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test-2101
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7674721
|
{'Chief complaints': 'A 47-year-old male was admitted to our institution with a history of intellectual disability for more than 30 years and behavioral abnormalities for the past 3 mo. He had a poor academic performance, having dropped out after completing elementary school. The patient could talk with others in daily life, but he was unable to do housework.', 'Personal and family history': 'The proband is the 4 th child of 5 in a non-consanguineous Chinese family. His family history was negative for symptoms related to neurological disorders. He was divorced twice and had no children, and did not have a history of smoking or drinking. The proband’s parents had died and his mother had a history of uremia. All of his four sisters are healthy (Figure 1A ).', 'CASE SUMMARY': 'A Chinese family with CTX consisting of one patient and four heterozygous carriers was studied. The patient is a 47-year-old male, who mainly had psychiatric signs but without some cardinal features of CTX such as cataracts, cerebellar ataxia, pyramidal signs and chronic diarrhea. There was a significant increase in the concentration of free fatty acid compared to normal range. Doppler ultrasound of the urinary system showed multiple left kidney stones, a right kidney cyst, and a hypoechoic area in the bladder, which could move with body position. Sagittal and axial magnetic resonance imaging (MRI) of the right ankle joint showed apparent enlargement of the right Achilles tendon and upper medial malleolus flexor tendon, abnormal thickening of the plantar fat, and a small amount of exudation around the fascia in front of the Achilles tendon. Cerebral MRI suggested white matter (WM) demyelination and slight cerebral atrophy. The diagnosis was confirmed by targeted sequencing, which identified compound heterozygous mutations in exon 2 and intron 7 of the CYP27A1 gene (c.435G>T, c.1263+1G>A). Treatment for 3 wk with a combination of lipid-lowering and antipsychotic therapy improved his psychiatric symptoms and normalized the levels of serum free fatty acid. Sediments in the bladder disappeared after therapy.', 'Physical examination': 'The patient had dark skin and a poor mental state (Figure 2A ). Neurological examination indicated cervical rigidity and Kernig sign. Deep tendon reflexes and limb muscle strength were normal. Babinski sign was negative. Enlarged Achilles tendons and nodules on the bilateral tibial tubercles were observed (Figure 2B and C ). There was no evidence of cataract or xanthomas at other sites such as the eyelids.', 'Biological and imaging features': 'The biochemical abnormalities detected in CTX are significant for diagnosis. The lack of sterol 27-hydroxylase inhibits the conversion of cholesterol into cholic and chenodeoxycholic acids in the liver. The serum levels of cholesterol and triglyceride are usually normal while cholestanol levels are markedly high in the blood, bile and tendon xanthoma. Since cholesterol synthesis is systematically decreased, cholesterol precursors increase substantially; this could also be regarded as a hallmark of CTX. Although a high cholestanol level indicates CTX, it does not correlate with any symptoms or disability at diagnosis assessed by the Expanded Disability Status Scale. Fast atom bombardment mass spectrometry is a semiquantitative technique which can be applied to analyze urinary bile acids. It will strongly support a diagnosis of CTX if increased bile alcohol glucuronides and reduced primary bile acid are detected. However, when the urinary bile acid profile is consistent with CTX, propofol administration should be taken into account as another possible cause, to avoid misdiagnoses. The combination of extremely low levels of 27-hydroxycholesterol (< 5 ng/mL or lower than the detection limit) and extremely high serum levels of 7 alpha-hydroxycholesterol (7α-OH-C) or 7 alpha-hydroxy-4-cholesten-3-one (7αC4) is a distinctive feature of CTX. Both 7α-OH-C and 7αC4 have been suggested as ideal biomarkers for evaluating treatment effects. With respect to auxiliary examinations, 56.57% of patients showed EEG abnormalities including diffuse slowing, which is a common feature of CTX patients. In addition, 76.72% had abnormal magnetic resonance (MR) images ( Supplementary Table 1 ). The main brain MRI abnormalities include supratentorial and infratentorial atrophy, as well as T2W/FLAIR (fluid-attenuated inversion recovery) hyperintensity involving the subcortical, periventricular and cerebellar WM and the brainstem. Bilateral hyperintensity of the dentate nuclei (DN) and surrounding WM on T2 and FLAIR sequences is considered a representative radiological feature of CTX. DN plays a critical role in saccade motor planning within a network that involves the frontal cortex and basal ganglia. Patients with DN lesions showed abnormal latency of reflexive and voluntary saccades, impaired precision and more uncorrected directional errors. There is a strong correlation between DN hyperintensity in brain MRI and neurological manifestations including ataxia, spasticity and cognitive impairment. Patients without DN hyperintensity are considered to have a better prognosis. A 6-year MR follow-up study revealed that cerebellar hyperintensity in T1-weighted and FLAIR images tend to be replaced by hypointense areas, suggesting vacuolation. Cerebellar hyperintensity on FLAIR images is probably due to lipid deposits, while hypointense areas may indicate cerebellar degeneration because of cholestanol-induced apoptosis or other mechanisms causing axonal injury. Cerebellar vacuolation and calcification have been observed in a large number of patients. The former was positively related to the extent of DN hyperintensity in T1W and FLAIR images, and could be a useful indicator of disease progression and inadequate therapeutic response. Additionally, cerebral micro- and macro-angiopathies such as micro-hemorrhages, vascular dilatation and calcification are common in CTX patients. The xanthomas located within the ventricular region have also been observed in CTX cases. The main components of xanthoma are connective tissue and foam cells (foamy macrophages) bathed in cholestanol, cholesterol, cholesterol esters, triglycerides and phospholipids. The presence of Touton giant cells is a characteristic pathological finding. The development of tendon xanthomas may be associated with low-grade tendon inflammation. A tendon MRI study indicated that the enlargement of tendon xanthomas is primarily due to an increase in tendon water content, rather than in fat content. Tendinous xanthomas have different appearances on MR depending on the proportions of the following components: cholesterol, which does not produce a measurable signal; triglycerides, which produce a high signal on T1-weighted images; and associated inflammation, which causes high signal intensity regions in contrast-enhanced T1-weighted images. The diffuse reticulated pattern of xanthomas on axial images is a representative MRI feature of tendinous xanthoma. This patient’s MRI showed enlargement of the Achilles tendon, which showed up as low signal intensity on both T1- and T2-weighted images. This fits well with previous reports and could be attributed to the low percentage of triglycerides. In conclusion, we described a 47-year-old patient displaying psychiatric and behavioral disturbances, cognitive decline, a history of renal calculus, bilateral xanthomas of the Achilles tendon and tibial tubercles, peripheral neuropathy, high signal intensity in the WM and mild cerebral atrophy on brain MRI. The diagnosis was confirmed by compound heterozygous mutations in exon 2 (c.435G>T, p.Gly145Gly) and intron 7 (c.1263+1G>A) of the CYP27A1 gene. These lead to alternative pre-mRNA splicing and a skipping of exon 7 in the transcript, respectively. Three weeks′ treatment with a combination of lipid-lowering and antipsychotic therapy improved his psychiatric symptoms and normalized levels of serum free fatty acid. Sediments in the bladder disappeared after therapy.', 'Imaging examinations': 'X-ray of the lower limbs showed soft tissue swelling above the tibial tuberosities bilaterally (Figure 2E ). Sagittal and axial magnetic resonance imaging (MRI) of the right ankle joint showed apparent enlargement of the right Achilles tendon and upper medial malleolus flexor tendon (consisting of low signal intensity on both T1- and T2-weighted images), abnormal thickening of the plantar fat, and a small amount of exudation around the fascia in front of the Achilles tendon (Figure 2F ). The electroencephalogram (EEG) showed increased slow activities than normal and electrophysiological examination found mixed sensorimotor neuropathy of the upper and lower limbs. Cerebral MRI suggested white matter (WM) demyelination and slight cerebral atrophy (Figure 2G and H ).', 'Laboratory examinations': 'The laboratory results (Table 1 ) were as follows: Increased leukocyte count, neutrophil ratio and high erythrocyte sedimentation rate. There was also a significant increase in concentration of free fatty acid compared to normal range. In contrast, levels of high-density lipoprotein cholesterol were low. Serum cholesterol, glucose, electrolytes, and adrenocorticotropic hormone (ACTH) levels were all normal, as were the liver function tests. Doppler ultrasound of the urinary system showed multiple left kidney stones, a right kidney cyst, and a hypoechoic area in the bladder which could move with body position (Figure 2D ). Cerebrospinal fluid protein was mildly elevated: 680.4 mg/L (normal range: 150-400 mg/L).', 'Genetic testing': 'Genomic DNA was isolated from blood samples of the patient and his four healthy sisters. Mutation screening of all exons and flanking regions was performed on the patient’s sample by targeted sequencing as previously reported. Targeted sequencing revealed that the proband had compound heterozygous mutations in the CYP27A1 gene and that his four sisters were mutation carriers (Figure 1B - E, and Table 2 ). Both of the variants found are known pathogenic mutations of CTX. The variant in exon 2 (c.435G>T, p.Gly145Gly), a functionally silent nucleotide substitution, has been reported to activate a 5’ splice site, leading to alternative pre-mRNA splicing. The other variant (c.1263+1G>A) is a splice site mutation that disrupts normal mRNA splicing and results in exon 7 being skipped in the transcript. In Italian and Japanese patients, the variant has been found to cause loss of a heme binding domain, a vital part of hydroxylase, and to damage bile acid synthesis.', 'History of present illness': 'Three months ago, he underwent an operation for renal calculus, after which he showed progressive delusion (he believed unreasonably that he had a serious disease and was going to die), combined with slow response and speech reduction. At 1 wk before admission, he was unable to answer questions and developed an eating difficulty, incontinence, fever (T ≤ 38.2 °C) and severe weight loss. Chronic diarrhea was absent.'}
|
{'Chief complaints': 'A 47-year-old male was admitted to our institution with a history of intellectual disability for more than 30 years and behavioral abnormalities for the past 3 mo. He had a poor academic performance, having dropped out after completing elementary school. The patient could talk with others in daily life, but he was unable to do housework.', 'Personal and family history': 'The proband is the 4 th child of 5 in a non-consanguineous Chinese family. His family history was negative for symptoms related to neurological disorders. He was divorced twice and had no children, and did not have a history of smoking or drinking. The proband’s parents had died and his mother had a history of uremia. All of his four sisters are healthy (Figure 1A ).', 'CASE SUMMARY': 'A Chinese family with CTX consisting of one patient and four heterozygous carriers was studied. The patient is a 47-year-old male, who mainly had psychiatric signs but without some cardinal features of CTX such as cataracts, cerebellar ataxia, pyramidal signs and chronic diarrhea. There was a significant increase in the concentration of free fatty acid compared to normal range. Doppler ultrasound of the urinary system showed multiple left kidney stones, a right kidney cyst, and a hypoechoic area in the bladder, which could move with body position. Sagittal and axial magnetic resonance imaging (MRI) of the right ankle joint showed apparent enlargement of the right Achilles tendon and upper medial malleolus flexor tendon, abnormal thickening of the plantar fat, and a small amount of exudation around the fascia in front of the Achilles tendon. Cerebral MRI suggested white matter (WM) demyelination and slight cerebral atrophy. The diagnosis was confirmed by targeted sequencing, which identified compound heterozygous mutations in exon 2 and intron 7 of the CYP27A1 gene (c.435G>T, c.1263+1G>A). Treatment for 3 wk with a combination of lipid-lowering and antipsychotic therapy improved his psychiatric symptoms and normalized the levels of serum free fatty acid. Sediments in the bladder disappeared after therapy.', 'Physical examination': 'The patient had dark skin and a poor mental state (Figure 2A ). Neurological examination indicated cervical rigidity and Kernig sign. Deep tendon reflexes and limb muscle strength were normal. Babinski sign was negative. Enlarged Achilles tendons and nodules on the bilateral tibial tubercles were observed (Figure 2B and C ). There was no evidence of cataract or xanthomas at other sites such as the eyelids.', 'Biological and imaging features': 'The biochemical abnormalities detected in CTX are significant for diagnosis. The lack of sterol 27-hydroxylase inhibits the conversion of cholesterol into cholic and chenodeoxycholic acids in the liver. The serum levels of cholesterol and triglyceride are usually normal while cholestanol levels are markedly high in the blood, bile and tendon xanthoma. Since cholesterol synthesis is systematically decreased, cholesterol precursors increase substantially; this could also be regarded as a hallmark of CTX. Although a high cholestanol level indicates CTX, it does not correlate with any symptoms or disability at diagnosis assessed by the Expanded Disability Status Scale. Fast atom bombardment mass spectrometry is a semiquantitative technique which can be applied to analyze urinary bile acids. It will strongly support a diagnosis of CTX if increased bile alcohol glucuronides and reduced primary bile acid are detected. However, when the urinary bile acid profile is consistent with CTX, propofol administration should be taken into account as another possible cause, to avoid misdiagnoses. The combination of extremely low levels of 27-hydroxycholesterol (< 5 ng/mL or lower than the detection limit) and extremely high serum levels of 7 alpha-hydroxycholesterol (7α-OH-C) or 7 alpha-hydroxy-4-cholesten-3-one (7αC4) is a distinctive feature of CTX. Both 7α-OH-C and 7αC4 have been suggested as ideal biomarkers for evaluating treatment effects. With respect to auxiliary examinations, 56.57% of patients showed EEG abnormalities including diffuse slowing, which is a common feature of CTX patients. In addition, 76.72% had abnormal magnetic resonance (MR) images ( Supplementary Table 1 ). The main brain MRI abnormalities include supratentorial and infratentorial atrophy, as well as T2W/FLAIR (fluid-attenuated inversion recovery) hyperintensity involving the subcortical, periventricular and cerebellar WM and the brainstem. Bilateral hyperintensity of the dentate nuclei (DN) and surrounding WM on T2 and FLAIR sequences is considered a representative radiological feature of CTX. DN plays a critical role in saccade motor planning within a network that involves the frontal cortex and basal ganglia. Patients with DN lesions showed abnormal latency of reflexive and voluntary saccades, impaired precision and more uncorrected directional errors. There is a strong correlation between DN hyperintensity in brain MRI and neurological manifestations including ataxia, spasticity and cognitive impairment. Patients without DN hyperintensity are considered to have a better prognosis. A 6-year MR follow-up study revealed that cerebellar hyperintensity in T1-weighted and FLAIR images tend to be replaced by hypointense areas, suggesting vacuolation. Cerebellar hyperintensity on FLAIR images is probably due to lipid deposits, while hypointense areas may indicate cerebellar degeneration because of cholestanol-induced apoptosis or other mechanisms causing axonal injury. Cerebellar vacuolation and calcification have been observed in a large number of patients. The former was positively related to the extent of DN hyperintensity in T1W and FLAIR images, and could be a useful indicator of disease progression and inadequate therapeutic response. Additionally, cerebral micro- and macro-angiopathies such as micro-hemorrhages, vascular dilatation and calcification are common in CTX patients. The xanthomas located within the ventricular region have also been observed in CTX cases. The main components of xanthoma are connective tissue and foam cells (foamy macrophages) bathed in cholestanol, cholesterol, cholesterol esters, triglycerides and phospholipids. The presence of Touton giant cells is a characteristic pathological finding. The development of tendon xanthomas may be associated with low-grade tendon inflammation. A tendon MRI study indicated that the enlargement of tendon xanthomas is primarily due to an increase in tendon water content, rather than in fat content. Tendinous xanthomas have different appearances on MR depending on the proportions of the following components: cholesterol, which does not produce a measurable signal; triglycerides, which produce a high signal on T1-weighted images; and associated inflammation, which causes high signal intensity regions in contrast-enhanced T1-weighted images. The diffuse reticulated pattern of xanthomas on axial images is a representative MRI feature of tendinous xanthoma. This patient’s MRI showed enlargement of the Achilles tendon, which showed up as low signal intensity on both T1- and T2-weighted images. This fits well with previous reports and could be attributed to the low percentage of triglycerides. In conclusion, we described a 47-year-old patient displaying psychiatric and behavioral disturbances, cognitive decline, a history of renal calculus, bilateral xanthomas of the Achilles tendon and tibial tubercles, peripheral neuropathy, high signal intensity in the WM and mild cerebral atrophy on brain MRI. The diagnosis was confirmed by compound heterozygous mutations in exon 2 (c.435G>T, p.Gly145Gly) and intron 7 (c.1263+1G>A) of the CYP27A1 gene. These lead to alternative pre-mRNA splicing and a skipping of exon 7 in the transcript, respectively. Three weeks′ treatment with a combination of lipid-lowering and antipsychotic therapy improved his psychiatric symptoms and normalized levels of serum free fatty acid. Sediments in the bladder disappeared after therapy.', 'Imaging examinations': 'X-ray of the lower limbs showed soft tissue swelling above the tibial tuberosities bilaterally (Figure 2E ). Sagittal and axial magnetic resonance imaging (MRI) of the right ankle joint showed apparent enlargement of the right Achilles tendon and upper medial malleolus flexor tendon (consisting of low signal intensity on both T1- and T2-weighted images), abnormal thickening of the plantar fat, and a small amount of exudation around the fascia in front of the Achilles tendon (Figure 2F ). The electroencephalogram (EEG) showed increased slow activities than normal and electrophysiological examination found mixed sensorimotor neuropathy of the upper and lower limbs. Cerebral MRI suggested white matter (WM) demyelination and slight cerebral atrophy (Figure 2G and H ).', 'Laboratory examinations': 'The laboratory results (Table 1 ) were as follows: Increased leukocyte count, neutrophil ratio and high erythrocyte sedimentation rate. There was also a significant increase in concentration of free fatty acid compared to normal range. In contrast, levels of high-density lipoprotein cholesterol were low. Serum cholesterol, glucose, electrolytes, and adrenocorticotropic hormone (ACTH) levels were all normal, as were the liver function tests. Doppler ultrasound of the urinary system showed multiple left kidney stones, a right kidney cyst, and a hypoechoic area in the bladder which could move with body position (Figure 2D ). Cerebrospinal fluid protein was mildly elevated: 680.4 mg/L (normal range: 150-400 mg/L).', 'Genetic testing': 'Genomic DNA was isolated from blood samples of the patient and his four healthy sisters. Mutation screening of all exons and flanking regions was performed on the patient’s sample by targeted sequencing as previously reported. Targeted sequencing revealed that the proband had compound heterozygous mutations in the CYP27A1 gene and that his four sisters were mutation carriers (Figure 1B - E, and Table 2 ). Both of the variants found are known pathogenic mutations of CTX. The variant in exon 2 (c.435G>T, p.Gly145Gly), a functionally silent nucleotide substitution, has been reported to activate a 5’ splice site, leading to alternative pre-mRNA splicing. The other variant (c.1263+1G>A) is a splice site mutation that disrupts normal mRNA splicing and results in exon 7 being skipped in the transcript. In Italian and Japanese patients, the variant has been found to cause loss of a heme binding domain, a vital part of hydroxylase, and to damage bile acid synthesis.', 'History of present illness': 'Three months ago, he underwent an operation for renal calculus, after which he showed progressive delusion (he believed unreasonably that he had a serious disease and was going to die), combined with slow response and speech reduction. At 1 wk before admission, he was unable to answer questions and developed an eating difficulty, incontinence, fever (T ≤ 38.2 °C) and severe weight loss. Chronic diarrhea was absent.'}
|
Pregnancy
|
Pregnancy
|
[] |
test-2102
|
7674721
|
{'Chief complaints': 'A 47-year-old male was admitted to our institution with a history of intellectual disability for more than 30 years and behavioral abnormalities for the past 3 mo. He had a poor academic performance, having dropped out after completing elementary school. The patient could talk with others in daily life, but he was unable to do housework.', 'Personal and family history': 'The proband is the 4 th child of 5 in a non-consanguineous Chinese family. His family history was negative for symptoms related to neurological disorders. He was divorced twice and had no children, and did not have a history of smoking or drinking. The proband’s parents had died and his mother had a history of uremia. All of his four sisters are healthy (Figure 1A ).', 'CASE SUMMARY': 'A Chinese family with CTX consisting of one patient and four heterozygous carriers was studied. The patient is a 47-year-old male, who mainly had psychiatric signs but without some cardinal features of CTX such as cataracts, cerebellar ataxia, pyramidal signs and chronic diarrhea. There was a significant increase in the concentration of free fatty acid compared to normal range. Doppler ultrasound of the urinary system showed multiple left kidney stones, a right kidney cyst, and a hypoechoic area in the bladder, which could move with body position. Sagittal and axial magnetic resonance imaging (MRI) of the right ankle joint showed apparent enlargement of the right Achilles tendon and upper medial malleolus flexor tendon, abnormal thickening of the plantar fat, and a small amount of exudation around the fascia in front of the Achilles tendon. Cerebral MRI suggested white matter (WM) demyelination and slight cerebral atrophy. The diagnosis was confirmed by targeted sequencing, which identified compound heterozygous mutations in exon 2 and intron 7 of the CYP27A1 gene (c.435G>T, c.1263+1G>A). Treatment for 3 wk with a combination of lipid-lowering and antipsychotic therapy improved his psychiatric symptoms and normalized the levels of serum free fatty acid. Sediments in the bladder disappeared after therapy.', 'Physical examination': 'The patient had dark skin and a poor mental state (Figure 2A ). Neurological examination indicated cervical rigidity and Kernig sign. Deep tendon reflexes and limb muscle strength were normal. Babinski sign was negative. Enlarged Achilles tendons and nodules on the bilateral tibial tubercles were observed (Figure 2B and C ). There was no evidence of cataract or xanthomas at other sites such as the eyelids.', 'Biological and imaging features': 'The biochemical abnormalities detected in CTX are significant for diagnosis. The lack of sterol 27-hydroxylase inhibits the conversion of cholesterol into cholic and chenodeoxycholic acids in the liver. The serum levels of cholesterol and triglyceride are usually normal while cholestanol levels are markedly high in the blood, bile and tendon xanthoma. Since cholesterol synthesis is systematically decreased, cholesterol precursors increase substantially; this could also be regarded as a hallmark of CTX. Although a high cholestanol level indicates CTX, it does not correlate with any symptoms or disability at diagnosis assessed by the Expanded Disability Status Scale. Fast atom bombardment mass spectrometry is a semiquantitative technique which can be applied to analyze urinary bile acids. It will strongly support a diagnosis of CTX if increased bile alcohol glucuronides and reduced primary bile acid are detected. However, when the urinary bile acid profile is consistent with CTX, propofol administration should be taken into account as another possible cause, to avoid misdiagnoses. The combination of extremely low levels of 27-hydroxycholesterol (< 5 ng/mL or lower than the detection limit) and extremely high serum levels of 7 alpha-hydroxycholesterol (7α-OH-C) or 7 alpha-hydroxy-4-cholesten-3-one (7αC4) is a distinctive feature of CTX. Both 7α-OH-C and 7αC4 have been suggested as ideal biomarkers for evaluating treatment effects. With respect to auxiliary examinations, 56.57% of patients showed EEG abnormalities including diffuse slowing, which is a common feature of CTX patients. In addition, 76.72% had abnormal magnetic resonance (MR) images ( Supplementary Table 1 ). The main brain MRI abnormalities include supratentorial and infratentorial atrophy, as well as T2W/FLAIR (fluid-attenuated inversion recovery) hyperintensity involving the subcortical, periventricular and cerebellar WM and the brainstem. Bilateral hyperintensity of the dentate nuclei (DN) and surrounding WM on T2 and FLAIR sequences is considered a representative radiological feature of CTX. DN plays a critical role in saccade motor planning within a network that involves the frontal cortex and basal ganglia. Patients with DN lesions showed abnormal latency of reflexive and voluntary saccades, impaired precision and more uncorrected directional errors. There is a strong correlation between DN hyperintensity in brain MRI and neurological manifestations including ataxia, spasticity and cognitive impairment. Patients without DN hyperintensity are considered to have a better prognosis. A 6-year MR follow-up study revealed that cerebellar hyperintensity in T1-weighted and FLAIR images tend to be replaced by hypointense areas, suggesting vacuolation. Cerebellar hyperintensity on FLAIR images is probably due to lipid deposits, while hypointense areas may indicate cerebellar degeneration because of cholestanol-induced apoptosis or other mechanisms causing axonal injury. Cerebellar vacuolation and calcification have been observed in a large number of patients. The former was positively related to the extent of DN hyperintensity in T1W and FLAIR images, and could be a useful indicator of disease progression and inadequate therapeutic response. Additionally, cerebral micro- and macro-angiopathies such as micro-hemorrhages, vascular dilatation and calcification are common in CTX patients. The xanthomas located within the ventricular region have also been observed in CTX cases. The main components of xanthoma are connective tissue and foam cells (foamy macrophages) bathed in cholestanol, cholesterol, cholesterol esters, triglycerides and phospholipids. The presence of Touton giant cells is a characteristic pathological finding. The development of tendon xanthomas may be associated with low-grade tendon inflammation. A tendon MRI study indicated that the enlargement of tendon xanthomas is primarily due to an increase in tendon water content, rather than in fat content. Tendinous xanthomas have different appearances on MR depending on the proportions of the following components: cholesterol, which does not produce a measurable signal; triglycerides, which produce a high signal on T1-weighted images; and associated inflammation, which causes high signal intensity regions in contrast-enhanced T1-weighted images. The diffuse reticulated pattern of xanthomas on axial images is a representative MRI feature of tendinous xanthoma. This patient’s MRI showed enlargement of the Achilles tendon, which showed up as low signal intensity on both T1- and T2-weighted images. This fits well with previous reports and could be attributed to the low percentage of triglycerides. In conclusion, we described a 47-year-old patient displaying psychiatric and behavioral disturbances, cognitive decline, a history of renal calculus, bilateral xanthomas of the Achilles tendon and tibial tubercles, peripheral neuropathy, high signal intensity in the WM and mild cerebral atrophy on brain MRI. The diagnosis was confirmed by compound heterozygous mutations in exon 2 (c.435G>T, p.Gly145Gly) and intron 7 (c.1263+1G>A) of the CYP27A1 gene. These lead to alternative pre-mRNA splicing and a skipping of exon 7 in the transcript, respectively. Three weeks′ treatment with a combination of lipid-lowering and antipsychotic therapy improved his psychiatric symptoms and normalized levels of serum free fatty acid. Sediments in the bladder disappeared after therapy.', 'Imaging examinations': 'X-ray of the lower limbs showed soft tissue swelling above the tibial tuberosities bilaterally (Figure 2E ). Sagittal and axial magnetic resonance imaging (MRI) of the right ankle joint showed apparent enlargement of the right Achilles tendon and upper medial malleolus flexor tendon (consisting of low signal intensity on both T1- and T2-weighted images), abnormal thickening of the plantar fat, and a small amount of exudation around the fascia in front of the Achilles tendon (Figure 2F ). The electroencephalogram (EEG) showed increased slow activities than normal and electrophysiological examination found mixed sensorimotor neuropathy of the upper and lower limbs. Cerebral MRI suggested white matter (WM) demyelination and slight cerebral atrophy (Figure 2G and H ).', 'Laboratory examinations': 'The laboratory results (Table 1 ) were as follows: Increased leukocyte count, neutrophil ratio and high erythrocyte sedimentation rate. There was also a significant increase in concentration of free fatty acid compared to normal range. In contrast, levels of high-density lipoprotein cholesterol were low. Serum cholesterol, glucose, electrolytes, and adrenocorticotropic hormone (ACTH) levels were all normal, as were the liver function tests. Doppler ultrasound of the urinary system showed multiple left kidney stones, a right kidney cyst, and a hypoechoic area in the bladder which could move with body position (Figure 2D ). Cerebrospinal fluid protein was mildly elevated: 680.4 mg/L (normal range: 150-400 mg/L).', 'Genetic testing': 'Genomic DNA was isolated from blood samples of the patient and his four healthy sisters. Mutation screening of all exons and flanking regions was performed on the patient’s sample by targeted sequencing as previously reported. Targeted sequencing revealed that the proband had compound heterozygous mutations in the CYP27A1 gene and that his four sisters were mutation carriers (Figure 1B - E, and Table 2 ). Both of the variants found are known pathogenic mutations of CTX. The variant in exon 2 (c.435G>T, p.Gly145Gly), a functionally silent nucleotide substitution, has been reported to activate a 5’ splice site, leading to alternative pre-mRNA splicing. The other variant (c.1263+1G>A) is a splice site mutation that disrupts normal mRNA splicing and results in exon 7 being skipped in the transcript. In Italian and Japanese patients, the variant has been found to cause loss of a heme binding domain, a vital part of hydroxylase, and to damage bile acid synthesis.', 'History of present illness': 'Three months ago, he underwent an operation for renal calculus, after which he showed progressive delusion (he believed unreasonably that he had a serious disease and was going to die), combined with slow response and speech reduction. At 1 wk before admission, he was unable to answer questions and developed an eating difficulty, incontinence, fever (T ≤ 38.2 °C) and severe weight loss. Chronic diarrhea was absent.'}
|
{'Chief complaints': 'A 47-year-old male was admitted to our institution with a history of intellectual disability for more than 30 years and behavioral abnormalities for the past 3 mo. He had a poor academic performance, having dropped out after completing elementary school. The patient could talk with others in daily life, but he was unable to do housework.', 'Personal and family history': 'The proband is the 4 th child of 5 in a non-consanguineous Chinese family. His family history was negative for symptoms related to neurological disorders. He was divorced twice and had no children, and did not have a history of smoking or drinking. The proband’s parents had died and his mother had a history of uremia. All of his four sisters are healthy (Figure 1A ).', 'CASE SUMMARY': 'A Chinese family with CTX consisting of one patient and four heterozygous carriers was studied. The patient is a 47-year-old male, who mainly had psychiatric signs but without some cardinal features of CTX such as cataracts, cerebellar ataxia, pyramidal signs and chronic diarrhea. There was a significant increase in the concentration of free fatty acid compared to normal range. Doppler ultrasound of the urinary system showed multiple left kidney stones, a right kidney cyst, and a hypoechoic area in the bladder, which could move with body position. Sagittal and axial magnetic resonance imaging (MRI) of the right ankle joint showed apparent enlargement of the right Achilles tendon and upper medial malleolus flexor tendon, abnormal thickening of the plantar fat, and a small amount of exudation around the fascia in front of the Achilles tendon. Cerebral MRI suggested white matter (WM) demyelination and slight cerebral atrophy. The diagnosis was confirmed by targeted sequencing, which identified compound heterozygous mutations in exon 2 and intron 7 of the CYP27A1 gene (c.435G>T, c.1263+1G>A). Treatment for 3 wk with a combination of lipid-lowering and antipsychotic therapy improved his psychiatric symptoms and normalized the levels of serum free fatty acid. Sediments in the bladder disappeared after therapy.', 'Physical examination': 'The patient had dark skin and a poor mental state (Figure 2A ). Neurological examination indicated cervical rigidity and Kernig sign. Deep tendon reflexes and limb muscle strength were normal. Babinski sign was negative. Enlarged Achilles tendons and nodules on the bilateral tibial tubercles were observed (Figure 2B and C ). There was no evidence of cataract or xanthomas at other sites such as the eyelids.', 'Biological and imaging features': 'The biochemical abnormalities detected in CTX are significant for diagnosis. The lack of sterol 27-hydroxylase inhibits the conversion of cholesterol into cholic and chenodeoxycholic acids in the liver. The serum levels of cholesterol and triglyceride are usually normal while cholestanol levels are markedly high in the blood, bile and tendon xanthoma. Since cholesterol synthesis is systematically decreased, cholesterol precursors increase substantially; this could also be regarded as a hallmark of CTX. Although a high cholestanol level indicates CTX, it does not correlate with any symptoms or disability at diagnosis assessed by the Expanded Disability Status Scale. Fast atom bombardment mass spectrometry is a semiquantitative technique which can be applied to analyze urinary bile acids. It will strongly support a diagnosis of CTX if increased bile alcohol glucuronides and reduced primary bile acid are detected. However, when the urinary bile acid profile is consistent with CTX, propofol administration should be taken into account as another possible cause, to avoid misdiagnoses. The combination of extremely low levels of 27-hydroxycholesterol (< 5 ng/mL or lower than the detection limit) and extremely high serum levels of 7 alpha-hydroxycholesterol (7α-OH-C) or 7 alpha-hydroxy-4-cholesten-3-one (7αC4) is a distinctive feature of CTX. Both 7α-OH-C and 7αC4 have been suggested as ideal biomarkers for evaluating treatment effects. With respect to auxiliary examinations, 56.57% of patients showed EEG abnormalities including diffuse slowing, which is a common feature of CTX patients. In addition, 76.72% had abnormal magnetic resonance (MR) images ( Supplementary Table 1 ). The main brain MRI abnormalities include supratentorial and infratentorial atrophy, as well as T2W/FLAIR (fluid-attenuated inversion recovery) hyperintensity involving the subcortical, periventricular and cerebellar WM and the brainstem. Bilateral hyperintensity of the dentate nuclei (DN) and surrounding WM on T2 and FLAIR sequences is considered a representative radiological feature of CTX. DN plays a critical role in saccade motor planning within a network that involves the frontal cortex and basal ganglia. Patients with DN lesions showed abnormal latency of reflexive and voluntary saccades, impaired precision and more uncorrected directional errors. There is a strong correlation between DN hyperintensity in brain MRI and neurological manifestations including ataxia, spasticity and cognitive impairment. Patients without DN hyperintensity are considered to have a better prognosis. A 6-year MR follow-up study revealed that cerebellar hyperintensity in T1-weighted and FLAIR images tend to be replaced by hypointense areas, suggesting vacuolation. Cerebellar hyperintensity on FLAIR images is probably due to lipid deposits, while hypointense areas may indicate cerebellar degeneration because of cholestanol-induced apoptosis or other mechanisms causing axonal injury. Cerebellar vacuolation and calcification have been observed in a large number of patients. The former was positively related to the extent of DN hyperintensity in T1W and FLAIR images, and could be a useful indicator of disease progression and inadequate therapeutic response. Additionally, cerebral micro- and macro-angiopathies such as micro-hemorrhages, vascular dilatation and calcification are common in CTX patients. The xanthomas located within the ventricular region have also been observed in CTX cases. The main components of xanthoma are connective tissue and foam cells (foamy macrophages) bathed in cholestanol, cholesterol, cholesterol esters, triglycerides and phospholipids. The presence of Touton giant cells is a characteristic pathological finding. The development of tendon xanthomas may be associated with low-grade tendon inflammation. A tendon MRI study indicated that the enlargement of tendon xanthomas is primarily due to an increase in tendon water content, rather than in fat content. Tendinous xanthomas have different appearances on MR depending on the proportions of the following components: cholesterol, which does not produce a measurable signal; triglycerides, which produce a high signal on T1-weighted images; and associated inflammation, which causes high signal intensity regions in contrast-enhanced T1-weighted images. The diffuse reticulated pattern of xanthomas on axial images is a representative MRI feature of tendinous xanthoma. This patient’s MRI showed enlargement of the Achilles tendon, which showed up as low signal intensity on both T1- and T2-weighted images. This fits well with previous reports and could be attributed to the low percentage of triglycerides. In conclusion, we described a 47-year-old patient displaying psychiatric and behavioral disturbances, cognitive decline, a history of renal calculus, bilateral xanthomas of the Achilles tendon and tibial tubercles, peripheral neuropathy, high signal intensity in the WM and mild cerebral atrophy on brain MRI. The diagnosis was confirmed by compound heterozygous mutations in exon 2 (c.435G>T, p.Gly145Gly) and intron 7 (c.1263+1G>A) of the CYP27A1 gene. These lead to alternative pre-mRNA splicing and a skipping of exon 7 in the transcript, respectively. Three weeks′ treatment with a combination of lipid-lowering and antipsychotic therapy improved his psychiatric symptoms and normalized levels of serum free fatty acid. Sediments in the bladder disappeared after therapy.', 'Imaging examinations': 'X-ray of the lower limbs showed soft tissue swelling above the tibial tuberosities bilaterally (Figure 2E ). Sagittal and axial magnetic resonance imaging (MRI) of the right ankle joint showed apparent enlargement of the right Achilles tendon and upper medial malleolus flexor tendon (consisting of low signal intensity on both T1- and T2-weighted images), abnormal thickening of the plantar fat, and a small amount of exudation around the fascia in front of the Achilles tendon (Figure 2F ). The electroencephalogram (EEG) showed increased slow activities than normal and electrophysiological examination found mixed sensorimotor neuropathy of the upper and lower limbs. Cerebral MRI suggested white matter (WM) demyelination and slight cerebral atrophy (Figure 2G and H ).', 'Laboratory examinations': 'The laboratory results (Table 1 ) were as follows: Increased leukocyte count, neutrophil ratio and high erythrocyte sedimentation rate. There was also a significant increase in concentration of free fatty acid compared to normal range. In contrast, levels of high-density lipoprotein cholesterol were low. Serum cholesterol, glucose, electrolytes, and adrenocorticotropic hormone (ACTH) levels were all normal, as were the liver function tests. Doppler ultrasound of the urinary system showed multiple left kidney stones, a right kidney cyst, and a hypoechoic area in the bladder which could move with body position (Figure 2D ). Cerebrospinal fluid protein was mildly elevated: 680.4 mg/L (normal range: 150-400 mg/L).', 'Genetic testing': 'Genomic DNA was isolated from blood samples of the patient and his four healthy sisters. Mutation screening of all exons and flanking regions was performed on the patient’s sample by targeted sequencing as previously reported. Targeted sequencing revealed that the proband had compound heterozygous mutations in the CYP27A1 gene and that his four sisters were mutation carriers (Figure 1B - E, and Table 2 ). Both of the variants found are known pathogenic mutations of CTX. The variant in exon 2 (c.435G>T, p.Gly145Gly), a functionally silent nucleotide substitution, has been reported to activate a 5’ splice site, leading to alternative pre-mRNA splicing. The other variant (c.1263+1G>A) is a splice site mutation that disrupts normal mRNA splicing and results in exon 7 being skipped in the transcript. In Italian and Japanese patients, the variant has been found to cause loss of a heme binding domain, a vital part of hydroxylase, and to damage bile acid synthesis.', 'History of present illness': 'Three months ago, he underwent an operation for renal calculus, after which he showed progressive delusion (he believed unreasonably that he had a serious disease and was going to die), combined with slow response and speech reduction. At 1 wk before admission, he was unable to answer questions and developed an eating difficulty, incontinence, fever (T ≤ 38.2 °C) and severe weight loss. Chronic diarrhea was absent.'}
|
Lymphatic-System
|
LYMPH
|
[] |
test-2103
|
7674721
|
