype. He was discharged from the neonatal intensive care unit at 21 days of age. At the age of 3 months, the patient was admitted to the hospital for colostomy takedown, anorectoplasty, and endoscopic dextranomer/hyaluronic acid copolymer injection for VUR. After the surgery, the patient was febrile and hypotensive and his abdomen was distended and discolored. An exploratory laparotomy revealed bowel necrosis. Bowel resection with colostomy and jejunostomy was performed 3 times, which resulted in short-bowel syndrome. He could not be discharged because parenteral nutrition was required. The remnant small bowel extended from the Treitz ligament to the jejunocolonic anastomosis and the length of the remnant bowel was only 40 cm. At the age of 7 months, a takedown of the colostomy and jejunostomy was performed. The patient’s mother observed slight bronzing of the patient’s skin after repeated surgeries At 17 months of age, the patient had an episode of sepsis and peritonitis secondary to Acinetobacter baumannii infection and an exploratory laparotomy was performed to check for bowel necrosis. At this time, generalized hyperpigmentation was noted by the doctor and the mother stated that the child's hyperpigmentation was markedly exacerbated after exploratory laparotomy for the episode of peritonitis with sepsis. The patient was referred to our department for the evaluation of the hyperpigmentation. He experienced occasional nausea and vomiting. His heart rate was 120 beats per minute and his blood pressure was 100/65 mmHg. His weight and height were 12.8 kg (1.5 SDS) and 86 cm (2 SDS), respectively. At this point, he was noted to have generalized hyperpigmentation, normal male genitalia, and postaxial polydactyly of the left foot. He was able to ascend stairs with the support of a hand grasp. He could stack 3 cubes, eat without assistance, and pronounce 10 words, meaning that the patient’s developmental status was normal for his age. Laboratory investigations revealed a slightly decreased sodium level (132 mmol/L) but normal potassium (4.8 mEq/L) and glucose (86 mg/dL) levels; complete blood count, blood gas profile, hepatic and renal function, thyroid function test and sex hormone levels were obtained. Decreased cortisol (1.0 μg/dL) and markedly elevated adrenocorticotropic hormone (ACTH) (16,064 pg/mL) levels were noted. The patient's cortisol levels did not respond to stimulation with ACTH (125 μg) ( Table 1 ). Meanwhile, he presented a normal 17-hydroxyprogesterone level (0.42 ng/mL). Plasma renin activity and aldosterone levels were 7.28 ng/mL/hr (normal range, 1.0–6.5 ng/mL/hr) and 0.1 ng/dL (normal range, 3–35 ng/dL), respectively. The abdominal ultrasound revealed no abnormalities, such as adrenal enlargement, hydronephrosis, distal ureter dilatation, or bowel wall thickening. Based on the patient’s symptoms and laboratory results, we considered several genetic causes for primary adrenal insufficiency, and the causative genes of candidate diseases were listed as STAR for NCCLAH and CYP11A1 for congenital adrenal insufficiency. Additionally, melanocortin-2 receptor (MC2R) and MC2R accessory protein for familial glucocorticoid deficiency (FGD) were listed as candidate genes with a low probability because the patient did not have elevated aldosterone. Targeted gene-panel sequencing was performed to check for pathogenic variants in those genes responsible for primary adrenal insufficiency. Genomic DNA was extracted from the peripheral blood of the patient and both parents. Library preparation was done using the TruSight One Sequencing Panel (Illumina, Inc., San Diego, CA, USA), which enriches a 12-Mb region spanning 62,000 target exons of a total of 4,813 genes. Massively parallel sequencing was performed on the Illumina NextSeq platform. Sequence reads were mapped to the UCSC hg19 standard database for comparative analysis. The average depth of the panel was 85.86X, and percentages of bases above 10X of CYP11A1 and STAR were 99.37%, and 100%, respectively. Meanwhile, no pathogenic variants were detected in CYP11A1 genes. The exome-sequencing results revealed compound heterozygous mutations for c.653C>T and c.661G>A (p.Gly221Ser) in exon 6 of the STAR gene. Sanger sequencing confirmed the presence of these variants and each of the same heterozygous variant was found in his father and mother, respectively ( Fig. 1 ). This variant has been previously reported in association with CLAH. Hydrocortisone (7.8 mg/m 2 /day) and fludrocortisone (50 μg/day) were started as therapy for primary adrenal insufficiency. The dose of hydrocortisone was gradually increased until the age of 24 months for sufficient ACTH suppression and levels of ACTH and cortisol were subsequently decreased to the optimal range ( Fig. 2 ). Finally, at 28 months of age, he was discharged and went home with the attainment of oral feeding without nausea and vomiting. He showed no symptoms of hypoglycemia and continued to show normal growth and development. Our last evaluation of the patient was when he was 36 months of age, during which point, his body weight and length were 16.7 kg (0.5 SDS) and 99.7 cm (1.5 SDS), respectively. Laboratory tests revealed normal levels of cortisol (4.6 μg/dL), sodium (139 mmol/L), potassium (4.9 mEq/L), glucose (70 mg/dL), and ACTH (53.6 pg/mL). The generalized hyperpigmentation had improved, and he continued to visit the outpatient clinic regularly without additional admission."}
|
Age-at-Presentation
|
Age (at case presentation)
|
[] |
test-1996
|
7136505
|
{'Case report': "A male child was born at a gestational age of 39 weeks with no history of antenatal or perinatal problems. Apgar scores were 9 points at one minute and 10 points at 5 minutes. His birth weight and height were 3,800 g ( z -score, +1 standard deviation score) and 52.5 cm ( z -score, +1.4 SDS), respectively. There was no family history of consanguineous marriages. The patient was born with an imperforate anus and a colostomy was performed the day after birth. He had normal male genitalia, with both testes palpable, and postaxial polydactyly of the left foot. A grade 2 systolic murmur was heard in the left upper sternal border and echocardiography revealed a patent ductus arteriosus. Bilateral grade 3 vesicoureteral reflux (VUR) was revealed via voiding cystourethrography. Spine ultrasound revealed no vertebral anomalies, and tracheoesophageal fistula was not suspected clinically. Based on this clinical information, including anal atresia, renal anomalies, and limb abnormalities, he was diagnosed with VACTERL association which is defined by the presence of at least 3 of the following congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. Laboratory test results, including electrolyte levels, were normal. Neonatal screening tests for metabolic disease were also normal, including the 17-alpha-hydroxyprogesterone level. Chromosome analysis revealed a 46, XY karyotype. He was discharged from the neonatal intensive care unit at 21 days of age. At the age of 3 months, the patient was admitted to the hospital for colostomy takedown, anorectoplasty, and endoscopic dextranomer/hyaluronic acid copolymer injection for VUR. After the surgery, the patient was febrile and hypotensive and his abdomen was distended and discolored. An exploratory laparotomy revealed bowel necrosis. Bowel resection with colostomy and jejunostomy was performed 3 times, which resulted in short-bowel syndrome. He could not be discharged because parenteral nutrition was required. The remnant small bowel extended from the Treitz ligament to the jejunocolonic anastomosis and the length of the remnant bowel was only 40 cm. At the age of 7 months, a takedown of the colostomy and jejunostomy was performed. The patient’s mother observed slight bronzing of the patient’s skin after repeated surgeries At 17 months of age, the patient had an episode of sepsis and peritonitis secondary to Acinetobacter baumannii infection and an exploratory laparotomy was performed to check for bowel necrosis. At this time, generalized hyperpigmentation was noted by the doctor and the mother stated that the child's hyperpigmentation was markedly exacerbated after exploratory laparotomy for the episode of peritonitis with sepsis. The patient was referred to our department for the evaluation of the hyperpigmentation. He experienced occasional nausea and vomiting. His heart rate was 120 beats per minute and his blood pressure was 100/65 mmHg. His weight and height were 12.8 kg (1.5 SDS) and 86 cm (2 SDS), respectively. At this point, he was noted to have generalized hyperpigmentation, normal male genitalia, and postaxial polydactyly of the left foot. He was able to ascend stairs with the support of a hand grasp. He could stack 3 cubes, eat without assistance, and pronounce 10 words, meaning that the patient’s developmental status was normal for his age. Laboratory investigations revealed a slightly decreased sodium level (132 mmol/L) but normal potassium (4.8 mEq/L) and glucose (86 mg/dL) levels; complete blood count, blood gas profile, hepatic and renal function, thyroid function test and sex hormone levels were obtained. Decreased cortisol (1.0 μg/dL) and markedly elevated adrenocorticotropic hormone (ACTH) (16,064 pg/mL) levels were noted. The patient's cortisol levels did not respond to stimulation with ACTH (125 μg) ( Table 1 ). Meanwhile, he presented a normal 17-hydroxyprogesterone level (0.42 ng/mL). Plasma renin activity and aldosterone levels were 7.28 ng/mL/hr (normal range, 1.0–6.5 ng/mL/hr) and 0.1 ng/dL (normal range, 3–35 ng/dL), respectively. The abdominal ultrasound revealed no abnormalities, such as adrenal enlargement, hydronephrosis, distal ureter dilatation, or bowel wall thickening. Based on the patient’s symptoms and laboratory results, we considered several genetic causes for primary adrenal insufficiency, and the causative genes of candidate diseases were listed as STAR for NCCLAH and CYP11A1 for congenital adrenal insufficiency. Additionally, melanocortin-2 receptor (MC2R) and MC2R accessory protein for familial glucocorticoid deficiency (FGD) were listed as candidate genes with a low probability because the patient did not have elevated aldosterone. Targeted gene-panel sequencing was performed to check for pathogenic variants in those genes responsible for primary adrenal insufficiency. Genomic DNA was extracted from the peripheral blood of the patient and both parents. Library preparation was done using the TruSight One Sequencing Panel (Illumina, Inc., San Diego, CA, USA), which enriches a 12-Mb region spanning 62,000 target exons of a total of 4,813 genes. Massively parallel sequencing was performed on the Illumina NextSeq platform. Sequence reads were mapped to the UCSC hg19 standard database for comparative analysis. The average depth of the panel was 85.86X, and percentages of bases above 10X of CYP11A1 and STAR were 99.37%, and 100%, respectively. Meanwhile, no pathogenic variants were detected in CYP11A1 genes. The exome-sequencing results revealed compound heterozygous mutations for c.653C>T and c.661G>A (p.Gly221Ser) in exon 6 of the STAR gene. Sanger sequencing confirmed the presence of these variants and each of the same heterozygous variant was found in his father and mother, respectively ( Fig. 1 ). This variant has been previously reported in association with CLAH. Hydrocortisone (7.8 mg/m 2 /day) and fludrocortisone (50 μg/day) were started as therapy for primary adrenal insufficiency. The dose of hydrocortisone was gradually increased until the age of 24 months for sufficient ACTH suppression and levels of ACTH and cortisol were subsequently decreased to the optimal range ( Fig. 2 ). Finally, at 28 months of age, he was discharged and went home with the attainment of oral feeding without nausea and vomiting. He showed no symptoms of hypoglycemia and continued to show normal growth and development. Our last evaluation of the patient was when he was 36 months of age, during which point, his body weight and length were 16.7 kg (0.5 SDS) and 99.7 cm (1.5 SDS), respectively. Laboratory tests revealed normal levels of cortisol (4.6 μg/dL), sodium (139 mmol/L), potassium (4.9 mEq/L), glucose (70 mg/dL), and ACTH (53.6 pg/mL). The generalized hyperpigmentation had improved, and he continued to visit the outpatient clinic regularly without additional admission."}
|
{'Case report': "A male child was born at a gestational age of 39 weeks with no history of antenatal or perinatal problems. Apgar scores were 9 points at one minute and 10 points at 5 minutes. His birth weight and height were 3,800 g ( z -score, +1 standard deviation score) and 52.5 cm ( z -score, +1.4 SDS), respectively. There was no family history of consanguineous marriages. The patient was born with an imperforate anus and a colostomy was performed the day after birth. He had normal male genitalia, with both testes palpable, and postaxial polydactyly of the left foot. A grade 2 systolic murmur was heard in the left upper sternal border and echocardiography revealed a patent ductus arteriosus. Bilateral grade 3 vesicoureteral reflux (VUR) was revealed via voiding cystourethrography. Spine ultrasound revealed no vertebral anomalies, and tracheoesophageal fistula was not suspected clinically. Based on this clinical information, including anal atresia, renal anomalies, and limb abnormalities, he was diagnosed with VACTERL association which is defined by the presence of at least 3 of the following congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. Laboratory test results, including electrolyte levels, were normal. Neonatal screening tests for metabolic disease were also normal, including the 17-alpha-hydroxyprogesterone level. Chromosome analysis revealed a 46, XY karyotype. He was discharged from the neonatal intensive care unit at 21 days of age. At the age of 3 months, the patient was admitted to the hospital for colostomy takedown, anorectoplasty, and endoscopic dextranomer/hyaluronic acid copolymer injection for VUR. After the surgery, the patient was febrile and hypotensive and his abdomen was distended and discolored. An exploratory laparotomy revealed bowel necrosis. Bowel resection with colostomy and jejunostomy was performed 3 times, which resulted in short-bowel syndrome. He could not be discharged because parenteral nutrition was required. The remnant small bowel extended from the Treitz ligament to the jejunocolonic anastomosis and the length of the remnant bowel was only 40 cm. At the age of 7 months, a takedown of the colostomy and jejunostomy was performed. The patient’s mother observed slight bronzing of the patient’s skin after repeated surgeries At 17 months of age, the patient had an episode of sepsis and peritonitis secondary to Acinetobacter baumannii infection and an exploratory laparotomy was performed to check for bowel necrosis. At this time, generalized hyperpigmentation was noted by the doctor and the mother stated that the child's hyperpigmentation was markedly exacerbated after exploratory laparotomy for the episode of peritonitis with sepsis. The patient was referred to our department for the evaluation of the hyperpigmentation. He experienced occasional nausea and vomiting. His heart rate was 120 beats per minute and his blood pressure was 100/65 mmHg. His weight and height were 12.8 kg (1.5 SDS) and 86 cm (2 SDS), respectively. At this point, he was noted to have generalized hyperpigmentation, normal male genitalia, and postaxial polydactyly of the left foot. He was able to ascend stairs with the support of a hand grasp. He could stack 3 cubes, eat without assistance, and pronounce 10 words, meaning that the patient’s developmental status was normal for his age. Laboratory investigations revealed a slightly decreased sodium level (132 mmol/L) but normal potassium (4.8 mEq/L) and glucose (86 mg/dL) levels; complete blood count, blood gas profile, hepatic and renal function, thyroid function test and sex hormone levels were obtained. Decreased cortisol (1.0 μg/dL) and markedly elevated adrenocorticotropic hormone (ACTH) (16,064 pg/mL) levels were noted. The patient's cortisol levels did not respond to stimulation with ACTH (125 μg) ( Table 1 ). Meanwhile, he presented a normal 17-hydroxyprogesterone level (0.42 ng/mL). Plasma renin activity and aldosterone levels were 7.28 ng/mL/hr (normal range, 1.0–6.5 ng/mL/hr) and 0.1 ng/dL (normal range, 3–35 ng/dL), respectively. The abdominal ultrasound revealed no abnormalities, such as adrenal enlargement, hydronephrosis, distal ureter