{'Chief complaints': 'A 47-year-old male was admitted to our institution with a history of intellectual disability for more than 30 years and behavioral abnormalities for the past 3 mo. He had a poor academic performance, having dropped out after completing elementary school. The patient could talk with others in daily life, but he was unable to do housework.', 'Personal and family history': 'The proband is the 4 th child of 5 in a non-consanguineous Chinese family. His family history was negative for symptoms related to neurological disorders. He was divorced twice and had no children, and did not have a history of smoking or drinking. The proband’s parents had died and his mother had a history of uremia. All of his four sisters are healthy (Figure 1A ).', 'CASE SUMMARY': 'A Chinese family with CTX consisting of one patient and four heterozygous carriers was studied. The patient is a 47-year-old male, who mainly had psychiatric signs but without some cardinal features of CTX such as cataracts, cerebellar ataxia, pyramidal signs and chronic diarrhea. There was a significant increase in the concentration of free fatty acid compared to normal range. Doppler ultrasound of the urinary system showed multiple left kidney stones, a right kidney cyst, and a hypoechoic area in the bladder, which could move with body position. Sagittal and axial magnetic resonance imaging (MRI) of the right ankle joint showed apparent enlargement of the right Achilles tendon and upper medial malleolus flexor tendon, abnormal thickening of the plantar fat, and a small amount of exudation around the fascia in front of the Achilles tendon. Cerebral MRI suggested white matter (WM) demyelination and slight cerebral atrophy. The diagnosis was confirmed by targeted sequencing, which identified compound heterozygous mutations in exon 2 and intron 7 of the CYP27A1 gene (c.435G>T, c.1263+1G>A). Treatment for 3 wk with a combination of lipid-lowering and antipsychotic therapy improved his psychiatric symptoms and normalized the levels of serum free fatty acid. Sediments in the bladder disappeared after therapy.', 'Physical examination': 'The patient had dark skin and a poor mental state (Figure 2A ). Neurological examination indicated cervical rigidity and Kernig sign. Deep tendon reflexes and limb muscle strength were normal. Babinski sign was negative. Enlarged Achilles tendons and nodules on the bilateral tibial tubercles were observed (Figure 2B and C ). There was no evidence of cataract or xanthomas at other sites such as the eyelids.', 'Biological and imaging features': 'The biochemical abnormalities detected in CTX are significant for diagnosis. The lack of sterol 27-hydroxylase inhibits the conversion of cholesterol into cholic and chenodeoxycholic acids in the liver. The serum levels of cholesterol and triglyceride are usually normal while cholestanol levels are markedly high in the blood, bile and tendon xanthoma. Since cholesterol synthesis is systematically decreased, cholesterol precursors increase substantially; this could also be regarded as a hallmark of CTX. Although a high cholestanol level indicates CTX, it does not correlate with any symptoms or disability at diagnosis assessed by the Expanded Disability Status Scale. Fast atom bombardment mass spectrometry is a semiquantitative technique which can be applied to analyze urinary bile acids. It will strongly support a diagnosis of CTX if increased bile alcohol glucuronides and reduced primary bile acid are detected. However, when the urinary bile acid profile is consistent with CTX, propofol administration should be taken into account as another possible cause, to avoid misdiagnoses. The combination of extremely low levels of 27-hydroxycholesterol (< 5 ng/mL or lower than the detection limit) and extremely high serum levels of 7 alpha-hydroxycholesterol (7α-OH-C) or 7 alpha-hydroxy-4-cholesten-3-one (7αC4) is a distinctive feature of CTX. Both 7α-OH-C and 7αC4 have been suggested as ideal biomarkers for evaluating treatment effects. With respect to auxiliary examinations, 56.57% of patients showed EEG abnormalities including diffuse slowing, which is a common feature of CTX patients. In addition, 76.72% had abnormal magnetic resonance (MR) images ( Supplementary Table 1 ). The main brain MRI abnormalities include supratentorial and infratentorial atrophy, as well as T2W/FLAIR (fluid-attenuated inversion recovery) hyperintensity involving the subcortical, periventricular and cerebellar WM and the brainstem. Bilateral hyperintensity of the dentate nuclei (DN) and surrounding WM on T2 and FLAIR sequences is considered a representative radiological feature of CTX. DN plays a critical role in saccade motor planning within a network that involves the frontal cortex and basal ganglia. Patients with DN lesions showed abnormal latency of reflexive and voluntary saccades, impaired precision and more uncorrected directional errors. There is a strong correlation between DN hyperintensity in brain MRI and neurological manifestations including ataxia, spasticity and cognitive impairment. Patients without DN hyperintensity are considered to have a better prognosis. A 6-year MR follow-up study revealed that cerebellar hyperintensity in T1-weighted and FLAIR images tend to be replaced by hypointense areas, suggesting vacuolation. Cerebellar hyperintensity on FLAIR images is probably due to lipid deposits, while hypointense areas may indicate cerebellar degeneration because of cholestanol-induced apoptosis or other mechanisms causing axonal injury. Cerebellar vacuolation and calcification have been observed in a large number of patients. The former was positively related to the extent of DN hyperintensity in T1W and FLAIR images, and could be a useful indicator of disease progression and inadequate therapeutic response. Additionally, cerebral micro- and macro-angiopathies such as micro-hemorrhages, vascular dilatation and calcification are common in CTX patients. The xanthomas located within the ventricular region have also been observed in CTX cases. The main components of xanthoma are connective tissue and foam cells (foamy macrophages) bathed in cholestanol, cholesterol, cholesterol esters, triglycerides and phospholipids. The presence of Touton giant cells is a characteristic pathological finding. The development of tendon xanthomas may be associated with low-grade tendon inflammation. A tendon MRI study indicated that the enlargement of tendon xanthomas is primarily due to an increase in tendon water content, rather than in fat content. Tendinous xanthomas have different appearances on MR depending on the proportions of the following components: cholesterol, which does not produce a measurable signal; triglycerides, which produce a high signal on T1-weighted images; and associated inflammation, which causes high signal intensity regions in contrast-enhanced T1-weighted images. The diffuse reticulated pattern of xanthomas on axial images is a representative MRI feature of tendinous xanthoma. This patient’s MRI showed enlargement of the Achilles tendon, which showed up as low signal intensity on both T1- and T2-weighted images. This fits well with previous reports and could be attributed to the low percentage of triglycerides. In conclusion, we described a 47-year-old patient displaying psychiatric and behavioral disturbances, cognitive decline, a history of renal calculus, bilateral xanthomas of the Achilles tendon and tibial tubercles, peripheral neuropathy, high signal intensity in the WM and mild cerebral atrophy on brain MRI. The diagnosis was confirmed by compound heterozygous mutations in exon 2 (c.435G>T, p.Gly145Gly) and intron 7 (c.1263+1G>A) of the CYP27A1 gene. These lead to alternative pre-mRNA splicing and a skipping of exon 7 in the transcript, respectively. Three weeks′ treatment with a combination of lipid-lowering and antipsychotic therapy improved his psychiatric symptoms and normalized levels of serum free fatty acid. Sediments in the bladder disappeared after therapy.', 'Imaging examinations': 'X-ray of the lower limbs showed soft tissue swelling above the tibial tuberosities bilaterally (Figure 2E ). Sagittal and axial magnetic resonance imaging (MRI) of the right ankle joint showed apparent enlargement of the right Achilles tendon and upper medial malleolus flexor tendon (consisting of low signal intensity on both T1- and T2-weighted images), abnormal thickening of the plantar fat, and a small amount of exudation around the fascia in front of the Achilles tendon (Figure 2F ). The electroencephalogram (EEG) showed increased slow activities than normal and electrophysiological examination found mixed sensorimotor neuropathy of the upper and lower limbs. Cerebral MRI suggested white matter (WM) demyelination and slight cerebral atrophy (Figure 2G and H ).', 'Laboratory examinations': 'The laboratory results (Table 1 ) were as follows: Increased leukocyte count, neutrophil ratio and high erythrocyte sedimentation rate. There was also a significant increase in concentration of free fatty acid compared to normal range. In contrast, levels of high-density lipoprotein cholesterol were low. Serum cholesterol, glucose, electrolytes, and adrenocorticotropic hormone (ACTH) levels were all normal, as were the liver function tests. Doppler ultrasound of the urinary system showed multiple left kidney stones, a right kidney cyst, and a hypoechoic area in the bladder which could move with body position (Figure 2D ). Cerebrospinal fluid protein was mildly elevated: 680.4 mg/L (normal range: 150-400 mg/L).', 'Genetic testing': 'Genomic DNA was isolated from blood samples of the patient and his four healthy sisters. Mutation screening of all exons and flanking regions was performed on the patient’s sample by targeted sequencing as previously reported. Targeted sequencing revealed that the proband had compound heterozygous mutations in the CYP27A1 gene and that his four sisters were mutation carriers (Figure 1B - E, and Table 2 ). Both of the variants found are known pathogenic mutations of CTX. The variant in exon 2 (c.435G>T, p.Gly145Gly), a functionally silent nucleotide substitution, has been reported to activate a 5’ splice site, leading to alternative pre-mRNA splicing. The other variant (c.1263+1G>A) is a splice site mutation that disrupts normal mRNA splicing and results in exon 7 being skipped in the transcript. In Italian and Japanese patients, the variant has been found to cause loss of a heme binding domain, a vital part of hydroxylase, and to damage bile acid synthesis.', 'History of present illness': 'Three months ago, he underwent an operation for renal calculus, after which he showed progressive delusion (he believed unreasonably that he had a serious disease and was going to die), combined with slow response and speech reduction. At 1 wk before admission, he was unable to answer questions and developed an eating difficulty, incontinence, fever (T ≤ 38.2 °C) and severe weight loss. Chronic diarrhea was absent.'}
|
{'Chief complaints': 'A 47-year-old male was admitted to our institution with a history of intellectual disability for more than 30 years and behavioral abnormalities for the past 3 mo. He had a poor academic performance, having dropped out after completing elementary school. The patient could talk with others in daily life, but he was unable to do housework.', 'Personal and family history': 'The proband is the 4 th child of 5 in a non-consanguineous Chinese family. His family history was negative for symptoms related to neurological disorders. He was divorced twice and had no children, and did not have a history of smoking or drinking. The proband’s parents had died and his mother had a history of uremia. All of his four sisters are healthy (Figure 1A ).', 'CASE SUMMARY': 'A Chinese family with CTX consisting of one patient and four heterozygous carriers was studied. The patient is a 47-year-old male, who mainly had psychiatric signs but without some cardinal features of CTX such as cataracts, cerebellar ataxia, pyramidal signs and chronic diarrhea. There was a significant increase in the concentration of free fatty acid compared to normal range. Doppler ultrasound of the urinary system showed multiple left kidney stones, a right kidney cyst, and a hypoechoic area in the bladder, which could move with body position. Sagittal and axial magnetic resonance imaging (MRI) of the right ankle joint showed apparent enlargement of the right Achilles tendon and upper medial malleolus flexor tendon, abnormal thickening of the plantar fat, and a small amount of exudation around the fascia in front of the Achilles tendon. Cerebral MRI suggested white matter (WM) demyelination and slight cerebral atrophy. The diagnosis was confirmed by targeted sequencing, which identified compound heterozygous mutations in exon 2 and intron 7 of the CYP27A1 gene (c.435G>T, c.1263+1G>A). Treatment for 3 wk with a combination of lipid-lowering and antipsychotic therapy improved his psychiatric symptoms and normalized the levels of serum free fatty acid. Sediments in the bladder disappeared after therapy.', 'Physical examination': 'The patient had dark skin and a poor mental state (Figure 2A ). Neurological examination indicated cervical rigidity and Kernig sign. Deep tendon reflexes and limb muscle strength were normal. Babinski sign was negative. Enlarged Achilles tendons and nodules on the bilateral tibial tubercles were observed (Figure 2B and C ). There was no evidence of cataract or xanthomas at other sites such as the eyelids.', 'Biological and imaging features': 'The biochemical abnormalities detected in CTX are significant for diagnosis. The lack of sterol 27-hydroxylase inhibits the conversion of cholesterol into cholic and chenodeoxycholic acids in the liver. The serum levels of cholesterol and triglyceride are usually normal while cholestanol levels are markedly high in the blood, bile and tendon xanthoma. Since cholesterol synthesis is systematically decreased, cholesterol precursors increase substantially; this could also be regarded as a hallmark of CTX. Although a high cholestanol level indicates CTX, it does not correlate with any symptoms or disability at diagnosis assessed by the Expanded Disability Status Scale. Fast atom bombardment mass spectrometry is a semiquantitative technique which can be applied to analyze urinary bile acids. It will strongly support a diagnosis of CTX if increased bile alcohol glucuronides and reduced primary bile acid are detected. However, when the urinary bile acid profile is consistent with CTX, propofol administration should be taken into account as another possible cause, to avoid misdiagnoses. The combination of extremely low levels of 27-hydroxycholesterol (< 5 ng/mL or lower than the detection limit) and extremely high serum levels of 7 alpha-hydroxycholesterol (7α-OH-C) or 7 alpha-hydroxy-4-cholesten-3-one (7αC4) is a distinctive feature of CTX. Both 7α-OH-C and 7αC4 have been suggested as ideal biomarkers for evaluating treatment effects. With respect to auxiliary examinations, 56.57% of patients showed EEG abnormalities including diffuse slowing, which is a common feature of CTX patients. In addition, 76.72% had abnormal magnetic resonance (MR) images ( Supplementary Table 1 ). The main brain MRI abnormalities include supratentorial and infratentorial atrophy, as well as T2W/FLAIR (fluid-attenuated inversion recovery) hyperintensity involving the subcortical, periventricular and cerebellar WM and the brainstem. Bilateral hyperintensity of the dentate nuclei (DN) and surrounding WM on T2 and FLAIR sequences is considered a representative radiological feature of CTX. DN plays a critical role in saccade motor planning within a network that involves the frontal cortex and basal ganglia. Patients with DN lesions showed abnormal latency of reflexive and voluntary saccades, impaired precision and more uncorrected directional errors. There is a strong correlation between DN hyperintensity in brain MRI and neurological manifestations including ataxia, spasticity and cognitive impairment. Patients without DN hyperintensity are considered to have a better prognosis. A 6-year MR follow-up study revealed that cerebellar hyperintensity in T1-weighted and FLAIR images tend to be replaced by hypointense areas, suggesting vacuolation. Cerebellar hyperintensity on FLAIR images is probably due to lipid deposits, while hypointense areas may indicate cerebellar degeneration because of cholestanol-induced apoptosis or other mechanisms causing axonal injury. Cerebellar vacuolation and calcification have been observed in a large number of patients. The former was positively related to the extent of DN hyperintensity in T1W and FLAIR images, and could be a useful indicator of disease progression and inadequate therapeutic response. Additionally, cerebral micro- and macro-angiopathies such as micro-hemorrhages, vascular dilatation and calcification are common in CTX patients. The xanthomas located within the ventricular region have also been observed in CTX cases. The main components of xanthoma are connective tissue and foam cells (foamy macrophages) bathed in cholestanol, cholesterol, cholesterol esters, triglycerides and phospholipids. The presence of Touton giant cells is a characteristic pathological finding. The development of tendon xanthomas may be associated with low-grade tendon inflammation. A tendon MRI study indicated that the enlargement of tendon xanthomas is primarily due to an increase in tendon water content, rather than in fat content. Tendinous xanthomas have different appearances on MR depending on the proportions of the following components: cholesterol, which does not produce a measurable signal; triglycerides, which produce a high signal on T1-weighted images; and associated inflammation, which causes high signal intensity regions in contrast-enhanced T1-weighted images. The diffuse reticulated pattern of xanthomas on axial images is a representative MRI feature of tendinous xanthoma. This patient’s MRI showed enlargement of the Achilles tendon, which showed up as low signal intensity on both T1- and T2-weighted images. This fits well with previous reports and could be attributed to the low percentage of triglycerides. In conclusion, we described a 47-year-old patient displaying psychiatric and behavioral disturbances, cognitive decline, a history of renal calculus, bilateral xanthomas of the Achilles tendon and tibial tubercles, peripheral neuropathy, high signal intensity in the WM and mild cerebral atrophy on brain MRI. The diagnosis was confirmed by compound heterozygous mutations in exon 2 (c.435G>T, p.Gly145Gly) and intron 7 (c.1263+1G>A) of the CYP27A1 gene. These lead to alternative pre-mRNA splicing and a skipping of exon 7 in the transcript, respectively. Three weeks′ treatment with a combination of lipid-lowering and antipsychotic therapy improved his psychiatric symptoms and normalized levels of serum free fatty acid. Sediments in the bladder disappeared after therapy.', 'Imaging examinations': 'X-ray of the lower limbs showed soft tissue swelling above the tibial tuberosities bilaterally (Figure 2E ). Sagittal and axial magnetic resonance imaging (MRI) of the right ankle joint showed apparent enlargement of the right Achilles tendon and upper medial malleolus flexor tendon (consisting of low signal intensity on both T1- and T2-weighted images), abnormal thickening of the plantar fat, and a small amount of exudation around the fascia in front of the Achilles tendon (Figure 2F ). The electroencephalogram (EEG) showed increased slow activities than normal and electrophysiological examination found mixed sensorimotor neuropathy of the upper and lower limbs. Cerebral MRI suggested white matter (WM) demyelination and slight cerebral atrophy (Figure 2G and H ).', 'Laboratory examinations': 'The laboratory results (Table 1 ) were as follows: Increased leukocyte count, neutrophil ratio and high erythrocyte sedimentation rate. There was also a significant increase in concentration of free fatty acid compared to normal range. In contrast, levels of high-density lipoprotein cholesterol were low. Serum cholesterol, glucose, electrolytes, and adrenocorticotropic hormone (ACTH) levels were all normal, as were the liver function tests. Doppler ultrasound of the urinary system showed multiple left kidney stones, a right kidney cyst, and a hypoechoic area in the bladder which could move with body position (Figure 2D ). Cerebrospinal fluid protein was mildly elevated: 680.4 mg/L (normal range: 150-400 mg/L).', 'Genetic testing': 'Genomic DNA was isolated from blood samples of the patient and his four healthy sisters. Mutation screening of all exons and flanking regions was performed on the patient’s sample by targeted sequencing as previously reported. Targeted sequencing revealed that the proband had compound heterozygous mutations in the CYP27A1 gene and that his four sisters were mutation carriers (Figure 1B - E, and Table 2 ). Both of the variants found are known pathogenic mutations of CTX. The variant in exon 2 (c.435G>T, p.Gly145Gly), a functionally silent nucleotide substitution, has been reported to activate a 5’ splice site, leading to alternative pre-mRNA splicing. The other variant (c.1263+1G>A) is a splice site mutation that disrupts normal mRNA splicing and results in exon 7 being skipped in the transcript. In Italian and Japanese patients, the variant has been found to cause loss of a heme binding domain, a vital part of hydroxylase, and to damage bile acid synthesis.', 'History of present illness': 'Three months ago, he underwent an operation for renal calculus, after which he showed progressive delusion (he believed unreasonably that he had a serious disease and was going to die), combined with slow response and speech reduction. At 1 wk before admission, he was unable to answer questions and developed an eating difficulty, incontinence, fever (T ≤ 38.2 °C) and severe weight loss. Chronic diarrhea was absent.'}
|
Age-at-Presentation
|
Age (at case presentation)
|
[
"47 - year - old",
"47 - year - old"
] |
test-2104
|
7674721
|
{'Chief complaints': 'A 47-year-old male was admitted to our institution with a history of intellectual disability for more than 30 years and behavioral abnormalities for the past 3 mo. He had a poor academic performance, having dropped out after completing elementary school. The patient could talk with others in daily life, but he was unable to do housework.', 'Personal and family history': 'The proband is the 4 th child of 5 in a non-consanguineous Chinese family. His family history was negative for symptoms related to neurological disorders. He was divorced twice and had no children, and did not have a history of smoking or drinking. The proband’s parents had died and his mother had a history of uremia. All of his four sisters are healthy (Figure 1A ).', 'CASE SUMMARY': 'A Chinese family with CTX consisting of one patient and four heterozygous carriers was studied. The patient is a 47-year-old male, who mainly had psychiatric signs but without some cardinal features of CTX such as cataracts, cerebellar ataxia, pyramidal signs and chronic diarrhea. There was a significant increase in the concentration of free fatty acid compared to normal range. Doppler ultrasound of the urinary system showed multiple left kidney stones, a right kidney cyst, and a hypoechoic area in the bladder, which could move with body position. Sagittal and axial magnetic resonance imaging (MRI) of the right ankle joint showed apparent enlargement of the right Achilles tendon and upper medial malleolus flexor tendon, abnormal thickening of the plantar fat, and a small amount of exudation around the fascia in front of the Achilles tendon. Cerebral MRI suggested white matter (WM) demyelination and slight cerebral atrophy. The diagnosis was confirmed by targeted sequencing, which identified compound heterozygous mutations in exon 2 and intron 7 of the CYP27A1 gene (c.435G>T, c.1263+1G>A). Treatment for 3 wk with a combination of lipid-lowering and antipsychotic therapy improved his psychiatric symptoms and normalized the levels of serum free fatty acid. Sediments in the bladder disappeared after therapy.', 'Physical examination': 'The patient had dark skin and a poor mental state (Figure 2A ). Neurological examination indicated cervical rigidity and Kernig sign. Deep tendon reflexes and limb muscle strength were normal. Babinski sign was negative. Enlarged Achilles tendons and nodules on the bilateral tibial tubercles were observed (Figure 2B and C ). There was no evidence of cataract or xanthomas at other sites such as the eyelids.', 'Biological and imaging features': 'The biochemical abnormalities detected in CTX are significant for diagnosis. The lack of sterol 27-hydroxylase inhibits the conversion of cholesterol into cholic and chenodeoxycholic acids in the liver. The serum levels of cholesterol and triglyceride are usually normal while cholestanol levels are markedly high in the blood, bile and tendon xanthoma. Since cholesterol synthesis is systematically decreased, cholesterol precursors increase substantially; this could also be regarded as a hallmark of CTX. Although a high cholestanol level indicates CTX, it does not correlate with any symptoms or disability at diagnosis assessed by the Expanded Disability Status Scale. Fast atom bombardment mass spectrometry is a semiquantitative technique which can be applied to analyze urinary bile acids. It will strongly support a diagnosis of CTX if increased bile alcohol glucuronides and reduced primary bile acid are detected. However, when the urinary bile acid profile is consistent with CTX, propofol administration should be taken into account as another possible cause, to avoid misdiagnoses. The combination of extremely low levels of 27-hydroxycholesterol (< 5 ng/mL or lower than the detection limit) and extremely high serum levels of 7 alpha-hydroxycholesterol (7α-OH-C) or 7 alpha-hydroxy-4-cholesten-3-one (7αC4) is a distinctive feature of CTX. Both 7α-OH-C and 7αC4 have been suggested as ideal biomarkers for evaluating treatment effects. With respect to auxiliary examinations, 56.57% of patients showed EEG abnormalities including diffuse slowing, which is a common feature of CTX patients. In addition, 76.72% had abnormal magnetic resonance (MR) images ( Supplementary Table 1 ). The main brain MRI abnormalities include supratentorial and infratentorial atrophy, as well as T2W/FLAIR (fluid-attenuated inversion recovery) hyperintensity involving the subcortical, periventricular and cerebellar WM and the brainstem. Bilateral hyperintensity of the dentate nuclei (DN) and surrounding WM on T2 and FLAIR sequences is considered a representative radiological feature of CTX. DN plays a critical role in saccade motor planning within a network that involves the frontal cortex and basal ganglia. Patients with DN lesions showed abnormal latency of reflexive and voluntary saccades, impaired precision and more uncorrected directional errors. There is a strong correlation between DN hyperintensity in brain MRI and neurological manifestations including ataxia, spasticity and cognitive impairment. Patients without DN hyperintensity are considered to have a better prognosis. A 6-year MR follow-up study revealed that cerebellar hyperintensity in T1-weighted and FLAIR images tend to be replaced by hypointense areas, suggesting vacuolation. Cerebellar hyperintensity on FLAIR images is probably due to lipid deposits, while hypointense areas may indicate cerebellar degeneration because of cholestanol-induced apoptosis or other mechanisms causing axonal injury. Cerebellar vacuolation and calcification have been observed in a large number of patients. The former was positively related to the extent of DN hyperintensity in T1W and FLAIR images, and could be a useful indicator of disease progression and inadequate therapeutic response. Additionally, cerebral micro- and macro-angiopathies such as micro-hemorrhages, vascular dilatation and calcification are common in CTX patients. The xanthomas located within the ventricular region have also been observed in CTX cases. The main components of xanthoma are connective tissue and foam cells (foamy macrophages) bathed in cholestanol, cholesterol, cholesterol esters, triglycerides and phospholipids. The presence of Touton giant cells is a characteristic pathological finding. The development of tendon xanthomas may be associated with low-grade tendon inflammation. A tendon MRI study indicated that the enlargement of tendon xanthomas is primarily due to an increase in tendon water content, rather than in fat content. Tendinous xanthomas have different appearances on MR depending on the proportions of the following components: cholesterol, which does not produce a measurable signal; triglycerides, which produce a high signal on T1-weighted images; and associated inflammation, which causes high signal intensity regions in contrast-enhanced T1-weighted images. The diffuse reticulated pattern of xanthomas on axial images is a representative MRI feature of tendinous xanthoma. This patient’s MRI showed enlargement of the Achilles tendon, which showed up as low signal intensity on both T1- and T2-weighted images. This fits well with previous reports and could be attributed to the low percentage of triglycerides. In conclusion, we described a 47-year-old patient displaying psychiatric and behavioral disturbances, cognitive decline, a history of renal calculus, bilateral xanthomas of the Achilles tendon and tibial tubercles, peripheral neuropathy, high signal intensity in the WM and mild cerebral atrophy on brain MRI. The diagnosis was confirmed by compound heterozygous mutations in exon 2 (c.435G>T, p.Gly145Gly) and intron 7 (c.1263+1G>A) of the CYP27A1 gene. These lead to alternative pre-mRNA splicing and a skipping of exon 7 in the transcript, respectively. Three weeks′ treatment with a combination of lipid-lowering and antipsychotic therapy improved his psychiatric symptoms and normalized levels of serum free fatty acid. Sediments in the bladder disappeared after therapy.', 'Imaging examinations': 'X-ray of the lower limbs showed soft tissue swelling above the tibial tuberosities bilaterally (Figure 2E ). Sagittal and axial magnetic resonance imaging (MRI) of the right ankle joint showed apparent enlargement of the right Achilles tendon and upper medial malleolus flexor tendon (consisting of low signal intensity on both T1- and T2-weighted images), abnormal thickening of the plantar fat, and a small amount of exudation around the fascia in front of the Achilles tendon (Figure 2F ). The electroencephalogram (EEG) showed increased slow activities than normal and electrophysiological examination found mixed sensorimotor neuropathy of the upper and lower limbs. Cerebral MRI suggested white matter (WM) demyelination and slight cerebral atrophy (Figure 2G and H ).', 'Laboratory examinations': 'The laboratory results (Table 1 ) were as follows: Increased leukocyte count, neutrophil ratio and high erythrocyte sedimentation rate. There was also a significant increase in concentration of free fatty acid compared to normal range. In contrast, levels of high-density lipoprotein cholesterol were low. Serum cholesterol, glucose, electrolytes, and adrenocorticotropic hormone (ACTH) levels were all normal, as were the liver function tests. Doppler ultrasound of the urinary system showed multiple left kidney stones, a right kidney cyst, and a hypoechoic area in the bladder which could move with body position (Figure 2D ). Cerebrospinal fluid protein was mildly elevated: 680.4 mg/L (normal range: 150-400 mg/L).', 'Genetic testing': 'Genomic DNA was isolated from blood samples of the patient and his four healthy sisters. Mutation screening of all exons and flanking regions was performed on the patient’s sample by targeted sequencing as previously reported. Targeted sequencing revealed that the proband had compound heterozygous mutations in the CYP27A1 gene and that his four sisters were mutation carriers (Figure 1B - E, and Table 2 ). Both of the variants found are known pathogenic mutations of CTX. The variant in exon 2 (c.435G>T, p.Gly145Gly), a functionally silent nucleotide substitution, has been reported to activate a 5’ splice site, leading to alternative pre-mRNA splicing. The other variant (c.1263+1G>A) is a splice site mutation that disrupts normal mRNA splicing and results in exon 7 being skipped in the transcript. In Italian and Japanese patients, the variant has been found to cause loss of a heme binding domain, a vital part of hydroxylase, and to damage bile acid synthesis.', 'History of present illness': 'Three months ago, he underwent an operation for renal calculus, after which he showed progressive delusion (he believed unreasonably that he had a serious disease and was going to die), combined with slow response and speech reduction. At 1 wk before admission, he was unable to answer questions and developed an eating difficulty, incontinence, fever (T ≤ 38.2 °C) and severe weight loss. Chronic diarrhea was absent.'}
|
{'Chief complaints': 'A 47-year-old male was admitted to our institution with a history of intellectual disability for more than 30 years and behavioral abnormalities for the past 3 mo. He had a poor academic performance, having dropped out after completing elementary school. The patient could talk with others in daily life, but he was unable to do housework.', 'Personal and family history': 'The proband is the 4 th child of 5 in a non-consanguineous Chinese family. His family history was negative for symptoms related to neurological disorders. He was divorced twice and had no children, and did not have a history of smoking or drinking. The proband’s parents had died and his mother had a history of uremia. All of his four sisters are healthy (Figure 1A ).', 'CASE SUMMARY': 'A Chinese family with CTX consisting of one patient and four heterozygous carriers was studied. The patient is a 47-year-old male, who mainly had psychiatric signs but without some cardinal features of CTX such as cataracts, cerebellar ataxia, pyramidal signs and chronic diarrhea. There was a significant increase in the concentration of free fatty acid compared to normal range. Doppler ultrasound of the urinary system showed multiple left kidney stones, a right kidney cyst, and a hypoechoic area in the bladder, which could move with body position. Sagittal and axial magnetic resonance imaging (MRI) of the right ankle joint showed apparent enlargement of the right Achilles tendon and upper medial malleolus flexor tendon, abnormal thickening of the plantar fat, and a small amount of exudation around the fascia in front of the Achilles tendon. Cerebral MRI suggested white matter (WM) demyelination and slight cerebral atrophy. The diagnosis was confirmed by targeted sequencing, which identified compound heterozygous mutations in exon 2 and intron 7 of the CYP27A1 gene (c.435G>T, c.1263+1G>A). Treatment for 3 wk with a combination of lipid-lowering and antipsychotic therapy improved his psychiatric symptoms and normalized the levels of serum free fatty acid. Sediments in the bladder disappeared after therapy.', 'Physical examination': 'The patient had dark skin and a poor mental state (Figure 2A ). Neurological examination indicated cervical rigidity and Kernig sign. Deep tendon reflexes and limb muscle strength were normal. Babinski sign was negative. Enlarged Achilles tendons and nodules on the bilateral tibial tubercles were observed (Figure 2B and C ). There was no evidence of cataract or xanthomas at other sites such as the eyelids.', 'Biological and imaging features': 'The biochemical abnormalities detected in CTX are significant for diagnosis. The lack of sterol 27-hydroxylase inhibits the conversion of cholesterol into cholic and chenodeoxycholic acids in the liver. The serum levels of cholesterol and triglyceride are usually normal while cholestanol levels are markedly high in the blood, bile and tendon xanthoma. Since cholesterol synthesis is systematically decreased, cholesterol precursors increase substantially; this could also be regarded as a hallmark of CTX. Although a high cholestanol level indicates CTX, it does not correlate with any symptoms or disability at diagnosis assessed by the Expanded Disability Status Scale. Fast atom bombardment mass spectrometry is a semiquantitative technique which can be applied to analyze urinary bile acids. It will strongly support a diagnosis of CTX if increased bile alcohol glucuronides and reduced primary bile acid are detected. However, when the urinary bile acid profile is consistent with CTX, propofol administration should be taken into account as another possible cause, to avoid misdiagnoses. The combination of extremely low levels of 27-hydroxycholesterol (< 5 ng/mL or lower than the detection limit) and extremely high serum levels of 7 alpha-hydroxycholesterol (7α-OH-C) or 7 alpha-hydroxy-4-cholesten-3-one (7αC4) is a distinctive feature of CTX. Both 7α-OH-C and 7αC4 have been suggested as ideal biomarkers for evaluating treatment effects. With respect to auxiliary examinations, 56.57% of patients showed EEG abnormalities including diffuse slowing, which is a common feature of CTX patients. In addition, 76.72% had abnormal magnetic resonance (MR) images ( Supplementary Table 1 ). The main brain MRI abnormalities include supratentorial and infratentorial atrophy, as well as T2W/FLAIR (fluid-attenuated inversion recovery) hyperintensity involving the subcortical, periventricular and cerebellar WM and the brainstem. Bilateral hyperintensity of the dentate nuclei (DN) and surrounding WM on T2 and FLAIR sequences is considered a representative radiological feature of CTX. DN plays a critical role in saccade motor planning within a network that involves the frontal cortex and basal ganglia. Patients with DN lesions showed abnormal latency of reflexive and voluntary saccades, impaired precision and more uncorrected directional errors. There is a strong correlation between DN hyperintensity in brain MRI and neurological manifestations including ataxia, spasticity and cognitive impairment. Patients without DN hyperintensity are considered to have a better prognosis. A 6-year MR follow-up study revealed that cerebellar hyperintensity in T1-weighted and FLAIR images tend to be replaced by hypointense areas, suggesting vacuolation. Cerebellar hyperintensity on FLAIR images is probably due to lipid deposits, while hypointense areas may indicate cerebellar degeneration because of cholestanol-induced apoptosis or other mechanisms causing axonal injury. Cerebellar vacuolation and calcification have been observed in a large number of patients. The former was positively related to the extent of DN hyperintensity in T1W and FLAIR images, and could be a useful indicator of disease progression and inadequate therapeutic response. Additionally, cerebral micro- and macro-angiopathies such as micro-hemorrhages, vascular dilatation and calcification are common in CTX patients. The xanthomas located within the ventricular region have also been observed in CTX cases. The main components of xanthoma are connective tissue and foam cells (foamy macrophages) bathed in cholestanol, cholesterol, cholesterol esters, triglycerides and phospholipids. The presence of Touton giant cells is a characteristic pathological finding. The development of tendon xanthomas may be associated with low-grade tendon inflammation. A tendon MRI study indicated that the enlargement of tendon xanthomas is primarily due to an increase in tendon water content, rather than in fat content. Tendinous xanthomas have different appearances on MR depending on the proportions of the following components: cholesterol, which does not produce a measurable signal; triglycerides, which produce a high signal on T1-weighted images; and associated inflammation, which causes high signal intensity regions in contrast-enhanced T1-weighted images. The diffuse reticulated pattern of xanthomas on axial images is a representative MRI feature of tendinous xanthoma. This patient’s MRI showed enlargement of the Achilles tendon, which showed up as low signal intensity on both T1- and T2-weighted images. This fits well with previous reports and could be attributed to the low percentage of triglycerides. In conclusion, we described a 47-year-old patient displaying psychiatric and behavioral disturbances, cognitive decline, a history of renal calculus, bilateral xanthomas of the Achilles tendon and tibial tubercles, peripheral neuropathy, high signal intensity in the WM and mild cerebral atrophy on brain MRI. The diagnosis was confirmed by compound heterozygous mutations in exon 2 (c.435G>T, p.Gly145Gly) and intron 7 (c.1263+1G>A) of the CYP27A1 gene. These lead to alternative pre-mRNA splicing and a skipping of exon 7 in the transcript, respectively. Three weeks′ treatment with a combination of lipid-lowering and antipsychotic therapy improved his psychiatric symptoms and normalized levels of serum free fatty acid. Sediments in the bladder disappeared after therapy.', 'Imaging examinations': 'X-ray of the lower limbs showed soft tissue swelling above the tibial tuberosities bilaterally (Figure 2E ). Sagittal and axial magnetic resonance imaging (MRI) of the right ankle joint showed apparent enlargement of the right Achilles tendon and upper medial malleolus flexor tendon (consisting of low signal intensity on both T1- and T2-weighted images), abnormal thickening of the plantar fat, and a small amount of exudation around the fascia in front of the Achilles tendon (Figure 2F ). The electroencephalogram (EEG) showed increased slow activities than normal and electrophysiological examination found mixed sensorimotor neuropathy of the upper and lower limbs. Cerebral MRI suggested white matter (WM) demyelination and slight cerebral atrophy (Figure 2G and H ).', 'Laboratory examinations': 'The laboratory results (Table 1 ) were as follows: Increased leukocyte count, neutrophil ratio and high erythrocyte sedimentation rate. There was also a significant increase in concentration of free fatty acid compared to normal range. In contrast, levels of high-density lipoprotein cholesterol were low. Serum cholesterol, glucose, electrolytes, and adrenocorticotropic hormone (ACTH) levels were all normal, as were the liver function tests. Doppler ultrasound of the urinary system showed multiple left kidney stones, a right kidney cyst, and a hypoechoic area in the bladder which could move with body position (Figure 2D ). Cerebrospinal fluid protein was mildly elevated: 680.4 mg/L (normal range: 150-400 mg/L).', 'Genetic testing': 'Genomic DNA was isolated from blood samples of the patient and his four healthy sisters. Mutation screening of all exons and flanking regions was performed on the patient’s sample by targeted sequencing as previously reported. Targeted sequencing revealed that the proband had compound heterozygous mutations in the CYP27A1 gene and that his four sisters were mutation carriers (Figure 1B - E, and Table 2 ). Both of the variants found are known pathogenic mutations of CTX. The variant in exon 2 (c.435G>T, p.Gly145Gly), a functionally silent nucleotide substitution, has been reported to activate a 5’ splice site, leading to alternative pre-mRNA splicing. The other variant (c.1263+1G>A) is a splice site mutation that disrupts normal mRNA splicing and results in exon 7 being skipped in the transcript. In Italian and Japanese patients, the variant has been found to cause loss of a heme binding domain, a vital part of hydroxylase, and to damage bile acid synthesis.', 'History of present illness': 'Three months ago, he underwent an operation for renal calculus, after which he showed progressive delusion (he believed unreasonably that he had a serious disease and was going to die), combined with slow response and speech reduction. At 1 wk before admission, he was unable to answer questions and developed an eating difficulty, incontinence, fever (T ≤ 38.2 °C) and severe weight loss. Chronic diarrhea was absent.'}
|
Age-of-Onset
|
Age (of onset)
|
[] |
test-2105
|
7674721
|