dilatation, or bowel wall thickening. Based on the patient’s symptoms and laboratory results, we considered several genetic causes for primary adrenal insufficiency, and the causative genes of candidate diseases were listed as STAR for NCCLAH and CYP11A1 for congenital adrenal insufficiency. Additionally, melanocortin-2 receptor (MC2R) and MC2R accessory protein for familial glucocorticoid deficiency (FGD) were listed as candidate genes with a low probability because the patient did not have elevated aldosterone. Targeted gene-panel sequencing was performed to check for pathogenic variants in those genes responsible for primary adrenal insufficiency. Genomic DNA was extracted from the peripheral blood of the patient and both parents. Library preparation was done using the TruSight One Sequencing Panel (Illumina, Inc., San Diego, CA, USA), which enriches a 12-Mb region spanning 62,000 target exons of a total of 4,813 genes. Massively parallel sequencing was performed on the Illumina NextSeq platform. Sequence reads were mapped to the UCSC hg19 standard database for comparative analysis. The average depth of the panel was 85.86X, and percentages of bases above 10X of CYP11A1 and STAR were 99.37%, and 100%, respectively. Meanwhile, no pathogenic variants were detected in CYP11A1 genes. The exome-sequencing results revealed compound heterozygous mutations for c.653C>T and c.661G>A (p.Gly221Ser) in exon 6 of the STAR gene. Sanger sequencing confirmed the presence of these variants and each of the same heterozygous variant was found in his father and mother, respectively ( Fig. 1 ). This variant has been previously reported in association with CLAH. Hydrocortisone (7.8 mg/m 2 /day) and fludrocortisone (50 μg/day) were started as therapy for primary adrenal insufficiency. The dose of hydrocortisone was gradually increased until the age of 24 months for sufficient ACTH suppression and levels of ACTH and cortisol were subsequently decreased to the optimal range ( Fig. 2 ). Finally, at 28 months of age, he was discharged and went home with the attainment of oral feeding without nausea and vomiting. He showed no symptoms of hypoglycemia and continued to show normal growth and development. Our last evaluation of the patient was when he was 36 months of age, during which point, his body weight and length were 16.7 kg (0.5 SDS) and 99.7 cm (1.5 SDS), respectively. Laboratory tests revealed normal levels of cortisol (4.6 μg/dL), sodium (139 mmol/L), potassium (4.9 mEq/L), glucose (70 mg/dL), and ACTH (53.6 pg/mL). The generalized hyperpigmentation had improved, and he continued to visit the outpatient clinic regularly without additional admission."}
|
Age-of-Onset
|
Age (of onset)
|
[] |
test-1997
|
7136505
|
{'Case report': "A male child was born at a gestational age of 39 weeks with no history of antenatal or perinatal problems. Apgar scores were 9 points at one minute and 10 points at 5 minutes. His birth weight and height were 3,800 g ( z -score, +1 standard deviation score) and 52.5 cm ( z -score, +1.4 SDS), respectively. There was no family history of consanguineous marriages. The patient was born with an imperforate anus and a colostomy was performed the day after birth. He had normal male genitalia, with both testes palpable, and postaxial polydactyly of the left foot. A grade 2 systolic murmur was heard in the left upper sternal border and echocardiography revealed a patent ductus arteriosus. Bilateral grade 3 vesicoureteral reflux (VUR) was revealed via voiding cystourethrography. Spine ultrasound revealed no vertebral anomalies, and tracheoesophageal fistula was not suspected clinically. Based on this clinical information, including anal atresia, renal anomalies, and limb abnormalities, he was diagnosed with VACTERL association which is defined by the presence of at least 3 of the following congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. Laboratory test results, including electrolyte levels, were normal. Neonatal screening tests for metabolic disease were also normal, including the 17-alpha-hydroxyprogesterone level. Chromosome analysis revealed a 46, XY karyotype. He was discharged from the neonatal intensive care unit at 21 days of age. At the age of 3 months, the patient was admitted to the hospital for colostomy takedown, anorectoplasty, and endoscopic dextranomer/hyaluronic acid copolymer injection for VUR. After the surgery, the patient was febrile and hypotensive and his abdomen was distended and discolored. An exploratory laparotomy revealed bowel necrosis. Bowel resection with colostomy and jejunostomy was performed 3 times, which resulted in short-bowel syndrome. He could not be discharged because parenteral nutrition was required. The remnant small bowel extended from the Treitz ligament to the jejunocolonic anastomosis and the length of the remnant bowel was only 40 cm. At the age of 7 months, a takedown of the colostomy and jejunostomy was performed. The patient’s mother observed slight bronzing of the patient’s skin after repeated surgeries At 17 months of age, the patient had an episode of sepsis and peritonitis secondary to Acinetobacter baumannii infection and an exploratory laparotomy was performed to check for bowel necrosis. At this time, generalized hyperpigmentation was noted by the doctor and the mother stated that the child's hyperpigmentation was markedly exacerbated after exploratory laparotomy for the episode of peritonitis with sepsis. The patient was referred to our department for the evaluation of the hyperpigmentation. He experienced occasional nausea and vomiting. His heart rate was 120 beats per minute and his blood pressure was 100/65 mmHg. His weight and height were 12.8 kg (1.5 SDS) and 86 cm (2 SDS), respectively. At this point, he was noted to have generalized hyperpigmentation, normal male genitalia, and postaxial polydactyly of the left foot. He was able to ascend stairs with the support of a hand grasp. He could stack 3 cubes, eat without assistance, and pronounce 10 words, meaning that the patient’s developmental status was normal for his age. Laboratory investigations revealed a slightly decreased sodium level (132 mmol/L) but normal potassium (4.8 mEq/L) and glucose (86 mg/dL) levels; complete blood count, blood gas profile, hepatic and renal function, thyroid function test and sex hormone levels were obtained. Decreased cortisol (1.0 μg/dL) and markedly elevated adrenocorticotropic hormone (ACTH) (16,064 pg/mL) levels were noted. The patient's cortisol levels did not respond to stimulation with ACTH (125 μg) ( Table 1 ). Meanwhile, he presented a normal 17-hydroxyprogesterone level (0.42 ng/mL). Plasma renin activity and aldosterone levels were 7.28 ng/mL/hr (normal range, 1.0–6.5 ng/mL/hr) and 0.1 ng/dL (normal range, 3–35 ng/dL), respectively. The abdominal ultrasound revealed no abnormalities, such as adrenal enlargement, hydronephrosis, distal ureter dilatation, or bowel wall thickening. Based on the patient’s symptoms and laboratory results, we considered several genetic causes for primary adrenal insufficiency, and the causative genes of candidate diseases were listed as STAR for NCCLAH and CYP11A1 for congenital adrenal insufficiency. Additionally, melanocortin-2 receptor (MC2R) and MC2R accessory protein for familial glucocorticoid deficiency (FGD) were listed as candidate genes with a low probability because the patient did not have elevated aldosterone. Targeted gene-panel sequencing was performed to check for pathogenic variants in those genes responsible for primary adrenal insufficiency. Genomic DNA was extracted from the peripheral blood of the patient and both parents. Library preparation was done using the TruSight One Sequencing Panel (Illumina, Inc., San Diego, CA, USA), which enriches a 12-Mb region spanning 62,000 target exons of a total of 4,813 genes. Massively parallel sequencing was performed on the Illumina NextSeq platform. Sequence reads were mapped to the UCSC hg19 standard database for comparative analysis. The average depth of the panel was 85.86X, and percentages of bases above 10X of CYP11A1 and STAR were 99.37%, and 100%, respectively. Meanwhile, no pathogenic variants were detected in CYP11A1 genes. The exome-sequencing results revealed compound heterozygous mutations for c.653C>T and c.661G>A (p.Gly221Ser) in exon 6 of the STAR gene. Sanger sequencing confirmed the presence of these variants and each of the same heterozygous variant was found in his father and mother, respectively ( Fig. 1 ). This variant has been previously reported in association with CLAH. Hydrocortisone (7.8 mg/m 2 /day) and fludrocortisone (50 μg/day) were started as therapy for primary adrenal insufficiency. The dose of hydrocortisone was gradually increased until the age of 24 months for sufficient ACTH suppression and levels of ACTH and cortisol were subsequently decreased to the optimal range ( Fig. 2 ). Finally, at 28 months of age, he was discharged and went home with the attainment of oral feeding without nausea and vomiting. He showed no symptoms of hypoglycemia and continued to show normal growth and development. Our last evaluation of the patient was when he was 36 months of age, during which point, his body weight and length were 16.7 kg (0.5 SDS) and 99.7 cm (1.5 SDS), respectively. Laboratory tests revealed normal levels of cortisol (4.6 μg/dL), sodium (139 mmol/L), potassium (4.9 mEq/L), glucose (70 mg/dL), and ACTH (53.6 pg/mL). The generalized hyperpigmentation had improved, and he continued to visit the outpatient clinic regularly without additional admission."}
|
{'Case report': "A male child was born at a gestational age of 39 weeks with no history of antenatal or perinatal problems. Apgar scores were 9 points at one minute and 10 points at 5 minutes. His birth weight and height were 3,800 g ( z -score, +1 standard deviation score) and 52.5 cm ( z -score, +1.4 SDS), respectively. There was no family history of consanguineous marriages. The patient was born with an imperforate anus and a colostomy was performed the day after birth. He had normal male genitalia, with both testes palpable, and postaxial polydactyly of the left foot. A grade 2 systolic murmur was heard in the left upper sternal border and echocardiography revealed a patent ductus arteriosus. Bilateral grade 3 vesicoureteral reflux (VUR) was revealed via voiding cystourethrography. Spine ultrasound revealed no vertebral anomalies, and tracheoesophageal fistula was not suspected clinically. Based on this clinical information, including anal atresia, renal anomalies, and limb abnormalities, he was diagnosed with VACTERL association which is defined by the presence of at least 3 of the following congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. Laboratory test results, including electrolyte levels, were normal. Neonatal screening tests for metabolic disease were also normal, including the 17-alpha-hydroxyprogesterone level. Chromosome analysis revealed a 46, XY karyotype. He was discharged from the neonatal intensive care unit at 21 days of age. At the age of 3 months, the patient was admitted to the hospital for colostomy takedown, anorectoplasty, and endoscopic dextranomer/hyaluronic acid copolymer injection for VUR. After the surgery, the patient was febrile and hypotensive and his abdomen was distended and discolored. An exploratory laparotomy revealed bowel necrosis. Bowel resection with colostomy and jejunostomy was performed 3 times, which resulted in short-bowel syndrome. He could not be discharged because parenteral nutrition was required. The remnant small bowel extended from the Treitz ligament to the jejunocolonic anastomosis and the length of the remnant bowel was only 40 cm. At the age of 7 months, a takedown of the colostomy and jejunostomy was performed. The patient’s mother observed slight bronzing of the patient’s skin after repeated surgeries At 17 months of age, the patient had an episode of sepsis and peritonitis secondary to Acinetobacter baumannii infection and an exploratory laparotomy was performed to check for bowel necrosis. At this time, generalized hyperpigmentation was noted by the doctor and the mother stated that the child's hyperpigmentation was markedly exacerbated after exploratory laparotomy for the episode of peritonitis with sepsis. The patient was referred to our department for the evaluation of the hyperpigmentation. He experienced occasional nausea and vomiting. His heart rate was 120 beats per minute and his blood pressure was 100/65 mmHg. His weight and height were 12.8 kg (1.5 SDS) and 86 cm (2 SDS), respectively. At this point, he was noted to have generalized hyperpigmentation, normal male genitalia, and postaxial polydactyly of the left foot. He was able to ascend stairs with the support of a hand grasp. He could stack 3 cubes, eat without assistance, and pronounce 10 words, meaning that the patient’s developmental status was normal for his age. Laboratory investigations revealed a slightly decreased sodium level (132 mmol/L) but normal potassium (4.8 mEq/L) and glucose (86 mg/dL) levels; complete blood count, blood gas profile, hepatic and renal function, thyroid function test and sex hormone levels were obtained. Decreased cortisol (1.0 μg/dL) and markedly elevated adrenocorticotropic hormone (ACTH) (16,064 pg/mL) levels were noted. The patient's cortisol levels did not respond to stimulation with ACTH (125 μg) ( Table 1 ). Meanwhile, he presented a normal 17-hydroxyprogesterone level (0.42 ng/mL). Plasma renin activity and aldosterone levels were 7.28 ng/mL/hr (normal range, 1.0–6.5 ng/mL/hr) and 0.1 ng/dL (normal range, 3–35 ng/dL), respectively. The abdominal ultrasound revealed no abnormalities, such as adrenal enlargement, hydronephrosis, distal ureter dilatation, or bowel wall thickening. Based on the patient’s symptoms and laboratory results, we considered several genetic causes for primary adrenal insufficiency, and the causative genes of candidate diseases were listed as STAR for NCCLAH and CYP11A1 for congenital adrenal insufficiency. Additionally, melanocortin-2 receptor (MC2R) and MC2R accessory protein for familial glucocorticoid deficiency (FGD) were listed as candidate genes with a low probability because the patient did not have elevated aldosterone. Targeted gene-panel sequencing was performed to check for pathogenic variants in those genes responsible for primary adrenal insufficiency. Genomic DNA was extracted from the peripheral blood of the patient and both parents. Library preparation was done using the TruSight One Sequencing Panel (Illumina, Inc., San Diego, CA, USA), which enriches a 12-Mb region spanning 62,000 target exons of a total of 4,813 genes. Massively parallel sequencing was performed on the Illumina NextSeq platform. Sequence reads were mapped to the UCSC hg19 standard database for comparative analysis. The average depth of the panel was 85.86X, and percentages of bases above 10X of CYP11A1 and STAR were 99.37%, and 100%, respectively. Meanwhile, no pathogenic variants were detected in CYP11A1 genes. The exome-sequencing results revealed compound heterozygous mutations for c.653C>T and c.661G>A (p.Gly221Ser) in exon 6 of the STAR gene. Sanger sequencing confirmed the presence of these variants and each of the same heterozygous variant was found in his father and mother, respectively ( Fig. 1 ). This variant has been previously reported in association with CLAH. Hydrocortisone (7.8 mg/m 2 /day) and fludrocortisone (50 μg/day) were started as therapy for primary adrenal insufficiency. The dose of hydrocortisone was gradually increased until the age of 24 months for sufficient ACTH suppression and levels of ACTH and cortisol were subsequently decreased to the optimal range ( Fig. 2 ). Finally, at 28 months of age, he was discharged and went home with the attainment of oral feeding without nausea and vomiting. He showed no symptoms of hypoglycemia and continued to show normal growth and development. Our last evaluation of the patient was when he was 36 months of age, during which point, his body weight and length were 16.7 kg (0.5 SDS) and 99.7 cm (1.5 SDS), respectively. Laboratory tests revealed normal levels of cortisol (4.6 μg/dL), sodium (139 mmol/L), potassium (4.9 mEq/L), glucose (70 mg/dL), and ACTH (53.6 pg/mL). The generalized hyperpigmentation had improved, and he continued to visit the outpatient clinic regularly without additional admission."}
|
Confirmed-Diagnosis-IEM
|
Confirmed_Diagnosis(IEM)
|
[
"This variant has been previously reported in association with CLAH ."