{'Chief complaints': 'A 47-year-old male was admitted to our institution with a history of intellectual disability for more than 30 years and behavioral abnormalities for the past 3 mo. He had a poor academic performance, having dropped out after completing elementary school. The patient could talk with others in daily life, but he was unable to do housework.', 'Personal and family history': 'The proband is the 4 th child of 5 in a non-consanguineous Chinese family. His family history was negative for symptoms related to neurological disorders. He was divorced twice and had no children, and did not have a history of smoking or drinking. The proband’s parents had died and his mother had a history of uremia. All of his four sisters are healthy (Figure 1A ).', 'CASE SUMMARY': 'A Chinese family with CTX consisting of one patient and four heterozygous carriers was studied. The patient is a 47-year-old male, who mainly had psychiatric signs but without some cardinal features of CTX such as cataracts, cerebellar ataxia, pyramidal signs and chronic diarrhea. There was a significant increase in the concentration of free fatty acid compared to normal range. Doppler ultrasound of the urinary system showed multiple left kidney stones, a right kidney cyst, and a hypoechoic area in the bladder, which could move with body position. Sagittal and axial magnetic resonance imaging (MRI) of the right ankle joint showed apparent enlargement of the right Achilles tendon and upper medial malleolus flexor tendon, abnormal thickening of the plantar fat, and a small amount of exudation around the fascia in front of the Achilles tendon. Cerebral MRI suggested white matter (WM) demyelination and slight cerebral atrophy. The diagnosis was confirmed by targeted sequencing, which identified compound heterozygous mutations in exon 2 and intron 7 of the CYP27A1 gene (c.435G>T, c.1263+1G>A). Treatment for 3 wk with a combination of lipid-lowering and antipsychotic therapy improved his psychiatric symptoms and normalized the levels of serum free fatty acid. Sediments in the bladder disappeared after therapy.', 'Physical examination': 'The patient had dark skin and a poor mental state (Figure 2A ). Neurological examination indicated cervical rigidity and Kernig sign. Deep tendon reflexes and limb muscle strength were normal. Babinski sign was negative. Enlarged Achilles tendons and nodules on the bilateral tibial tubercles were observed (Figure 2B and C ). There was no evidence of cataract or xanthomas at other sites such as the eyelids.', 'Biological and imaging features': 'The biochemical abnormalities detected in CTX are significant for diagnosis. The lack of sterol 27-hydroxylase inhibits the conversion of cholesterol into cholic and chenodeoxycholic acids in the liver. The serum levels of cholesterol and triglyceride are usually normal while cholestanol levels are markedly high in the blood, bile and tendon xanthoma. Since cholesterol synthesis is systematically decreased, cholesterol precursors increase substantially; this could also be regarded as a hallmark of CTX. Although a high cholestanol level indicates CTX, it does not correlate with any symptoms or disability at diagnosis assessed by the Expanded Disability Status Scale. Fast atom bombardment mass spectrometry is a semiquantitative technique which can be applied to analyze urinary bile acids. It will strongly support a diagnosis of CTX if increased bile alcohol glucuronides and reduced primary bile acid are detected. However, when the urinary bile acid profile is consistent with CTX, propofol administration should be taken into account as another possible cause, to avoid misdiagnoses. The combination of extremely low levels of 27-hydroxycholesterol (< 5 ng/mL or lower than the detection limit) and extremely high serum levels of 7 alpha-hydroxycholesterol (7α-OH-C) or 7 alpha-hydroxy-4-cholesten-3-one (7αC4) is a distinctive feature of CTX. Both 7α-OH-C and 7αC4 have been suggested as ideal biomarkers for evaluating treatment effects. With respect to auxiliary examinations, 56.57% of patients showed EEG abnormalities including diffuse slowing, which is a common feature of CTX patients. In addition, 76.72% had abnormal magnetic resonance (MR) images ( Supplementary Table 1 ). The main brain MRI abnormalities include supratentorial and infratentorial atrophy, as well as T2W/FLAIR (fluid-attenuated inversion recovery) hyperintensity involving the subcortical, periventricular and cerebellar WM and the brainstem. Bilateral hyperintensity of the dentate nuclei (DN) and surrounding WM on T2 and FLAIR sequences is considered a representative radiological feature of CTX. DN plays a critical role in saccade motor planning within a network that involves the frontal cortex and basal ganglia. Patients with DN lesions showed abnormal latency of reflexive and voluntary saccades, impaired precision and more uncorrected directional errors. There is a strong correlation between DN hyperintensity in brain MRI and neurological manifestations including ataxia, spasticity and cognitive impairment. Patients without DN hyperintensity are considered to have a better prognosis. A 6-year MR follow-up study revealed that cerebellar hyperintensity in T1-weighted and FLAIR images tend to be replaced by hypointense areas, suggesting vacuolation. Cerebellar hyperintensity on FLAIR images is probably due to lipid deposits, while hypointense areas may indicate cerebellar degeneration because of cholestanol-induced apoptosis or other mechanisms causing axonal injury. Cerebellar vacuolation and calcification have been observed in a large number of patients. The former was positively related to the extent of DN hyperintensity in T1W and FLAIR images, and could be a useful indicator of disease progression and inadequate therapeutic response. Additionally, cerebral micro- and macro-angiopathies such as micro-hemorrhages, vascular dilatation and calcification are common in CTX patients. The xanthomas located within the ventricular region have also been observed in CTX cases. The main components of xanthoma are connective tissue and foam cells (foamy macrophages) bathed in cholestanol, cholesterol, cholesterol esters, triglycerides and phospholipids. The presence of Touton giant cells is a characteristic pathological finding. The development of tendon xanthomas may be associated with low-grade tendon inflammation. A tendon MRI study indicated that the enlargement of tendon xanthomas is primarily due to an increase in tendon water content, rather than in fat content. Tendinous xanthomas have different appearances on MR depending on the proportions of the following components: cholesterol, which does not produce a measurable signal; triglycerides, which produce a high signal on T1-weighted images; and associated inflammation, which causes high signal intensity regions in contrast-enhanced T1-weighted images. The diffuse reticulated pattern of xanthomas on axial images is a representative MRI feature of tendinous xanthoma. This patient’s MRI showed enlargement of the Achilles tendon, which showed up as low signal intensity on both T1- and T2-weighted images. This fits well with previous reports and could be attributed to the low percentage of triglycerides. In conclusion, we described a 47-year-old patient displaying psychiatric and behavioral disturbances, cognitive decline, a history of renal calculus, bilateral xanthomas of the Achilles tendon and tibial tubercles, peripheral neuropathy, high signal intensity in the WM and mild cerebral atrophy on brain MRI. The diagnosis was confirmed by compound heterozygous mutations in exon 2 (c.435G>T, p.Gly145Gly) and intron 7 (c.1263+1G>A) of the CYP27A1 gene. These lead to alternative pre-mRNA splicing and a skipping of exon 7 in the transcript, respectively. Three weeks′ treatment with a combination of lipid-lowering and antipsychotic therapy improved his psychiatric symptoms and normalized levels of serum free fatty acid. Sediments in the bladder disappeared after therapy.', 'Imaging examinations': 'X-ray of the lower limbs showed soft tissue swelling above the tibial tuberosities bilaterally (Figure 2E ). Sagittal and axial magnetic resonance imaging (MRI) of the right ankle joint showed apparent enlargement of the right Achilles tendon and upper medial malleolus flexor tendon (consisting of low signal intensity on both T1- and T2-weighted images), abnormal thickening of the plantar fat, and a small amount of exudation around the fascia in front of the Achilles tendon (Figure 2F ). The electroencephalogram (EEG) showed increased slow activities than normal and electrophysiological examination found mixed sensorimotor neuropathy of the upper and lower limbs. Cerebral MRI suggested white matter (WM) demyelination and slight cerebral atrophy (Figure 2G and H ).', 'Laboratory examinations': 'The laboratory results (Table 1 ) were as follows: Increased leukocyte count, neutrophil ratio and high erythrocyte sedimentation rate. There was also a significant increase in concentration of free fatty acid compared to normal range. In contrast, levels of high-density lipoprotein cholesterol were low. Serum cholesterol, glucose, electrolytes, and adrenocorticotropic hormone (ACTH) levels were all normal, as were the liver function tests. Doppler ultrasound of the urinary system showed multiple left kidney stones, a right kidney cyst, and a hypoechoic area in the bladder which could move with body position (Figure 2D ). Cerebrospinal fluid protein was mildly elevated: 680.4 mg/L (normal range: 150-400 mg/L).', 'Genetic testing': 'Genomic DNA was isolated from blood samples of the patient and his four healthy sisters. Mutation screening of all exons and flanking regions was performed on the patient’s sample by targeted sequencing as previously reported. Targeted sequencing revealed that the proband had compound heterozygous mutations in the CYP27A1 gene and that his four sisters were mutation carriers (Figure 1B - E, and Table 2 ). Both of the variants found are known pathogenic mutations of CTX. The variant in exon 2 (c.435G>T, p.Gly145Gly), a functionally silent nucleotide substitution, has been reported to activate a 5’ splice site, leading to alternative pre-mRNA splicing. The other variant (c.1263+1G>A) is a splice site mutation that disrupts normal mRNA splicing and results in exon 7 being skipped in the transcript. In Italian and Japanese patients, the variant has been found to cause loss of a heme binding domain, a vital part of hydroxylase, and to damage bile acid synthesis.', 'History of present illness': 'Three months ago, he underwent an operation for renal calculus, after which he showed progressive delusion (he believed unreasonably that he had a serious disease and was going to die), combined with slow response and speech reduction. At 1 wk before admission, he was unable to answer questions and developed an eating difficulty, incontinence, fever (T ≤ 38.2 °C) and severe weight loss. Chronic diarrhea was absent.'}
|
{'Chief complaints': 'A 47-year-old male was admitted to our institution with a history of intellectual disability for more than 30 years and behavioral abnormalities for the past 3 mo. He had a poor academic performance, having dropped out after completing elementary school. The patient could talk with others in daily life, but he was unable to do housework.', 'Personal and family history': 'The proband is the 4 th child of 5 in a non-consanguineous Chinese family. His family history was negative for symptoms related to neurological disorders. He was divorced twice and had no children, and did not have a history of smoking or drinking. The proband’s parents had died and his mother had a history of uremia. All of his four sisters are healthy (Figure 1A ).', 'CASE SUMMARY': 'A Chinese family with CTX consisting of one patient and four heterozygous carriers was studied. The patient is a 47-year-old male, who mainly had psychiatric signs but without some cardinal features of CTX such as cataracts, cerebellar ataxia, pyramidal signs and chronic diarrhea. There was a significant increase in the concentration of free fatty acid compared to normal range. Doppler ultrasound of the urinary system showed multiple left kidney stones, a right kidney cyst, and a hypoechoic area in the bladder, which could move with body position. Sagittal and axial magnetic resonance imaging (MRI) of the right ankle joint showed apparent enlargement of the right Achilles tendon and upper medial malleolus flexor tendon, abnormal thickening of the plantar fat, and a small amount of exudation around the fascia in front of the Achilles tendon. Cerebral MRI suggested white matter (WM) demyelination and slight cerebral atrophy. The diagnosis was confirmed by targeted sequencing, which identified compound heterozygous mutations in exon 2 and intron 7 of the CYP27A1 gene (c.435G>T, c.1263+1G>A). Treatment for 3 wk with a combination of lipid-lowering and antipsychotic therapy improved his psychiatric symptoms and normalized the levels of serum free fatty acid. Sediments in the bladder disappeared after therapy.', 'Physical examination': 'The patient had dark skin and a poor mental state (Figure 2A ). Neurological examination indicated cervical rigidity and Kernig sign. Deep tendon reflexes and limb muscle strength were normal. Babinski sign was negative. Enlarged Achilles tendons and nodules on the bilateral tibial tubercles were observed (Figure 2B and C ). There was no evidence of cataract or xanthomas at other sites such as the eyelids.', 'Biological and imaging features': 'The biochemical abnormalities detected in CTX are significant for diagnosis. The lack of sterol 27-hydroxylase inhibits the conversion of cholesterol into cholic and chenodeoxycholic acids in the liver. The serum levels of cholesterol and triglyceride are usually normal while cholestanol levels are markedly high in the blood, bile and tendon xanthoma. Since cholesterol synthesis is systematically decreased, cholesterol precursors increase substantially; this could also be regarded as a hallmark of CTX. Although a high cholestanol level indicates CTX, it does not correlate with any symptoms or disability at diagnosis assessed by the Expanded Disability Status Scale. Fast atom bombardment mass spectrometry is a semiquantitative technique which can be applied to analyze urinary bile acids. It will strongly support a diagnosis of CTX if increased bile alcohol glucuronides and reduced primary bile acid are detected. However, when the urinary bile acid profile is consistent with CTX, propofol administration should be taken into account as another possible cause, to avoid misdiagnoses. The combination of extremely low levels of 27-hydroxycholesterol (< 5 ng/mL or lower than the detection limit) and extremely high serum levels of 7 alpha-hydroxycholesterol (7α-OH-C) or 7 alpha-hydroxy-4-cholesten-3-one (7αC4) is a distinctive feature of CTX. Both 7α-OH-C and 7αC4 have been suggested as ideal biomarkers for evaluating treatment effects. With respect to auxiliary examinations, 56.57% of patients showed EEG abnormalities including diffuse slowing, which is a common feature of CTX patients. In addition, 76.72% had abnormal magnetic resonance (MR) images ( Supplementary Table 1 ). The main brain MRI abnormalities include supratentorial and infratentorial atrophy, as well as T2W/FLAIR (fluid-attenuated inversion recovery) hyperintensity involving the subcortical, periventricular and cerebellar WM and the brainstem. Bilateral hyperintensity of the dentate nuclei (DN) and surrounding WM on T2 and FLAIR sequences is considered a representative radiological feature of CTX. DN plays a critical role in saccade motor planning within a network that involves the frontal cortex and basal ganglia. Patients with DN lesions showed abnormal latency of reflexive and voluntary saccades, impaired precision and more uncorrected directional errors. There is a strong correlation between DN hyperintensity in brain MRI and neurological manifestations including ataxia, spasticity and cognitive impairment. Patients without DN hyperintensity are considered to have a better prognosis. A 6-year MR follow-up study revealed that cerebellar hyperintensity in T1-weighted and FLAIR images tend to be replaced by hypointense areas, suggesting vacuolation. Cerebellar hyperintensity on FLAIR images is probably due to lipid deposits, while hypointense areas may indicate cerebellar degeneration because of cholestanol-induced apoptosis or other mechanisms causing axonal injury. Cerebellar vacuolation and calcification have been observed in a large number of patients. The former was positively related to the extent of DN hyperintensity in T1W and FLAIR images, and could be a useful indicator of disease progression and inadequate therapeutic response. Additionally, cerebral micro- and macro-angiopathies such as micro-hemorrhages, vascular dilatation and calcification are common in CTX patients. The xanthomas located within the ventricular region have also been observed in CTX cases. The main components of xanthoma are connective tissue and foam cells (foamy macrophages) bathed in cholestanol, cholesterol, cholesterol esters, triglycerides and phospholipids. The presence of Touton giant cells is a characteristic pathological finding. The development of tendon xanthomas may be associated with low-grade tendon inflammation. A tendon MRI study indicated that the enlargement of tendon xanthomas is primarily due to an increase in tendon water content, rather than in fat content. Tendinous xanthomas have different appearances on MR depending on the proportions of the following components: cholesterol, which does not produce a measurable signal; triglycerides, which produce a high signal on T1-weighted images; and associated inflammation, which causes high signal intensity regions in contrast-enhanced T1-weighted images. The diffuse reticulated pattern of xanthomas on axial images is a representative MRI feature of tendinous xanthoma. This patient’s MRI showed enlargement of the Achilles tendon, which showed up as low signal intensity on both T1- and T2-weighted images. This fits well with previous reports and could be attributed to the low percentage of triglycerides. In conclusion, we described a 47-year-old patient displaying psychiatric and behavioral disturbances, cognitive decline, a history of renal calculus, bilateral xanthomas of the Achilles tendon and tibial tubercles, peripheral neuropathy, high signal intensity in the WM and mild cerebral atrophy on brain MRI. The diagnosis was confirmed by compound heterozygous mutations in exon 2 (c.435G>T, p.Gly145Gly) and intron 7 (c.1263+1G>A) of the CYP27A1 gene. These lead to alternative pre-mRNA splicing and a skipping of exon 7 in the transcript, respectively. Three weeks′ treatment with a combination of lipid-lowering and antipsychotic therapy improved his psychiatric symptoms and normalized levels of serum free fatty acid. Sediments in the bladder disappeared after therapy.', 'Imaging examinations': 'X-ray of the lower limbs showed soft tissue swelling above the tibial tuberosities bilaterally (Figure 2E ). Sagittal and axial magnetic resonance imaging (MRI) of the right ankle joint showed apparent enlargement of the right Achilles tendon and upper medial malleolus flexor tendon (consisting of low signal intensity on both T1- and T2-weighted images), abnormal thickening of the plantar fat, and a small amount of exudation around the fascia in front of the Achilles tendon (Figure 2F ). The electroencephalogram (EEG) showed increased slow activities than normal and electrophysiological examination found mixed sensorimotor neuropathy of the upper and lower limbs. Cerebral MRI suggested white matter (WM) demyelination and slight cerebral atrophy (Figure 2G and H ).', 'Laboratory examinations': 'The laboratory results (Table 1 ) were as follows: Increased leukocyte count, neutrophil ratio and high erythrocyte sedimentation rate. There was also a significant increase in concentration of free fatty acid compared to normal range. In contrast, levels of high-density lipoprotein cholesterol were low. Serum cholesterol, glucose, electrolytes, and adrenocorticotropic hormone (ACTH) levels were all normal, as were the liver function tests. Doppler ultrasound of the urinary system showed multiple left kidney stones, a right kidney cyst, and a hypoechoic area in the bladder which could move with body position (Figure 2D ). Cerebrospinal fluid protein was mildly elevated: 680.4 mg/L (normal range: 150-400 mg/L).', 'Genetic testing': 'Genomic DNA was isolated from blood samples of the patient and his four healthy sisters. Mutation screening of all exons and flanking regions was performed on the patient’s sample by targeted sequencing as previously reported. Targeted sequencing revealed that the proband had compound heterozygous mutations in the CYP27A1 gene and that his four sisters were mutation carriers (Figure 1B - E, and Table 2 ). Both of the variants found are known pathogenic mutations of CTX. The variant in exon 2 (c.435G>T, p.Gly145Gly), a functionally silent nucleotide substitution, has been reported to activate a 5’ splice site, leading to alternative pre-mRNA splicing. The other variant (c.1263+1G>A) is a splice site mutation that disrupts normal mRNA splicing and results in exon 7 being skipped in the transcript. In Italian and Japanese patients, the variant has been found to cause loss of a heme binding domain, a vital part of hydroxylase, and to damage bile acid synthesis.', 'History of present illness': 'Three months ago, he underwent an operation for renal calculus, after which he showed progressive delusion (he believed unreasonably that he had a serious disease and was going to die), combined with slow response and speech reduction. At 1 wk before admission, he was unable to answer questions and developed an eating difficulty, incontinence, fever (T ≤ 38.2 °C) and severe weight loss. Chronic diarrhea was absent.'}
|
Confirmed-Diagnosis-IEM
|
Confirmed_Diagnosis(IEM)
|
[
"CTX",
"CTX"
] |
test-2106
|
7674721
|
{'Chief complaints': 'A 47-year-old male was admitted to our institution with a history of intellectual disability for more than 30 years and behavioral abnormalities for the past 3 mo. He had a poor academic performance, having dropped out after completing elementary school. The patient could talk with others in daily life, but he was unable to do housework.', 'Personal and family history': 'The proband is the 4 th child of 5 in a non-consanguineous Chinese family. His family history was negative for symptoms related to neurological disorders. He was divorced twice and had no children, and did not have a history of smoking or drinking. The proband’s parents had died and his mother had a history of uremia. All of his four sisters are healthy (Figure 1A ).', 'CASE SUMMARY': 'A Chinese family with CTX consisting of one patient and four heterozygous carriers was studied. The patient is a 47-year-old male, who mainly had psychiatric signs but without some cardinal features of CTX such as cataracts, cerebellar ataxia, pyramidal signs and chronic diarrhea. There was a significant increase in the concentration of free fatty acid compared to normal range. Doppler ultrasound of the urinary system showed multiple left kidney stones, a right kidney cyst, and a hypoechoic area in the bladder, which could move with body position. Sagittal and axial magnetic resonance imaging (MRI) of the right ankle joint showed apparent enlargement of the right Achilles tendon and upper medial malleolus flexor tendon, abnormal thickening of the plantar fat, and a small amount of exudation around the fascia in front of the Achilles tendon. Cerebral MRI suggested white matter (WM) demyelination and slight cerebral atrophy. The diagnosis was confirmed by targeted sequencing, which identified compound heterozygous mutations in exon 2 and intron 7 of the CYP27A1 gene (c.435G>T, c.1263+1G>A). Treatment for 3 wk with a combination of lipid-lowering and antipsychotic therapy improved his psychiatric symptoms and normalized the levels of serum free fatty acid. Sediments in the bladder disappeared after therapy.', 'Physical examination': 'The patient had dark skin and a poor mental state (Figure 2A ). Neurological examination indicated cervical rigidity and Kernig sign. Deep tendon reflexes and limb muscle strength were normal. Babinski sign was negative. Enlarged Achilles tendons and nodules on the bilateral tibial tubercles were observed (Figure 2B and C ). There was no evidence of cataract or xanthomas at other sites such as the eyelids.', 'Biological and imaging features': 'The biochemical abnormalities detected in CTX are significant for diagnosis. The lack of sterol 27-hydroxylase inhibits the conversion of cholesterol into cholic and chenodeoxycholic acids in the liver. The serum levels of cholesterol and triglyceride are usually normal while cholestanol levels are markedly high in the blood, bile and tendon xanthoma. Since cholesterol synthesis is systematically decreased, cholesterol precursors increase substantially; this could also be regarded as a hallmark of CTX. Although a high cholestanol level indicates CTX, it does not correlate with any symptoms or disability at diagnosis assessed by the Expanded Disability Status Scale. Fast atom bombardment mass spectrometry is a semiquantitative technique which can be applied to analyze urinary bile acids. It will strongly support a diagnosis of CTX if increased bile alcohol glucuronides and reduced primary bile acid are detected. However, when the urinary bile acid profile is consistent with CTX, propofol administration should be taken into account as another possible cause, to avoid misdiagnoses. The combination of extremely low levels of 27-hydroxycholesterol (< 5 ng/mL or lower than the detection limit) and extremely high serum levels of 7 alpha-hydroxycholesterol (7α-OH-C) or 7 alpha-hydroxy-4-cholesten-3-one (7αC4) is a distinctive feature of CTX. Both 7α-OH-C and 7αC4 have been suggested as ideal biomarkers for evaluating treatment effects. With respect to auxiliary examinations, 56.57% of patients showed EEG abnormalities including diffuse slowing, which is a common feature of CTX patients. In addition, 76.72% had abnormal magnetic resonance (MR) images ( Supplementary Table 1 ). The main brain MRI abnormalities include supratentorial and infratentorial atrophy, as well as T2W/FLAIR (fluid-attenuated inversion recovery) hyperintensity involving the subcortical, periventricular and cerebellar WM and the brainstem. Bilateral hyperintensity of the dentate nuclei (DN) and surrounding WM on T2 and FLAIR sequences is considered a representative radiological feature of CTX. DN plays a critical role in saccade motor planning within a network that involves the frontal cortex and basal ganglia. Patients with DN lesions showed abnormal latency of reflexive and voluntary saccades, impaired precision and more uncorrected directional errors. There is a strong correlation between DN hyperintensity in brain MRI and neurological manifestations including ataxia, spasticity and cognitive impairment. Patients without DN hyperintensity are considered to have a better prognosis. A 6-year MR follow-up study revealed that cerebellar hyperintensity in T1-weighted and FLAIR images tend to be replaced by hypointense areas, suggesting vacuolation. Cerebellar hyperintensity on FLAIR images is probably due to lipid deposits, while hypointense areas may indicate cerebellar degeneration because of cholestanol-induced apoptosis or other mechanisms causing axonal injury. Cerebellar vacuolation and calcification have been observed in a large number of patients. The former was positively related to the extent of DN hyperintensity in T1W and FLAIR images, and could be a useful indicator of disease progression and inadequate therapeutic response. Additionally, cerebral micro- and macro-angiopathies such as micro-hemorrhages, vascular dilatation and calcification are common in CTX patients. The xanthomas located within the ventricular region have also been observed in CTX cases. The main components of xanthoma are connective tissue and foam cells (foamy macrophages) bathed in cholestanol, cholesterol, cholesterol esters, triglycerides and phospholipids. The presence of Touton giant cells is a characteristic pathological finding. The development of tendon xanthomas may be associated with low-grade tendon inflammation. A tendon MRI study indicated that the enlargement of tendon xanthomas is primarily due to an increase in tendon water content, rather than in fat content. Tendinous xanthomas have different appearances on MR depending on the proportions of the following components: cholesterol, which does not produce a measurable signal; triglycerides, which produce a high signal on T1-weighted images; and associated inflammation, which causes high signal intensity regions in contrast-enhanced T1-weighted images. The diffuse reticulated pattern of xanthomas on axial images is a representative MRI feature of tendinous xanthoma. This patient’s MRI showed enlargement of the Achilles tendon, which showed up as low signal intensity on both T1- and T2-weighted images. This fits well with previous reports and could be attributed to the low percentage of triglycerides. In conclusion, we described a 47-year-old patient displaying psychiatric and behavioral disturbances, cognitive decline, a history of renal calculus, bilateral xanthomas of the Achilles tendon and tibial tubercles, peripheral neuropathy, high signal intensity in the WM and mild cerebral atrophy on brain MRI. The diagnosis was confirmed by compound heterozygous mutations in exon 2 (c.435G>T, p.Gly145Gly) and intron 7 (c.1263+1G>A) of the CYP27A1 gene. These lead to alternative pre-mRNA splicing and a skipping of exon 7 in the transcript, respectively. Three weeks′ treatment with a combination of lipid-lowering and antipsychotic therapy improved his psychiatric symptoms and normalized levels of serum free fatty acid. Sediments in the bladder disappeared after therapy.', 'Imaging examinations': 'X-ray of the lower limbs showed soft tissue swelling above the tibial tuberosities bilaterally (Figure 2E ). Sagittal and axial magnetic resonance imaging (MRI) of the right ankle joint showed apparent enlargement of the right Achilles tendon and upper medial malleolus flexor tendon (consisting of low signal intensity on both T1- and T2-weighted images), abnormal thickening of the plantar fat, and a small amount of exudation around the fascia in front of the Achilles tendon (Figure 2F ). The electroencephalogram (EEG) showed increased slow activities than normal and electrophysiological examination found mixed sensorimotor neuropathy of the upper and lower limbs. Cerebral MRI suggested white matter (WM) demyelination and slight cerebral atrophy (Figure 2G and H ).', 'Laboratory examinations': 'The laboratory results (Table 1 ) were as follows: Increased leukocyte count, neutrophil ratio and high erythrocyte sedimentation rate. There was also a significant increase in concentration of free fatty acid compared to normal range. In contrast, levels of high-density lipoprotein cholesterol were low. Serum cholesterol, glucose, electrolytes, and adrenocorticotropic hormone (ACTH) levels were all normal, as were the liver function tests. Doppler ultrasound of the urinary system showed multiple left kidney stones, a right kidney cyst, and a hypoechoic area in the bladder which could move with body position (Figure 2D ). Cerebrospinal fluid protein was mildly elevated: 680.4 mg/L (normal range: 150-400 mg/L).', 'Genetic testing': 'Genomic DNA was isolated from blood samples of the patient and his four healthy sisters. Mutation screening of all exons and flanking regions was performed on the patient’s sample by targeted sequencing as previously reported. Targeted sequencing revealed that the proband had compound heterozygous mutations in the CYP27A1 gene and that his four sisters were mutation carriers (Figure 1B - E, and Table 2 ). Both of the variants found are known pathogenic mutations of CTX. The variant in exon 2 (c.435G>T, p.Gly145Gly), a functionally silent nucleotide substitution, has been reported to activate a 5’ splice site, leading to alternative pre-mRNA splicing. The other variant (c.1263+1G>A) is a splice site mutation that disrupts normal mRNA splicing and results in exon 7 being skipped in the transcript. In Italian and Japanese patients, the variant has been found to cause loss of a heme binding domain, a vital part of hydroxylase, and to damage bile acid synthesis.', 'History of present illness': 'Three months ago, he underwent an operation for renal calculus, after which he showed progressive delusion (he believed unreasonably that he had a serious disease and was going to die), combined with slow response and speech reduction. At 1 wk before admission, he was unable to answer questions and developed an eating difficulty, incontinence, fever (T ≤ 38.2 °C) and severe weight loss. Chronic diarrhea was absent.'}
|
{'Chief complaints': 'A 47-year-old male was admitted to our institution with a history of intellectual disability for more than 30 years and behavioral abnormalities for the past 3 mo. He had a poor academic performance, having dropped out after completing elementary school. The patient could talk with others in daily life, but he was unable to do housework.', 'Personal and family history': 'The proband is the 4 th child of 5 in a non-consanguineous Chinese family. His family history was negative for symptoms related to neurological disorders. He was divorced twice and had no children, and did not have a history of smoking or drinking. The proband’s parents had died and his mother had a history of uremia. All of his four sisters are healthy (Figure 1A ).', 'CASE SUMMARY': 'A Chinese family with CTX consisting of one patient and four heterozygous carriers was studied. The patient is a 47-year-old male, who mainly had psychiatric signs but without some cardinal features of CTX such as cataracts, cerebellar ataxia, pyramidal signs and chronic diarrhea. There was a significant increase in the concentration of free fatty acid compared to normal range. Doppler ultrasound of the urinary system showed multiple left kidney stones, a right kidney cyst, and a hypoechoic area in the bladder, which could move with body position. Sagittal and axial magnetic resonance imaging (MRI) of the right ankle joint showed apparent enlargement of the right Achilles tendon and upper medial malleolus flexor tendon, abnormal thickening of the plantar fat, and a small amount of exudation around the fascia in front of the Achilles tendon. Cerebral MRI suggested white matter (WM) demyelination and slight cerebral atrophy. The diagnosis was confirmed by targeted sequencing, which identified compound heterozygous mutations in exon 2 and intron 7 of the CYP27A1 gene (c.435G>T, c.1263+1G>A). Treatment for 3 wk with a combination of lipid-lowering and antipsychotic therapy improved his psychiatric symptoms and normalized the levels of serum free fatty acid. Sediments in the bladder disappeared after therapy.', 'Physical examination': 'The patient had dark skin and a poor mental state (Figure 2A ). Neurological examination indicated cervical rigidity and Kernig sign. Deep tendon reflexes and limb muscle strength were normal. Babinski sign was negative. Enlarged Achilles tendons and nodules on the bilateral tibial tubercles were observed (Figure 2B and C ). There was no evidence of cataract or xanthomas at other sites such as the eyelids.', 'Biological and imaging features': 'The biochemical abnormalities detected in CTX are significant for diagnosis. The lack of sterol 27-hydroxylase inhibits the conversion of cholesterol into cholic and chenodeoxycholic acids in the liver. The serum levels of cholesterol and triglyceride are usually normal while cholestanol levels are markedly high in the blood, bile and tendon xanthoma. Since cholesterol synthesis is systematically decreased, cholesterol precursors increase substantially; this could also be regarded as a hallmark of CTX. Although a high cholestanol level indicates CTX, it does not correlate with any symptoms or disability at diagnosis assessed by the Expanded Disability Status Scale. Fast atom bombardment mass spectrometry is a semiquantitative technique which can be applied to analyze urinary bile acids. It will strongly support a diagnosis of CTX if increased bile alcohol glucuronides and reduced primary bile acid are detected. However, when the urinary bile acid profile is consistent with CTX, propofol administration should be taken into account as another possible cause, to avoid misdiagnoses. The combination of extremely low levels of 27-hydroxycholesterol (< 5 ng/mL or lower than the detection limit) and extremely high serum levels of 7 alpha-hydroxycholesterol (7α-OH-C) or 7 alpha-hydroxy-4-cholesten-3-one (7αC4) is a distinctive feature of CTX. Both 7α-OH-C and 7αC4 have been suggested as ideal biomarkers for evaluating treatment effects. With respect to auxiliary examinations, 56.57% of patients showed EEG abnormalities including diffuse slowing, which is a common feature of CTX patients. In addition, 76.72% had abnormal magnetic resonance (MR) images ( Supplementary Table 1 ). The main brain MRI abnormalities include supratentorial and infratentorial atrophy, as well as T2W/FLAIR (fluid-attenuated inversion recovery) hyperintensity involving the subcortical, periventricular and cerebellar WM and the brainstem. Bilateral hyperintensity of the dentate nuclei (DN) and surrounding WM on T2 and FLAIR sequences is considered a representative radiological feature of CTX. DN plays a critical role in saccade motor planning within a network that involves the frontal cortex and basal ganglia. Patients with DN lesions showed abnormal latency of reflexive and voluntary saccades, impaired precision and more uncorrected directional errors. There is a strong correlation between DN hyperintensity in brain MRI and neurological manifestations including ataxia, spasticity and cognitive impairment. Patients without DN hyperintensity are considered to have a better prognosis. A 6-year MR follow-up study revealed that cerebellar hyperintensity in T1-weighted and FLAIR images tend to be replaced by hypointense areas, suggesting vacuolation. Cerebellar hyperintensity on FLAIR images is probably due to lipid deposits, while hypointense areas may indicate cerebellar degeneration because of cholestanol-induced apoptosis or other mechanisms causing axonal injury. Cerebellar vacuolation and calcification have been observed in a large number of patients. The former was positively related to the extent of DN hyperintensity in T1W and FLAIR images, and could be a useful indicator of disease progression and inadequate therapeutic response. Additionally, cerebral micro- and macro-angiopathies such as micro-hemorrhages, vascular dilatation and calcification are common in CTX patients. The xanthomas located within the ventricular region have also been observed in CTX cases. The main components of xanthoma are connective tissue and foam cells (foamy macrophages) bathed in cholestanol, cholesterol, cholesterol esters, triglycerides and phospholipids. The presence of Touton giant cells is a characteristic pathological finding. The development of tendon xanthomas may be associated with low-grade tendon inflammation. A tendon MRI study indicated that the enlargement of tendon xanthomas is primarily due to an increase in tendon water content, rather than in fat content. Tendinous xanthomas have different appearances on MR depending on the proportions of the following components: cholesterol, which does not produce a measurable signal; triglycerides, which produce a high signal on T1-weighted images; and associated inflammation, which causes high signal intensity regions in contrast-enhanced T1-weighted images. The diffuse reticulated pattern of xanthomas on axial images is a representative MRI feature of tendinous xanthoma. This patient’s MRI showed enlargement of the Achilles tendon, which showed up as low signal intensity on both T1- and T2-weighted images. This fits well with previous reports and could be attributed to the low percentage of triglycerides. In conclusion, we described a 47-year-old patient displaying psychiatric and behavioral disturbances, cognitive decline, a history of renal calculus, bilateral xanthomas of the Achilles tendon and tibial tubercles, peripheral neuropathy, high signal intensity in the WM and mild cerebral atrophy on brain MRI. The diagnosis was confirmed by compound heterozygous mutations in exon 2 (c.435G>T, p.Gly145Gly) and intron 7 (c.1263+1G>A) of the CYP27A1 gene. These lead to alternative pre-mRNA splicing and a skipping of exon 7 in the transcript, respectively. Three weeks′ treatment with a combination of lipid-lowering and antipsychotic therapy improved his psychiatric symptoms and normalized levels of serum free fatty acid. Sediments in the bladder disappeared after therapy.', 'Imaging examinations': 'X-ray of the lower limbs showed soft tissue swelling above the tibial tuberosities bilaterally (Figure 2E ). Sagittal and axial magnetic resonance imaging (MRI) of the right ankle joint showed apparent enlargement of the right Achilles tendon and upper medial malleolus flexor tendon (consisting of low signal intensity on both T1- and T2-weighted images), abnormal thickening of the plantar fat, and a small amount of exudation around the fascia in front of the Achilles tendon (Figure 2F ). The electroencephalogram (EEG) showed increased slow activities than normal and electrophysiological examination found mixed sensorimotor neuropathy of the upper and lower limbs. Cerebral MRI suggested white matter (WM) demyelination and slight cerebral atrophy (Figure 2G and H ).', 'Laboratory examinations': 'The laboratory results (Table 1 ) were as follows: Increased leukocyte count, neutrophil ratio and high erythrocyte sedimentation rate. There was also a significant increase in concentration of free fatty acid compared to normal range. In contrast, levels of high-density lipoprotein cholesterol were low. Serum cholesterol, glucose, electrolytes, and adrenocorticotropic hormone (ACTH) levels were all normal, as were the liver function tests. Doppler ultrasound of the urinary system showed multiple left kidney stones, a right kidney cyst, and a hypoechoic area in the bladder which could move with body position (Figure 2D ). Cerebrospinal fluid protein was mildly elevated: 680.4 mg/L (normal range: 150-400 mg/L).', 'Genetic testing': 'Genomic DNA was isolated from blood samples of the patient and his four healthy sisters. Mutation screening of all exons and flanking regions was performed on the patient’s sample by targeted sequencing as previously reported. Targeted sequencing revealed that the proband had compound heterozygous mutations in the CYP27A1 gene and that his four sisters were mutation carriers (Figure 1B - E, and Table 2 ). Both of the variants found are known pathogenic mutations of CTX. The variant in exon 2 (c.435G>T, p.Gly145Gly), a functionally silent nucleotide substitution, has been reported to activate a 5’ splice site, leading to alternative pre-mRNA splicing. The other variant (c.1263+1G>A) is a splice site mutation that disrupts normal mRNA splicing and results in exon 7 being skipped in the transcript. In Italian and Japanese patients, the variant has been found to cause loss of a heme binding domain, a vital part of hydroxylase, and to damage bile acid synthesis.', 'History of present illness': 'Three months ago, he underwent an operation for renal calculus, after which he showed progressive delusion (he believed unreasonably that he had a serious disease and was going to die), combined with slow response and speech reduction. At 1 wk before admission, he was unable to answer questions and developed an eating difficulty, incontinence, fever (T ≤ 38.2 °C) and severe weight loss. Chronic diarrhea was absent.'}
|
IEM-Treatment
|
IEM_Treatment
|
[] |
test-2107
|
7292164
|
{'Case presentation': 'A 15‐day‐old 46, XY neonate presented with severe adrenal insufficiency. Congenital lipoid adrenal hyperplasia was diagnosed after detection of steroidogenic acute regulatory gene mutations. At 2 years and 5 months, she underwent bilateral gonadectomy. Leydig cells were observed both with and without lipid droplets in the testes of this patient. We also demonstrated immunohistochemically that some testosterone‐synthesizing enzymes were maintained in this patient. The patient was born at full term with completely normal female external genitalia. No abnormalities were identified in routine newborn screenings. At 15 days, she was brought to the hospital with poor feeding and poor weight gain. Hyperpigmentation suggestive of adrenal insufficiency was noted. Laboratory tests revealed severe hyponatremia (115 mEq/L) and hyperkalemia (8.6 mEq/L). She was immediately treated with hydrocortisone and examined for all adrenocortical hormones and associated metabolites in serum and urine. Not only mineralocorticoids and glucocorticoids, but also adrenal androgens and their metabolic products were barely detectable. On the other hand, concentrations of adrenocorticotropic hormone were extremely high, at 387 pg/mL (normal 7.2–63.3 pg/mL). CT showed enlargement of bilateral adrenal glands (Fig. 1 a). Bilateral gonads were not palpable but were detectable near the internal inguinal rings on ultrasonography and MRI (Fig. 1 b). Since congenital adrenal hyperplasia was strongly suspected, chromosomal genetic testing was performed and revealed a 46,XY karyotype. Sequence analysis of the StAR gene revealed compound heterozygous mutations for p.Q258X and p.D246fs. From these results, lipoid CAH was diagnosed. Laparoscopic bilateral gonadectomy was performed at 2 years and 5 months. Both gonads were identified as normal testes accompanied by vas deferens and epididymis. The testes measured 16 × 10 × 6 mm on the right and 14 × 8 × 8 mm on the left (Fig. 2 a,b). As of the time of writing, she is continuing adrenocortical hormone replacement therapy, and will receive combination estrogen replacement therapy at the time of puberty.', 'Histopathological findings': 'Light microscopy showed seminiferous tubules mainly comprising spermatogonia and Sertoli cells, with no spermatocytes or spermatids (Fig. 2 c). Two types of LCs were identified, filled with and without lipid droplets in the testicular interstitium. The nuclei of LCs depressed by excessive lipid droplets were more clearly observable under electron microscopy (Fig. 2 d). Testosterone‐synthesizing enzymes in the testis of this patient were investigated by immunostaining and Western blotting methods using antibodies reacting with StAR protein, Ad4BP/SF‐1, CYP11A1, CYP17A1, 3β‐HSD, and 17β‐HSD. As control samples, we used biopsy tissues from three individuals with cryptorchidism ( n = 3; mean age, 5). All these steroid synthesis‐related proteins were observed in LCs of control samples using immunohistochemistry (Fig. 3 ). Western blotting analysis showed negative results for StAR protein in the testis of this patient (data not shown). LCs both with and without lipid droplets in this patient expressed all the steroid synthesis‐related proteins except StAR, 3β‐HSD, and 17β‐HSD (Fig. 3 ). This was part of a study approved by the ethics committee of Fukushima Medical University School of Medicine (2245). Informed consent was obtained after explaining the purpose and methods.'}
|