] |
test-1998
|
7136505
|
{'Case report': "A male child was born at a gestational age of 39 weeks with no history of antenatal or perinatal problems. Apgar scores were 9 points at one minute and 10 points at 5 minutes. His birth weight and height were 3,800 g ( z -score, +1 standard deviation score) and 52.5 cm ( z -score, +1.4 SDS), respectively. There was no family history of consanguineous marriages. The patient was born with an imperforate anus and a colostomy was performed the day after birth. He had normal male genitalia, with both testes palpable, and postaxial polydactyly of the left foot. A grade 2 systolic murmur was heard in the left upper sternal border and echocardiography revealed a patent ductus arteriosus. Bilateral grade 3 vesicoureteral reflux (VUR) was revealed via voiding cystourethrography. Spine ultrasound revealed no vertebral anomalies, and tracheoesophageal fistula was not suspected clinically. Based on this clinical information, including anal atresia, renal anomalies, and limb abnormalities, he was diagnosed with VACTERL association which is defined by the presence of at least 3 of the following congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. Laboratory test results, including electrolyte levels, were normal. Neonatal screening tests for metabolic disease were also normal, including the 17-alpha-hydroxyprogesterone level. Chromosome analysis revealed a 46, XY karyotype. He was discharged from the neonatal intensive care unit at 21 days of age. At the age of 3 months, the patient was admitted to the hospital for colostomy takedown, anorectoplasty, and endoscopic dextranomer/hyaluronic acid copolymer injection for VUR. After the surgery, the patient was febrile and hypotensive and his abdomen was distended and discolored. An exploratory laparotomy revealed bowel necrosis. Bowel resection with colostomy and jejunostomy was performed 3 times, which resulted in short-bowel syndrome. He could not be discharged because parenteral nutrition was required. The remnant small bowel extended from the Treitz ligament to the jejunocolonic anastomosis and the length of the remnant bowel was only 40 cm. At the age of 7 months, a takedown of the colostomy and jejunostomy was performed. The patient’s mother observed slight bronzing of the patient’s skin after repeated surgeries At 17 months of age, the patient had an episode of sepsis and peritonitis secondary to Acinetobacter baumannii infection and an exploratory laparotomy was performed to check for bowel necrosis. At this time, generalized hyperpigmentation was noted by the doctor and the mother stated that the child's hyperpigmentation was markedly exacerbated after exploratory laparotomy for the episode of peritonitis with sepsis. The patient was referred to our department for the evaluation of the hyperpigmentation. He experienced occasional nausea and vomiting. His heart rate was 120 beats per minute and his blood pressure was 100/65 mmHg. His weight and height were 12.8 kg (1.5 SDS) and 86 cm (2 SDS), respectively. At this point, he was noted to have generalized hyperpigmentation, normal male genitalia, and postaxial polydactyly of the left foot. He was able to ascend stairs with the support of a hand grasp. He could stack 3 cubes, eat without assistance, and pronounce 10 words, meaning that the patient’s developmental status was normal for his age. Laboratory investigations revealed a slightly decreased sodium level (132 mmol/L) but normal potassium (4.8 mEq/L) and glucose (86 mg/dL) levels; complete blood count, blood gas profile, hepatic and renal function, thyroid function test and sex hormone levels were obtained. Decreased cortisol (1.0 μg/dL) and markedly elevated adrenocorticotropic hormone (ACTH) (16,064 pg/mL) levels were noted. The patient's cortisol levels did not respond to stimulation with ACTH (125 μg) ( Table 1 ). Meanwhile, he presented a normal 17-hydroxyprogesterone level (0.42 ng/mL). Plasma renin activity and aldosterone levels were 7.28 ng/mL/hr (normal range, 1.0–6.5 ng/mL/hr) and 0.1 ng/dL (normal range, 3–35 ng/dL), respectively. The abdominal ultrasound revealed no abnormalities, such as adrenal enlargement, hydronephrosis, distal ureter dilatation, or bowel wall thickening. Based on the patient’s symptoms and laboratory results, we considered several genetic causes for primary adrenal insufficiency, and the causative genes of candidate diseases were listed as STAR for NCCLAH and CYP11A1 for congenital adrenal insufficiency. Additionally, melanocortin-2 receptor (MC2R) and MC2R accessory protein for familial glucocorticoid deficiency (FGD) were listed as candidate genes with a low probability because the patient did not have elevated aldosterone. Targeted gene-panel sequencing was performed to check for pathogenic variants in those genes responsible for primary adrenal insufficiency. Genomic DNA was extracted from the peripheral blood of the patient and both parents. Library preparation was done using the TruSight One Sequencing Panel (Illumina, Inc., San Diego, CA, USA), which enriches a 12-Mb region spanning 62,000 target exons of a total of 4,813 genes. Massively parallel sequencing was performed on the Illumina NextSeq platform. Sequence reads were mapped to the UCSC hg19 standard database for comparative analysis. The average depth of the panel was 85.86X, and percentages of bases above 10X of CYP11A1 and STAR were 99.37%, and 100%, respectively. Meanwhile, no pathogenic variants were detected in CYP11A1 genes. The exome-sequencing results revealed compound heterozygous mutations for c.653C>T and c.661G>A (p.Gly221Ser) in exon 6 of the STAR gene. Sanger sequencing confirmed the presence of these variants and each of the same heterozygous variant was found in his father and mother, respectively ( Fig. 1 ). This variant has been previously reported in association with CLAH. Hydrocortisone (7.8 mg/m 2 /day) and fludrocortisone (50 μg/day) were started as therapy for primary adrenal insufficiency. The dose of hydrocortisone was gradually increased until the age of 24 months for sufficient ACTH suppression and levels of ACTH and cortisol were subsequently decreased to the optimal range ( Fig. 2 ). Finally, at 28 months of age, he was discharged and went home with the attainment of oral feeding without nausea and vomiting. He showed no symptoms of hypoglycemia and continued to show normal growth and development. Our last evaluation of the patient was when he was 36 months of age, during which point, his body weight and length were 16.7 kg (0.5 SDS) and 99.7 cm (1.5 SDS), respectively. Laboratory tests revealed normal levels of cortisol (4.6 μg/dL), sodium (139 mmol/L), potassium (4.9 mEq/L), glucose (70 mg/dL), and ACTH (53.6 pg/mL). The generalized hyperpigmentation had improved, and he continued to visit the outpatient clinic regularly without additional admission."}
|
{'Case report': "A male child was born at a gestational age of 39 weeks with no history of antenatal or perinatal problems. Apgar scores were 9 points at one minute and 10 points at 5 minutes. His birth weight and height were 3,800 g ( z -score, +1 standard deviation score) and 52.5 cm ( z -score, +1.4 SDS), respectively. There was no family history of consanguineous marriages. The patient was born with an imperforate anus and a colostomy was performed the day after birth. He had normal male genitalia, with both testes palpable, and postaxial polydactyly of the left foot. A grade 2 systolic murmur was heard in the left upper sternal border and echocardiography revealed a patent ductus arteriosus. Bilateral grade 3 vesicoureteral reflux (VUR) was revealed via voiding cystourethrography. Spine ultrasound revealed no vertebral anomalies, and tracheoesophageal fistula was not suspected clinically. Based on this clinical information, including anal atresia, renal anomalies, and limb abnormalities, he was diagnosed with VACTERL association which is defined by the presence of at least 3 of the following congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. Laboratory test results, including electrolyte levels, were normal. Neonatal screening tests for metabolic disease were also normal, including the 17-alpha-hydroxyprogesterone level. Chromosome analysis revealed a 46, XY karyotype. He was discharged from the neonatal intensive care unit at 21 days of age. At the age of 3 months, the patient was admitted to the hospital for colostomy takedown, anorectoplasty, and endoscopic dextranomer/hyaluronic acid copolymer injection for VUR. After the surgery, the patient was febrile and hypotensive and his abdomen was distended and discolored. An exploratory laparotomy revealed bowel necrosis. Bowel resection with colostomy and jejunostomy was performed 3 times, which resulted in short-bowel syndrome. He could not be discharged because parenteral nutrition was required. The remnant small bowel extended from the Treitz ligament to the jejunocolonic anastomosis and the length of the remnant bowel was only 40 cm. At the age of 7 months, a takedown of the colostomy and jejunostomy was performed. The patient’s mother observed slight bronzing of the patient’s skin after repeated surgeries At 17 months of age, the patient had an episode of sepsis and peritonitis secondary to Acinetobacter baumannii infection and an exploratory laparotomy was performed to check for bowel necrosis. At this time, generalized hyperpigmentation was noted by the doctor and the mother stated that the child's hyperpigmentation was markedly exacerbated after exploratory laparotomy for the episode of peritonitis with sepsis. The patient was referred to our department for the evaluation of the hyperpigmentation. He experienced occasional nausea and vomiting. His heart rate was 120 beats per minute and his blood pressure was 100/65 mmHg. His weight and height were 12.8 kg (1.5 SDS) and 86 cm (2 SDS), respectively. At this point, he was noted to have generalized hyperpigmentation, normal male genitalia, and postaxial polydactyly of the left foot. He was able to ascend stairs with the support of a hand grasp. He could stack 3 cubes, eat without assistance, and pronounce 10 words, meaning that the patient’s developmental status was normal for his age. Laboratory investigations revealed a slightly decreased sodium level (132 mmol/L) but normal potassium (4.8 mEq/L) and glucose (86 mg/dL) levels; complete blood count, blood gas profile, hepatic and renal function, thyroid function test and sex hormone levels were obtained. Decreased cortisol (1.0 μg/dL) and markedly elevated adrenocorticotropic hormone (ACTH) (16,064 pg/mL) levels were noted. The patient's cortisol levels did not respond to stimulation with ACTH (125 μg) ( Table 1 ). Meanwhile, he presented a normal 17-hydroxyprogesterone level (0.42 ng/mL). Plasma renin activity and aldosterone levels were 7.28 ng/mL/hr (normal range, 1.0–6.5 ng/mL/hr) and 0.1 ng/dL (normal range, 3–35 ng/dL), respectively. The abdominal ultrasound revealed no abnormalities, such as adrenal enlargement, hydronephrosis, distal ureter dilatation, or bowel wall thickening. Based on the patient’s symptoms and laboratory results, we considered several genetic causes for primary adrenal insufficiency, and the causative genes of candidate diseases were listed as STAR for NCCLAH and CYP11A1 for congenital adrenal insufficiency. Additionally, melanocortin-2 receptor (MC2R) and MC2R accessory protein for familial glucocorticoid deficiency (FGD) were listed as candidate genes with a low probability because the patient did not have elevated aldosterone. Targeted gene-panel sequencing was performed to check for pathogenic variants in those genes responsible for primary adrenal insufficiency. Genomic DNA was extracted from the peripheral blood of the patient and both parents. Library preparation was done using the TruSight One Sequencing Panel (Illumina, Inc., San Diego, CA, USA), which enriches a 12-Mb region spanning 62,000 target exons of a total of 4,813 genes. Massively parallel sequencing was performed on the Illumina NextSeq platform. Sequence reads were mapped to the UCSC hg19 standard database for comparative analysis. The average depth of the panel was 85.86X, and percentages of bases above 10X of CYP11A1 and STAR were 99.37%, and 100%, respectively. Meanwhile, no pathogenic variants were detected in CYP11A1 genes. The exome-sequencing results revealed compound heterozygous mutations for c.653C>T and c.661G>A (p.Gly221Ser) in exon 6 of the STAR gene. Sanger sequencing confirmed the presence of these variants and each of the same heterozygous variant was found in his father and mother, respectively ( Fig. 1 ). This variant has been previously reported in association with CLAH. Hydrocortisone (7.8 mg/m 2 /day) and fludrocortisone (50 μg/day) were started as therapy for primary adrenal insufficiency. The dose of hydrocortisone was gradually increased until the age of 24 months for sufficient ACTH suppression and levels of ACTH and cortisol were subsequently decreased to the optimal range ( Fig. 2 ). Finally, at 28 months of age, he was discharged and went home with the attainment of oral feeding without nausea and vomiting. He showed no symptoms of hypoglycemia and continued to show normal growth and development. Our last evaluation of the patient was when he was 36 months of age, during which point, his body weight and length were 16.7 kg (0.5 SDS) and 99.7 cm (1.5 SDS), respectively. Laboratory tests revealed normal levels of cortisol (4.6 μg/dL), sodium (139 mmol/L), potassium (4.9 mEq/L), glucose (70 mg/dL), and ACTH (53.6 pg/mL). The generalized hyperpigmentation had improved, and he continued to visit the outpatient clinic regularly without additional admission."}
|
IEM-Treatment
|
IEM_Treatment
|
[
"Hydrocortisone ( 7.8 mg / m 2 /day ) and fludrocortisone ( 50 μg / day ) were started as therapy for primary adrenal insufficiency . The dose of hydrocortisone was gradually increased until the age of 24 months for sufficient ACTH suppression and levels of ACTH and cortisol were subsequently decreased to the optimal range"
] |
test-1999
|
7890005
|
{'Case presentation': 'We report a 38-year old woman who presented with chronic diarrhea and progressive spastic paraparesis in her twenties. Brain magnetic resonance imaging (MRI) showed cerebral atrophy with diffuse periventricular white matter hyperintensities. Spinal MRI was normal. CYP27A1 gene sequencing confirmed the diagnosis of CTX. Chenodeoxycholic acid (CDCA) treatment was introduced with remission of diarrhea. Unfortunately, the treatment had to be discontinued several times and the patient developed psychosis and an severe ataxospastic gait. Spinal MRI revealed new linear hyperintensities of the corticospinal and gracile tracts. Thirty-three spinal CTX patients were identified by searching in Pubmed, EMBASE™ and Web of Science databases. All patients presented pyramidal signs and 48% had dorsal column signs. Juvenile cataracts were described in 78% of patients, chronic diarrhea in 65%, and tendon xanthomas in 31%. Disease improvement or stabilization with chenodeoxycholic acid was observed in 69% of patients. A higher prevalence of the Arg395Cys allele was observed in patients with spinal CTX as compared to CTX in general (ᵡ 2 ; p < 0.00001). A 38-year-old woman presented with progressive muscle stiffness, calf cramps and urinary frequency appeared in her twenties ( Fig. 1 ). Her past medical history included chronic diarrhea, scoliosis and bilateral cataract surgery at age 25. She did not take any treatment and had normal schooling. Family history was not relevant. Neurological examination revealed spastic paraparesis with pyramidal signs more prominent on the left lower extremity and flat feet. A neurocognitive study demonstrated severe anterograde verbal memory difficulties and minor executive dysfunction. Electroneuromyography (ENMG) was normal. Brain MRI showed subtle symmetric, bilateral hyperintense T2 ground-glass appearance of the deep white matter, possible symmetric T2 hyperintensity of the cerebellar dentate nuclei and two small ischemic infarct sequelae of the right cerebellar hemisphere ( Fig. 2 ). Spinal MRI was normal. 7 years later, due to progression of spastic paraparesis, CTX was considered. Cholestanol was increased to 64 μmol/L (3.3–12.5 μmol/L). A careful assessment did not found any tendinous xanthomas. Genetic analysis found two monoallelic mutations in the gene CYP27A1 : a missense mutation (c.1183C > T; p. Arg395Cys) in exon 6 and a splicing mutation (c.1184 + 1G > A) in intron 6 and confirmed CTX diagnosis. A treatment with 750 mg/d chenodeoxycholic acid (CDCA) and 20 mg/d simvastatine was introduced ( Fig. 1 ). Three months later, diarrhea was disappeared and no adverse effect was observed. One-year follow-up showed stabilization of neurologic and radiologic signs. Fig. 1 Patient timeline of clinical symptoms and biochemical values. Abbreviations: SP: spastic paraparesia; m: month; CDCA: chenodeoxycholic acid. Normal values for cholestanol (N: 0–15.45 μmol/L); bile acid (N: 0–10.02 μmol/L) Fig. 1 Fig. 2 Brain and spinal cord magnetic resonance imaging (MRI) of the patient. Brain and spinal cord MRI performed in 2008 (a,b,e) and 2019 (c,d,f,g). Axial plane T2 weighted images (a-d) at the level of the dentate nuclei and periventricular white matter showing stable minimal increased signal in the dentate nuclei (arrowheads) and questionable slightly abnormal periventricular white matter T2 hyperintensity (“ground-glass appearance”). The rest of brain MRI was unremarkable except for two small old infarcts in the right cerebellar hemisphere (one lesion shown in a and b*). Spinal cord MRI