{'Case presentation': 'A 15‐day‐old 46, XY neonate presented with severe adrenal insufficiency. Congenital lipoid adrenal hyperplasia was diagnosed after detection of steroidogenic acute regulatory gene mutations. At 2 years and 5 months, she underwent bilateral gonadectomy. Leydig cells were observed both with and without lipid droplets in the testes of this patient. We also demonstrated immunohistochemically that some testosterone‐synthesizing enzymes were maintained in this patient. The patient was born at full term with completely normal female external genitalia. No abnormalities were identified in routine newborn screenings. At 15 days, she was brought to the hospital with poor feeding and poor weight gain. Hyperpigmentation suggestive of adrenal insufficiency was noted. Laboratory tests revealed severe hyponatremia (115 mEq/L) and hyperkalemia (8.6 mEq/L). She was immediately treated with hydrocortisone and examined for all adrenocortical hormones and associated metabolites in serum and urine. Not only mineralocorticoids and glucocorticoids, but also adrenal androgens and their metabolic products were barely detectable. On the other hand, concentrations of adrenocorticotropic hormone were extremely high, at 387 pg/mL (normal 7.2–63.3 pg/mL). CT showed enlargement of bilateral adrenal glands (Fig. 1 a). Bilateral gonads were not palpable but were detectable near the internal inguinal rings on ultrasonography and MRI (Fig. 1 b). Since congenital adrenal hyperplasia was strongly suspected, chromosomal genetic testing was performed and revealed a 46,XY karyotype. Sequence analysis of the StAR gene revealed compound heterozygous mutations for p.Q258X and p.D246fs. From these results, lipoid CAH was diagnosed. Laparoscopic bilateral gonadectomy was performed at 2 years and 5 months. Both gonads were identified as normal testes accompanied by vas deferens and epididymis. The testes measured 16 × 10 × 6 mm on the right and 14 × 8 × 8 mm on the left (Fig. 2 a,b). As of the time of writing, she is continuing adrenocortical hormone replacement therapy, and will receive combination estrogen replacement therapy at the time of puberty.', 'Histopathological findings': 'Light microscopy showed seminiferous tubules mainly comprising spermatogonia and Sertoli cells, with no spermatocytes or spermatids (Fig. 2 c). Two types of LCs were identified, filled with and without lipid droplets in the testicular interstitium. The nuclei of LCs depressed by excessive lipid droplets were more clearly observable under electron microscopy (Fig. 2 d). Testosterone‐synthesizing enzymes in the testis of this patient were investigated by immunostaining and Western blotting methods using antibodies reacting with StAR protein, Ad4BP/SF‐1, CYP11A1, CYP17A1, 3β‐HSD, and 17β‐HSD. As control samples, we used biopsy tissues from three individuals with cryptorchidism ( n = 3; mean age, 5). All these steroid synthesis‐related proteins were observed in LCs of control samples using immunohistochemistry (Fig. 3 ). Western blotting analysis showed negative results for StAR protein in the testis of this patient (data not shown). LCs both with and without lipid droplets in this patient expressed all the steroid synthesis‐related proteins except StAR, 3β‐HSD, and 17β‐HSD (Fig. 3 ). This was part of a study approved by the ethics committee of Fukushima Medical University School of Medicine (2245). Informed consent was obtained after explaining the purpose and methods.'}
|
Vitals-and-Hematology
|
Vitals_Hema
|
[] |
test-2108
|
7292164
|
{'Case presentation': 'A 15‐day‐old 46, XY neonate presented with severe adrenal insufficiency. Congenital lipoid adrenal hyperplasia was diagnosed after detection of steroidogenic acute regulatory gene mutations. At 2 years and 5 months, she underwent bilateral gonadectomy. Leydig cells were observed both with and without lipid droplets in the testes of this patient. We also demonstrated immunohistochemically that some testosterone‐synthesizing enzymes were maintained in this patient. The patient was born at full term with completely normal female external genitalia. No abnormalities were identified in routine newborn screenings. At 15 days, she was brought to the hospital with poor feeding and poor weight gain. Hyperpigmentation suggestive of adrenal insufficiency was noted. Laboratory tests revealed severe hyponatremia (115 mEq/L) and hyperkalemia (8.6 mEq/L). She was immediately treated with hydrocortisone and examined for all adrenocortical hormones and associated metabolites in serum and urine. Not only mineralocorticoids and glucocorticoids, but also adrenal androgens and their metabolic products were barely detectable. On the other hand, concentrations of adrenocorticotropic hormone were extremely high, at 387 pg/mL (normal 7.2–63.3 pg/mL). CT showed enlargement of bilateral adrenal glands (Fig. 1 a). Bilateral gonads were not palpable but were detectable near the internal inguinal rings on ultrasonography and MRI (Fig. 1 b). Since congenital adrenal hyperplasia was strongly suspected, chromosomal genetic testing was performed and revealed a 46,XY karyotype. Sequence analysis of the StAR gene revealed compound heterozygous mutations for p.Q258X and p.D246fs. From these results, lipoid CAH was diagnosed. Laparoscopic bilateral gonadectomy was performed at 2 years and 5 months. Both gonads were identified as normal testes accompanied by vas deferens and epididymis. The testes measured 16 × 10 × 6 mm on the right and 14 × 8 × 8 mm on the left (Fig. 2 a,b). As of the time of writing, she is continuing adrenocortical hormone replacement therapy, and will receive combination estrogen replacement therapy at the time of puberty.', 'Histopathological findings': 'Light microscopy showed seminiferous tubules mainly comprising spermatogonia and Sertoli cells, with no spermatocytes or spermatids (Fig. 2 c). Two types of LCs were identified, filled with and without lipid droplets in the testicular interstitium. The nuclei of LCs depressed by excessive lipid droplets were more clearly observable under electron microscopy (Fig. 2 d). Testosterone‐synthesizing enzymes in the testis of this patient were investigated by immunostaining and Western blotting methods using antibodies reacting with StAR protein, Ad4BP/SF‐1, CYP11A1, CYP17A1, 3β‐HSD, and 17β‐HSD. As control samples, we used biopsy tissues from three individuals with cryptorchidism ( n = 3; mean age, 5). All these steroid synthesis‐related proteins were observed in LCs of control samples using immunohistochemistry (Fig. 3 ). Western blotting analysis showed negative results for StAR protein in the testis of this patient (data not shown). LCs both with and without lipid droplets in this patient expressed all the steroid synthesis‐related proteins except StAR, 3β‐HSD, and 17β‐HSD (Fig. 3 ). This was part of a study approved by the ethics committee of Fukushima Medical University School of Medicine (2245). Informed consent was obtained after explaining the purpose and methods.'}
|
{'Case presentation': 'A 15‐day‐old 46, XY neonate presented with severe adrenal insufficiency. Congenital lipoid adrenal hyperplasia was diagnosed after detection of steroidogenic acute regulatory gene mutations. At 2 years and 5 months, she underwent bilateral gonadectomy. Leydig cells were observed both with and without lipid droplets in the testes of this patient. We also demonstrated immunohistochemically that some testosterone‐synthesizing enzymes were maintained in this patient. The patient was born at full term with completely normal female external genitalia. No abnormalities were identified in routine newborn screenings. At 15 days, she was brought to the hospital with poor feeding and poor weight gain. Hyperpigmentation suggestive of adrenal insufficiency was noted. Laboratory tests revealed severe hyponatremia (115 mEq/L) and hyperkalemia (8.6 mEq/L). She was immediately treated with hydrocortisone and examined for all adrenocortical hormones and associated metabolites in serum and urine. Not only mineralocorticoids and glucocorticoids, but also adrenal androgens and their metabolic products were barely detectable. On the other hand, concentrations of adrenocorticotropic hormone were extremely high, at 387 pg/mL (normal 7.2–63.3 pg/mL). CT showed enlargement of bilateral adrenal glands (Fig. 1 a). Bilateral gonads were not palpable but were detectable near the internal inguinal rings on ultrasonography and MRI (Fig. 1 b). Since congenital adrenal hyperplasia was strongly suspected, chromosomal genetic testing was performed and revealed a 46,XY karyotype. Sequence analysis of the StAR gene revealed compound heterozygous mutations for p.Q258X and p.D246fs. From these results, lipoid CAH was diagnosed. Laparoscopic bilateral gonadectomy was performed at 2 years and 5 months. Both gonads were identified as normal testes accompanied by vas deferens and epididymis. The testes measured 16 × 10 × 6 mm on the right and 14 × 8 × 8 mm on the left (Fig. 2 a,b). As of the time of writing, she is continuing adrenocortical hormone replacement therapy, and will receive combination estrogen replacement therapy at the time of puberty.', 'Histopathological findings': 'Light microscopy showed seminiferous tubules mainly comprising spermatogonia and Sertoli cells, with no spermatocytes or spermatids (Fig. 2 c). Two types of LCs were identified, filled with and without lipid droplets in the testicular interstitium. The nuclei of LCs depressed by excessive lipid droplets were more clearly observable under electron microscopy (Fig. 2 d). Testosterone‐synthesizing enzymes in the testis of this patient were investigated by immunostaining and Western blotting methods using antibodies reacting with StAR protein, Ad4BP/SF‐1, CYP11A1, CYP17A1, 3β‐HSD, and 17β‐HSD. As control samples, we used biopsy tissues from three individuals with cryptorchidism ( n = 3; mean age, 5). All these steroid synthesis‐related proteins were observed in LCs of control samples using immunohistochemistry (Fig. 3 ). Western blotting analysis showed negative results for StAR protein in the testis of this patient (data not shown). LCs both with and without lipid droplets in this patient expressed all the steroid synthesis‐related proteins except StAR, 3β‐HSD, and 17β‐HSD (Fig. 3 ). This was part of a study approved by the ethics committee of Fukushima Medical University School of Medicine (2245). Informed consent was obtained after explaining the purpose and methods.'}
|
Gastrointestinal-System
|
GI
|
[
"poor feeding and poor weight gain."
] |
test-2109
|
7292164
|
{'Case presentation': 'A 15‐day‐old 46, XY neonate presented with severe adrenal insufficiency. Congenital lipoid adrenal hyperplasia was diagnosed after detection of steroidogenic acute regulatory gene mutations. At 2 years and 5 months, she underwent bilateral gonadectomy. Leydig cells were observed both with and without lipid droplets in the testes of this patient. We also demonstrated immunohistochemically that some testosterone‐synthesizing enzymes were maintained in this patient. The patient was born at full term with completely normal female external genitalia. No abnormalities were identified in routine newborn screenings. At 15 days, she was brought to the hospital with poor feeding and poor weight gain. Hyperpigmentation suggestive of adrenal insufficiency was noted. Laboratory tests revealed severe hyponatremia (115 mEq/L) and hyperkalemia (8.6 mEq/L). She was immediately treated with hydrocortisone and examined for all adrenocortical hormones and associated metabolites in serum and urine. Not only mineralocorticoids and glucocorticoids, but also adrenal androgens and their metabolic products were barely detectable. On the other hand, concentrations of adrenocorticotropic hormone were extremely high, at 387 pg/mL (normal 7.2–63.3 pg/mL). CT showed enlargement of bilateral adrenal glands (Fig. 1 a). Bilateral gonads were not palpable but were detectable near the internal inguinal rings on ultrasonography and MRI (Fig. 1 b). Since congenital adrenal hyperplasia was strongly suspected, chromosomal genetic testing was performed and revealed a 46,XY karyotype. Sequence analysis of the StAR gene revealed compound heterozygous mutations for p.Q258X and p.D246fs. From these results, lipoid CAH was diagnosed. Laparoscopic bilateral gonadectomy was performed at 2 years and 5 months. Both gonads were identified as normal testes accompanied by vas deferens and epididymis. The testes measured 16 × 10 × 6 mm on the right and 14 × 8 × 8 mm on the left (Fig. 2 a,b). As of the time of writing, she is continuing adrenocortical hormone replacement therapy, and will receive combination estrogen replacement therapy at the time of puberty.', 'Histopathological findings': 'Light microscopy showed seminiferous tubules mainly comprising spermatogonia and Sertoli cells, with no spermatocytes or spermatids (Fig. 2 c). Two types of LCs were identified, filled with and without lipid droplets in the testicular interstitium. The nuclei of LCs depressed by excessive lipid droplets were more clearly observable under electron microscopy (Fig. 2 d). Testosterone‐synthesizing enzymes in the testis of this patient were investigated by immunostaining and Western blotting methods using antibodies reacting with StAR protein, Ad4BP/SF‐1, CYP11A1, CYP17A1, 3β‐HSD, and 17β‐HSD. As control samples, we used biopsy tissues from three individuals with cryptorchidism ( n = 3; mean age, 5). All these steroid synthesis‐related proteins were observed in LCs of control samples using immunohistochemistry (Fig. 3 ). Western blotting analysis showed negative results for StAR protein in the testis of this patient (data not shown). LCs both with and without lipid droplets in this patient expressed all the steroid synthesis‐related proteins except StAR, 3β‐HSD, and 17β‐HSD (Fig. 3 ). This was part of a study approved by the ethics committee of Fukushima Medical University School of Medicine (2245). Informed consent was obtained after explaining the purpose and methods.'}
|
{'Case presentation': 'A 15‐day‐old 46, XY neonate presented with severe adrenal insufficiency. Congenital lipoid adrenal hyperplasia was diagnosed after detection of steroidogenic acute regulatory gene mutations. At 2 years and 5 months, she underwent bilateral gonadectomy. Leydig cells were observed both with and without lipid droplets in the testes of this patient. We also demonstrated immunohistochemically that some testosterone‐synthesizing enzymes were maintained in this patient. The patient was born at full term with completely normal female external genitalia. No abnormalities were identified in routine newborn screenings. At 15 days, she was brought to the hospital with poor feeding and poor weight gain. Hyperpigmentation suggestive of adrenal insufficiency was noted. Laboratory tests revealed severe hyponatremia (115 mEq/L) and hyperkalemia (8.6 mEq/L). She was immediately treated with hydrocortisone and examined for all adrenocortical hormones and associated metabolites in serum and urine. Not only mineralocorticoids and glucocorticoids, but also adrenal androgens and their metabolic products were barely detectable. On the other hand, concentrations of adrenocorticotropic hormone were extremely high, at 387 pg/mL (normal 7.2–63.3 pg/mL). CT showed enlargement of bilateral adrenal glands (Fig. 1 a). Bilateral gonads were not palpable but were detectable near the internal inguinal rings on ultrasonography and MRI (Fig. 1 b). Since congenital adrenal hyperplasia was strongly suspected, chromosomal genetic testing was performed and revealed a 46,XY karyotype. Sequence analysis of the StAR gene revealed compound heterozygous mutations for p.Q258X and p.D246fs. From these results, lipoid CAH was diagnosed. Laparoscopic bilateral gonadectomy was performed at 2 years and 5 months. Both gonads were identified as normal testes accompanied by vas deferens and epididymis. The testes measured 16 × 10 × 6 mm on the right and 14 × 8 × 8 mm on the left (Fig. 2 a,b). As of the time of writing, she is continuing adrenocortical hormone replacement therapy, and will receive combination estrogen replacement therapy at the time of puberty.', 'Histopathological findings': 'Light microscopy showed seminiferous tubules mainly comprising spermatogonia and Sertoli cells, with no spermatocytes or spermatids (Fig. 2 c). Two types of LCs were identified, filled with and without lipid droplets in the testicular interstitium. The nuclei of LCs depressed by excessive lipid droplets were more clearly observable under electron microscopy (Fig. 2 d). Testosterone‐synthesizing enzymes in the testis of this patient were investigated by immunostaining and Western blotting methods using antibodies reacting with StAR protein, Ad4BP/SF‐1, CYP11A1, CYP17A1, 3β‐HSD, and 17β‐HSD. As control samples, we used biopsy tissues from three individuals with cryptorchidism ( n = 3; mean age, 5). All these steroid synthesis‐related proteins were observed in LCs of control samples using immunohistochemistry (Fig. 3 ). Western blotting analysis showed negative results for StAR protein in the testis of this patient (data not shown). LCs both with and without lipid droplets in this patient expressed all the steroid synthesis‐related proteins except StAR, 3β‐HSD, and 17β‐HSD (Fig. 3 ). This was part of a study approved by the ethics committee of Fukushima Medical University School of Medicine (2245). Informed consent was obtained after explaining the purpose and methods.'}
|
Patient-History
|
History
|
[
"A 15â€dayâ€old 46, XY neonate presented with severe adrenal insufficiency",
"At 2 years and 5 months, she underwent bilateral gonadectomy"
] |
test-2110
|
7292164
|
{'Case presentation': 'A 15‐day‐old 46, XY neonate presented with severe adrenal insufficiency. Congenital lipoid adrenal hyperplasia was diagnosed after detection of steroidogenic acute regulatory gene mutations. At 2 years and 5 months, she underwent bilateral gonadectomy. Leydig cells were observed both with and without lipid droplets in the testes of this patient. We also demonstrated immunohistochemically that some testosterone‐synthesizing enzymes were maintained in this patient. The patient was born at full term with completely normal female external genitalia. No abnormalities were identified in routine newborn screenings. At 15 days, she was brought to the hospital with poor feeding and poor weight gain. Hyperpigmentation suggestive of adrenal insufficiency was noted. Laboratory tests revealed severe hyponatremia (115 mEq/L) and hyperkalemia (8.6 mEq/L). She was immediately treated with hydrocortisone and examined for all adrenocortical hormones and associated metabolites in serum and urine. Not only mineralocorticoids and glucocorticoids, but also adrenal androgens and their metabolic products were barely detectable. On the other hand, concentrations of adrenocorticotropic hormone were extremely high, at 387 pg/mL (normal 7.2–63.3 pg/mL). CT showed enlargement of bilateral adrenal glands (Fig. 1 a). Bilateral gonads were not palpable but were detectable near the internal inguinal rings on ultrasonography and MRI (Fig. 1 b). Since congenital adrenal hyperplasia was strongly suspected, chromosomal genetic testing was performed and revealed a 46,XY karyotype. Sequence analysis of the StAR gene revealed compound heterozygous mutations for p.Q258X and p.D246fs. From these results, lipoid CAH was diagnosed. Laparoscopic bilateral gonadectomy was performed at 2 years and 5 months. Both gonads were identified as normal testes accompanied by vas deferens and epididymis. The testes measured 16 × 10 × 6 mm on the right and 14 × 8 × 8 mm on the left (Fig. 2 a,b). As of the time of writing, she is continuing adrenocortical hormone replacement therapy, and will receive combination estrogen replacement therapy at the time of puberty.', 'Histopathological findings': 'Light microscopy showed seminiferous tubules mainly comprising spermatogonia and Sertoli cells, with no spermatocytes or spermatids (Fig. 2 c). Two types of LCs were identified, filled with and without lipid droplets in the testicular interstitium. The nuclei of LCs depressed by excessive lipid droplets were more clearly observable under electron microscopy (Fig. 2 d). Testosterone‐synthesizing enzymes in the testis of this patient were investigated by immunostaining and Western blotting methods using antibodies reacting with StAR protein, Ad4BP/SF‐1, CYP11A1, CYP17A1, 3β‐HSD, and 17β‐HSD. As control samples, we used biopsy tissues from three individuals with cryptorchidism ( n = 3; mean age, 5). All these steroid synthesis‐related proteins were observed in LCs of control samples using immunohistochemistry (Fig. 3 ). Western blotting analysis showed negative results for StAR protein in the testis of this patient (data not shown). LCs both with and without lipid droplets in this patient expressed all the steroid synthesis‐related proteins except StAR, 3β‐HSD, and 17β‐HSD (Fig. 3 ). This was part of a study approved by the ethics committee of Fukushima Medical University School of Medicine (2245). Informed consent was obtained after explaining the purpose and methods.'}
|
{'Case presentation': 'A 15‐day‐old 46, XY neonate presented with severe adrenal insufficiency. Congenital lipoid adrenal hyperplasia was diagnosed after detection of steroidogenic acute regulatory gene mutations. At 2 years and 5 months, she underwent bilateral gonadectomy. Leydig cells were observed both with and without lipid droplets in the testes of this patient. We also demonstrated immunohistochemically that some testosterone‐synthesizing enzymes were maintained in this patient. The patient was born at full term with completely normal female external genitalia. No abnormalities were identified in routine newborn screenings. At 15 days, she was brought to the hospital with poor feeding and poor weight gain. Hyperpigmentation suggestive of adrenal insufficiency was noted. Laboratory tests revealed severe hyponatremia (115 mEq/L) and hyperkalemia (8.6 mEq/L). She was immediately treated with hydrocortisone and examined for all adrenocortical hormones and associated metabolites in serum and urine. Not only mineralocorticoids and glucocorticoids, but also adrenal androgens and their metabolic products were barely detectable. On the other hand, concentrations of adrenocorticotropic hormone were extremely high, at 387 pg/mL (normal 7.2–63.3 pg/mL). CT showed enlargement of bilateral adrenal glands (Fig. 1 a). Bilateral gonads were not palpable but were detectable near the internal inguinal rings on ultrasonography and MRI (Fig. 1 b). Since congenital adrenal hyperplasia was strongly suspected, chromosomal genetic testing was performed and revealed a 46,XY karyotype. Sequence analysis of the StAR gene revealed compound heterozygous mutations for p.Q258X and p.D246fs. From these results, lipoid CAH was diagnosed. Laparoscopic bilateral gonadectomy was performed at 2 years and 5 months. Both gonads were identified as normal testes accompanied by vas deferens and epididymis. The testes measured 16 × 10 × 6 mm on the right and 14 × 8 × 8 mm on the left (Fig. 2 a,b). As of the time of writing, she is continuing adrenocortical hormone replacement therapy, and will receive combination estrogen replacement therapy at the time of puberty.', 'Histopathological findings': 'Light microscopy showed seminiferous tubules mainly comprising spermatogonia and Sertoli cells, with no spermatocytes or spermatids (Fig. 2 c). Two types of LCs were identified, filled with and without lipid droplets in the testicular interstitium. The nuclei of LCs depressed by excessive lipid droplets were more clearly observable under electron microscopy (Fig. 2 d). Testosterone‐synthesizing enzymes in the testis of this patient were investigated by immunostaining and Western blotting methods using antibodies reacting with StAR protein, Ad4BP/SF‐1, CYP11A1, CYP17A1, 3β‐HSD, and 17β‐HSD. As control samples, we used biopsy tissues from three individuals with cryptorchidism ( n = 3; mean age, 5). All these steroid synthesis‐related proteins were observed in LCs of control samples using immunohistochemistry (Fig. 3 ). Western blotting analysis showed negative results for StAR protein in the testis of this patient (data not shown). LCs both with and without lipid droplets in this patient expressed all the steroid synthesis‐related proteins except StAR, 3β‐HSD, and 17β‐HSD (Fig. 3 ). This was part of a study approved by the ethics committee of Fukushima Medical University School of Medicine (2245). Informed consent was obtained after explaining the purpose and methods.'}
|
Neurology
|
Neuro
|
[] |
test-2111
|
7292164
|
{'Case presentation': 'A 15‐day‐old 46, XY neonate presented with severe adrenal insufficiency. Congenital lipoid adrenal hyperplasia was diagnosed after detection of steroidogenic acute regulatory gene mutations. At 2 years and 5 months, she underwent bilateral gonadectomy. Leydig cells were observed both with and without lipid droplets in the testes of this patient. We also demonstrated immunohistochemically that some testosterone‐synthesizing enzymes were maintained in this patient. The patient was born at full term with completely normal female external genitalia. No abnormalities were identified in routine newborn screenings. At 15 days, she was brought to the hospital with poor feeding and poor weight gain. Hyperpigmentation suggestive of adrenal insufficiency was noted. Laboratory tests revealed severe hyponatremia (115 mEq/L) and hyperkalemia (8.6 mEq/L). She was immediately treated with hydrocortisone and examined for all adrenocortical hormones and associated metabolites in serum and urine. Not only mineralocorticoids and glucocorticoids, but also adrenal androgens and their metabolic products were barely detectable. On the other hand, concentrations of adrenocorticotropic hormone were extremely high, at 387 pg/mL (normal 7.2–63.3 pg/mL). CT showed enlargement of bilateral adrenal glands (Fig. 1 a). Bilateral gonads were not palpable but were detectable near the internal inguinal rings on ultrasonography and MRI (Fig. 1 b). Since congenital adrenal hyperplasia was strongly suspected, chromosomal genetic testing was performed and revealed a 46,XY karyotype. Sequence analysis of the StAR gene revealed compound heterozygous mutations for p.Q258X and p.D246fs. From these results, lipoid CAH was diagnosed. Laparoscopic bilateral gonadectomy was performed at 2 years and 5 months. Both gonads were identified as normal testes accompanied by vas deferens and epididymis. The testes measured 16 × 10 × 6 mm on the right and 14 × 8 × 8 mm on the left (Fig. 2 a,b). As of the time of writing, she is continuing adrenocortical hormone replacement therapy, and will receive combination estrogen replacement therapy at the time of puberty.', 'Histopathological findings': 'Light microscopy showed seminiferous tubules mainly comprising spermatogonia and Sertoli cells, with no spermatocytes or spermatids (Fig. 2 c). Two types of LCs were identified, filled with and without lipid droplets in the testicular interstitium. The nuclei of LCs depressed by excessive lipid droplets were more clearly observable under electron microscopy (Fig. 2 d). Testosterone‐synthesizing enzymes in the testis of this patient were investigated by immunostaining and Western blotting methods using antibodies reacting with StAR protein, Ad4BP/SF‐1, CYP11A1, CYP17A1, 3β‐HSD, and 17β‐HSD. As control samples, we used biopsy tissues from three individuals with cryptorchidism ( n = 3; mean age, 5). All these steroid synthesis‐related proteins were observed in LCs of control samples using immunohistochemistry (Fig. 3 ). Western blotting analysis showed negative results for StAR protein in the testis of this patient (data not shown). LCs both with and without lipid droplets in this patient expressed all the steroid synthesis‐related proteins except StAR, 3β‐HSD, and 17β‐HSD (Fig. 3 ). This was part of a study approved by the ethics committee of Fukushima Medical University School of Medicine (2245). Informed consent was obtained after explaining the purpose and methods.'}
|
{'Case presentation': 'A 15‐day‐old 46, XY neonate presented with severe adrenal insufficiency. Congenital lipoid adrenal hyperplasia was diagnosed after detection of steroidogenic acute regulatory gene mutations. At 2 years and 5 months, she underwent bilateral gonadectomy. Leydig cells were observed both with and without lipid droplets in the testes of this patient. We also demonstrated immunohistochemically that some testosterone‐synthesizing enzymes were maintained in this patient. The patient was born at full term with completely normal female external genitalia. No abnormalities were identified in routine newborn screenings. At 15 days, she was brought to the hospital with poor feeding and poor weight gain. Hyperpigmentation suggestive of adrenal insufficiency was noted. Laboratory tests revealed severe hyponatremia (115 mEq/L) and hyperkalemia (8.6 mEq/L). She was immediately treated with hydrocortisone and examined for all adrenocortical hormones and associated metabolites in serum and urine. Not only mineralocorticoids and glucocorticoids, but also adrenal androgens and their metabolic products were barely detectable. On the other hand, concentrations of adrenocorticotropic hormone were extremely high, at 387 pg/mL (normal 7.2–63.3 pg/mL). CT showed enlargement of bilateral adrenal glands (Fig. 1 a). Bilateral gonads were not palpable but were detectable near the internal inguinal rings on ultrasonography and MRI (Fig. 1 b). Since congenital adrenal hyperplasia was strongly suspected, chromosomal genetic testing was performed and revealed a 46,XY karyotype. Sequence analysis of the StAR gene revealed compound heterozygous mutations for p.Q258X and p.D246fs. From these results, lipoid CAH was diagnosed. Laparoscopic bilateral gonadectomy was performed at 2 years and 5 months. Both gonads were identified as normal testes accompanied by vas deferens and epididymis. The testes measured 16 × 10 × 6 mm on the right and 14 × 8 × 8 mm on the left (Fig. 2 a,b). As of the time of writing, she is continuing adrenocortical hormone replacement therapy, and will receive combination estrogen replacement therapy at the time of puberty.', 'Histopathological findings': 'Light microscopy showed seminiferous tubules mainly comprising spermatogonia and Sertoli cells, with no spermatocytes or spermatids (Fig. 2 c). Two types of LCs were identified, filled with and without lipid droplets in the testicular interstitium. The nuclei of LCs depressed by excessive lipid droplets were more clearly observable under electron microscopy (Fig. 2 d). Testosterone‐synthesizing enzymes in the testis of this patient were investigated by immunostaining and Western blotting methods using antibodies reacting with StAR protein, Ad4BP/SF‐1, CYP11A1, CYP17A1, 3β‐HSD, and 17β‐HSD. As control samples, we used biopsy tissues from three individuals with cryptorchidism ( n = 3; mean age, 5). All these steroid synthesis‐related proteins were observed in LCs of control samples using immunohistochemistry (Fig. 3 ). Western blotting analysis showed negative results for StAR protein in the testis of this patient (data not shown). LCs both with and without lipid droplets in this patient expressed all the steroid synthesis‐related proteins except StAR, 3β‐HSD, and 17β‐HSD (Fig. 3 ). This was part of a study approved by the ethics committee of Fukushima Medical University School of Medicine (2245). Informed consent was obtained after explaining the purpose and methods.'}
|
Laboratory-and-Imaging
|
Lab_Image
|
[
"Laboratory tests revealed severe hyponatremia ( 115 mEq / L ) and hyperkalemia ( 8.6 mEq / L ).",
"Not only mineralocorticoids and glucocorticoids, but also adrenal androgens and their metabolic products were barely detectable. On the other hand, concentrations of adrenocorticotropic hormone were extremely high, at 387 pg / mL ( normal 7.2–63.3 pg / mL ). CT showed enlargement of bilateral adrenal glands ( Fig. 1 a ). Bilateral gonads were not palpable but were detectable near the internal inguinal rings on ultrasonography and MRI ( Fig. 1 b ). Since congenital adrenal hyperplasia was strongly suspected, chromosomal genetic testing was performed and revealed a 46,XY karyotype. Sequence analysis of the StAR gene revealed compound heterozygous mutations for p. Q258X and p. D246fs. From these results, lipoid CAH was diagnosed.",
"Histopathological findings ' : ' Light microscopy showed seminiferous tubules mainly comprising spermatogonia and Sertoli cells, with no spermatocytes or spermatids ( Fig. 2 c ). Two types of LCs were identified, filled with and without lipid droplets in the testicular interstitium. The nuclei of LCs depressed by excessive lipid droplets were more clearly observable under electron microscopy ( Fig. 2 d ). Testosteroneâ€synthesizing enzymes in the testis of this patient were investigated by immunostaining and Western blotting methods using antibodies reacting with StAR protein, Ad4BP / SFâ€1, CYP11A1, CYP17A1, 3βâ€HSD, and 17βâ€HSD. As control samples, we used biopsy tissues from three individuals with cryptorchidism ( n = 3; mean age, 5 ). All these steroid synthesisâ€related proteins were observed in LCs of control samples using immunohistochemistry ( Fig. 3 ). Western blotting analysis showed negative results for StAR protein in the testis of this patient ( data not shown ). LCs both with and without lipid droplets in this patient expressed all the steroid synthesisâ€related proteins except StAR, 3βâ€HSD, and 17βâ€HSD"
] |
test-2112
|
7292164
|
{'Case presentation': 'A 15‐day‐old 46, XY neonate presented with severe adrenal insufficiency. Congenital lipoid adrenal hyperplasia was diagnosed after detection of steroidogenic acute regulatory gene mutations. At 2 years and 5 months, she underwent bilateral gonadectomy. Leydig cells were observed both with and without lipid droplets in the testes of this patient. We also demonstrated immunohistochemically that some testosterone‐synthesizing enzymes were maintained in this patient. The patient was born at full term with completely normal female external genitalia. No abnormalities were identified in routine newborn screenings. At 15 days, she was brought to the hospital with poor feeding and poor weight gain. Hyperpigmentation suggestive of adrenal insufficiency was noted. Laboratory tests revealed severe hyponatremia (115 mEq/L) and hyperkalemia (8.6 mEq/L). She was immediately treated with hydrocortisone and examined for all adrenocortical hormones and associated metabolites in serum and urine. Not only mineralocorticoids and glucocorticoids, but also adrenal androgens and their metabolic products were barely detectable. On the other hand, concentrations of adrenocorticotropic hormone were extremely high, at 387 pg/mL (normal 7.2–63.3 pg/mL). CT showed enlargement of bilateral adrenal glands (Fig. 1 a). Bilateral gonads were not palpable but were detectable near the internal inguinal rings on ultrasonography and MRI (Fig. 1 b). Since congenital adrenal hyperplasia was strongly suspected, chromosomal genetic testing was performed and revealed a 46,XY karyotype. Sequence analysis of the StAR gene revealed compound heterozygous mutations for p.Q258X and p.D246fs. From these results, lipoid CAH was diagnosed. Laparoscopic bilateral gonadectomy was performed at 2 years and 5 months. Both gonads were identified as normal testes accompanied by vas deferens and epididymis. The testes measured 16 × 10 × 6 mm on the right and 14 × 8 × 8 mm on the left (Fig. 2 a,b). As of the time of writing, she is continuing adrenocortical hormone replacement therapy, and will receive combination estrogen replacement therapy at the time of puberty.', 'Histopathological findings': 'Light microscopy showed seminiferous tubules mainly comprising spermatogonia and Sertoli cells, with no spermatocytes or spermatids (Fig. 2 c). Two types of LCs were identified, filled with and without lipid droplets in the testicular interstitium. The nuclei of LCs depressed by excessive lipid droplets were more clearly observable under electron microscopy (Fig. 2 d). Testosterone‐synthesizing enzymes in the testis of this patient were investigated by immunostaining and Western blotting methods using antibodies reacting with StAR protein, Ad4BP/SF‐1, CYP11A1, CYP17A1, 3β‐HSD, and 17β‐HSD. As control samples, we used biopsy tissues from three individuals with cryptorchidism ( n = 3; mean age, 5). All these steroid synthesis‐related proteins were observed in LCs of control samples using immunohistochemistry (Fig. 3 ). Western blotting analysis showed negative results for StAR protein in the testis of this patient (data not shown). LCs both with and without lipid droplets in this patient expressed all the steroid synthesis‐related proteins except StAR, 3β‐HSD, and 17β‐HSD (Fig. 3 ). This was part of a study approved by the ethics committee of Fukushima Medical University School of Medicine (2245). Informed consent was obtained after explaining the purpose and methods.'}
|
{'Case presentation': 'A 15‐day‐old 46, XY neonate presented with severe adrenal insufficiency. Congenital lipoid adrenal hyperplasia was diagnosed after detection of steroidogenic acute regulatory gene mutations. At 2 years and 5 months, she underwent bilateral gonadectomy. Leydig cells were observed both with and without lipid droplets in the testes of this patient. We also demonstrated immunohistochemically that some testosterone‐synthesizing enzymes were maintained in this patient. The patient was born at full term with completely normal female external genitalia. No abnormalities were identified in routine newborn screenings. At 15 days, she was brought to the hospital with poor feeding and poor weight gain. Hyperpigmentation suggestive of adrenal insufficiency was noted. Laboratory tests revealed severe hyponatremia (115 mEq/L) and hyperkalemia (8.6 mEq/L). She was immediately treated with hydrocortisone and examined for all adrenocortical hormones and associated metabolites in serum and urine. Not only mineralocorticoids and glucocorticoids, but also adrenal androgens and their metabolic products were barely detectable. On the other hand, concentrations of adrenocorticotropic hormone were extremely high, at 387 pg/mL (normal 7.2–63.3 pg/mL). CT showed enlargement of bilateral adrenal glands (Fig. 1 a). Bilateral gonads were not palpable but were detectable near the internal inguinal rings on ultrasonography and MRI (Fig. 1 b). Since congenital adrenal hyperplasia was strongly suspected, chromosomal genetic testing was performed and revealed a 46,XY karyotype. Sequence analysis of the StAR gene revealed compound heterozygous mutations for p.Q258X and p.D246fs. From these results, lipoid CAH was diagnosed. Laparoscopic bilateral gonadectomy was performed at 2 years and 5 months. Both gonads were identified as normal testes accompanied by vas deferens and epididymis. The testes measured 16 × 10 × 6 mm on the right and 14 × 8 × 8 mm on the left (Fig. 2 a,b). As of the time of writing, she is continuing adrenocortical hormone replacement therapy, and will receive combination estrogen replacement therapy at the time of puberty.', 'Histopathological findings': 'Light microscopy showed seminiferous tubules mainly comprising spermatogonia and Sertoli cells, with no spermatocytes or spermatids (Fig. 2 c). Two types of LCs were identified, filled with and without lipid droplets in the testicular interstitium. The nuclei of LCs depressed by excessive lipid droplets were more clearly observable under electron microscopy (Fig. 2 d). Testosterone‐synthesizing enzymes in the testis of this patient were investigated by immunostaining and Western blotting methods using antibodies reacting with StAR protein, Ad4BP/SF‐1, CYP11A1, CYP17A1, 3β‐HSD, and 17β‐HSD. As control samples, we used biopsy tissues from three individuals with cryptorchidism ( n = 3; mean age, 5). All these steroid synthesis‐related proteins were observed in LCs of control samples using immunohistochemistry (Fig. 3 ). Western blotting analysis showed negative results for StAR protein in the testis of this patient (data not shown). LCs both with and without lipid droplets in this patient expressed all the steroid synthesis‐related proteins except StAR, 3β‐HSD, and 17β‐HSD (Fig. 3 ). This was part of a study approved by the ethics committee of Fukushima Medical University School of Medicine (2245). Informed consent was obtained after explaining the purpose and methods.'}
|
Cardiovascular-System
|
CVS
|
[] |
test-2113
|
7292164
|
{'Case presentation': 'A 15‐day‐old 46, XY neonate presented with severe adrenal insufficiency. Congenital lipoid adrenal hyperplasia was diagnosed after detection of steroidogenic acute regulatory gene mutations. At 2 years and 5 months, she underwent bilateral gonadectomy. Leydig cells were observed both with and without lipid droplets in the testes of this patient. We also demonstrated immunohistochemically that some testosterone‐synthesizing enzymes were maintained in this patient. The patient was born at full term with completely normal female external genitalia. No abnormalities were identified in routine newborn screenings. At 15 days, she was brought to the hospital with poor feeding and poor weight gain. Hyperpigmentation suggestive of adrenal insufficiency was noted. Laboratory tests revealed severe hyponatremia (115 mEq/L) and hyperkalemia (8.6 mEq/L). She was immediately treated with hydrocortisone and examined for all adrenocortical hormones and associated metabolites in serum and urine. Not only mineralocorticoids and glucocorticoids, but also adrenal androgens and their metabolic products were barely detectable. On the other hand, concentrations of adrenocorticotropic hormone were extremely high, at 387 pg/mL (normal 7.2–63.3 pg/mL). CT showed enlargement of bilateral adrenal glands (Fig. 1 a). Bilateral gonads were not palpable but were detectable near the internal inguinal rings on ultrasonography and MRI (Fig. 1 b). Since congenital adrenal hyperplasia was strongly suspected, chromosomal genetic testing was performed and revealed a 46,XY karyotype. Sequence analysis of the StAR gene revealed compound heterozygous mutations for p.Q258X and p.D246fs. From these results, lipoid CAH was diagnosed. Laparoscopic bilateral gonadectomy was performed at 2 years and 5 months. Both gonads were identified as normal testes accompanied by vas deferens and epididymis. The testes measured 16 × 10 × 6 mm on the right and 14 × 8 × 8 mm on the left (Fig. 2 a,b). As of the time of writing, she is continuing adrenocortical hormone replacement therapy, and will receive combination estrogen replacement therapy at the time of puberty.', 'Histopathological findings': 'Light microscopy showed seminiferous tubules mainly comprising spermatogonia and Sertoli cells, with no spermatocytes or spermatids (Fig. 2 c). Two types of LCs were identified, filled with and without lipid droplets in the testicular interstitium. The nuclei of LCs depressed by excessive lipid droplets were more clearly observable under electron microscopy (Fig. 2 d). Testosterone‐synthesizing enzymes in the testis of this patient were investigated by immunostaining and Western blotting methods using antibodies reacting with StAR protein, Ad4BP/SF‐1, CYP11A1, CYP17A1, 3β‐HSD, and 17β‐HSD. As control samples, we used biopsy tissues from three individuals with cryptorchidism ( n = 3; mean age, 5). All these steroid synthesis‐related proteins were observed in LCs of control samples using immunohistochemistry (Fig. 3 ). Western blotting analysis showed negative results for StAR protein in the testis of this patient (data not shown). LCs both with and without lipid droplets in this patient expressed all the steroid synthesis‐related proteins except StAR, 3β‐HSD, and 17β‐HSD (Fig. 3 ). This was part of a study approved by the ethics committee of Fukushima Medical University School of Medicine (2245). Informed consent was obtained after explaining the purpose and methods.'}
|
{'Case presentation': 'A 15‐day‐old 46, XY neonate presented with severe adrenal insufficiency. Congenital lipoid adrenal hyperplasia was diagnosed after detection of steroidogenic acute regulatory gene mutations. At 2 years and 5 months, she underwent bilateral gonadectomy. Leydig cells were observed both with and without lipid droplets in the testes of this patient. We also demonstrated immunohistochemically that some testosterone‐synthesizing enzymes were maintained in this patient. The patient was born at full term with completely normal female external genitalia. No abnormalities were identified in routine newborn screenings. At 15 days, she was brought to the hospital with poor feeding and poor weight gain. Hyperpigmentation suggestive of adrenal insufficiency was noted. Laboratory tests revealed severe hyponatremia (115 mEq/L) and hyperkalemia (8.6 mEq/L). She was immediately treated with hydrocortisone and examined for all adrenocortical hormones and associated metabolites in serum and urine. Not only mineralocorticoids and glucocorticoids, but also adrenal androgens and their metabolic products were barely detectable. On the other hand, concentrations of adrenocorticotropic hormone were extremely high, at 387 pg/mL (normal 7.2–63.3 pg/mL). CT showed enlargement of bilateral adrenal glands (Fig. 1 a). Bilateral gonads were not palpable but were detectable near the internal inguinal rings on ultrasonography and MRI (Fig. 1 b). Since congenital adrenal hyperplasia was strongly suspected, chromosomal genetic testing was performed and revealed a 46,XY karyotype. Sequence analysis of the StAR gene revealed compound heterozygous mutations for p.Q258X and p.D246fs. From these results, lipoid CAH was diagnosed. Laparoscopic bilateral gonadectomy was performed at 2 years and 5 months. Both gonads were identified as normal testes accompanied by vas deferens and epididymis. The testes measured 16 × 10 × 6 mm on the right and 14 × 8 × 8 mm on the left (Fig. 2 a,b). As of the time of writing, she is continuing adrenocortical hormone replacement therapy, and will receive combination estrogen replacement therapy at the time of puberty.', 'Histopathological findings': 'Light microscopy showed seminiferous tubules mainly comprising spermatogonia and Sertoli cells, with no spermatocytes or spermatids (Fig. 2 c). Two types of LCs were identified, filled with and without lipid droplets in the testicular interstitium. The nuclei of LCs depressed by excessive lipid droplets were more clearly observable under electron microscopy (Fig. 2 d). Testosterone‐synthesizing enzymes in the testis of this patient were investigated by immunostaining and Western blotting methods using antibodies reacting with StAR protein, Ad4BP/SF‐1, CYP11A1, CYP17A1, 3β‐HSD, and 17β‐HSD. As control samples, we used biopsy tissues from three individuals with cryptorchidism ( n = 3; mean age, 5). All these steroid synthesis‐related proteins were observed in LCs of control samples using immunohistochemistry (Fig. 3 ). Western blotting analysis showed negative results for StAR protein in the testis of this patient (data not shown). LCs both with and without lipid droplets in this patient expressed all the steroid synthesis‐related proteins except StAR, 3β‐HSD, and 17β‐HSD (Fig. 3 ). This was part of a study approved by the ethics committee of Fukushima Medical University School of Medicine (2245). Informed consent was obtained after explaining the purpose and methods.'}