from 2008 (e) was unremarkable, though no axial plane images were performed. Spinal cord MRI in 2019 revealed subtle longitudinal high signal (white arrow-heads) of the posterior columns at the cervico-dorsal junction and middle dorsal region on sagittal T2-weighted images (f). Axial T2-weighted images confirmed bilateral, symmetric signal abnormalities corresponding to the gracilis tracts (g, black arrowhead) and the lateral cortico-spinal tracts (g, white arrows) at different cervical and dorsal levels, without spinal cord atrophy or contrast material (gadolinium) uptake. Fig. 2 CDCA treatment was stopped for 16 months due to product withdrawal. Over this period, diarrhea recurred and walking worsened. She had increased stiffness with muscle pain, new apallesthesia of the lower limbs and onset of cerebellar ataxia. When CDCA treatment was reintroduced (500 mg/d) walking, pain and diarrhea improved. Due to renewed product shortage and patient non-compliance, CDCA treatment was repeatedly discontinued, following which the patient developed an acute psychosis and, short after, a rapid worsening of her gait becaming rollator dependent. Neurologic evaluation showed a severe ataxospastic gait with knee recurvatum (additional files: video). ENMG was normal. Brain MRI was unchanged. Spinal MRI revealed extensive linear T2 weighted hyperintensities appearing bilaterally in lateral corticospinal and gracile tracts ( Fig. 2 ). Despite normal cholestanol levels (6.18 μmol/L; normal range 3.3–12.5 μmol/L), CDCA posology was increased to 750 mg/d. Six months later, the patient had resolution of diarrhea and psychiatric symptoms but no improvement of gait.'}
|
{'Case presentation': 'We report a 38-year old woman who presented with chronic diarrhea and progressive spastic paraparesis in her twenties. Brain magnetic resonance imaging (MRI) showed cerebral atrophy with diffuse periventricular white matter hyperintensities. Spinal MRI was normal. CYP27A1 gene sequencing confirmed the diagnosis of CTX. Chenodeoxycholic acid (CDCA) treatment was introduced with remission of diarrhea. Unfortunately, the treatment had to be discontinued several times and the patient developed psychosis and an severe ataxospastic gait. Spinal MRI revealed new linear hyperintensities of the corticospinal and gracile tracts. Thirty-three spinal CTX patients were identified by searching in Pubmed, EMBASE™ and Web of Science databases. All patients presented pyramidal signs and 48% had dorsal column signs. Juvenile cataracts were described in 78% of patients, chronic diarrhea in 65%, and tendon xanthomas in 31%. Disease improvement or stabilization with chenodeoxycholic acid was observed in 69% of patients. A higher prevalence of the Arg395Cys allele was observed in patients with spinal CTX as compared to CTX in general (ᵡ 2 ; p < 0.00001). A 38-year-old woman presented with progressive muscle stiffness, calf cramps and urinary frequency appeared in her twenties ( Fig. 1 ). Her past medical history included chronic diarrhea, scoliosis and bilateral cataract surgery at age 25. She did not take any treatment and had normal schooling. Family history was not relevant. Neurological examination revealed spastic paraparesis with pyramidal signs more prominent on the left lower extremity and flat feet. A neurocognitive study demonstrated severe anterograde verbal memory difficulties and minor executive dysfunction. Electroneuromyography (ENMG) was normal. Brain MRI showed subtle symmetric, bilateral hyperintense T2 ground-glass appearance of the deep white matter, possible symmetric T2 hyperintensity of the cerebellar dentate nuclei and two small ischemic infarct sequelae of the right cerebellar hemisphere ( Fig. 2 ). Spinal MRI was normal. 7 years later, due to progression of spastic paraparesis, CTX was considered. Cholestanol was increased to 64 μmol/L (3.3–12.5 μmol/L). A careful assessment did not found any tendinous xanthomas. Genetic analysis found two monoallelic mutations in the gene CYP27A1 : a missense mutation (c.1183C > T; p. Arg395Cys) in exon 6 and a splicing mutation (c.1184 + 1G > A) in intron 6 and confirmed CTX diagnosis. A treatment with 750 mg/d chenodeoxycholic acid (CDCA) and 20 mg/d simvastatine was introduced ( Fig. 1 ). Three months later, diarrhea was disappeared and no adverse effect was observed. One-year follow-up showed stabilization of neurologic and radiologic signs. Fig. 1 Patient timeline of clinical symptoms and biochemical values. Abbreviations: SP: spastic paraparesia; m: month; CDCA: chenodeoxycholic acid. Normal values for cholestanol (N: 0–15.45 μmol/L); bile acid (N: 0–10.02 μmol/L) Fig. 1 Fig. 2 Brain and spinal cord magnetic resonance imaging (MRI) of the patient. Brain and spinal cord MRI performed in 2008 (a,b,e) and 2019 (c,d,f,g). Axial plane T2 weighted images (a-d) at the level of the dentate nuclei and periventricular white matter showing stable minimal increased signal in the dentate nuclei (arrowheads) and questionable slightly abnormal periventricular white matter T2 hyperintensity (“ground-glass appearance”). The rest of brain MRI was unremarkable except for two small old infarcts in the right cerebellar hemisphere (one lesion shown in a and b*). Spinal cord MRI from 2008 (e) was unremarkable, though no axial plane images were performed. Spinal cord MRI in 2019 revealed subtle longitudinal high signal (white arrow-heads) of the posterior columns at the cervico-dorsal junction and middle dorsal region on sagittal T2-weighted images (f). Axial T2-weighted images confirmed bilateral, symmetric signal abnormalities corresponding to the gracilis tracts (g, black arrowhead) and the lateral cortico-spinal tracts (g, white arrows) at different cervical and dorsal levels, without spinal cord atrophy or contrast material (gadolinium) uptake. Fig. 2 CDCA treatment was stopped for 16 months due to product withdrawal. Over this period, diarrhea recurred and walking worsened. She had increased stiffness with muscle pain, new apallesthesia of the lower limbs and onset of cerebellar ataxia. When CDCA treatment was reintroduced (500 mg/d) walking, pain and diarrhea improved. Due to renewed product shortage and patient non-compliance, CDCA treatment was repeatedly discontinued, following which the patient developed an acute psychosis and, short after, a rapid worsening of her gait becaming rollator dependent. Neurologic evaluation showed a severe ataxospastic gait with knee recurvatum (additional files: video). ENMG was normal. Brain MRI was unchanged. Spinal MRI revealed extensive linear T2 weighted hyperintensities appearing bilaterally in lateral corticospinal and gracile tracts ( Fig. 2 ). Despite normal cholestanol levels (6.18 μmol/L; normal range 3.3–12.5 μmol/L), CDCA posology was increased to 750 mg/d. Six months later, the patient had resolution of diarrhea and psychiatric symptoms but no improvement of gait.'}
|
Vitals-and-Hematology
|
Vitals_Hema
|
[] |
test-2000
|
7890005
|
{'Case presentation': 'We report a 38-year old woman who presented with chronic diarrhea and progressive spastic paraparesis in her twenties. Brain magnetic resonance imaging (MRI) showed cerebral atrophy with diffuse periventricular white matter hyperintensities. Spinal MRI was normal. CYP27A1 gene sequencing confirmed the diagnosis of CTX. Chenodeoxycholic acid (CDCA) treatment was introduced with remission of diarrhea. Unfortunately, the treatment had to be discontinued several times and the patient developed psychosis and an severe ataxospastic gait. Spinal MRI revealed new linear hyperintensities of the corticospinal and gracile tracts. Thirty-three spinal CTX patients were identified by searching in Pubmed, EMBASE™ and Web of Science databases. All patients presented pyramidal signs and 48% had dorsal column signs. Juvenile cataracts were described in 78% of patients, chronic diarrhea in 65%, and tendon xanthomas in 31%. Disease improvement or stabilization with chenodeoxycholic acid was observed in 69% of patients. A higher prevalence of the Arg395Cys allele was observed in patients with spinal CTX as compared to CTX in general (ᵡ 2 ; p < 0.00001). A 38-year-old woman presented with progressive muscle stiffness, calf cramps and urinary frequency appeared in her twenties ( Fig. 1 ). Her past medical history included chronic diarrhea, scoliosis and bilateral cataract surgery at age 25. She did not take any treatment and had normal schooling. Family history was not relevant. Neurological examination revealed spastic paraparesis with pyramidal signs more prominent on the left lower extremity and flat feet. A neurocognitive study demonstrated severe anterograde verbal memory difficulties and minor executive dysfunction. Electroneuromyography (ENMG) was normal. Brain MRI showed subtle symmetric, bilateral hyperintense T2 ground-glass appearance of the deep white matter, possible symmetric T2 hyperintensity of the cerebellar dentate nuclei and two small ischemic infarct sequelae of the right cerebellar hemisphere ( Fig. 2 ). Spinal MRI was normal. 