|
Endocrinology
|
ENDO
|
[
"severe adrenal insufficiency",
"Leydig cells were observed both with and without lipid droplets in the testes of this patient. We also demonstrated immunohistochemically that some testosterone‐synthesizing enzymes were maintained in this patient",
"severe hyponatremia ( 115 mEq / L ) and hyperkalemia ( 8.6 mEq / L ).",
"Not only mineralocorticoids and glucocorticoids, but also adrenal androgens and their metabolic products were barely detectable. On the other hand, concentrations of adrenocorticotropic hormone were extremely high, at 387 pg / mL ( normal 7.2–63.3 pg / mL ). CT showed enlargement of bilateral adrenal glands",
"Testosterone‐synthesizing enzymes in the testis of this patient were investigated by immunostaining and Western blotting methods using antibodies reacting with StAR protein, Ad4BP / SF‐1, CYP11A1, CYP17A1, 3β‐HSD, and 17β‐HSD. As control samples, we used biopsy tissues from three individuals with cryptorchidism ( n = 3; mean age, 5 ). All these steroid synthesis‐related proteins were observed in LCs of control samples using immunohistochemistry ( Fig. 3 ). Western blotting analysis showed negative results for StAR protein in the testis of this patient ( data not shown ). LCs both with and without lipid droplets in this patient expressed all the steroid synthesis‐related proteins except StAR, 3β‐HSD, and 17β‐HSD"
] |
test-2114
|
7292164
|
{'Case presentation': 'A 15‐day‐old 46, XY neonate presented with severe adrenal insufficiency. Congenital lipoid adrenal hyperplasia was diagnosed after detection of steroidogenic acute regulatory gene mutations. At 2 years and 5 months, she underwent bilateral gonadectomy. Leydig cells were observed both with and without lipid droplets in the testes of this patient. We also demonstrated immunohistochemically that some testosterone‐synthesizing enzymes were maintained in this patient. The patient was born at full term with completely normal female external genitalia. No abnormalities were identified in routine newborn screenings. At 15 days, she was brought to the hospital with poor feeding and poor weight gain. Hyperpigmentation suggestive of adrenal insufficiency was noted. Laboratory tests revealed severe hyponatremia (115 mEq/L) and hyperkalemia (8.6 mEq/L). She was immediately treated with hydrocortisone and examined for all adrenocortical hormones and associated metabolites in serum and urine. Not only mineralocorticoids and glucocorticoids, but also adrenal androgens and their metabolic products were barely detectable. On the other hand, concentrations of adrenocorticotropic hormone were extremely high, at 387 pg/mL (normal 7.2–63.3 pg/mL). CT showed enlargement of bilateral adrenal glands (Fig. 1 a). Bilateral gonads were not palpable but were detectable near the internal inguinal rings on ultrasonography and MRI (Fig. 1 b). Since congenital adrenal hyperplasia was strongly suspected, chromosomal genetic testing was performed and revealed a 46,XY karyotype. Sequence analysis of the StAR gene revealed compound heterozygous mutations for p.Q258X and p.D246fs. From these results, lipoid CAH was diagnosed. Laparoscopic bilateral gonadectomy was performed at 2 years and 5 months. Both gonads were identified as normal testes accompanied by vas deferens and epididymis. The testes measured 16 × 10 × 6 mm on the right and 14 × 8 × 8 mm on the left (Fig. 2 a,b). As of the time of writing, she is continuing adrenocortical hormone replacement therapy, and will receive combination estrogen replacement therapy at the time of puberty.', 'Histopathological findings': 'Light microscopy showed seminiferous tubules mainly comprising spermatogonia and Sertoli cells, with no spermatocytes or spermatids (Fig. 2 c). Two types of LCs were identified, filled with and without lipid droplets in the testicular interstitium. The nuclei of LCs depressed by excessive lipid droplets were more clearly observable under electron microscopy (Fig. 2 d). Testosterone‐synthesizing enzymes in the testis of this patient were investigated by immunostaining and Western blotting methods using antibodies reacting with StAR protein, Ad4BP/SF‐1, CYP11A1, CYP17A1, 3β‐HSD, and 17β‐HSD. As control samples, we used biopsy tissues from three individuals with cryptorchidism ( n = 3; mean age, 5). All these steroid synthesis‐related proteins were observed in LCs of control samples using immunohistochemistry (Fig. 3 ). Western blotting analysis showed negative results for StAR protein in the testis of this patient (data not shown). LCs both with and without lipid droplets in this patient expressed all the steroid synthesis‐related proteins except StAR, 3β‐HSD, and 17β‐HSD (Fig. 3 ). This was part of a study approved by the ethics committee of Fukushima Medical University School of Medicine (2245). Informed consent was obtained after explaining the purpose and methods.'}
|
{'Case presentation': 'A 15‐day‐old 46, XY neonate presented with severe adrenal insufficiency. Congenital lipoid adrenal hyperplasia was diagnosed after detection of steroidogenic acute regulatory gene mutations. At 2 years and 5 months, she underwent bilateral gonadectomy. Leydig cells were observed both with and without lipid droplets in the testes of this patient. We also demonstrated immunohistochemically that some testosterone‐synthesizing enzymes were maintained in this patient. The patient was born at full term with completely normal female external genitalia. No abnormalities were identified in routine newborn screenings. At 15 days, she was brought to the hospital with poor feeding and poor weight gain. Hyperpigmentation suggestive of adrenal insufficiency was noted. Laboratory tests revealed severe hyponatremia (115 mEq/L) and hyperkalemia (8.6 mEq/L). She was immediately treated with hydrocortisone and examined for all adrenocortical hormones and associated metabolites in serum and urine. Not only mineralocorticoids and glucocorticoids, but also adrenal androgens and their metabolic products were barely detectable. On the other hand, concentrations of adrenocorticotropic hormone were extremely high, at 387 pg/mL (normal 7.2–63.3 pg/mL). CT showed enlargement of bilateral adrenal glands (Fig. 1 a). Bilateral gonads were not palpable but were detectable near the internal inguinal rings on ultrasonography and MRI (Fig. 1 b). Since congenital adrenal hyperplasia was strongly suspected, chromosomal genetic testing was performed and revealed a 46,XY karyotype. Sequence analysis of the StAR gene revealed compound heterozygous mutations for p.Q258X and p.D246fs. From these results, lipoid CAH was diagnosed. Laparoscopic bilateral gonadectomy was performed at 2 years and 5 months. Both gonads were identified as normal testes accompanied by vas deferens and epididymis. The testes measured 16 × 10 × 6 mm on the right and 14 × 8 × 8 mm on the left (Fig. 2 a,b). As of the time of writing, she is continuing adrenocortical hormone replacement therapy, and will receive combination estrogen replacement therapy at the time of puberty.', 'Histopathological findings': 'Light microscopy showed seminiferous tubules mainly comprising spermatogonia and Sertoli cells, with no spermatocytes or spermatids (Fig. 2 c). Two types of LCs were identified, filled with and without lipid droplets in the testicular interstitium. The nuclei of LCs depressed by excessive lipid droplets were more clearly observable under electron microscopy (Fig. 2 d). Testosterone‐synthesizing enzymes in the testis of this patient were investigated by immunostaining and Western blotting methods using antibodies reacting with StAR protein, Ad4BP/SF‐1, CYP11A1, CYP17A1, 3β‐HSD, and 17β‐HSD. As control samples, we used biopsy tissues from three individuals with cryptorchidism ( n = 3; mean age, 5). All these steroid synthesis‐related proteins were observed in LCs of control samples using immunohistochemistry (Fig. 3 ). Western blotting analysis showed negative results for StAR protein in the testis of this patient (data not shown). LCs both with and without lipid droplets in this patient expressed all the steroid synthesis‐related proteins except StAR, 3β‐HSD, and 17β‐HSD (Fig. 3 ). This was part of a study approved by the ethics committee of Fukushima Medical University School of Medicine (2245). Informed consent was obtained after explaining the purpose and methods.'}
|
Genitourinary-System
|
GU
|
[
"severe hyponatremia ( 115 mEq / L ) and hyperkalemia ( 8.6 mEq / L ).",
"Bilateral gonads were not palpable but were detectable near the internal inguinal rings on ultrasonography and MRI",
"Both gonads were identified as normal testes accompanied by vas deferens and epididymis. The testes measured 16 × 10 × 6 mm on the right and 14 × 8 × 8 mm on the left",
"Light microscopy showed seminiferous tubules mainly comprising spermatogonia and Sertoli cells, with no spermatocytes or spermatids ( Fig. 2 c ). Two types of LCs were identified, filled with and without lipid droplets in the testicular interstitium. The nuclei of LCs depressed by excessive lipid droplets were more clearly observable under electron microscopy"
] |
test-2115
|
7292164
|
{'Case presentation': 'A 15‐day‐old 46, XY neonate presented with severe adrenal insufficiency. Congenital lipoid adrenal hyperplasia was diagnosed after detection of steroidogenic acute regulatory gene mutations. At 2 years and 5 months, she underwent bilateral gonadectomy. Leydig cells were observed both with and without lipid droplets in the testes of this patient. We also demonstrated immunohistochemically that some testosterone‐synthesizing enzymes were maintained in this patient. The patient was born at full term with completely normal female external genitalia. No abnormalities were identified in routine newborn screenings. At 15 days, she was brought to the hospital with poor feeding and poor weight gain. Hyperpigmentation suggestive of adrenal insufficiency was noted. Laboratory tests revealed severe hyponatremia (115 mEq/L) and hyperkalemia (8.6 mEq/L). She was immediately treated with hydrocortisone and examined for all adrenocortical hormones and associated metabolites in serum and urine. Not only mineralocorticoids and glucocorticoids, but also adrenal androgens and their metabolic products were barely detectable. On the other hand, concentrations of adrenocorticotropic hormone were extremely high, at 387 pg/mL (normal 7.2–63.3 pg/mL). CT showed enlargement of bilateral adrenal glands (Fig. 1 a). Bilateral gonads were not palpable but were detectable near the internal inguinal rings on ultrasonography and MRI (Fig. 1 b). Since congenital adrenal hyperplasia was strongly suspected, chromosomal genetic testing was performed and revealed a 46,XY karyotype. Sequence analysis of the StAR gene revealed compound heterozygous mutations for p.Q258X and p.D246fs. From these results, lipoid CAH was diagnosed. Laparoscopic bilateral gonadectomy was performed at 2 years and 5 months. Both gonads were identified as normal testes accompanied by vas deferens and epididymis. The testes measured 16 × 10 × 6 mm on the right and 14 × 8 × 8 mm on the left (Fig. 2 a,b). As of the time of writing, she is continuing adrenocortical hormone replacement therapy, and will receive combination estrogen replacement therapy at the time of puberty.', 'Histopathological findings': 'Light microscopy showed seminiferous tubules mainly comprising spermatogonia and Sertoli cells, with no spermatocytes or spermatids (Fig. 2 c). Two types of LCs were identified, filled with and without lipid droplets in the testicular interstitium. The nuclei of LCs depressed by excessive lipid droplets were more clearly observable under electron microscopy (Fig. 2 d). Testosterone‐synthesizing enzymes in the testis of this patient were investigated by immunostaining and Western blotting methods using antibodies reacting with StAR protein, Ad4BP/SF‐1, CYP11A1, CYP17A1, 3β‐HSD, and 17β‐HSD. As control samples, we used biopsy tissues from three individuals with cryptorchidism ( n = 3; mean age, 5). All these steroid synthesis‐related proteins were observed in LCs of control samples using immunohistochemistry (Fig. 3 ). Western blotting analysis showed negative results for StAR protein in the testis of this patient (data not shown). LCs both with and without lipid droplets in this patient expressed all the steroid synthesis‐related proteins except StAR, 3β‐HSD, and 17β‐HSD (Fig. 3 ). This was part of a study approved by the ethics committee of Fukushima Medical University School of Medicine (2245). Informed consent was obtained after explaining the purpose and methods.'}
|
{'Case presentation': 'A 15‐day‐old 46, XY neonate presented with severe adrenal insufficiency. Congenital lipoid adrenal hyperplasia was diagnosed after detection of steroidogenic acute regulatory gene mutations. At 2 years and 5 months, she underwent bilateral gonadectomy. Leydig cells were observed both with and without lipid droplets in the testes of this patient. We also demonstrated immunohistochemically that some testosterone‐synthesizing enzymes were maintained in this patient. The patient was born at full term with completely normal female external genitalia. No abnormalities were identified in routine newborn screenings. At 15 days, she was brought to the hospital with poor feeding and poor weight gain. Hyperpigmentation suggestive of adrenal insufficiency was noted. Laboratory tests revealed severe hyponatremia (115 mEq/L) and hyperkalemia (8.6 mEq/L). She was immediately treated with hydrocortisone and examined for all adrenocortical hormones and associated metabolites in serum and urine. Not only mineralocorticoids and glucocorticoids, but also adrenal androgens and their metabolic products were barely detectable. On the other hand, concentrations of adrenocorticotropic hormone were extremely high, at 387 pg/mL (normal 7.2–63.3 pg/mL). CT showed enlargement of bilateral adrenal glands (Fig. 1 a). Bilateral gonads were not palpable but were detectable near the internal inguinal rings on ultrasonography and MRI (Fig. 1 b). Since congenital adrenal hyperplasia was strongly suspected, chromosomal genetic testing was performed and revealed a 46,XY karyotype. Sequence analysis of the StAR gene revealed compound heterozygous mutations for p.Q258X and p.D246fs. From these results, lipoid CAH was diagnosed. Laparoscopic bilateral gonadectomy was performed at 2 years and 5 months. Both gonads were identified as normal testes accompanied by vas deferens and epididymis. The testes measured 16 × 10 × 6 mm on the right and 14 × 8 × 8 mm on the left (Fig. 2 a,b). As of the time of writing, she is continuing adrenocortical hormone replacement therapy, and will receive combination estrogen replacement therapy at the time of puberty.', 'Histopathological findings': 'Light microscopy showed seminiferous tubules mainly comprising spermatogonia and Sertoli cells, with no spermatocytes or spermatids (Fig. 2 c). Two types of LCs were identified, filled with and without lipid droplets in the testicular interstitium. The nuclei of LCs depressed by excessive lipid droplets were more clearly observable under electron microscopy (Fig. 2 d). Testosterone‐synthesizing enzymes in the testis of this patient were investigated by immunostaining and Western blotting methods using antibodies reacting with StAR protein, Ad4BP/SF‐1, CYP11A1, CYP17A1, 3β‐HSD, and 17β‐HSD. As control samples, we used biopsy tissues from three individuals with cryptorchidism ( n = 3; mean age, 5). All these steroid synthesis‐related proteins were observed in LCs of control samples using immunohistochemistry (Fig. 3 ). Western blotting analysis showed negative results for StAR protein in the testis of this patient (data not shown). LCs both with and without lipid droplets in this patient expressed all the steroid synthesis‐related proteins except StAR, 3β‐HSD, and 17β‐HSD (Fig. 3 ). This was part of a study approved by the ethics committee of Fukushima Medical University School of Medicine (2245). Informed consent was obtained after explaining the purpose and methods.'}
|
Respiratory-System
|
RESP
|
[] |
test-2116
|
7292164
|
{'Case presentation': 'A 15‐day‐old 46, XY neonate presented with severe adrenal insufficiency. Congenital lipoid adrenal hyperplasia was diagnosed after detection of steroidogenic acute regulatory gene mutations. At 2 years and 5 months, she underwent bilateral gonadectomy. Leydig cells were observed both with and without lipid droplets in the testes of this patient. We also demonstrated immunohistochemically that some testosterone‐synthesizing enzymes were maintained in this patient. The patient was born at full term with completely normal female external genitalia. No abnormalities were identified in routine newborn screenings. At 15 days, she was brought to the hospital with poor feeding and poor weight gain. Hyperpigmentation suggestive of adrenal insufficiency was noted. Laboratory tests revealed severe hyponatremia (115 mEq/L) and hyperkalemia (8.6 mEq/L). She was immediately treated with hydrocortisone and examined for all adrenocortical hormones and associated metabolites in serum and urine. Not only mineralocorticoids and glucocorticoids, but also adrenal androgens and their metabolic products were barely detectable. On the other hand, concentrations of adrenocorticotropic hormone were extremely high, at 387 pg/mL (normal 7.2–63.3 pg/mL). CT showed enlargement of bilateral adrenal glands (Fig. 1 a). Bilateral gonads were not palpable but were detectable near the internal inguinal rings on ultrasonography and MRI (Fig. 1 b). Since congenital adrenal hyperplasia was strongly suspected, chromosomal genetic testing was performed and revealed a 46,XY karyotype. Sequence analysis of the StAR gene revealed compound heterozygous mutations for p.Q258X and p.D246fs. From these results, lipoid CAH was diagnosed. Laparoscopic bilateral gonadectomy was performed at 2 years and 5 months. Both gonads were identified as normal testes accompanied by vas deferens and epididymis. The testes measured 16 × 10 × 6 mm on the right and 14 × 8 × 8 mm on the left (Fig. 2 a,b). As of the time of writing, she is continuing adrenocortical hormone replacement therapy, and will receive combination estrogen replacement therapy at the time of puberty.', 'Histopathological findings': 'Light microscopy showed seminiferous tubules mainly comprising spermatogonia and Sertoli cells, with no spermatocytes or spermatids (Fig. 2 c). Two types of LCs were identified, filled with and without lipid droplets in the testicular interstitium. The nuclei of LCs depressed by excessive lipid droplets were more clearly observable under electron microscopy (Fig. 2 d). Testosterone‐synthesizing enzymes in the testis of this patient were investigated by immunostaining and Western blotting methods using antibodies reacting with StAR protein, Ad4BP/SF‐1, CYP11A1, CYP17A1, 3β‐HSD, and 17β‐HSD. As control samples, we used biopsy tissues from three individuals with cryptorchidism ( n = 3; mean age, 5). All these steroid synthesis‐related proteins were observed in LCs of control samples using immunohistochemistry (Fig. 3 ). Western blotting analysis showed negative results for StAR protein in the testis of this patient (data not shown). LCs both with and without lipid droplets in this patient expressed all the steroid synthesis‐related proteins except StAR, 3β‐HSD, and 17β‐HSD (Fig. 3 ). This was part of a study approved by the ethics committee of Fukushima Medical University School of Medicine (2245). Informed consent was obtained after explaining the purpose and methods.'}
|
{'Case presentation': 'A 15‐day‐old 46, XY neonate presented with severe adrenal insufficiency. Congenital lipoid adrenal hyperplasia was diagnosed after detection of steroidogenic acute regulatory gene mutations. At 2 years and 5 months, she underwent bilateral gonadectomy. Leydig cells were observed both with and without lipid droplets in the testes of this patient. We also demonstrated immunohistochemically that some testosterone‐synthesizing enzymes were maintained in this patient. The patient was born at full term with completely normal female external genitalia. No abnormalities were identified in routine newborn screenings. At 15 days, she was brought to the hospital with poor feeding and poor weight gain. Hyperpigmentation suggestive of adrenal insufficiency was noted. Laboratory tests revealed severe hyponatremia (115 mEq/L) and hyperkalemia (8.6 mEq/L). She was immediately treated with hydrocortisone and examined for all adrenocortical hormones and associated metabolites in serum and urine. Not only mineralocorticoids and glucocorticoids, but also adrenal androgens and their metabolic products were barely detectable. On the other hand, concentrations of adrenocorticotropic hormone were extremely high, at 387 pg/mL (normal 7.2–63.3 pg/mL). CT showed enlargement of bilateral adrenal glands (Fig. 1 a). Bilateral gonads were not palpable but were detectable near the internal inguinal rings on ultrasonography and MRI (Fig. 1 b). Since congenital adrenal hyperplasia was strongly suspected, chromosomal genetic testing was performed and revealed a 46,XY karyotype. Sequence analysis of the StAR gene revealed compound heterozygous mutations for p.Q258X and p.D246fs. From these results, lipoid CAH was diagnosed. Laparoscopic bilateral gonadectomy was performed at 2 years and 5 months. Both gonads were identified as normal testes accompanied by vas deferens and epididymis. The testes measured 16 × 10 × 6 mm on the right and 14 × 8 × 8 mm on the left (Fig. 2 a,b). As of the time of writing, she is continuing adrenocortical hormone replacement therapy, and will receive combination estrogen replacement therapy at the time of puberty.', 'Histopathological findings': 'Light microscopy showed seminiferous tubules mainly comprising spermatogonia and Sertoli cells, with no spermatocytes or spermatids (Fig. 2 c). Two types of LCs were identified, filled with and without lipid droplets in the testicular interstitium. The nuclei of LCs depressed by excessive lipid droplets were more clearly observable under electron microscopy (Fig. 2 d). Testosterone‐synthesizing enzymes in the testis of this patient were investigated by immunostaining and Western blotting methods using antibodies reacting with StAR protein, Ad4BP/SF‐1, CYP11A1, CYP17A1, 3β‐HSD, and 17β‐HSD. As control samples, we used biopsy tissues from three individuals with cryptorchidism ( n = 3; mean age, 5). All these steroid synthesis‐related proteins were observed in LCs of control samples using immunohistochemistry (Fig. 3 ). Western blotting analysis showed negative results for StAR protein in the testis of this patient (data not shown). LCs both with and without lipid droplets in this patient expressed all the steroid synthesis‐related proteins except StAR, 3β‐HSD, and 17β‐HSD (Fig. 3 ). This was part of a study approved by the ethics committee of Fukushima Medical University School of Medicine (2245). Informed consent was obtained after explaining the purpose and methods.'}
|
Musculoskeletal-System
|
MSK
|
[] |
test-2117
|
7292164
|
{'Case presentation': 'A 15‐day‐old 46, XY neonate presented with severe adrenal insufficiency. Congenital lipoid adrenal hyperplasia was diagnosed after detection of steroidogenic acute regulatory gene mutations. At 2 years and 5 months, she underwent bilateral gonadectomy. Leydig cells were observed both with and without lipid droplets in the testes of this patient. We also demonstrated immunohistochemically that some testosterone‐synthesizing enzymes were maintained in this patient. The patient was born at full term with completely normal female external genitalia. No abnormalities were identified in routine newborn screenings. At 15 days, she was brought to the hospital with poor feeding and poor weight gain. Hyperpigmentation suggestive of adrenal insufficiency was noted. Laboratory tests revealed severe hyponatremia (115 mEq/L) and hyperkalemia (8.6 mEq/L). She was immediately treated with hydrocortisone and examined for all adrenocortical hormones and associated metabolites in serum and urine. Not only mineralocorticoids and glucocorticoids, but also adrenal androgens and their metabolic products were barely detectable. On the other hand, concentrations of adrenocorticotropic hormone were extremely high, at 387 pg/mL (normal 7.2–63.3 pg/mL). CT showed enlargement of bilateral adrenal glands (Fig. 1 a). Bilateral gonads were not palpable but were detectable near the internal inguinal rings on ultrasonography and MRI (Fig. 1 b). Since congenital adrenal hyperplasia was strongly suspected, chromosomal genetic testing was performed and revealed a 46,XY karyotype. Sequence analysis of the StAR gene revealed compound heterozygous mutations for p.Q258X and p.D246fs. From these results, lipoid CAH was diagnosed. Laparoscopic bilateral gonadectomy was performed at 2 years and 5 months. Both gonads were identified as normal testes accompanied by vas deferens and epididymis. The testes measured 16 × 10 × 6 mm on the right and 14 × 8 × 8 mm on the left (Fig. 2 a,b). As of the time of writing, she is continuing adrenocortical hormone replacement therapy, and will receive combination estrogen replacement therapy at the time of puberty.', 'Histopathological findings': 'Light microscopy showed seminiferous tubules mainly comprising spermatogonia and Sertoli cells, with no spermatocytes or spermatids (Fig. 2 c). Two types of LCs were identified, filled with and without lipid droplets in the testicular interstitium. The nuclei of LCs depressed by excessive lipid droplets were more clearly observable under electron microscopy (Fig. 2 d). Testosterone‐synthesizing enzymes in the testis of this patient were investigated by immunostaining and Western blotting methods using antibodies reacting with StAR protein, Ad4BP/SF‐1, CYP11A1, CYP17A1, 3β‐HSD, and 17β‐HSD. As control samples, we used biopsy tissues from three individuals with cryptorchidism ( n = 3; mean age, 5). All these steroid synthesis‐related proteins were observed in LCs of control samples using immunohistochemistry (Fig. 3 ). Western blotting analysis showed negative results for StAR protein in the testis of this patient (data not shown). LCs both with and without lipid droplets in this patient expressed all the steroid synthesis‐related proteins except StAR, 3β‐HSD, and 17β‐HSD (Fig. 3 ). This was part of a study approved by the ethics committee of Fukushima Medical University School of Medicine (2245). Informed consent was obtained after explaining the purpose and methods.'}
|
{'Case presentation': 'A 15‐day‐old 46, XY neonate presented with severe adrenal insufficiency. Congenital lipoid adrenal hyperplasia was diagnosed after detection of steroidogenic acute regulatory gene mutations. At 2 years and 5 months, she underwent bilateral gonadectomy. Leydig cells were observed both with and without lipid droplets in the testes of this patient. We also demonstrated immunohistochemically that some testosterone‐synthesizing enzymes were maintained in this patient. The patient was born at full term with completely normal female external genitalia. No abnormalities were identified in routine newborn screenings. At 15 days, she was brought to the hospital with poor feeding and poor weight gain. Hyperpigmentation suggestive of adrenal insufficiency was noted. Laboratory tests revealed severe hyponatremia (115 mEq/L) and hyperkalemia (8.6 mEq/L). She was immediately treated with hydrocortisone and examined for all adrenocortical hormones and associated metabolites in serum and urine. Not only mineralocorticoids and glucocorticoids, but also adrenal androgens and their metabolic products were barely detectable. On the other hand, concentrations of adrenocorticotropic hormone were extremely high, at 387 pg/mL (normal 7.2–63.3 pg/mL). CT showed enlargement of bilateral adrenal glands (Fig. 1 a). Bilateral gonads were not palpable but were detectable near the internal inguinal rings on ultrasonography and MRI (Fig. 1 b). Since congenital adrenal hyperplasia was strongly suspected, chromosomal genetic testing was performed and revealed a 46,XY karyotype. Sequence analysis of the StAR gene revealed compound heterozygous mutations for p.Q258X and p.D246fs. From these results, lipoid CAH was diagnosed. Laparoscopic bilateral gonadectomy was performed at 2 years and 5 months. Both gonads were identified as normal testes accompanied by vas deferens and epididymis. The testes measured 16 × 10 × 6 mm on the right and 14 × 8 × 8 mm on the left (Fig. 2 a,b). As of the time of writing, she is continuing adrenocortical hormone replacement therapy, and will receive combination estrogen replacement therapy at the time of puberty.', 'Histopathological findings': 'Light microscopy showed seminiferous tubules mainly comprising spermatogonia and Sertoli cells, with no spermatocytes or spermatids (Fig. 2 c). Two types of LCs were identified, filled with and without lipid droplets in the testicular interstitium. The nuclei of LCs depressed by excessive lipid droplets were more clearly observable under electron microscopy (Fig. 2 d). Testosterone‐synthesizing enzymes in the testis of this patient were investigated by immunostaining and Western blotting methods using antibodies reacting with StAR protein, Ad4BP/SF‐1, CYP11A1, CYP17A1, 3β‐HSD, and 17β‐HSD. As control samples, we used biopsy tissues from three individuals with cryptorchidism ( n = 3; mean age, 5). All these steroid synthesis‐related proteins were observed in LCs of control samples using immunohistochemistry (Fig. 3 ). Western blotting analysis showed negative results for StAR protein in the testis of this patient (data not shown). LCs both with and without lipid droplets in this patient expressed all the steroid synthesis‐related proteins except StAR, 3β‐HSD, and 17β‐HSD (Fig. 3 ). This was part of a study approved by the ethics committee of Fukushima Medical University School of Medicine (2245). Informed consent was obtained after explaining the purpose and methods.'}
|
Eyes-Ears-Nose-Throat
|
EENT
|
[] |
test-2118
|
7292164
|
{'Case presentation': 'A 15‐day‐old 46, XY neonate presented with severe adrenal insufficiency. Congenital lipoid adrenal hyperplasia was diagnosed after detection of steroidogenic acute regulatory gene mutations. At 2 years and 5 months, she underwent bilateral gonadectomy. Leydig cells were observed both with and without lipid droplets in the testes of this patient. We also demonstrated immunohistochemically that some testosterone‐synthesizing enzymes were maintained in this patient. The patient was born at full term with completely normal female external genitalia. No abnormalities were identified in routine newborn screenings. At 15 days, she was brought to the hospital with poor feeding and poor weight gain. Hyperpigmentation suggestive of adrenal insufficiency was noted. Laboratory tests revealed severe hyponatremia (115 mEq/L) and hyperkalemia (8.6 mEq/L). She was immediately treated with hydrocortisone and examined for all adrenocortical hormones and associated metabolites in serum and urine. Not only mineralocorticoids and glucocorticoids, but also adrenal androgens and their metabolic products were barely detectable. On the other hand, concentrations of adrenocorticotropic hormone were extremely high, at 387 pg/mL (normal 7.2–63.3 pg/mL). CT showed enlargement of bilateral adrenal glands (Fig. 1 a). Bilateral gonads were not palpable but were detectable near the internal inguinal rings on ultrasonography and MRI (Fig. 1 b). Since congenital adrenal hyperplasia was strongly suspected, chromosomal genetic testing was performed and revealed a 46,XY karyotype. Sequence analysis of the StAR gene revealed compound heterozygous mutations for p.Q258X and p.D246fs. From these results, lipoid CAH was diagnosed. Laparoscopic bilateral gonadectomy was performed at 2 years and 5 months. Both gonads were identified as normal testes accompanied by vas deferens and epididymis. The testes measured 16 × 10 × 6 mm on the right and 14 × 8 × 8 mm on the left (Fig. 2 a,b). As of the time of writing, she is continuing adrenocortical hormone replacement therapy, and will receive combination estrogen replacement therapy at the time of puberty.', 'Histopathological findings': 'Light microscopy showed seminiferous tubules mainly comprising spermatogonia and Sertoli cells, with no spermatocytes or spermatids (Fig. 2 c). Two types of LCs were identified, filled with and without lipid droplets in the testicular interstitium. The nuclei of LCs depressed by excessive lipid droplets were more clearly observable under electron microscopy (Fig. 2 d). Testosterone‐synthesizing enzymes in the testis of this patient were investigated by immunostaining and Western blotting methods using antibodies reacting with StAR protein, Ad4BP/SF‐1, CYP11A1, CYP17A1, 3β‐HSD, and 17β‐HSD. As control samples, we used biopsy tissues from three individuals with cryptorchidism ( n = 3; mean age, 5). All these steroid synthesis‐related proteins were observed in LCs of control samples using immunohistochemistry (Fig. 3 ). Western blotting analysis showed negative results for StAR protein in the testis of this patient (data not shown). LCs both with and without lipid droplets in this patient expressed all the steroid synthesis‐related proteins except StAR, 3β‐HSD, and 17β‐HSD (Fig. 3 ). This was part of a study approved by the ethics committee of Fukushima Medical University School of Medicine (2245). Informed consent was obtained after explaining the purpose and methods.'}
|
{'Case presentation': 'A 15‐day‐old 46, XY neonate presented with severe adrenal insufficiency. Congenital lipoid adrenal hyperplasia was diagnosed after detection of steroidogenic acute regulatory gene mutations. At 2 years and 5 months, she underwent bilateral gonadectomy. Leydig cells were observed both with and without lipid droplets in the testes of this patient. We also demonstrated immunohistochemically that some testosterone‐synthesizing enzymes were maintained in this patient. The patient was born at full term with completely normal female external genitalia. No abnormalities were identified in routine newborn screenings. At 15 days, she was brought to the hospital with poor feeding and poor weight gain. Hyperpigmentation suggestive of adrenal insufficiency was noted. Laboratory tests revealed severe hyponatremia (115 mEq/L) and hyperkalemia (8.6 mEq/L). She was immediately treated with hydrocortisone and examined for all adrenocortical hormones and associated metabolites in serum and urine. Not only mineralocorticoids and glucocorticoids, but also adrenal androgens and their metabolic products were barely detectable. On the other hand, concentrations of adrenocorticotropic hormone were extremely high, at 387 pg/mL (normal 7.2–63.3 pg/mL). CT showed enlargement of bilateral adrenal glands (Fig. 1 a). Bilateral gonads were not palpable but were detectable near the internal inguinal rings on ultrasonography and MRI (Fig. 1 b). Since congenital adrenal hyperplasia was strongly suspected, chromosomal genetic testing was performed and revealed a 46,XY karyotype. Sequence analysis of the StAR gene revealed compound heterozygous mutations for p.Q258X and p.D246fs. From these results, lipoid CAH was diagnosed. Laparoscopic bilateral gonadectomy was performed at 2 years and 5 months. Both gonads were identified as normal testes accompanied by vas deferens and epididymis. The testes measured 16 × 10 × 6 mm on the right and 14 × 8 × 8 mm on the left (Fig. 2 a,b). As of the time of writing, she is continuing adrenocortical hormone replacement therapy, and will receive combination estrogen replacement therapy at the time of puberty.', 'Histopathological findings': 'Light microscopy showed seminiferous tubules mainly comprising spermatogonia and Sertoli cells, with no spermatocytes or spermatids (Fig. 2 c). Two types of LCs were identified, filled with and without lipid droplets in the testicular interstitium. The nuclei of LCs depressed by excessive lipid droplets were more clearly observable under electron microscopy (Fig. 2 d). Testosterone‐synthesizing enzymes in the testis of this patient were investigated by immunostaining and Western blotting methods using antibodies reacting with StAR protein, Ad4BP/SF‐1, CYP11A1, CYP17A1, 3β‐HSD, and 17β‐HSD. As control samples, we used biopsy tissues from three individuals with cryptorchidism ( n = 3; mean age, 5). All these steroid synthesis‐related proteins were observed in LCs of control samples using immunohistochemistry (Fig. 3 ). Western blotting analysis showed negative results for StAR protein in the testis of this patient (data not shown). LCs both with and without lipid droplets in this patient expressed all the steroid synthesis‐related proteins except StAR, 3β‐HSD, and 17β‐HSD (Fig. 3 ). This was part of a study approved by the ethics committee of Fukushima Medical University School of Medicine (2245). Informed consent was obtained after explaining the purpose and methods.'}
|
Dermatology
|
DERM
|
[
"Hyperpigmentation suggestive of adrenal insufficiency was noted"
] |
test-2119
|
7292164
|
{'Case presentation': 'A 15‐day‐old 46, XY neonate presented with severe adrenal insufficiency. Congenital lipoid adrenal hyperplasia was diagnosed after detection of steroidogenic acute regulatory gene mutations. At 2 years and 5 months, she underwent bilateral gonadectomy. Leydig cells were observed both with and without lipid droplets in the testes of this patient. We also demonstrated immunohistochemically that some testosterone‐synthesizing enzymes were maintained in this patient. The patient was born at full term with completely normal female external genitalia. No abnormalities were identified in routine newborn screenings. At 15 days, she was brought to the hospital with poor feeding and poor weight gain. Hyperpigmentation suggestive of adrenal insufficiency was noted. Laboratory tests revealed severe hyponatremia (115 mEq/L) and hyperkalemia (8.6 mEq/L). She was immediately treated with hydrocortisone and examined for all adrenocortical hormones and associated metabolites in serum and urine. Not only mineralocorticoids and glucocorticoids, but also adrenal androgens and their metabolic products were barely detectable. On the other hand, concentrations of adrenocorticotropic hormone were extremely high, at 387 pg/mL (normal 7.2–63.3 pg/mL). CT showed enlargement of bilateral adrenal glands (Fig. 1 a). Bilateral gonads were not palpable but were detectable near the internal inguinal rings on ultrasonography and MRI (Fig. 1 b). Since congenital adrenal hyperplasia was strongly suspected, chromosomal genetic testing was performed and revealed a 46,XY karyotype. Sequence analysis of the StAR gene revealed compound heterozygous mutations for p.Q258X and p.D246fs. From these results, lipoid CAH was diagnosed. Laparoscopic bilateral gonadectomy was performed at 2 years and 5 months. Both gonads were identified as normal testes accompanied by vas deferens and epididymis. The testes measured 16 × 10 × 6 mm on the right and 14 × 8 × 8 mm on the left (Fig. 2 a,b). As of the time of writing, she is continuing adrenocortical hormone replacement therapy, and will receive combination estrogen replacement therapy at the time of puberty.', 'Histopathological findings': 'Light microscopy showed seminiferous tubules mainly comprising spermatogonia and Sertoli cells, with no spermatocytes or spermatids (Fig. 2 c). Two types of LCs were identified, filled with and without lipid droplets in the testicular interstitium. The nuclei of LCs depressed by excessive lipid droplets were more clearly observable under electron microscopy (Fig. 2 d). Testosterone‐synthesizing enzymes in the testis of this patient were investigated by immunostaining and Western blotting methods using antibodies reacting with StAR protein, Ad4BP/SF‐1, CYP11A1, CYP17A1, 3β‐HSD, and 17β‐HSD. As control samples, we used biopsy tissues from three individuals with cryptorchidism ( n = 3; mean age, 5). All these steroid synthesis‐related proteins were observed in LCs of control samples using immunohistochemistry (Fig. 3 ). Western blotting analysis showed negative results for StAR protein in the testis of this patient (data not shown). LCs both with and without lipid droplets in this patient expressed all the steroid synthesis‐related proteins except StAR, 3β‐HSD, and 17β‐HSD (Fig. 3 ). This was part of a study approved by the ethics committee of Fukushima Medical University School of Medicine (2245). Informed consent was obtained after explaining the purpose and methods.'}
|
{'Case presentation': 'A 15‐day‐old 46, XY neonate presented with severe adrenal insufficiency. Congenital lipoid adrenal hyperplasia was diagnosed after detection of steroidogenic acute regulatory gene mutations. At 2 years and 5 months, she underwent bilateral gonadectomy. Leydig cells were observed both with and without lipid droplets in the testes of this patient. We also demonstrated immunohistochemically that some testosterone‐synthesizing enzymes were maintained in this patient. The patient was born at full term with completely normal female external genitalia. No abnormalities were identified in routine newborn screenings. At 15 days, she was brought to the hospital with poor feeding and poor weight gain. Hyperpigmentation suggestive of adrenal insufficiency was noted. Laboratory tests revealed severe hyponatremia (115 mEq/L) and hyperkalemia (8.6 mEq/L). She was immediately treated with hydrocortisone and examined for all adrenocortical hormones and associated metabolites in serum and urine. Not only mineralocorticoids and glucocorticoids, but also adrenal androgens and their metabolic products were barely detectable. On the other hand, concentrations of adrenocorticotropic hormone were extremely high, at 387 pg/mL (normal 7.2–63.3 pg/mL). CT showed enlargement of bilateral adrenal glands (Fig. 1 a). Bilateral gonads were not palpable but were detectable near the internal inguinal rings on ultrasonography and MRI (Fig. 1 b). Since congenital adrenal hyperplasia was strongly suspected, chromosomal genetic testing was performed and revealed a 46,XY karyotype. Sequence analysis of the StAR gene revealed compound heterozygous mutations for p.Q258X and p.D246fs. From these results, lipoid CAH was diagnosed. Laparoscopic bilateral gonadectomy was performed at 2 years and 5 months. Both gonads were identified as normal testes accompanied by vas deferens and epididymis. The testes measured 16 × 10 × 6 mm on the right and 14 × 8 × 8 mm on the left (Fig. 2 a,b). As of the time of writing, she is continuing adrenocortical hormone replacement therapy, and will receive combination estrogen replacement therapy at the time of puberty.', 'Histopathological findings': 'Light microscopy showed seminiferous tubules mainly comprising spermatogonia and Sertoli cells, with no spermatocytes or spermatids (Fig. 2 c). Two types of LCs were identified, filled with and without lipid droplets in the testicular interstitium. The nuclei of LCs depressed by excessive lipid droplets were more clearly observable under electron microscopy (Fig. 2 d). Testosterone‐synthesizing enzymes in the testis of this patient were investigated by immunostaining and Western blotting methods using antibodies reacting with StAR protein, Ad4BP/SF‐1, CYP11A1, CYP17A1, 3β‐HSD, and 17β‐HSD. As control samples, we used biopsy tissues from three individuals with cryptorchidism ( n = 3; mean age, 5). All these steroid synthesis‐related proteins were observed in LCs of control samples using immunohistochemistry (Fig. 3 ). Western blotting analysis showed negative results for StAR protein in the testis of this patient (data not shown). LCs both with and without lipid droplets in this patient expressed all the steroid synthesis‐related proteins except StAR, 3β‐HSD, and 17β‐HSD (Fig. 3 ). This was part of a study approved by the ethics committee of Fukushima Medical University School of Medicine (2245). Informed consent was obtained after explaining the purpose and methods.'}
|
Pregnancy
|
Pregnancy
|
[
"born at full term with completely normal female external genitalia. No abnormalities were identified in routine newborn screenings."
] |
test-2120
|
7292164
|
{'Case presentation': 'A 15‐day‐old 46, XY neonate presented with severe adrenal insufficiency. Congenital lipoid adrenal hyperplasia was diagnosed after detection of steroidogenic acute regulatory gene mutations. At 2 years and 5 months, she underwent bilateral gonadectomy. Leydig cells were observed both with and without lipid droplets in the testes of this patient. We also demonstrated immunohistochemically that some testosterone‐synthesizing enzymes were maintained in this patient. The patient was born at full term with completely normal female external genitalia. No abnormalities were identified in routine newborn screenings. At 15 days, she was brought to the hospital with poor feeding and poor weight gain. Hyperpigmentation suggestive of adrenal insufficiency was noted. Laboratory tests revealed severe hyponatremia (115 mEq/L) and hyperkalemia (8.6 mEq/L). She was immediately treated with hydrocortisone and examined for all adrenocortical hormones and associated metabolites in serum and urine. Not only mineralocorticoids and glucocorticoids, but also adrenal androgens and their metabolic products were barely detectable. On the other hand, concentrations of adrenocorticotropic hormone were extremely high, at 387 pg/mL (normal 7.2–63.3 pg/mL). CT showed enlargement of bilateral adrenal glands (Fig. 1 a). Bilateral gonads were not palpable but were detectable near the internal inguinal rings on ultrasonography and MRI (Fig. 1 b). Since congenital adrenal hyperplasia was strongly suspected, chromosomal genetic testing was performed and revealed a 46,XY karyotype. Sequence analysis of the StAR gene revealed compound heterozygous mutations for p.Q258X and p.D246fs. From these results, lipoid CAH was diagnosed. Laparoscopic bilateral gonadectomy was performed at 2 years and 5 months. Both gonads were identified as normal testes accompanied by vas deferens and epididymis. The testes measured 16 × 10 × 6 mm on the right and 14 × 8 × 8 mm on the left (Fig. 2 a,b). As of the time of writing, she is continuing adrenocortical hormone replacement therapy, and will receive combination estrogen replacement therapy at the time of puberty.', 'Histopathological findings': 'Light microscopy showed seminiferous tubules mainly comprising spermatogonia and Sertoli cells, with no spermatocytes or spermatids (Fig. 2 c). Two types of LCs were identified, filled with and without lipid droplets in the testicular interstitium. The nuclei of LCs depressed by excessive lipid droplets were more clearly observable under electron microscopy (Fig. 2 d). Testosterone‐synthesizing enzymes in the testis of this patient were investigated by immunostaining and Western blotting methods using antibodies reacting with StAR protein, Ad4BP/SF‐1, CYP11A1, CYP17A1, 3β‐HSD, and 17β‐HSD. As control samples, we used biopsy tissues from three individuals with cryptorchidism ( n = 3; mean age, 5). All these steroid synthesis‐related proteins were observed in LCs of control samples using immunohistochemistry (Fig. 3 ). Western blotting analysis showed negative results for StAR protein in the testis of this patient (data not shown). LCs both with and without lipid droplets in this patient expressed all the steroid synthesis‐related proteins except StAR, 3β‐HSD, and 17β‐HSD (Fig. 3 ). This was part of a study approved by the ethics committee of Fukushima Medical University School of Medicine (2245). Informed consent was obtained after explaining the purpose and methods.'}
|
{'Case presentation': 'A 15‐day‐old 46, XY neonate presented with severe adrenal insufficiency. Congenital lipoid adrenal hyperplasia was diagnosed after detection of steroidogenic acute regulatory gene mutations. At 2 years and 5 months, she underwent bilateral gonadectomy. Leydig cells were observed both with and without lipid droplets in the testes of this patient. We also demonstrated immunohistochemically that some testosterone‐synthesizing enzymes were maintained in this patient. The patient was born at full term with completely normal female external genitalia. No abnormalities were identified in routine newborn screenings. At 15 days, she was brought to the hospital with poor feeding and poor weight gain. Hyperpigmentation suggestive of adrenal insufficiency was noted. Laboratory tests revealed severe hyponatremia (115 mEq/L) and hyperkalemia (8.6 mEq/L). She was immediately treated with hydrocortisone and examined for all adrenocortical hormones and associated metabolites in serum and urine. Not only mineralocorticoids and glucocorticoids, but also adrenal androgens and their metabolic products were barely detectable. On the other hand, concentrations of adrenocorticotropic hormone were extremely high, at 387 pg/mL (normal 7.2–63.3 pg/mL). CT showed enlargement of bilateral adrenal glands (Fig. 1 a). Bilateral gonads were not palpable but were detectable near the internal inguinal rings on ultrasonography and MRI (Fig. 1 b). Since congenital adrenal hyperplasia was strongly suspected, chromosomal genetic testing was performed and revealed a 46,XY karyotype. Sequence analysis of the StAR gene revealed compound heterozygous mutations for p.Q258X and p.D246fs. From these results, lipoid CAH was diagnosed. Laparoscopic bilateral gonadectomy was performed at 2 years and 5 months. Both gonads were identified as normal testes accompanied by vas deferens and epididymis. The testes measured 16 × 10 × 6 mm on the right and 14 × 8 × 8 mm on the left (Fig. 2 a,b). As of the time of writing, she is continuing adrenocortical hormone replacement therapy, and will receive combination estrogen replacement therapy at the time of puberty.', 'Histopathological findings': 'Light microscopy showed seminiferous tubules mainly comprising spermatogonia and Sertoli cells, with no spermatocytes or spermatids (Fig. 2 c). Two types of LCs were identified, filled with and without lipid droplets in the testicular interstitium. The nuclei of LCs depressed by excessive lipid droplets were more clearly observable under electron microscopy (Fig. 2 d). Testosterone‐synthesizing enzymes in the testis of this patient were investigated by immunostaining and Western blotting methods using antibodies reacting with StAR protein, Ad4BP/SF‐1, CYP11A1, CYP17A1, 3β‐HSD, and 17β‐HSD. As control samples, we used biopsy tissues from three individuals with cryptorchidism ( n = 3; mean age, 5). All these steroid synthesis‐related proteins were observed in LCs of control samples using immunohistochemistry (Fig. 3 ). Western blotting analysis showed negative results for StAR protein in the testis of this patient (data not shown). LCs both with and without lipid droplets in this patient expressed all the steroid synthesis‐related proteins except StAR, 3β‐HSD, and 17β‐HSD (Fig. 3 ). This was part of a study approved by the ethics committee of Fukushima Medical University School of Medicine (2245). Informed consent was obtained after explaining the purpose and methods.'}
|
Lymphatic-System
|
LYMPH
|
[] |
test-2121
|
7292164
|
{'Case presentation': 'A 15‐day‐old 46, XY neonate presented with severe adrenal insufficiency. Congenital lipoid adrenal hyperplasia was diagnosed after detection of steroidogenic acute regulatory gene mutations. At 2 years and 5 months, she underwent bilateral gonadectomy. Leydig cells were observed both with and without lipid droplets in the testes of this patient. We also demonstrated immunohistochemically that some testosterone‐synthesizing enzymes were maintained in this patient. The patient was born at full term with completely normal female external genitalia. No abnormalities were identified in routine newborn screenings. At 15 days, she was brought to the hospital with poor feeding and poor weight gain. Hyperpigmentation suggestive of adrenal insufficiency was noted. Laboratory tests revealed severe hyponatremia (115 mEq/L) and hyperkalemia (8.6 mEq/L). She was immediately treated with hydrocortisone and examined for all adrenocortical hormones and associated metabolites in serum and urine. Not only mineralocorticoids and glucocorticoids, but also adrenal androgens and their metabolic products were barely detectable. On the other hand, concentrations of adrenocorticotropic hormone were extremely high, at 387 pg/mL (normal 7.2–63.3 pg/mL). CT showed enlargement of bilateral adrenal glands (Fig. 1 a). Bilateral gonads were not palpable but were detectable near the internal inguinal rings on ultrasonography and MRI (Fig. 1 b). Since congenital adrenal hyperplasia was strongly suspected, chromosomal genetic testing was performed and revealed a 46,XY karyotype. Sequence analysis of the StAR gene revealed compound heterozygous mutations for p.Q258X and p.D246fs. From these results, lipoid CAH was diagnosed. Laparoscopic bilateral gonadectomy was performed at 2 years and 5 months. Both gonads were identified as normal testes accompanied by vas deferens and epididymis. The testes measured 16 × 10 × 6 mm on the right and 14 × 8 × 8 mm on the left (Fig. 2 a,b). As of the time of writing, she is continuing adrenocortical hormone replacement therapy, and will receive combination estrogen replacement therapy at the time of puberty.', 'Histopathological findings': 'Light microscopy showed seminiferous tubules mainly comprising spermatogonia and Sertoli cells, with no spermatocytes or spermatids (Fig. 2 c). Two types of LCs were identified, filled with and without lipid droplets in the testicular interstitium. The nuclei of LCs depressed by excessive lipid droplets were more clearly observable under electron microscopy (Fig. 2 d). Testosterone‐synthesizing enzymes in the testis of this patient were investigated by immunostaining and Western blotting methods using antibodies reacting with StAR protein, Ad4BP/SF‐1, CYP11A1, CYP17A1, 3β‐HSD, and 17β‐HSD. As control samples, we used biopsy tissues from three individuals with cryptorchidism ( n = 3; mean age, 5). All these steroid synthesis‐related proteins were observed in LCs of control samples using immunohistochemistry (Fig. 3 ). Western blotting analysis showed negative results for StAR protein in the testis of this patient (data not shown). LCs both with and without lipid droplets in this patient expressed all the steroid synthesis‐related proteins except StAR, 3β‐HSD, and 17β‐HSD (Fig. 3 ). This was part of a study approved by the ethics committee of Fukushima Medical University School of Medicine (2245). Informed consent was obtained after explaining the purpose and methods.'}
|
{'Case presentation': 'A 15‐day‐old 46, XY neonate presented with severe adrenal insufficiency. Congenital lipoid adrenal hyperplasia was diagnosed after detection of steroidogenic acute regulatory gene mutations. At 2 years and 5 months, she underwent bilateral gonadectomy. Leydig cells were observed both with and without lipid droplets in the testes of this patient. We also demonstrated immunohistochemically that some testosterone‐synthesizing enzymes were maintained in this patient. The patient was born at full term with completely normal female external genitalia. No abnormalities were identified in routine newborn screenings. At 15 days, she was brought to the hospital with poor feeding and poor weight gain. Hyperpigmentation suggestive of adrenal insufficiency was noted. Laboratory tests revealed severe hyponatremia (115 mEq/L) and hyperkalemia (8.6 mEq/L). She was immediately treated with hydrocortisone and examined for all adrenocortical hormones and associated metabolites in serum and urine. Not only mineralocorticoids and glucocorticoids, but also adrenal androgens and their metabolic products were barely detectable. On the other hand, concentrations of adrenocorticotropic hormone were extremely high, at 387 pg/mL (normal 7.2–63.3 pg/mL). CT showed enlargement of bilateral adrenal glands (Fig. 1 a). Bilateral gonads were not palpable but were detectable near the internal inguinal rings on ultrasonography and MRI (Fig. 1 b). Since congenital adrenal hyperplasia was strongly suspected, chromosomal genetic testing was performed and revealed a 46,XY karyotype. Sequence analysis of the StAR gene revealed compound heterozygous mutations for p.Q258X and p.D246fs. From these results, lipoid CAH was diagnosed. Laparoscopic bilateral gonadectomy was performed at 2 years and 5 months. Both gonads were identified as normal testes accompanied by vas deferens and epididymis. The testes measured 16 × 10 × 6 mm on the right and 14 × 8 × 8 mm on the left (Fig. 2 a,b). As of the time of writing, she is continuing adrenocortical hormone replacement therapy, and will receive combination estrogen replacement therapy at the time of puberty.', 'Histopathological findings': 'Light microscopy showed seminiferous tubules mainly comprising spermatogonia and Sertoli cells, with no spermatocytes or spermatids (Fig. 2 c). Two types of LCs were identified, filled with and without lipid droplets in the testicular interstitium. The nuclei of LCs depressed by excessive lipid droplets were more clearly observable under electron microscopy (Fig. 2 d). Testosterone‐synthesizing enzymes in the testis of this patient were investigated by immunostaining and Western blotting methods using antibodies reacting with StAR protein, Ad4BP/SF‐1, CYP11A1, CYP17A1, 3β‐HSD, and 17β‐HSD. As control samples, we used biopsy tissues from three individuals with cryptorchidism ( n = 3; mean age, 5). All these steroid synthesis‐related proteins were observed in LCs of control samples using immunohistochemistry (Fig. 3 ). Western blotting analysis showed negative results for StAR protein in the testis of this patient (data not shown). LCs both with and without lipid droplets in this patient expressed all the steroid synthesis‐related proteins except StAR, 3β‐HSD, and 17β‐HSD (Fig. 3 ). This was part of a study approved by the ethics committee of Fukushima Medical University School of Medicine (2245). Informed consent was obtained after explaining the purpose and methods.'}
|
Age-at-Presentation
|
Age (at case presentation)
|
[
"15‐day‐old"
] |
test-2122
|
7292164
|
{'Case presentation': 'A 15‐day‐old 46, XY neonate presented with severe adrenal insufficiency. Congenital lipoid adrenal hyperplasia was diagnosed after detection of steroidogenic acute regulatory gene mutations. At 2 years and 5 months, she underwent bilateral gonadectomy. Leydig cells were observed both with and without lipid droplets in the testes of this patient. We also demonstrated immunohistochemically that some testosterone‐synthesizing enzymes were maintained in this patient. The patient was born at full term with completely normal female external genitalia. No abnormalities were identified in routine newborn screenings. At 15 days, she was brought to the hospital with poor feeding and poor weight gain. Hyperpigmentation suggestive of adrenal insufficiency was noted. Laboratory tests revealed severe hyponatremia (115 mEq/L) and hyperkalemia (8.6 mEq/L). She was immediately treated with hydrocortisone and examined for all adrenocortical hormones and associated metabolites in serum and urine. Not only mineralocorticoids and glucocorticoids, but also adrenal androgens and their metabolic products were barely detectable. On the other hand, concentrations of adrenocorticotropic hormone were extremely high, at 387 pg/mL (normal 7.2–63.3 pg/mL). CT showed enlargement of bilateral adrenal glands (Fig. 1 a). Bilateral gonads were not palpable but were detectable near the internal inguinal rings on ultrasonography and MRI (Fig. 1 b). Since congenital adrenal hyperplasia was strongly suspected, chromosomal genetic testing was performed and revealed a 46,XY karyotype. Sequence analysis of the StAR gene revealed compound heterozygous mutations for p.Q258X and p.D246fs. From these results, lipoid CAH was diagnosed. Laparoscopic bilateral gonadectomy was performed at 2 years and 5 months. Both gonads were identified as normal testes accompanied by vas deferens and epididymis. The testes measured 16 × 10 × 6 mm on the right and 14 × 8 × 8 mm on the left (Fig. 2 a,b). As of the time of writing, she is continuing adrenocortical hormone replacement therapy, and will receive combination estrogen replacement therapy at the time of puberty.', 'Histopathological findings': 'Light microscopy showed seminiferous tubules mainly comprising spermatogonia and Sertoli cells, with no spermatocytes or spermatids (Fig. 2 c). Two types of LCs were identified, filled with and without lipid droplets in the testicular interstitium. The nuclei of LCs depressed by excessive lipid droplets were more clearly observable under electron microscopy (Fig. 2 d). Testosterone‐synthesizing enzymes in the testis of this patient were investigated by immunostaining and Western blotting methods using antibodies reacting with StAR protein, Ad4BP/SF‐1, CYP11A1, CYP17A1, 3β‐HSD, and 17β‐HSD. As control samples, we used biopsy tissues from three individuals with cryptorchidism ( n = 3; mean age, 5). All these steroid synthesis‐related proteins were observed in LCs of control samples using immunohistochemistry (Fig. 3 ). Western blotting analysis showed negative results for StAR protein in the testis of this patient (data not shown). LCs both with and without lipid droplets in this patient expressed all the steroid synthesis‐related proteins except StAR, 3β‐HSD, and 17β‐HSD (Fig. 3 ). This was part of a study approved by the ethics committee of Fukushima Medical University School of Medicine (2245). Informed consent was obtained after explaining the purpose and methods.'}
|
{'Case presentation': 'A 15‐day‐old 46, XY neonate presented with severe adrenal insufficiency. Congenital lipoid adrenal hyperplasia was diagnosed after detection of steroidogenic acute regulatory gene mutations. At 2 years and 5 months, she underwent bilateral gonadectomy. Leydig cells were observed both with and without lipid droplets in the testes of this patient. We also demonstrated immunohistochemically that some testosterone‐synthesizing enzymes were maintained in this patient. The patient was born at full term with completely normal female external genitalia. No abnormalities were identified in routine newborn screenings. At 15 days, she was brought to the hospital with poor feeding and poor weight gain. Hyperpigmentation suggestive of adrenal insufficiency was noted. Laboratory tests revealed severe hyponatremia (115 mEq/L) and hyperkalemia (8.6 mEq/L). She was immediately treated with hydrocortisone and examined for all adrenocortical hormones and associated metabolites in serum and urine. Not only mineralocorticoids and glucocorticoids, but also adrenal androgens and their metabolic products were barely detectable. On the other hand, concentrations of adrenocorticotropic hormone were extremely high, at 387 pg/mL (normal 7.2–63.3 pg/mL). CT showed enlargement of bilateral adrenal glands (Fig. 1 a). Bilateral gonads were not palpable but were detectable near the internal inguinal rings on ultrasonography and MRI (Fig. 1 b). Since congenital adrenal hyperplasia was strongly suspected, chromosomal genetic testing was performed and revealed a 46,XY karyotype. Sequence analysis of the StAR gene revealed compound heterozygous mutations for p.Q258X and p.D246fs. From these results, lipoid CAH was diagnosed. Laparoscopic bilateral gonadectomy was performed at 2 years and 5 months. Both gonads were identified as normal testes accompanied by vas deferens and epididymis. The testes measured 16 × 10 × 6 mm on the right and 14 × 8 × 8 mm on the left (Fig. 2 a,b). As of the time of writing, she is continuing adrenocortical hormone replacement therapy, and will receive combination estrogen replacement therapy at the time of puberty.', 'Histopathological findings': 'Light microscopy showed seminiferous tubules mainly comprising spermatogonia and Sertoli cells, with no spermatocytes or spermatids (Fig. 2 c). Two types of LCs were identified, filled with and without lipid droplets in the testicular interstitium. The nuclei of LCs depressed by excessive lipid droplets were more clearly observable under electron microscopy (Fig. 2 d). Testosterone‐synthesizing enzymes in the testis of this patient were investigated by immunostaining and Western blotting methods using antibodies reacting with StAR protein, Ad4BP/SF‐1, CYP11A1, CYP17A1, 3β‐HSD, and 17β‐HSD. As control samples, we used biopsy tissues from three individuals with cryptorchidism ( n = 3; mean age, 5). All these steroid synthesis‐related proteins were observed in LCs of control samples using immunohistochemistry (Fig. 3 ). Western blotting analysis showed negative results for StAR protein in the testis of this patient (data not shown). LCs both with and without lipid droplets in this patient expressed all the steroid synthesis‐related proteins except StAR, 3β‐HSD, and 17β‐HSD (Fig. 3 ). This was part of a study approved by the ethics committee of Fukushima Medical University School of Medicine (2245). Informed consent was obtained after explaining the purpose and methods.'}
|
Age-of-Onset
|
Age (of onset)
|
[
"15‐day‐old"
] |
test-2123
|
7292164
|
{'Case presentation': 'A 15‐day‐old 46, XY neonate presented with severe adrenal insufficiency. Congenital lipoid adrenal hyperplasia was diagnosed after detection of steroidogenic acute regulatory gene mutations. At 2 years and 5 months, she underwent bilateral gonadectomy. Leydig cells were observed both with and without lipid droplets in the testes of this patient. We also demonstrated immunohistochemically that some testosterone‐synthesizing enzymes were maintained in this patient. The patient was born at full term with completely normal female external genitalia. No abnormalities were identified in routine newborn screenings. At 15 days, she was brought to the hospital with poor feeding and poor weight gain. Hyperpigmentation suggestive of adrenal insufficiency was noted. Laboratory tests revealed severe hyponatremia (115 mEq/L) and hyperkalemia (8.6 mEq/L). She was immediately treated with hydrocortisone and examined for all adrenocortical hormones and associated metabolites in serum and urine. Not only mineralocorticoids and glucocorticoids, but also adrenal androgens and their metabolic products were barely detectable. On the other hand, concentrations of adrenocorticotropic hormone were extremely high, at 387 pg/mL (normal 7.2–63.3 pg/mL). CT showed enlargement of bilateral adrenal glands (Fig. 1 a). Bilateral gonads were not palpable but were detectable near the internal inguinal rings on ultrasonography and MRI (Fig. 1 b). Since congenital adrenal hyperplasia was strongly suspected, chromosomal genetic testing was performed and revealed a 46,XY karyotype. Sequence analysis of the StAR gene revealed compound heterozygous mutations for p.Q258X and p.D246fs. From these results, lipoid CAH was diagnosed. Laparoscopic bilateral gonadectomy was performed at 2 years and 5 months. Both gonads were identified as normal testes accompanied by vas deferens and epididymis. The testes measured 16 × 10 × 6 mm on the right and 14 × 8 × 8 mm on the left (Fig. 2 a,b). As of the time of writing, she is continuing adrenocortical hormone replacement therapy, and will receive combination estrogen replacement therapy at the time of puberty.', 'Histopathological findings': 'Light microscopy showed seminiferous tubules mainly comprising spermatogonia and Sertoli cells, with no spermatocytes or spermatids (Fig. 2 c). Two types of LCs were identified, filled with and without lipid droplets in the testicular interstitium. The nuclei of LCs depressed by excessive lipid droplets were more clearly observable under electron microscopy (Fig. 2 d). Testosterone‐synthesizing enzymes in the testis of this patient were investigated by immunostaining and Western blotting methods using antibodies reacting with StAR protein, Ad4BP/SF‐1, CYP11A1, CYP17A1, 3β‐HSD, and 17β‐HSD. As control samples, we used biopsy tissues from three individuals with cryptorchidism ( n = 3; mean age, 5). All these steroid synthesis‐related proteins were observed in LCs of control samples using immunohistochemistry (Fig. 3 ). Western blotting analysis showed negative results for StAR protein in the testis of this patient (data not shown). LCs both with and without lipid droplets in this patient expressed all the steroid synthesis‐related proteins except StAR, 3β‐HSD, and 17β‐HSD (Fig. 3 ). This was part of a study approved by the ethics committee of Fukushima Medical University School of Medicine (2245). Informed consent was obtained after explaining the purpose and methods.'}
|
{'Case presentation': 'A 15‐day‐old 46, XY neonate presented with severe adrenal insufficiency. Congenital lipoid adrenal hyperplasia was diagnosed after detection of steroidogenic acute regulatory gene mutations. At 2 years and 5 months, she underwent bilateral gonadectomy. Leydig cells were observed both with and without lipid droplets in the testes of this patient. We also demonstrated immunohistochemically that some testosterone‐synthesizing enzymes were maintained in this patient. The patient was born at full term with completely normal female external genitalia. No abnormalities were identified in routine newborn screenings. At 15 days, she was brought to the hospital with poor feeding and poor weight gain. Hyperpigmentation suggestive of adrenal insufficiency was noted. Laboratory tests revealed severe hyponatremia (115 mEq/L) and hyperkalemia (8.6 mEq/L). She was immediately treated with hydrocortisone and examined for all adrenocortical hormones and associated metabolites in serum and urine. Not only mineralocorticoids and glucocorticoids, but also adrenal androgens and their metabolic products were barely detectable. On the other hand, concentrations of adrenocorticotropic hormone were extremely high, at 387 pg/mL (normal 7.2–63.3 pg/mL). CT showed enlargement of bilateral adrenal glands (Fig. 1 a). Bilateral gonads were not palpable but were detectable near the internal inguinal rings on ultrasonography and MRI (Fig. 1 b). Since congenital adrenal hyperplasia was strongly suspected, chromosomal genetic testing was performed and revealed a 46,XY karyotype. Sequence analysis of the StAR gene revealed compound heterozygous mutations for p.Q258X and p.D246fs. From these results, lipoid CAH was diagnosed. Laparoscopic bilateral gonadectomy was performed at 2 years and 5 months. Both gonads were identified as normal testes accompanied by vas deferens and epididymis. The testes measured 16 × 10 × 6 mm on the right and 14 × 8 × 8 mm on the left (Fig. 2 a,b). As of the time of writing, she is continuing adrenocortical hormone replacement therapy, and will receive combination estrogen replacement therapy at the time of puberty.', 'Histopathological findings': 'Light microscopy showed seminiferous tubules mainly comprising spermatogonia and Sertoli cells, with no spermatocytes or spermatids (Fig. 2 c). Two types of LCs were identified, filled with and without lipid droplets in the testicular interstitium. The nuclei of LCs depressed by excessive lipid droplets were more clearly observable under electron microscopy (Fig. 2 d). Testosterone‐synthesizing enzymes in the testis of this patient were investigated by immunostaining and Western blotting methods using antibodies reacting with StAR protein, Ad4BP/SF‐1, CYP11A1, CYP17A1, 3β‐HSD, and 17β‐HSD. As control samples, we used biopsy tissues from three individuals with cryptorchidism ( n = 3; mean age, 5). All these steroid synthesis‐related proteins were observed in LCs of control samples using immunohistochemistry (Fig. 3 ). Western blotting analysis showed negative results for StAR protein in the testis of this patient (data not shown). LCs both with and without lipid droplets in this patient expressed all the steroid synthesis‐related proteins except StAR, 3β‐HSD, and 17β‐HSD (Fig. 3 ). This was part of a study approved by the ethics committee of Fukushima Medical University School of Medicine (2245). Informed consent was obtained after explaining the purpose and methods.'}
|
Confirmed-Diagnosis-IEM
|
Confirmed_Diagnosis(IEM)
|
[
"Congenital lipoid adrenal hyperplasia was diagnosed after detection of steroidogenic acute regulatory gene mutations ."