7 years later, due to progression of spastic paraparesis, CTX was considered. Cholestanol was increased to 64 μmol/L (3.3–12.5 μmol/L). A careful assessment did not found any tendinous xanthomas. Genetic analysis found two monoallelic mutations in the gene CYP27A1 : a missense mutation (c.1183C > T; p. Arg395Cys) in exon 6 and a splicing mutation (c.1184 + 1G > A) in intron 6 and confirmed CTX diagnosis. A treatment with 750 mg/d chenodeoxycholic acid (CDCA) and 20 mg/d simvastatine was introduced ( Fig. 1 ). Three months later, diarrhea was disappeared and no adverse effect was observed. One-year follow-up showed stabilization of neurologic and radiologic signs. Fig. 1 Patient timeline of clinical symptoms and biochemical values. Abbreviations: SP: spastic paraparesia; m: month; CDCA: chenodeoxycholic acid. Normal values for cholestanol (N: 0–15.45 μmol/L); bile acid (N: 0–10.02 μmol/L) Fig. 1 Fig. 2 Brain and spinal cord magnetic resonance imaging (MRI) of the patient. Brain and spinal cord MRI performed in 2008 (a,b,e) and 2019 (c,d,f,g). Axial plane T2 weighted images (a-d) at the level of the dentate nuclei and periventricular white matter showing stable minimal increased signal in the dentate nuclei (arrowheads) and questionable slightly abnormal periventricular white matter T2 hyperintensity (“ground-glass appearance”). The rest of brain MRI was unremarkable except for two small old infarcts in the right cerebellar hemisphere (one lesion shown in a and b*). Spinal cord MRI from 2008 (e) was unremarkable, though no axial plane images were performed. Spinal cord MRI in 2019 revealed subtle longitudinal high signal (white arrow-heads) of the posterior columns at the cervico-dorsal junction and middle dorsal region on sagittal T2-weighted images (f). Axial T2-weighted images confirmed bilateral, symmetric signal abnormalities corresponding to the gracilis tracts (g, black arrowhead) and the lateral cortico-spinal tracts (g, white arrows) at different cervical and dorsal levels, without spinal cord atrophy or contrast material (gadolinium) uptake. Fig. 2 CDCA treatment was stopped for 16 months due to product withdrawal. Over this period, diarrhea recurred and walking worsened. She had increased stiffness with muscle pain, new apallesthesia of the lower limbs and onset of cerebellar ataxia. When CDCA treatment was reintroduced (500 mg/d) walking, pain and diarrhea improved. Due to renewed product shortage and patient non-compliance, CDCA treatment was repeatedly discontinued, following which the patient developed an acute psychosis and, short after, a rapid worsening of her gait becaming rollator dependent. Neurologic evaluation showed a severe ataxospastic gait with knee recurvatum (additional files: video). ENMG was normal. Brain MRI was unchanged. Spinal MRI revealed extensive linear T2 weighted hyperintensities appearing bilaterally in lateral corticospinal and gracile tracts ( Fig. 2 ). Despite normal cholestanol levels (6.18 μmol/L; normal range 3.3–12.5 μmol/L), CDCA posology was increased to 750 mg/d. Six months later, the patient had resolution of diarrhea and psychiatric symptoms but no improvement of gait.'}
|
{'Case presentation': 'We report a 38-year old woman who presented with chronic diarrhea and progressive spastic paraparesis in her twenties. Brain magnetic resonance imaging (MRI) showed cerebral atrophy with diffuse periventricular white matter hyperintensities. Spinal MRI was normal. CYP27A1 gene sequencing confirmed the diagnosis of CTX. Chenodeoxycholic acid (CDCA) treatment was introduced with remission of diarrhea. Unfortunately, the treatment had to be discontinued several times and the patient developed psychosis and an severe ataxospastic gait. Spinal MRI revealed new linear hyperintensities of the corticospinal and gracile tracts. Thirty-three spinal CTX patients were identified by searching in Pubmed, EMBASE™ and Web of Science databases. All patients presented pyramidal signs and 48% had dorsal column signs. Juvenile cataracts were described in 78% of patients, chronic diarrhea in 65%, and tendon xanthomas in 31%. Disease improvement or stabilization with chenodeoxycholic acid was observed in 69% of patients. A higher prevalence of the Arg395Cys allele was observed in patients with spinal CTX as compared to CTX in general (ᵡ 2 ; p < 0.00001). A 38-year-old woman presented with progressive muscle stiffness, calf cramps and urinary frequency appeared in her twenties ( Fig. 1 ). Her past medical history included chronic diarrhea, scoliosis and bilateral cataract surgery at age 25. She did not take any treatment and had normal schooling. Family history was not relevant. Neurological examination revealed spastic paraparesis with pyramidal signs more prominent on the left lower extremity and flat feet. A neurocognitive study demonstrated severe anterograde verbal memory difficulties and minor executive dysfunction. Electroneuromyography (ENMG) was normal. Brain MRI showed subtle symmetric, bilateral hyperintense T2 ground-glass appearance of the deep white matter, possible symmetric T2 hyperintensity of the cerebellar dentate nuclei and two small ischemic infarct sequelae of the right cerebellar hemisphere ( Fig. 2 ). Spinal MRI was normal. 7 years later, due to progression of spastic paraparesis, CTX was considered. Cholestanol was increased to 64 μmol/L (3.3–12.5 μmol/L). A careful assessment did not found any tendinous xanthomas. Genetic analysis found two monoallelic mutations in the gene CYP27A1 : a missense mutation (c.1183C > T; p. Arg395Cys) in exon 6 and a splicing mutation (c.1184 + 1G > A) in intron 6 and confirmed CTX diagnosis. A treatment with 750 mg/d chenodeoxycholic acid (CDCA) and 20 mg/d simvastatine was introduced ( Fig. 1 ). Three months later, diarrhea was disappeared and no adverse effect was observed. One-year follow-up showed stabilization of neurologic and radiologic signs. Fig. 1 Patient timeline of clinical symptoms and biochemical values. Abbreviations: SP: spastic paraparesia; m: month; CDCA: chenodeoxycholic acid. Normal values for cholestanol (N: 0–15.45 μmol/L); bile acid (N: 0–10.02 μmol/L) Fig. 1 Fig. 2 Brain and spinal cord magnetic resonance imaging (MRI) of the patient. Brain and spinal cord MRI performed in 2008 (a,b,e) and 2019 (c,d,f,g). Axial plane T2 weighted images (a-d) at the level of the dentate nuclei and periventricular white matter showing stable minimal increased signal in the dentate nuclei (arrowheads) and questionable slightly abnormal periventricular white matter T2 hyperintensity (“ground-glass appearance”). The rest of brain MRI was unremarkable except for two small old infarcts in the right cerebellar hemisphere (one lesion shown in a and b*). Spinal cord MRI from 2008 (e) was unremarkable, though no axial plane images were performed. Spinal cord MRI in 2019 revealed subtle longitudinal high signal (white arrow-heads) of the posterior columns at the cervico-dorsal junction and middle dorsal region on sagittal T2-weighted images (f). Axial T2-weighted images confirmed bilateral, symmetric signal abnormalities corresponding to the gracilis tracts (g, black arrowhead) and the lateral cortico-spinal tracts (g, white arrows) at different cervical and dorsal levels, without spinal cord atrophy or contrast material (gadolinium) uptake. Fig. 2 CDCA treatment was stopped for 16 months due to product withdrawal. Over this period, diarrhea recurred and walking worsened. She had increased stiffness with muscle pain, new apallesthesia of the lower limbs and onset of cerebellar ataxia. When CDCA treatment was reintroduced (500 mg/d) walking, pain and diarrhea improved. Due to renewed product shortage and patient non-compliance, CDCA treatment was repeatedly discontinued, following which the patient developed an acute psychosis and, short after, a rapid worsening of her gait becaming rollator dependent. Neurologic evaluation showed a severe ataxospastic gait with knee recurvatum (additional files: video). ENMG was normal. Brain MRI was unchanged. Spinal MRI revealed extensive linear T2 weighted hyperintensities appearing bilaterally in lateral corticospinal and gracile tracts ( Fig. 2 ). Despite normal cholestanol levels (6.18 μmol/L; normal range 3.3–12.5 μmol/L), CDCA posology was increased to 750 mg/d. Six months later, the patient had resolution of diarrhea and psychiatric symptoms but no improvement of gait.'}
|
Gastrointestinal-System
|
GI
|
[
"chronic diarrhea",
"remission of diarrhea",
"chronic diarrhea",
"Three months later, diarrhea was disappeared",
"diarrhea recurred"
] |
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