] |
test-2124
|
7292164
|
{'Case presentation': 'A 15‐day‐old 46, XY neonate presented with severe adrenal insufficiency. Congenital lipoid adrenal hyperplasia was diagnosed after detection of steroidogenic acute regulatory gene mutations. At 2 years and 5 months, she underwent bilateral gonadectomy. Leydig cells were observed both with and without lipid droplets in the testes of this patient. We also demonstrated immunohistochemically that some testosterone‐synthesizing enzymes were maintained in this patient. The patient was born at full term with completely normal female external genitalia. No abnormalities were identified in routine newborn screenings. At 15 days, she was brought to the hospital with poor feeding and poor weight gain. Hyperpigmentation suggestive of adrenal insufficiency was noted. Laboratory tests revealed severe hyponatremia (115 mEq/L) and hyperkalemia (8.6 mEq/L). She was immediately treated with hydrocortisone and examined for all adrenocortical hormones and associated metabolites in serum and urine. Not only mineralocorticoids and glucocorticoids, but also adrenal androgens and their metabolic products were barely detectable. On the other hand, concentrations of adrenocorticotropic hormone were extremely high, at 387 pg/mL (normal 7.2–63.3 pg/mL). CT showed enlargement of bilateral adrenal glands (Fig. 1 a). Bilateral gonads were not palpable but were detectable near the internal inguinal rings on ultrasonography and MRI (Fig. 1 b). Since congenital adrenal hyperplasia was strongly suspected, chromosomal genetic testing was performed and revealed a 46,XY karyotype. Sequence analysis of the StAR gene revealed compound heterozygous mutations for p.Q258X and p.D246fs. From these results, lipoid CAH was diagnosed. Laparoscopic bilateral gonadectomy was performed at 2 years and 5 months. Both gonads were identified as normal testes accompanied by vas deferens and epididymis. The testes measured 16 × 10 × 6 mm on the right and 14 × 8 × 8 mm on the left (Fig. 2 a,b). As of the time of writing, she is continuing adrenocortical hormone replacement therapy, and will receive combination estrogen replacement therapy at the time of puberty.', 'Histopathological findings': 'Light microscopy showed seminiferous tubules mainly comprising spermatogonia and Sertoli cells, with no spermatocytes or spermatids (Fig. 2 c). Two types of LCs were identified, filled with and without lipid droplets in the testicular interstitium. The nuclei of LCs depressed by excessive lipid droplets were more clearly observable under electron microscopy (Fig. 2 d). Testosterone‐synthesizing enzymes in the testis of this patient were investigated by immunostaining and Western blotting methods using antibodies reacting with StAR protein, Ad4BP/SF‐1, CYP11A1, CYP17A1, 3β‐HSD, and 17β‐HSD. As control samples, we used biopsy tissues from three individuals with cryptorchidism ( n = 3; mean age, 5). All these steroid synthesis‐related proteins were observed in LCs of control samples using immunohistochemistry (Fig. 3 ). Western blotting analysis showed negative results for StAR protein in the testis of this patient (data not shown). LCs both with and without lipid droplets in this patient expressed all the steroid synthesis‐related proteins except StAR, 3β‐HSD, and 17β‐HSD (Fig. 3 ). This was part of a study approved by the ethics committee of Fukushima Medical University School of Medicine (2245). Informed consent was obtained after explaining the purpose and methods.'}
|
{'Case presentation': 'A 15‐day‐old 46, XY neonate presented with severe adrenal insufficiency. Congenital lipoid adrenal hyperplasia was diagnosed after detection of steroidogenic acute regulatory gene mutations. At 2 years and 5 months, she underwent bilateral gonadectomy. Leydig cells were observed both with and without lipid droplets in the testes of this patient. We also demonstrated immunohistochemically that some testosterone‐synthesizing enzymes were maintained in this patient. The patient was born at full term with completely normal female external genitalia. No abnormalities were identified in routine newborn screenings. At 15 days, she was brought to the hospital with poor feeding and poor weight gain. Hyperpigmentation suggestive of adrenal insufficiency was noted. Laboratory tests revealed severe hyponatremia (115 mEq/L) and hyperkalemia (8.6 mEq/L). She was immediately treated with hydrocortisone and examined for all adrenocortical hormones and associated metabolites in serum and urine. Not only mineralocorticoids and glucocorticoids, but also adrenal androgens and their metabolic products were barely detectable. On the other hand, concentrations of adrenocorticotropic hormone were extremely high, at 387 pg/mL (normal 7.2–63.3 pg/mL). CT showed enlargement of bilateral adrenal glands (Fig. 1 a). Bilateral gonads were not palpable but were detectable near the internal inguinal rings on ultrasonography and MRI (Fig. 1 b). Since congenital adrenal hyperplasia was strongly suspected, chromosomal genetic testing was performed and revealed a 46,XY karyotype. Sequence analysis of the StAR gene revealed compound heterozygous mutations for p.Q258X and p.D246fs. From these results, lipoid CAH was diagnosed. Laparoscopic bilateral gonadectomy was performed at 2 years and 5 months. Both gonads were identified as normal testes accompanied by vas deferens and epididymis. The testes measured 16 × 10 × 6 mm on the right and 14 × 8 × 8 mm on the left (Fig. 2 a,b). As of the time of writing, she is continuing adrenocortical hormone replacement therapy, and will receive combination estrogen replacement therapy at the time of puberty.', 'Histopathological findings': 'Light microscopy showed seminiferous tubules mainly comprising spermatogonia and Sertoli cells, with no spermatocytes or spermatids (Fig. 2 c). Two types of LCs were identified, filled with and without lipid droplets in the testicular interstitium. The nuclei of LCs depressed by excessive lipid droplets were more clearly observable under electron microscopy (Fig. 2 d). Testosterone‐synthesizing enzymes in the testis of this patient were investigated by immunostaining and Western blotting methods using antibodies reacting with StAR protein, Ad4BP/SF‐1, CYP11A1, CYP17A1, 3β‐HSD, and 17β‐HSD. As control samples, we used biopsy tissues from three individuals with cryptorchidism ( n = 3; mean age, 5). All these steroid synthesis‐related proteins were observed in LCs of control samples using immunohistochemistry (Fig. 3 ). Western blotting analysis showed negative results for StAR protein in the testis of this patient (data not shown). LCs both with and without lipid droplets in this patient expressed all the steroid synthesis‐related proteins except StAR, 3β‐HSD, and 17β‐HSD (Fig. 3 ). This was part of a study approved by the ethics committee of Fukushima Medical University School of Medicine (2245). Informed consent was obtained after explaining the purpose and methods.'}
|
IEM-Treatment
|
IEM_Treatment
|
[
"hydrocortisone",
"adrenocortical hormone replacement therapy"
] |
test-2125
|
7296395
|
{'Declaration of patient consent:': 'The authors certify that they have obtained all appropriate patient consent forms.', 'Gynecological issues': 'The first attack in our patient was most probably provoked by taking hormonal contraception. The progesterone and estrogen levels modified heme biosynthesis in subjects with AIP during menstrual cycle. Increased levels of progesterone were considered more important than estrogen in precipitating AIP attacks ( 2, 4 ). The clinical evidence suggests that hormonal oral contraceptives can lead to a manifestation of AIP in 25% of the women with AIP, in most cases can lead to their first attack ( 2 ). If, for any reason, e.g. irregular menstrual bleeding or threatened spontaneous abortion, oral hormonal contraceptives or gestagenes are used, monitoring of porphyrin precursor levels is recommended during the first month, in order to be able to interrupt the treatment should it increase concentrations ( 2, 4 ). The AIP gene carriers are advised to refrain from using oral contraceptives, in line with European recommendations ( 4 ). AIP is usually manifested in adult women, which means that it is seldom developed before puberty and after menopause the frequency of attacks declines ( 4 ).', 'Anaesthesiological considerations': 'Patients with AIP are at particular risk from general anaesthesia as most of the intravenous agents including barbiturates and volatile agents are contraindicated. Asymptomatic patients can benefit from local and regional anesthesia with bupivacaine for both labour analgesia and caesarean section ( 8, 9 ), but for symptomatic patients, or patients in crisis, we should rather choose general anaesthesia for caesarean section. Several clinical reports suggest that the hypnotic agent of choice for both induction and maintenance of such anaesthesia is propofol ( 8, 9 ). In our case short intravenous anaesthesia was induced with a bolus of propofol, alfentanil and diasepam. AIP may also trigger posterior reversible encephalopathy syndrome (PRES), a rare condition that is characterized by acute neurological symptoms, like in our case. The clinical and radiological symptoms usually disappear through the elimination of PRES-triggering factors and appropriate treatment ( 10 ).', 'CASE REPORT': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Previously, she had had a seizure attack at home. Her therapy was dydrogesterone 10 mg, three times per day, during two weeks. In her personal history she stated to have had a porphyria. The last acute attack happened 7 years beforethe spontaneous abortion, and she did not have a checkup in that period. In consultation with an anesthesiologist, in a short intravenous anesthesia, vacuum aspiration, andcurettage were performed. The patient regained consciousness immediately after the intervention and reached full orientation and cooperativeness within few minutes. The post-intervention period remained uneventful and the neurological and psychological symptoms returned to the pre-exacerbation status. In laboratory findings porphyrin derivatives (delta aminolevulinic acid 7.76 mg / dU- (reference range 1.5-7.5) and porphobilinogen 16.84 mg / dU- (reference range 0-3.4) were elevated. The therapy of glucose solution was administrated after which the patient’s condition stabilized. Porphyria markers decreased within the next four weeks. Seven years ago, the patient was admitted due to vomiting, severe intermittent pain in the abdomen, frequent urination, blood in the urine, and elevated body temperature. The last four months the patient was on oral contraceptives (0.035 mg ethinyl estradiol and 2.0 mg cyproteronacetat) due to irregular menstrual cycles. During hospitalization, at the time of the first day of menstruation, the patient developed grand mal seizures and expressed agitation. Seizures reached the epileptic status. Epileptic status cannot be ceased by maximal dose of diazepam, but only short intravenous anesthesia (midazolam maleate). The patient was in a state of high psychomotor agitation after the epileptic status. The brain CT pointed atthe left parietal paramedian hypodense area 16 mm in diameter. The MRI of the brain described the bilateral symmetric lesions of cortico-subcortical distribution, parieto occipital and frontal, which according to MRI characteristics primarily refer to posterior reversible encephalopathy within the metabolic disorder. In laboratory findings, pronounced hyponatremia, hypokalemia, hypomagnesemia, and hypocalcaemia were verified. Biochemical was proven of AIP, high positive variability of total porphyrins (700 μg / dU- reference interval <220), uroporphyrin (185 mg / dU), copro-porphyrin (515 mg / dU), delta amino levulinic acid (19.50 mg / dU) and porphobilinogen (98 mg / dU)). During hospitalization, the patient ceased to take harmful drugs and she was given haem arginate, glucose and symptomatic drugs, and she recovered completely.', 'Case report:': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Her therapy was dydrogesterone. In consultation with an anesthesiologist, a short intravenous anesthesia, vacuum aspiration, and curettage were performed.During hospitalization, the patient ceased to take harmful drugs and she was given haemarginate, glucose and symptomatic drugs, and she recovered completely.'}
|
{'Declaration of patient consent:': 'The authors certify that they have obtained all appropriate patient consent forms.', 'Gynecological issues': 'The first attack in our patient was most probably provoked by taking hormonal contraception. The progesterone and estrogen levels modified heme biosynthesis in subjects with AIP during menstrual cycle. Increased levels of progesterone were considered more important than estrogen in precipitating AIP attacks ( 2, 4 ). The clinical evidence suggests that hormonal oral contraceptives can lead to a manifestation of AIP in 25% of the women with AIP, in most cases can lead to their first attack ( 2 ). If, for any reason, e.g. irregular menstrual bleeding or threatened spontaneous abortion, oral hormonal contraceptives or gestagenes are used, monitoring of porphyrin precursor levels is recommended during the first month, in order to be able to interrupt the treatment should it increase concentrations ( 2, 4 ). The AIP gene carriers are advised to refrain from using oral contraceptives, in line with European recommendations ( 4 ). AIP is usually manifested in adult women, which means that it is seldom developed before puberty and after menopause the frequency of attacks declines ( 4 ).', 'Anaesthesiological considerations': 'Patients with AIP are at particular risk from general anaesthesia as most of the intravenous agents including barbiturates and volatile agents are contraindicated. Asymptomatic patients can benefit from local and regional anesthesia with bupivacaine for both labour analgesia and caesarean section ( 8, 9 ), but for symptomatic patients, or patients in crisis, we should rather choose general anaesthesia for caesarean section. Several clinical reports suggest that the hypnotic agent of choice for both induction and maintenance of such anaesthesia is propofol ( 8, 9 ). In our case short intravenous anaesthesia was induced with a bolus of propofol, alfentanil and diasepam. AIP may also trigger posterior reversible encephalopathy syndrome (PRES), a rare condition that is characterized by acute neurological symptoms, like in our case. The clinical and radiological symptoms usually disappear through the elimination of PRES-triggering factors and appropriate treatment ( 10 ).', 'CASE REPORT': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Previously, she had had a seizure attack at home. Her therapy was dydrogesterone 10 mg, three times per day, during two weeks. In her personal history she stated to have had a porphyria. The last acute attack happened 7 years beforethe spontaneous abortion, and she did not have a checkup in that period. In consultation with an anesthesiologist, in a short intravenous anesthesia, vacuum aspiration, andcurettage were performed. The patient regained consciousness immediately after the intervention and reached full orientation and cooperativeness within few minutes. The post-intervention period remained uneventful and the neurological and psychological symptoms returned to the pre-exacerbation status. In laboratory findings porphyrin derivatives (delta aminolevulinic acid 7.76 mg / dU- (reference range 1.5-7.5) and porphobilinogen 16.84 mg / dU- (reference range 0-3.4) were elevated. The therapy of glucose solution was administrated after which the patient’s condition stabilized. Porphyria markers decreased within the next four weeks. Seven years ago, the patient was admitted due to vomiting, severe intermittent pain in the abdomen, frequent urination, blood in the urine, and elevated body temperature. The last four months the patient was on oral contraceptives (0.035 mg ethinyl estradiol and 2.0 mg cyproteronacetat) due to irregular menstrual cycles. During hospitalization, at the time of the first day of menstruation, the patient developed grand mal seizures and expressed agitation. Seizures reached the epileptic status. Epileptic status cannot be ceased by maximal dose of diazepam, but only short intravenous anesthesia (midazolam maleate). The patient was in a state of high psychomotor agitation after the epileptic status. The brain CT pointed atthe left parietal paramedian hypodense area 16 mm in diameter. The MRI of the brain described the bilateral symmetric lesions of cortico-subcortical distribution, parieto occipital and frontal, which according to MRI characteristics primarily refer to posterior reversible encephalopathy within the metabolic disorder. In laboratory findings, pronounced hyponatremia, hypokalemia, hypomagnesemia, and hypocalcaemia were verified. Biochemical was proven of AIP, high positive variability of total porphyrins (700 μg / dU- reference interval <220), uroporphyrin (185 mg / dU), copro-porphyrin (515 mg / dU), delta amino levulinic acid (19.50 mg / dU) and porphobilinogen (98 mg / dU)). During hospitalization, the patient ceased to take harmful drugs and she was given haem arginate, glucose and symptomatic drugs, and she recovered completely.', 'Case report:': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Her therapy was dydrogesterone. In consultation with an anesthesiologist, a short intravenous anesthesia, vacuum aspiration, and curettage were performed.During hospitalization, the patient ceased to take harmful drugs and she was given haemarginate, glucose and symptomatic drugs, and she recovered completely.'}
|
Vitals-and-Hematology
|
Vitals_Hema
|
[
"blood in the urine"
] |
test-2126
|
7296395
|
{'Declaration of patient consent:': 'The authors certify that they have obtained all appropriate patient consent forms.', 'Gynecological issues': 'The first attack in our patient was most probably provoked by taking hormonal contraception. The progesterone and estrogen levels modified heme biosynthesis in subjects with AIP during menstrual cycle. Increased levels of progesterone were considered more important than estrogen in precipitating AIP attacks ( 2, 4 ). The clinical evidence suggests that hormonal oral contraceptives can lead to a manifestation of AIP in 25% of the women with AIP, in most cases can lead to their first attack ( 2 ). If, for any reason, e.g. irregular menstrual bleeding or threatened spontaneous abortion, oral hormonal contraceptives or gestagenes are used, monitoring of porphyrin precursor levels is recommended during the first month, in order to be able to interrupt the treatment should it increase concentrations ( 2, 4 ). The AIP gene carriers are advised to refrain from using oral contraceptives, in line with European recommendations ( 4 ). AIP is usually manifested in adult women, which means that it is seldom developed before puberty and after menopause the frequency of attacks declines ( 4 ).', 'Anaesthesiological considerations': 'Patients with AIP are at particular risk from general anaesthesia as most of the intravenous agents including barbiturates and volatile agents are contraindicated. Asymptomatic patients can benefit from local and regional anesthesia with bupivacaine for both labour analgesia and caesarean section ( 8, 9 ), but for symptomatic patients, or patients in crisis, we should rather choose general anaesthesia for caesarean section. Several clinical reports suggest that the hypnotic agent of choice for both induction and maintenance of such anaesthesia is propofol ( 8, 9 ). In our case short intravenous anaesthesia was induced with a bolus of propofol, alfentanil and diasepam. AIP may also trigger posterior reversible encephalopathy syndrome (PRES), a rare condition that is characterized by acute neurological symptoms, like in our case. The clinical and radiological symptoms usually disappear through the elimination of PRES-triggering factors and appropriate treatment ( 10 ).', 'CASE REPORT': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Previously, she had had a seizure attack at home. Her therapy was dydrogesterone 10 mg, three times per day, during two weeks. In her personal history she stated to have had a porphyria. The last acute attack happened 7 years beforethe spontaneous abortion, and she did not have a checkup in that period. In consultation with an anesthesiologist, in a short intravenous anesthesia, vacuum aspiration, andcurettage were performed. The patient regained consciousness immediately after the intervention and reached full orientation and cooperativeness within few minutes. The post-intervention period remained uneventful and the neurological and psychological symptoms returned to the pre-exacerbation status. In laboratory findings porphyrin derivatives (delta aminolevulinic acid 7.76 mg / dU- (reference range 1.5-7.5) and porphobilinogen 16.84 mg / dU- (reference range 0-3.4) were elevated. The therapy of glucose solution was administrated after which the patient’s condition stabilized. Porphyria markers decreased within the next four weeks. Seven years ago, the patient was admitted due to vomiting, severe intermittent pain in the abdomen, frequent urination, blood in the urine, and elevated body temperature. The last four months the patient was on oral contraceptives (0.035 mg ethinyl estradiol and 2.0 mg cyproteronacetat) due to irregular menstrual cycles. During hospitalization, at the time of the first day of menstruation, the patient developed grand mal seizures and expressed agitation. Seizures reached the epileptic status. Epileptic status cannot be ceased by maximal dose of diazepam, but only short intravenous anesthesia (midazolam maleate). The patient was in a state of high psychomotor agitation after the epileptic status. The brain CT pointed atthe left parietal paramedian hypodense area 16 mm in diameter. The MRI of the brain described the bilateral symmetric lesions of cortico-subcortical distribution, parieto occipital and frontal, which according to MRI characteristics primarily refer to posterior reversible encephalopathy within the metabolic disorder. In laboratory findings, pronounced hyponatremia, hypokalemia, hypomagnesemia, and hypocalcaemia were verified. Biochemical was proven of AIP, high positive variability of total porphyrins (700 μg / dU- reference interval <220), uroporphyrin (185 mg / dU), copro-porphyrin (515 mg / dU), delta amino levulinic acid (19.50 mg / dU) and porphobilinogen (98 mg / dU)). During hospitalization, the patient ceased to take harmful drugs and she was given haem arginate, glucose and symptomatic drugs, and she recovered completely.', 'Case report:': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Her therapy was dydrogesterone. In consultation with an anesthesiologist, a short intravenous anesthesia, vacuum aspiration, and curettage were performed.During hospitalization, the patient ceased to take harmful drugs and she was given haemarginate, glucose and symptomatic drugs, and she recovered completely.'}
|
{'Declaration of patient consent:': 'The authors certify that they have obtained all appropriate patient consent forms.', 'Gynecological issues': 'The first attack in our patient was most probably provoked by taking hormonal contraception. The progesterone and estrogen levels modified heme biosynthesis in subjects with AIP during menstrual cycle. Increased levels of progesterone were considered more important than estrogen in precipitating AIP attacks ( 2, 4 ). The clinical evidence suggests that hormonal oral contraceptives can lead to a manifestation of AIP in 25% of the women with AIP, in most cases can lead to their first attack ( 2 ). If, for any reason, e.g. irregular menstrual bleeding or threatened spontaneous abortion, oral hormonal contraceptives or gestagenes are used, monitoring of porphyrin precursor levels is recommended during the first month, in order to be able to interrupt the treatment should it increase concentrations ( 2, 4 ). The AIP gene carriers are advised to refrain from using oral contraceptives, in line with European recommendations ( 4 ). AIP is usually manifested in adult women, which means that it is seldom developed before puberty and after menopause the frequency of attacks declines ( 4 ).', 'Anaesthesiological considerations': 'Patients with AIP are at particular risk from general anaesthesia as most of the intravenous agents including barbiturates and volatile agents are contraindicated. Asymptomatic patients can benefit from local and regional anesthesia with bupivacaine for both labour analgesia and caesarean section ( 8, 9 ), but for symptomatic patients, or patients in crisis, we should rather choose general anaesthesia for caesarean section. Several clinical reports suggest that the hypnotic agent of choice for both induction and maintenance of such anaesthesia is propofol ( 8, 9 ). In our case short intravenous anaesthesia was induced with a bolus of propofol, alfentanil and diasepam. AIP may also trigger posterior reversible encephalopathy syndrome (PRES), a rare condition that is characterized by acute neurological symptoms, like in our case. The clinical and radiological symptoms usually disappear through the elimination of PRES-triggering factors and appropriate treatment ( 10 ).', 'CASE REPORT': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Previously, she had had a seizure attack at home. Her therapy was dydrogesterone 10 mg, three times per day, during two weeks. In her personal history she stated to have had a porphyria. The last acute attack happened 7 years beforethe spontaneous abortion, and she did not have a checkup in that period. In consultation with an anesthesiologist, in a short intravenous anesthesia, vacuum aspiration, andcurettage were performed. The patient regained consciousness immediately after the intervention and reached full orientation and cooperativeness within few minutes. The post-intervention period remained uneventful and the neurological and psychological symptoms returned to the pre-exacerbation status. In laboratory findings porphyrin derivatives (delta aminolevulinic acid 7.76 mg / dU- (reference range 1.5-7.5) and porphobilinogen 16.84 mg / dU- (reference range 0-3.4) were elevated. The therapy of glucose solution was administrated after which the patient’s condition stabilized. Porphyria markers decreased within the next four weeks. Seven years ago, the patient was admitted due to vomiting, severe intermittent pain in the abdomen, frequent urination, blood in the urine, and elevated body temperature. The last four months the patient was on oral contraceptives (0.035 mg ethinyl estradiol and 2.0 mg cyproteronacetat) due to irregular menstrual cycles. During hospitalization, at the time of the first day of menstruation, the patient developed grand mal seizures and expressed agitation. Seizures reached the epileptic status. Epileptic status cannot be ceased by maximal dose of diazepam, but only short intravenous anesthesia (midazolam maleate). The patient was in a state of high psychomotor agitation after the epileptic status. The brain CT pointed atthe left parietal paramedian hypodense area 16 mm in diameter. The MRI of the brain described the bilateral symmetric lesions of cortico-subcortical distribution, parieto occipital and frontal, which according to MRI characteristics primarily refer to posterior reversible encephalopathy within the metabolic disorder. In laboratory findings, pronounced hyponatremia, hypokalemia, hypomagnesemia, and hypocalcaemia were verified. Biochemical was proven of AIP, high positive variability of total porphyrins (700 μg / dU- reference interval <220), uroporphyrin (185 mg / dU), copro-porphyrin (515 mg / dU), delta amino levulinic acid (19.50 mg / dU) and porphobilinogen (98 mg / dU)). During hospitalization, the patient ceased to take harmful drugs and she was given haem arginate, glucose and symptomatic drugs, and she recovered completely.', 'Case report:': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Her therapy was dydrogesterone. In consultation with an anesthesiologist, a short intravenous anesthesia, vacuum aspiration, and curettage were performed.During hospitalization, the patient ceased to take harmful drugs and she was given haemarginate, glucose and symptomatic drugs, and she recovered completely.'}
|
Gastrointestinal-System
|
GI
|
[
"abdominal pain, constipation",
"vomiting",
"vomiting, severe intermittent pain in the abdomen",
"abdominal pain, constipation,",
"vomiting"
] |
test-2127
|
7296395
|
{'Declaration of patient consent:': 'The authors certify that they have obtained all appropriate patient consent forms.', 'Gynecological issues': 'The first attack in our patient was most probably provoked by taking hormonal contraception. The progesterone and estrogen levels modified heme biosynthesis in subjects with AIP during menstrual cycle. Increased levels of progesterone were considered more important than estrogen in precipitating AIP attacks ( 2, 4 ). The clinical evidence suggests that hormonal oral contraceptives can lead to a manifestation of AIP in 25% of the women with AIP, in most cases can lead to their first attack ( 2 ). If, for any reason, e.g. irregular menstrual bleeding or threatened spontaneous abortion, oral hormonal contraceptives or gestagenes are used, monitoring of porphyrin precursor levels is recommended during the first month, in order to be able to interrupt the treatment should it increase concentrations ( 2, 4 ). The AIP gene carriers are advised to refrain from using oral contraceptives, in line with European recommendations ( 4 ). AIP is usually manifested in adult women, which means that it is seldom developed before puberty and after menopause the frequency of attacks declines ( 4 ).', 'Anaesthesiological considerations': 'Patients with AIP are at particular risk from general anaesthesia as most of the intravenous agents including barbiturates and volatile agents are contraindicated. Asymptomatic patients can benefit from local and regional anesthesia with bupivacaine for both labour analgesia and caesarean section ( 8, 9 ), but for symptomatic patients, or patients in crisis, we should rather choose general anaesthesia for caesarean section. Several clinical reports suggest that the hypnotic agent of choice for both induction and maintenance of such anaesthesia is propofol ( 8, 9 ). In our case short intravenous anaesthesia was induced with a bolus of propofol, alfentanil and diasepam. AIP may also trigger posterior reversible encephalopathy syndrome (PRES), a rare condition that is characterized by acute neurological symptoms, like in our case. The clinical and radiological symptoms usually disappear through the elimination of PRES-triggering factors and appropriate treatment ( 10 ).', 'CASE REPORT': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Previously, she had had a seizure attack at home. Her therapy was dydrogesterone 10 mg, three times per day, during two weeks. In her personal history she stated to have had a porphyria. The last acute attack happened 7 years beforethe spontaneous abortion, and she did not have a checkup in that period. In consultation with an anesthesiologist, in a short intravenous anesthesia, vacuum aspiration, andcurettage were performed. The patient regained consciousness immediately after the intervention and reached full orientation and cooperativeness within few minutes. The post-intervention period remained uneventful and the neurological and psychological symptoms returned to the pre-exacerbation status. In laboratory findings porphyrin derivatives (delta aminolevulinic acid 7.76 mg / dU- (reference range 1.5-7.5) and porphobilinogen 16.84 mg / dU- (reference range 0-3.4) were elevated. The therapy of glucose solution was administrated after which the patient’s condition stabilized. Porphyria markers decreased within the next four weeks. Seven years ago, the patient was admitted due to vomiting, severe intermittent pain in the abdomen, frequent urination, blood in the urine, and elevated body temperature. The last four months the patient was on oral contraceptives (0.035 mg ethinyl estradiol and 2.0 mg cyproteronacetat) due to irregular menstrual cycles. During hospitalization, at the time of the first day of menstruation, the patient developed grand mal seizures and expressed agitation. Seizures reached the epileptic status. Epileptic status cannot be ceased by maximal dose of diazepam, but only short intravenous anesthesia (midazolam maleate). The patient was in a state of high psychomotor agitation after the epileptic status. The brain CT pointed atthe left parietal paramedian hypodense area 16 mm in diameter. The MRI of the brain described the bilateral symmetric lesions of cortico-subcortical distribution, parieto occipital and frontal, which according to MRI characteristics primarily refer to posterior reversible encephalopathy within the metabolic disorder. In laboratory findings, pronounced hyponatremia, hypokalemia, hypomagnesemia, and hypocalcaemia were verified. Biochemical was proven of AIP, high positive variability of total porphyrins (700 μg / dU- reference interval <220), uroporphyrin (185 mg / dU), copro-porphyrin (515 mg / dU), delta amino levulinic acid (19.50 mg / dU) and porphobilinogen (98 mg / dU)). During hospitalization, the patient ceased to take harmful drugs and she was given haem arginate, glucose and symptomatic drugs, and she recovered completely.', 'Case report:': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Her therapy was dydrogesterone. In consultation with an anesthesiologist, a short intravenous anesthesia, vacuum aspiration, and curettage were performed.During hospitalization, the patient ceased to take harmful drugs and she was given haemarginate, glucose and symptomatic drugs, and she recovered completely.'}
|
{'Declaration of patient consent:': 'The authors certify that they have obtained all appropriate patient consent forms.', 'Gynecological issues': 'The first attack in our patient was most probably provoked by taking hormonal contraception. The progesterone and estrogen levels modified heme biosynthesis in subjects with AIP during menstrual cycle. Increased levels of progesterone were considered more important than estrogen in precipitating AIP attacks ( 2, 4 ). The clinical evidence suggests that hormonal oral contraceptives can lead to a manifestation of AIP in 25% of the women with AIP, in most cases can lead to their first attack ( 2 ). If, for any reason, e.g. irregular menstrual bleeding or threatened spontaneous abortion, oral hormonal contraceptives or gestagenes are used, monitoring of porphyrin precursor levels is recommended during the first month, in order to be able to interrupt the treatment should it increase concentrations ( 2, 4 ). The AIP gene carriers are advised to refrain from using oral contraceptives, in line with European recommendations ( 4 ). AIP is usually manifested in adult women, which means that it is seldom developed before puberty and after menopause the frequency of attacks declines ( 4 ).', 'Anaesthesiological considerations': 'Patients with AIP are at particular risk from general anaesthesia as most of the intravenous agents including barbiturates and volatile agents are contraindicated. Asymptomatic patients can benefit from local and regional anesthesia with bupivacaine for both labour analgesia and caesarean section ( 8, 9 ), but for symptomatic patients, or patients in crisis, we should rather choose general anaesthesia for caesarean section. Several clinical reports suggest that the hypnotic agent of choice for both induction and maintenance of such anaesthesia is propofol ( 8, 9 ). In our case short intravenous anaesthesia was induced with a bolus of propofol, alfentanil and diasepam. AIP may also trigger posterior reversible encephalopathy syndrome (PRES), a rare condition that is characterized by acute neurological symptoms, like in our case. The clinical and radiological symptoms usually disappear through the elimination of PRES-triggering factors and appropriate treatment ( 10 ).', 'CASE REPORT': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Previously, she had had a seizure attack at home. Her therapy was dydrogesterone 10 mg, three times per day, during two weeks. In her personal history she stated to have had a porphyria. The last acute attack happened 7 years beforethe spontaneous abortion, and she did not have a checkup in that period. In consultation with an anesthesiologist, in a short intravenous anesthesia, vacuum aspiration, andcurettage were performed. The patient regained consciousness immediately after the intervention and reached full orientation and cooperativeness within few minutes. The post-intervention period remained uneventful and the neurological and psychological symptoms returned to the pre-exacerbation status. In laboratory findings porphyrin derivatives (delta aminolevulinic acid 7.76 mg / dU- (reference range 1.5-7.5) and porphobilinogen 16.84 mg / dU- (reference range 0-3.4) were elevated. The therapy of glucose solution was administrated after which the patient’s condition stabilized. Porphyria markers decreased within the next four weeks. Seven years ago, the patient was admitted due to vomiting, severe intermittent pain in the abdomen, frequent urination, blood in the urine, and elevated body temperature. The last four months the patient was on oral contraceptives (0.035 mg ethinyl estradiol and 2.0 mg cyproteronacetat) due to irregular menstrual cycles. During hospitalization, at the time of the first day of menstruation, the patient developed grand mal seizures and expressed agitation. Seizures reached the epileptic status. Epileptic status cannot be ceased by maximal dose of diazepam, but only short intravenous anesthesia (midazolam maleate). The patient was in a state of high psychomotor agitation after the epileptic status. The brain CT pointed atthe left parietal paramedian hypodense area 16 mm in diameter. The MRI of the brain described the bilateral symmetric lesions of cortico-subcortical distribution, parieto occipital and frontal, which according to MRI characteristics primarily refer to posterior reversible encephalopathy within the metabolic disorder. In laboratory findings, pronounced hyponatremia, hypokalemia, hypomagnesemia, and hypocalcaemia were verified. Biochemical was proven of AIP, high positive variability of total porphyrins (700 μg / dU- reference interval <220), uroporphyrin (185 mg / dU), copro-porphyrin (515 mg / dU), delta amino levulinic acid (19.50 mg / dU) and porphobilinogen (98 mg / dU)). During hospitalization, the patient ceased to take harmful drugs and she was given haem arginate, glucose and symptomatic drugs, and she recovered completely.', 'Case report:': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Her therapy was dydrogesterone. In consultation with an anesthesiologist, a short intravenous anesthesia, vacuum aspiration, and curettage were performed.During hospitalization, the patient ceased to take harmful drugs and she was given haemarginate, glucose and symptomatic drugs, and she recovered completely.'}
|
Patient-History
|
History
|
[
"A gynecologist examined 26 - year - old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Previously, she had had a seizure attack at home",
"In her personal history she stated to have had a porphyria"
] |
test-2128
|
7296395
|
{'Declaration of patient consent:': 'The authors certify that they have obtained all appropriate patient consent forms.', 'Gynecological issues': 'The first attack in our patient was most probably provoked by taking hormonal contraception. The progesterone and estrogen levels modified heme biosynthesis in subjects with AIP during menstrual cycle. Increased levels of progesterone were considered more important than estrogen in precipitating AIP attacks ( 2, 4 ). The clinical evidence suggests that hormonal oral contraceptives can lead to a manifestation of AIP in 25% of the women with AIP, in most cases can lead to their first attack ( 2 ). If, for any reason, e.g. irregular menstrual bleeding or threatened spontaneous abortion, oral hormonal contraceptives or gestagenes are used, monitoring of porphyrin precursor levels is recommended during the first month, in order to be able to interrupt the treatment should it increase concentrations ( 2, 4 ). The AIP gene carriers are advised to refrain from using oral contraceptives, in line with European recommendations ( 4 ). AIP is usually manifested in adult women, which means that it is seldom developed before puberty and after menopause the frequency of attacks declines ( 4 ).', 'Anaesthesiological considerations': 'Patients with AIP are at particular risk from general anaesthesia as most of the intravenous agents including barbiturates and volatile agents are contraindicated. Asymptomatic patients can benefit from local and regional anesthesia with bupivacaine for both labour analgesia and caesarean section ( 8, 9 ), but for symptomatic patients, or patients in crisis, we should rather choose general anaesthesia for caesarean section. Several clinical reports suggest that the hypnotic agent of choice for both induction and maintenance of such anaesthesia is propofol ( 8, 9 ). In our case short intravenous anaesthesia was induced with a bolus of propofol, alfentanil and diasepam. AIP may also trigger posterior reversible encephalopathy syndrome (PRES), a rare condition that is characterized by acute neurological symptoms, like in our case. The clinical and radiological symptoms usually disappear through the elimination of PRES-triggering factors and appropriate treatment ( 10 ).', 'CASE REPORT': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Previously, she had had a seizure attack at home. Her therapy was dydrogesterone 10 mg, three times per day, during two weeks. In her personal history she stated to have had a porphyria. The last acute attack happened 7 years beforethe spontaneous abortion, and she did not have a checkup in that period. In consultation with an anesthesiologist, in a short intravenous anesthesia, vacuum aspiration, andcurettage were performed. The patient regained consciousness immediately after the intervention and reached full orientation and cooperativeness within few minutes. The post-intervention period remained uneventful and the neurological and psychological symptoms returned to the pre-exacerbation status. In laboratory findings porphyrin derivatives (delta aminolevulinic acid 7.76 mg / dU- (reference range 1.5-7.5) and porphobilinogen 16.84 mg / dU- (reference range 0-3.4) were elevated. The therapy of glucose solution was administrated after which the patient’s condition stabilized. Porphyria markers decreased within the next four weeks. Seven years ago, the patient was admitted due to vomiting, severe intermittent pain in the abdomen, frequent urination, blood in the urine, and elevated body temperature. The last four months the patient was on oral contraceptives (0.035 mg ethinyl estradiol and 2.0 mg cyproteronacetat) due to irregular menstrual cycles. During hospitalization, at the time of the first day of menstruation, the patient developed grand mal seizures and expressed agitation. Seizures reached the epileptic status. Epileptic status cannot be ceased by maximal dose of diazepam, but only short intravenous anesthesia (midazolam maleate). The patient was in a state of high psychomotor agitation after the epileptic status. The brain CT pointed atthe left parietal paramedian hypodense area 16 mm in diameter. The MRI of the brain described the bilateral symmetric lesions of cortico-subcortical distribution, parieto occipital and frontal, which according to MRI characteristics primarily refer to posterior reversible encephalopathy within the metabolic disorder. In laboratory findings, pronounced hyponatremia, hypokalemia, hypomagnesemia, and hypocalcaemia were verified. Biochemical was proven of AIP, high positive variability of total porphyrins (700 μg / dU- reference interval <220), uroporphyrin (185 mg / dU), copro-porphyrin (515 mg / dU), delta amino levulinic acid (19.50 mg / dU) and porphobilinogen (98 mg / dU)). During hospitalization, the patient ceased to take harmful drugs and she was given haem arginate, glucose and symptomatic drugs, and she recovered completely.', 'Case report:': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Her therapy was dydrogesterone. In consultation with an anesthesiologist, a short intravenous anesthesia, vacuum aspiration, and curettage were performed.During hospitalization, the patient ceased to take harmful drugs and she was given haemarginate, glucose and symptomatic drugs, and she recovered completely.'}
|
{'Declaration of patient consent:': 'The authors certify that they have obtained all appropriate patient consent forms.', 'Gynecological issues': 'The first attack in our patient was most probably provoked by taking hormonal contraception. The progesterone and estrogen levels modified heme biosynthesis in subjects with AIP during menstrual cycle. Increased levels of progesterone were considered more important than estrogen in precipitating AIP attacks ( 2, 4 ). The clinical evidence suggests that hormonal oral contraceptives can lead to a manifestation of AIP in 25% of the women with AIP, in most cases can lead to their first attack ( 2 ). If, for any reason, e.g. irregular menstrual bleeding or threatened spontaneous abortion, oral hormonal contraceptives or gestagenes are used, monitoring of porphyrin precursor levels is recommended during the first month, in order to be able to interrupt the treatment should it increase concentrations ( 2, 4 ). The AIP gene carriers are advised to refrain from using oral contraceptives, in line with European recommendations ( 4 ). AIP is usually manifested in adult women, which means that it is seldom developed before puberty and after menopause the frequency of attacks declines ( 4 ).', 'Anaesthesiological considerations': 'Patients with AIP are at particular risk from general anaesthesia as most of the intravenous agents including barbiturates and volatile agents are contraindicated. Asymptomatic patients can benefit from local and regional anesthesia with bupivacaine for both labour analgesia and caesarean section ( 8, 9 ), but for symptomatic patients, or patients in crisis, we should rather choose general anaesthesia for caesarean section. Several clinical reports suggest that the hypnotic agent of choice for both induction and maintenance of such anaesthesia is propofol ( 8, 9 ). In our case short intravenous anaesthesia was induced with a bolus of propofol, alfentanil and diasepam. AIP may also trigger posterior reversible encephalopathy syndrome (PRES), a rare condition that is characterized by acute neurological symptoms, like in our case. The clinical and radiological symptoms usually disappear through the elimination of PRES-triggering factors and appropriate treatment ( 10 ).', 'CASE REPORT': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Previously, she had had a seizure attack at home. Her therapy was dydrogesterone 10 mg, three times per day, during two weeks. In her personal history she stated to have had a porphyria. The last acute attack happened 7 years beforethe spontaneous abortion, and she did not have a checkup in that period. In consultation with an anesthesiologist, in a short intravenous anesthesia, vacuum aspiration, andcurettage were performed. The patient regained consciousness immediately after the intervention and reached full orientation and cooperativeness within few minutes. The post-intervention period remained uneventful and the neurological and psychological symptoms returned to the pre-exacerbation status. In laboratory findings porphyrin derivatives (delta aminolevulinic acid 7.76 mg / dU- (reference range 1.5-7.5) and porphobilinogen 16.84 mg / dU- (reference range 0-3.4) were elevated. The therapy of glucose solution was administrated after which the patient’s condition stabilized. Porphyria markers decreased within the next four weeks. Seven years ago, the patient was admitted due to vomiting, severe intermittent pain in the abdomen, frequent urination, blood in the urine, and elevated body temperature. The last four months the patient was on oral contraceptives (0.035 mg ethinyl estradiol and 2.0 mg cyproteronacetat) due to irregular menstrual cycles. During hospitalization, at the time of the first day of menstruation, the patient developed grand mal seizures and expressed agitation. Seizures reached the epileptic status. Epileptic status cannot be ceased by maximal dose of diazepam, but only short intravenous anesthesia (midazolam maleate). The patient was in a state of high psychomotor agitation after the epileptic status. The brain CT pointed atthe left parietal paramedian hypodense area 16 mm in diameter. The MRI of the brain described the bilateral symmetric lesions of cortico-subcortical distribution, parieto occipital and frontal, which according to MRI characteristics primarily refer to posterior reversible encephalopathy within the metabolic disorder. In laboratory findings, pronounced hyponatremia, hypokalemia, hypomagnesemia, and hypocalcaemia were verified. Biochemical was proven of AIP, high positive variability of total porphyrins (700 μg / dU- reference interval <220), uroporphyrin (185 mg / dU), copro-porphyrin (515 mg / dU), delta amino levulinic acid (19.50 mg / dU) and porphobilinogen (98 mg / dU)). During hospitalization, the patient ceased to take harmful drugs and she was given haem arginate, glucose and symptomatic drugs, and she recovered completely.', 'Case report:': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Her therapy was dydrogesterone. In consultation with an anesthesiologist, a short intravenous anesthesia, vacuum aspiration, and curettage were performed.During hospitalization, the patient ceased to take harmful drugs and she was given haemarginate, glucose and symptomatic drugs, and she recovered completely.'}
|
Neurology
|
Neuro
|
[
"seizure attack at home",
"reached full orientation and cooperativeness within few minutes. The post - intervention period remained uneventful and the neurological and psychological symptoms returned to the pre - exacerbation status",
"patient developed grand mal seizures and expressed agitation. Seizures reached the epileptic status",
"state of high psychomotor agitation after the epileptic status",
"The brain CT pointed atthe left parietal paramedian hypodense area 16 mm in diameter. The MRI of the brain described the bilateral symmetric lesions of cortico - subcortical distribution, parieto occipital and frontal,"
] |
test-2129
|
7296395
|
{'Declaration of patient consent:': 'The authors certify that they have obtained all appropriate patient consent forms.', 'Gynecological issues': 'The first attack in our patient was most probably provoked by taking hormonal contraception. The progesterone and estrogen levels modified heme biosynthesis in subjects with AIP during menstrual cycle. Increased levels of progesterone were considered more important than estrogen in precipitating AIP attacks ( 2, 4 ). The clinical evidence suggests that hormonal oral contraceptives can lead to a manifestation of AIP in 25% of the women with AIP, in most cases can lead to their first attack ( 2 ). If, for any reason, e.g. irregular menstrual bleeding or threatened spontaneous abortion, oral hormonal contraceptives or gestagenes are used, monitoring of porphyrin precursor levels is recommended during the first month, in order to be able to interrupt the treatment should it increase concentrations ( 2, 4 ). The AIP gene carriers are advised to refrain from using oral contraceptives, in line with European recommendations ( 4 ). AIP is usually manifested in adult women, which means that it is seldom developed before puberty and after menopause the frequency of attacks declines ( 4 ).', 'Anaesthesiological considerations': 'Patients with AIP are at particular risk from general anaesthesia as most of the intravenous agents including barbiturates and volatile agents are contraindicated. Asymptomatic patients can benefit from local and regional anesthesia with bupivacaine for both labour analgesia and caesarean section ( 8, 9 ), but for symptomatic patients, or patients in crisis, we should rather choose general anaesthesia for caesarean section. Several clinical reports suggest that the hypnotic agent of choice for both induction and maintenance of such anaesthesia is propofol ( 8, 9 ). In our case short intravenous anaesthesia was induced with a bolus of propofol, alfentanil and diasepam. AIP may also trigger posterior reversible encephalopathy syndrome (PRES), a rare condition that is characterized by acute neurological symptoms, like in our case. The clinical and radiological symptoms usually disappear through the elimination of PRES-triggering factors and appropriate treatment ( 10 ).', 'CASE REPORT': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Previously, she had had a seizure attack at home. Her therapy was dydrogesterone 10 mg, three times per day, during two weeks. In her personal history she stated to have had a porphyria. The last acute attack happened 7 years beforethe spontaneous abortion, and she did not have a checkup in that period. In consultation with an anesthesiologist, in a short intravenous anesthesia, vacuum aspiration, andcurettage were performed. The patient regained consciousness immediately after the intervention and reached full orientation and cooperativeness within few minutes. The post-intervention period remained uneventful and the neurological and psychological symptoms returned to the pre-exacerbation status. In laboratory findings porphyrin derivatives (delta aminolevulinic acid 7.76 mg / dU- (reference range 1.5-7.5) and porphobilinogen 16.84 mg / dU- (reference range 0-3.4) were elevated. The therapy of glucose solution was administrated after which the patient’s condition stabilized. Porphyria markers decreased within the next four weeks. Seven years ago, the patient was admitted due to vomiting, severe intermittent pain in the abdomen, frequent urination, blood in the urine, and elevated body temperature. The last four months the patient was on oral contraceptives (0.035 mg ethinyl estradiol and 2.0 mg cyproteronacetat) due to irregular menstrual cycles. During hospitalization, at the time of the first day of menstruation, the patient developed grand mal seizures and expressed agitation. Seizures reached the epileptic status. Epileptic status cannot be ceased by maximal dose of diazepam, but only short intravenous anesthesia (midazolam maleate). The patient was in a state of high psychomotor agitation after the epileptic status. The brain CT pointed atthe left parietal paramedian hypodense area 16 mm in diameter. The MRI of the brain described the bilateral symmetric lesions of cortico-subcortical distribution, parieto occipital and frontal, which according to MRI characteristics primarily refer to posterior reversible encephalopathy within the metabolic disorder. In laboratory findings, pronounced hyponatremia, hypokalemia, hypomagnesemia, and hypocalcaemia were verified. Biochemical was proven of AIP, high positive variability of total porphyrins (700 μg / dU- reference interval <220), uroporphyrin (185 mg / dU), copro-porphyrin (515 mg / dU), delta amino levulinic acid (19.50 mg / dU) and porphobilinogen (98 mg / dU)). During hospitalization, the patient ceased to take harmful drugs and she was given haem arginate, glucose and symptomatic drugs, and she recovered completely.', 'Case report:': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Her therapy was dydrogesterone. In consultation with an anesthesiologist, a short intravenous anesthesia, vacuum aspiration, and curettage were performed.During hospitalization, the patient ceased to take harmful drugs and she was given haemarginate, glucose and symptomatic drugs, and she recovered completely.'}
|
{'Declaration of patient consent:': 'The authors certify that they have obtained all appropriate patient consent forms.', 'Gynecological issues': 'The first attack in our patient was most probably provoked by taking hormonal contraception. The progesterone and estrogen levels modified heme biosynthesis in subjects with AIP during menstrual cycle. Increased levels of progesterone were considered more important than estrogen in precipitating AIP attacks ( 2, 4 ). The clinical evidence suggests that hormonal oral contraceptives can lead to a manifestation of AIP in 25% of the women with AIP, in most cases can lead to their first attack ( 2 ). If, for any reason, e.g. irregular menstrual bleeding or threatened spontaneous abortion, oral hormonal contraceptives or gestagenes are used, monitoring of porphyrin precursor levels is recommended during the first month, in order to be able to interrupt the treatment should it increase concentrations ( 2, 4 ). The AIP gene carriers are advised to refrain from using oral contraceptives, in line with European recommendations ( 4 ). AIP is usually manifested in adult women, which means that it is seldom developed before puberty and after menopause the frequency of attacks declines ( 4 ).', 'Anaesthesiological considerations': 'Patients with AIP are at particular risk from general anaesthesia as most of the intravenous agents including barbiturates and volatile agents are contraindicated. Asymptomatic patients can benefit from local and regional anesthesia with bupivacaine for both labour analgesia and caesarean section ( 8, 9 ), but for symptomatic patients, or patients in crisis, we should rather choose general anaesthesia for caesarean section. Several clinical reports suggest that the hypnotic agent of choice for both induction and maintenance of such anaesthesia is propofol ( 8, 9 ). In our case short intravenous anaesthesia was induced with a bolus of propofol, alfentanil and diasepam. AIP may also trigger posterior reversible encephalopathy syndrome (PRES), a rare condition that is characterized by acute neurological symptoms, like in our case. The clinical and radiological symptoms usually disappear through the elimination of PRES-triggering factors and appropriate treatment ( 10 ).', 'CASE REPORT': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Previously, she had had a seizure attack at home. Her therapy was dydrogesterone 10 mg, three times per day, during two weeks. In her personal history she stated to have had a porphyria. The last acute attack happened 7 years beforethe spontaneous abortion, and she did not have a checkup in that period. In consultation with an anesthesiologist, in a short intravenous anesthesia, vacuum aspiration, andcurettage were performed. The patient regained consciousness immediately after the intervention and reached full orientation and cooperativeness within few minutes. The post-intervention period remained uneventful and the neurological and psychological symptoms returned to the pre-exacerbation status. In laboratory findings porphyrin derivatives (delta aminolevulinic acid 7.76 mg / dU- (reference range 1.5-7.5) and porphobilinogen 16.84 mg / dU- (reference range 0-3.4) were elevated. The therapy of glucose solution was administrated after which the patient’s condition stabilized. Porphyria markers decreased within the next four weeks. Seven years ago, the patient was admitted due to vomiting, severe intermittent pain in the abdomen, frequent urination, blood in the urine, and elevated body temperature. The last four months the patient was on oral contraceptives (0.035 mg ethinyl estradiol and 2.0 mg cyproteronacetat) due to irregular menstrual cycles. During hospitalization, at the time of the first day of menstruation, the patient developed grand mal seizures and expressed agitation. Seizures reached the epileptic status. Epileptic status cannot be ceased by maximal dose of diazepam, but only short intravenous anesthesia (midazolam maleate). The patient was in a state of high psychomotor agitation after the epileptic status. The brain CT pointed atthe left parietal paramedian hypodense area 16 mm in diameter. The MRI of the brain described the bilateral symmetric lesions of cortico-subcortical distribution, parieto occipital and frontal, which according to MRI characteristics primarily refer to posterior reversible encephalopathy within the metabolic disorder. In laboratory findings, pronounced hyponatremia, hypokalemia, hypomagnesemia, and hypocalcaemia were verified. Biochemical was proven of AIP, high positive variability of total porphyrins (700 μg / dU- reference interval <220), uroporphyrin (185 mg / dU), copro-porphyrin (515 mg / dU), delta amino levulinic acid (19.50 mg / dU) and porphobilinogen (98 mg / dU)). During hospitalization, the patient ceased to take harmful drugs and she was given haem arginate, glucose and symptomatic drugs, and she recovered completely.', 'Case report:': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Her therapy was dydrogesterone. In consultation with an anesthesiologist, a short intravenous anesthesia, vacuum aspiration, and curettage were performed.During hospitalization, the patient ceased to take harmful drugs and she was given haemarginate, glucose and symptomatic drugs, and she recovered completely.'}
|
Laboratory-and-Imaging
|
Lab_Image
|
[
"In laboratory findings porphyrin derivatives ( delta aminolevulinic acid 7.76 mg / dU- ( reference range 1.5 - 7.5 ) and porphobilinogen 16.84 mg / dU- ( reference range 0 - 3.4 ) were elevated",
"Porphyria markers decreased within the next four weeks",
"The brain CT pointed atthe left parietal paramedian hypodense area 16 mm in diameter. The MRI of the brain described the bilateral symmetric lesions of cortico - subcortical distribution, parieto occipital and frontal, which according to MRI characteristics primarily refer to posterior reversible encephalopathy within the metabolic disorder. In laboratory findings, pronounced hyponatremia, hypokalemia, hypomagnesemia, and hypocalcaemia were verified. Biochemical was proven of AIP, high positive variability of total porphyrins ( 700 μg / dU- reference interval < 220 ), uroporphyrin ( 185 mg / dU ), copro - porphyrin ( 515 mg / dU ), delta amino levulinic acid ( 19.50 mg / dU ) and porphobilinogen ( 98 mg / dU ) )"
] |
test-2130
|
7296395
|
{'Declaration of patient consent:': 'The authors certify that they have obtained all appropriate patient consent forms.', 'Gynecological issues': 'The first attack in our patient was most probably provoked by taking hormonal contraception. The progesterone and estrogen levels modified heme biosynthesis in subjects with AIP during menstrual cycle. Increased levels of progesterone were considered more important than estrogen in precipitating AIP attacks ( 2, 4 ). The clinical evidence suggests that hormonal oral contraceptives can lead to a manifestation of AIP in 25% of the women with AIP, in most cases can lead to their first attack ( 2 ). If, for any reason, e.g. irregular menstrual bleeding or threatened spontaneous abortion, oral hormonal contraceptives or gestagenes are used, monitoring of porphyrin precursor levels is recommended during the first month, in order to be able to interrupt the treatment should it increase concentrations ( 2, 4 ). The AIP gene carriers are advised to refrain from using oral contraceptives, in line with European recommendations ( 4 ). AIP is usually manifested in adult women, which means that it is seldom developed before puberty and after menopause the frequency of attacks declines ( 4 ).', 'Anaesthesiological considerations': 'Patients with AIP are at particular risk from general anaesthesia as most of the intravenous agents including barbiturates and volatile agents are contraindicated. Asymptomatic patients can benefit from local and regional anesthesia with bupivacaine for both labour analgesia and caesarean section ( 8, 9 ), but for symptomatic patients, or patients in crisis, we should rather choose general anaesthesia for caesarean section. Several clinical reports suggest that the hypnotic agent of choice for both induction and maintenance of such anaesthesia is propofol ( 8, 9 ). In our case short intravenous anaesthesia was induced with a bolus of propofol, alfentanil and diasepam. AIP may also trigger posterior reversible encephalopathy syndrome (PRES), a rare condition that is characterized by acute neurological symptoms, like in our case. The clinical and radiological symptoms usually disappear through the elimination of PRES-triggering factors and appropriate treatment ( 10 ).', 'CASE REPORT': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Previously, she had had a seizure attack at home. Her therapy was dydrogesterone 10 mg, three times per day, during two weeks. In her personal history she stated to have had a porphyria. The last acute attack happened 7 years beforethe spontaneous abortion, and she did not have a checkup in that period. In consultation with an anesthesiologist, in a short intravenous anesthesia, vacuum aspiration, andcurettage were performed. The patient regained consciousness immediately after the intervention and reached full orientation and cooperativeness within few minutes. The post-intervention period remained uneventful and the neurological and psychological symptoms returned to the pre-exacerbation status. In laboratory findings porphyrin derivatives (delta aminolevulinic acid 7.76 mg / dU- (reference range 1.5-7.5) and porphobilinogen 16.84 mg / dU- (reference range 0-3.4) were elevated. The therapy of glucose solution was administrated after which the patient’s condition stabilized. Porphyria markers decreased within the next four weeks. Seven years ago, the patient was admitted due to vomiting, severe intermittent pain in the abdomen, frequent urination, blood in the urine, and elevated body temperature. The last four months the patient was on oral contraceptives (0.035 mg ethinyl estradiol and 2.0 mg cyproteronacetat) due to irregular menstrual cycles. During hospitalization, at the time of the first day of menstruation, the patient developed grand mal seizures and expressed agitation. Seizures reached the epileptic status. Epileptic status cannot be ceased by maximal dose of diazepam, but only short intravenous anesthesia (midazolam maleate). The patient was in a state of high psychomotor agitation after the epileptic status. The brain CT pointed atthe left parietal paramedian hypodense area 16 mm in diameter. The MRI of the brain described the bilateral symmetric lesions of cortico-subcortical distribution, parieto occipital and frontal, which according to MRI characteristics primarily refer to posterior reversible encephalopathy within the metabolic disorder. In laboratory findings, pronounced hyponatremia, hypokalemia, hypomagnesemia, and hypocalcaemia were verified. Biochemical was proven of AIP, high positive variability of total porphyrins (700 μg / dU- reference interval <220), uroporphyrin (185 mg / dU), copro-porphyrin (515 mg / dU), delta amino levulinic acid (19.50 mg / dU) and porphobilinogen (98 mg / dU)). During hospitalization, the patient ceased to take harmful drugs and she was given haem arginate, glucose and symptomatic drugs, and she recovered completely.', 'Case report:': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Her therapy was dydrogesterone. In consultation with an anesthesiologist, a short intravenous anesthesia, vacuum aspiration, and curettage were performed.During hospitalization, the patient ceased to take harmful drugs and she was given haemarginate, glucose and symptomatic drugs, and she recovered completely.'}
|
{'Declaration of patient consent:': 'The authors certify that they have obtained all appropriate patient consent forms.', 'Gynecological issues': 'The first attack in our patient was most probably provoked by taking hormonal contraception. The progesterone and estrogen levels modified heme biosynthesis in subjects with AIP during menstrual cycle. Increased levels of progesterone were considered more important than estrogen in precipitating AIP attacks ( 2, 4 ). The clinical evidence suggests that hormonal oral contraceptives can lead to a manifestation of AIP in 25% of the women with AIP, in most cases can lead to their first attack ( 2 ). If, for any reason, e.g. irregular menstrual bleeding or threatened spontaneous abortion, oral hormonal contraceptives or gestagenes are used, monitoring of porphyrin precursor levels is recommended during the first month, in order to be able to interrupt the treatment should it increase concentrations ( 2, 4 ). The AIP gene carriers are advised to refrain from using oral contraceptives, in line with European recommendations ( 4 ). AIP is usually manifested in adult women, which means that it is seldom developed before puberty and after menopause the frequency of attacks declines ( 4 ).', 'Anaesthesiological considerations': 'Patients with AIP are at particular risk from general anaesthesia as most of the intravenous agents including barbiturates and volatile agents are contraindicated. Asymptomatic patients can benefit from local and regional anesthesia with bupivacaine for both labour analgesia and caesarean section ( 8, 9 ), but for symptomatic patients, or patients in crisis, we should rather choose general anaesthesia for caesarean section. Several clinical reports suggest that the hypnotic agent of choice for both induction and maintenance of such anaesthesia is propofol ( 8, 9 ). In our case short intravenous anaesthesia was induced with a bolus of propofol, alfentanil and diasepam. AIP may also trigger posterior reversible encephalopathy syndrome (PRES), a rare condition that is characterized by acute neurological symptoms, like in our case. The clinical and radiological symptoms usually disappear through the elimination of PRES-triggering factors and appropriate treatment ( 10 ).', 'CASE REPORT': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Previously, she had had a seizure attack at home. Her therapy was dydrogesterone 10 mg, three times per day, during two weeks. In her personal history she stated to have had a porphyria. The last acute attack happened 7 years beforethe spontaneous abortion, and she did not have a checkup in that period. In consultation with an anesthesiologist, in a short intravenous anesthesia, vacuum aspiration, andcurettage were performed. The patient regained consciousness immediately after the intervention and reached full orientation and cooperativeness within few minutes. The post-intervention period remained uneventful and the neurological and psychological symptoms returned to the pre-exacerbation status. In laboratory findings porphyrin derivatives (delta aminolevulinic acid 7.76 mg / dU- (reference range 1.5-7.5) and porphobilinogen 16.84 mg / dU- (reference range 0-3.4) were elevated. The therapy of glucose solution was administrated after which the patient’s condition stabilized. Porphyria markers decreased within the next four weeks. Seven years ago, the patient was admitted due to vomiting, severe intermittent pain in the abdomen, frequent urination, blood in the urine, and elevated body temperature. The last four months the patient was on oral contraceptives (0.035 mg ethinyl estradiol and 2.0 mg cyproteronacetat) due to irregular menstrual cycles. During hospitalization, at the time of the first day of menstruation, the patient developed grand mal seizures and expressed agitation. Seizures reached the epileptic status. Epileptic status cannot be ceased by maximal dose of diazepam, but only short intravenous anesthesia (midazolam maleate). The patient was in a state of high psychomotor agitation after the epileptic status. The brain CT pointed atthe left parietal paramedian hypodense area 16 mm in diameter. The MRI of the brain described the bilateral symmetric lesions of cortico-subcortical distribution, parieto occipital and frontal, which according to MRI characteristics primarily refer to posterior reversible encephalopathy within the metabolic disorder. In laboratory findings, pronounced hyponatremia, hypokalemia, hypomagnesemia, and hypocalcaemia were verified. Biochemical was proven of AIP, high positive variability of total porphyrins (700 μg / dU- reference interval <220), uroporphyrin (185 mg / dU), copro-porphyrin (515 mg / dU), delta amino levulinic acid (19.50 mg / dU) and porphobilinogen (98 mg / dU)). During hospitalization, the patient ceased to take harmful drugs and she was given haem arginate, glucose and symptomatic drugs, and she recovered completely.', 'Case report:': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Her therapy was dydrogesterone. In consultation with an anesthesiologist, a short intravenous anesthesia, vacuum aspiration, and curettage were performed.During hospitalization, the patient ceased to take harmful drugs and she was given haemarginate, glucose and symptomatic drugs, and she recovered completely.'}
|
Cardiovascular-System
|
CVS
|
[] |
test-2131
|
7296395
|
{'Declaration of patient consent:': 'The authors certify that they have obtained all appropriate patient consent forms.', 'Gynecological issues': 'The first attack in our patient was most probably provoked by taking hormonal contraception. The progesterone and estrogen levels modified heme biosynthesis in subjects with AIP during menstrual cycle. Increased levels of progesterone were considered more important than estrogen in precipitating AIP attacks ( 2, 4 ). The clinical evidence suggests that hormonal oral contraceptives can lead to a manifestation of AIP in 25% of the women with AIP, in most cases can lead to their first attack ( 2 ). If, for any reason, e.g. irregular menstrual bleeding or threatened spontaneous abortion, oral hormonal contraceptives or gestagenes are used, monitoring of porphyrin precursor levels is recommended during the first month, in order to be able to interrupt the treatment should it increase concentrations ( 2, 4 ). The AIP gene carriers are advised to refrain from using oral contraceptives, in line with European recommendations ( 4 ). AIP is usually manifested in adult women, which means that it is seldom developed before puberty and after menopause the frequency of attacks declines ( 4 ).', 'Anaesthesiological considerations': 'Patients with AIP are at particular risk from general anaesthesia as most of the intravenous agents including barbiturates and volatile agents are contraindicated. Asymptomatic patients can benefit from local and regional anesthesia with bupivacaine for both labour analgesia and caesarean section ( 8, 9 ), but for symptomatic patients, or patients in crisis, we should rather choose general anaesthesia for caesarean section. Several clinical reports suggest that the hypnotic agent of choice for both induction and maintenance of such anaesthesia is propofol ( 8, 9 ). In our case short intravenous anaesthesia was induced with a bolus of propofol, alfentanil and diasepam. AIP may also trigger posterior reversible encephalopathy syndrome (PRES), a rare condition that is characterized by acute neurological symptoms, like in our case. The clinical and radiological symptoms usually disappear through the elimination of PRES-triggering factors and appropriate treatment ( 10 ).', 'CASE REPORT': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Previously, she had had a seizure attack at home. Her therapy was dydrogesterone 10 mg, three times per day, during two weeks. In her personal history she stated to have had a porphyria. The last acute attack happened 7 years beforethe spontaneous abortion, and she did not have a checkup in that period. In consultation with an anesthesiologist, in a short intravenous anesthesia, vacuum aspiration, andcurettage were performed. The patient regained consciousness immediately after the intervention and reached full orientation and cooperativeness within few minutes. The post-intervention period remained uneventful and the neurological and psychological symptoms returned to the pre-exacerbation status. In laboratory findings porphyrin derivatives (delta aminolevulinic acid 7.76 mg / dU- (reference range 1.5-7.5) and porphobilinogen 16.84 mg / dU- (reference range 0-3.4) were elevated. The therapy of glucose solution was administrated after which the patient’s condition stabilized. Porphyria markers decreased within the next four weeks. Seven years ago, the patient was admitted due to vomiting, severe intermittent pain in the abdomen, frequent urination, blood in the urine, and elevated body temperature. The last four months the patient was on oral contraceptives (0.035 mg ethinyl estradiol and 2.0 mg cyproteronacetat) due to irregular menstrual cycles. During hospitalization, at the time of the first day of menstruation, the patient developed grand mal seizures and expressed agitation. Seizures reached the epileptic status. Epileptic status cannot be ceased by maximal dose of diazepam, but only short intravenous anesthesia (midazolam maleate). The patient was in a state of high psychomotor agitation after the epileptic status. The brain CT pointed atthe left parietal paramedian hypodense area 16 mm in diameter. The MRI of the brain described the bilateral symmetric lesions of cortico-subcortical distribution, parieto occipital and frontal, which according to MRI characteristics primarily refer to posterior reversible encephalopathy within the metabolic disorder. In laboratory findings, pronounced hyponatremia, hypokalemia, hypomagnesemia, and hypocalcaemia were verified. Biochemical was proven of AIP, high positive variability of total porphyrins (700 μg / dU- reference interval <220), uroporphyrin (185 mg / dU), copro-porphyrin (515 mg / dU), delta amino levulinic acid (19.50 mg / dU) and porphobilinogen (98 mg / dU)). During hospitalization, the patient ceased to take harmful drugs and she was given haem arginate, glucose and symptomatic drugs, and she recovered completely.', 'Case report:': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Her therapy was dydrogesterone. In consultation with an anesthesiologist, a short intravenous anesthesia, vacuum aspiration, and curettage were performed.During hospitalization, the patient ceased to take harmful drugs and she was given haemarginate, glucose and symptomatic drugs, and she recovered completely.'}
|
{'Declaration of patient consent:': 'The authors certify that they have obtained all appropriate patient consent forms.', 'Gynecological issues': 'The first attack in our patient was most probably provoked by taking hormonal contraception. The progesterone and estrogen levels modified heme biosynthesis in subjects with AIP during menstrual cycle. Increased levels of progesterone were considered more important than estrogen in precipitating AIP attacks ( 2, 4 ). The clinical evidence suggests that hormonal oral contraceptives can lead to a manifestation of AIP in 25% of the women with AIP, in most cases can lead to their first attack ( 2 ). If, for any reason, e.g. irregular menstrual bleeding or threatened spontaneous abortion, oral hormonal contraceptives or gestagenes are used, monitoring of porphyrin precursor levels is recommended during the first month, in order to be able to interrupt the treatment should it increase concentrations ( 2, 4 ). The AIP gene carriers are advised to refrain from using oral contraceptives, in line with European recommendations ( 4 ). AIP is usually manifested in adult women, which means that it is seldom developed before puberty and after menopause the frequency of attacks declines ( 4 ).', 'Anaesthesiological considerations': 'Patients with AIP are at particular risk from general anaesthesia as most of the intravenous agents including barbiturates and volatile agents are contraindicated. Asymptomatic patients can benefit from local and regional anesthesia with bupivacaine for both labour analgesia and caesarean section ( 8, 9 ), but for symptomatic patients, or patients in crisis, we should rather choose general anaesthesia for caesarean section. Several clinical reports suggest that the hypnotic agent of choice for both induction and maintenance of such anaesthesia is propofol ( 8, 9 ). In our case short intravenous anaesthesia was induced with a bolus of propofol, alfentanil and diasepam. AIP may also trigger posterior reversible encephalopathy syndrome (PRES), a rare condition that is characterized by acute neurological symptoms, like in our case. The clinical and radiological symptoms usually disappear through the elimination of PRES-triggering factors and appropriate treatment ( 10 ).', 'CASE REPORT': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Previously, she had had a seizure attack at home. Her therapy was dydrogesterone 10 mg, three times per day, during two weeks. In her personal history she stated to have had a porphyria. The last acute attack happened 7 years beforethe spontaneous abortion, and she did not have a checkup in that period. In consultation with an anesthesiologist, in a short intravenous anesthesia, vacuum aspiration, andcurettage were performed. The patient regained consciousness immediately after the intervention and reached full orientation and cooperativeness within few minutes. The post-intervention period remained uneventful and the neurological and psychological symptoms returned to the pre-exacerbation status. In laboratory findings porphyrin derivatives (delta aminolevulinic acid 7.76 mg / dU- (reference range 1.5-7.5) and porphobilinogen 16.84 mg / dU- (reference range 0-3.4) were elevated. The therapy of glucose solution was administrated after which the patient’s condition stabilized. Porphyria markers decreased within the next four weeks. Seven years ago, the patient was admitted due to vomiting, severe intermittent pain in the abdomen, frequent urination, blood in the urine, and elevated body temperature. The last four months the patient was on oral contraceptives (0.035 mg ethinyl estradiol and 2.0 mg cyproteronacetat) due to irregular menstrual cycles. During hospitalization, at the time of the first day of menstruation, the patient developed grand mal seizures and expressed agitation. Seizures reached the epileptic status. Epileptic status cannot be ceased by maximal dose of diazepam, but only short intravenous anesthesia (midazolam maleate). The patient was in a state of high psychomotor agitation after the epileptic status. The brain CT pointed atthe left parietal paramedian hypodense area 16 mm in diameter. The MRI of the brain described the bilateral symmetric lesions of cortico-subcortical distribution, parieto occipital and frontal, which according to MRI characteristics primarily refer to posterior reversible encephalopathy within the metabolic disorder. In laboratory findings, pronounced hyponatremia, hypokalemia, hypomagnesemia, and hypocalcaemia were verified. Biochemical was proven of AIP, high positive variability of total porphyrins (700 μg / dU- reference interval <220), uroporphyrin (185 mg / dU), copro-porphyrin (515 mg / dU), delta amino levulinic acid (19.50 mg / dU) and porphobilinogen (98 mg / dU)). During hospitalization, the patient ceased to take harmful drugs and she was given haem arginate, glucose and symptomatic drugs, and she recovered completely.', 'Case report:': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Her therapy was dydrogesterone. In consultation with an anesthesiologist, a short intravenous anesthesia, vacuum aspiration, and curettage were performed.During hospitalization, the patient ceased to take harmful drugs and she was given haemarginate, glucose and symptomatic drugs, and she recovered completely.'}
|
Endocrinology
|
ENDO
|
[
"The first attack in our patient was most probably provoked by taking hormonal contraception",
"The last four months the patient was on oral contraceptives ( 0.035 mg ethinyl estradiol and 2.0 mg cyproteronacetat ) due to irregular menstrual cycles",
"Her therapy was dydrogesterone."
] |
test-2132
|
7296395
|
{'Declaration of patient consent:': 'The authors certify that they have obtained all appropriate patient consent forms.', 'Gynecological issues': 'The first attack in our patient was most probably provoked by taking hormonal contraception. The progesterone and estrogen levels modified heme biosynthesis in subjects with AIP during menstrual cycle. Increased levels of progesterone were considered more important than estrogen in precipitating AIP attacks ( 2, 4 ). The clinical evidence suggests that hormonal oral contraceptives can lead to a manifestation of AIP in 25% of the women with AIP, in most cases can lead to their first attack ( 2 ). If, for any reason, e.g. irregular menstrual bleeding or threatened spontaneous abortion, oral hormonal contraceptives or gestagenes are used, monitoring of porphyrin precursor levels is recommended during the first month, in order to be able to interrupt the treatment should it increase concentrations ( 2, 4 ). The AIP gene carriers are advised to refrain from using oral contraceptives, in line with European recommendations ( 4 ). AIP is usually manifested in adult women, which means that it is seldom developed before puberty and after menopause the frequency of attacks declines ( 4 ).', 'Anaesthesiological considerations': 'Patients with AIP are at particular risk from general anaesthesia as most of the intravenous agents including barbiturates and volatile agents are contraindicated. Asymptomatic patients can benefit from local and regional anesthesia with bupivacaine for both labour analgesia and caesarean section ( 8, 9 ), but for symptomatic patients, or patients in crisis, we should rather choose general anaesthesia for caesarean section. Several clinical reports suggest that the hypnotic agent of choice for both induction and maintenance of such anaesthesia is propofol ( 8, 9 ). In our case short intravenous anaesthesia was induced with a bolus of propofol, alfentanil and diasepam. AIP may also trigger posterior reversible encephalopathy syndrome (PRES), a rare condition that is characterized by acute neurological symptoms, like in our case. The clinical and radiological symptoms usually disappear through the elimination of PRES-triggering factors and appropriate treatment ( 10 ).', 'CASE REPORT': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Previously, she had had a seizure attack at home. Her therapy was dydrogesterone 10 mg, three times per day, during two weeks. In her personal history she stated to have had a porphyria. The last acute attack happened 7 years beforethe spontaneous abortion, and she did not have a checkup in that period. In consultation with an anesthesiologist, in a short intravenous anesthesia, vacuum aspiration, andcurettage were performed. The patient regained consciousness immediately after the intervention and reached full orientation and cooperativeness within few minutes. The post-intervention period remained uneventful and the neurological and psychological symptoms returned to the pre-exacerbation status. In laboratory findings porphyrin derivatives (delta aminolevulinic acid 7.76 mg / dU- (reference range 1.5-7.5) and porphobilinogen 16.84 mg / dU- (reference range 0-3.4) were elevated. The therapy of glucose solution was administrated after which the patient’s condition stabilized. Porphyria markers decreased within the next four weeks. Seven years ago, the patient was admitted due to vomiting, severe intermittent pain in the abdomen, frequent urination, blood in the urine, and elevated body temperature. The last four months the patient was on oral contraceptives (0.035 mg ethinyl estradiol and 2.0 mg cyproteronacetat) due to irregular menstrual cycles. During hospitalization, at the time of the first day of menstruation, the patient developed grand mal seizures and expressed agitation. Seizures reached the epileptic status. Epileptic status cannot be ceased by maximal dose of diazepam, but only short intravenous anesthesia (midazolam maleate). The patient was in a state of high psychomotor agitation after the epileptic status. The brain CT pointed atthe left parietal paramedian hypodense area 16 mm in diameter. The MRI of the brain described the bilateral symmetric lesions of cortico-subcortical distribution, parieto occipital and frontal, which according to MRI characteristics primarily refer to posterior reversible encephalopathy within the metabolic disorder. In laboratory findings, pronounced hyponatremia, hypokalemia, hypomagnesemia, and hypocalcaemia were verified. Biochemical was proven of AIP, high positive variability of total porphyrins (700 μg / dU- reference interval <220), uroporphyrin (185 mg / dU), copro-porphyrin (515 mg / dU), delta amino levulinic acid (19.50 mg / dU) and porphobilinogen (98 mg / dU)). During hospitalization, the patient ceased to take harmful drugs and she was given haem arginate, glucose and symptomatic drugs, and she recovered completely.', 'Case report:': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Her therapy was dydrogesterone. In consultation with an anesthesiologist, a short intravenous anesthesia, vacuum aspiration, and curettage were performed.During hospitalization, the patient ceased to take harmful drugs and she was given haemarginate, glucose and symptomatic drugs, and she recovered completely.'}
|
{'Declaration of patient consent:': 'The authors certify that they have obtained all appropriate patient consent forms.', 'Gynecological issues': 'The first attack in our patient was most probably provoked by taking hormonal contraception. The progesterone and estrogen levels modified heme biosynthesis in subjects with AIP during menstrual cycle. Increased levels of progesterone were considered more important than estrogen in precipitating AIP attacks ( 2, 4 ). The clinical evidence suggests that hormonal oral contraceptives can lead to a manifestation of AIP in 25% of the women with AIP, in most cases can lead to their first attack ( 2 ). If, for any reason, e.g. irregular menstrual bleeding or threatened spontaneous abortion, oral hormonal contraceptives or gestagenes are used, monitoring of porphyrin precursor levels is recommended during the first month, in order to be able to interrupt the treatment should it increase concentrations ( 2, 4 ). The AIP gene carriers are advised to refrain from using oral contraceptives, in line with European recommendations ( 4 ). AIP is usually manifested in adult women, which means that it is seldom developed before puberty and after menopause the frequency of attacks declines ( 4 ).', 'Anaesthesiological considerations': 'Patients with AIP are at particular risk from general anaesthesia as most of the intravenous agents including barbiturates and volatile agents are contraindicated. Asymptomatic patients can benefit from local and regional anesthesia with bupivacaine for both labour analgesia and caesarean section ( 8, 9 ), but for symptomatic patients, or patients in crisis, we should rather choose general anaesthesia for caesarean section. Several clinical reports suggest that the hypnotic agent of choice for both induction and maintenance of such anaesthesia is propofol ( 8, 9 ). In our case short intravenous anaesthesia was induced with a bolus of propofol, alfentanil and diasepam. AIP may also trigger posterior reversible encephalopathy syndrome (PRES), a rare condition that is characterized by acute neurological symptoms, like in our case. The clinical and radiological symptoms usually disappear through the elimination of PRES-triggering factors and appropriate treatment ( 10 ).', 'CASE REPORT': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Previously, she had had a seizure attack at home. Her therapy was dydrogesterone 10 mg, three times per day, during two weeks. In her personal history she stated to have had a porphyria. The last acute attack happened 7 years beforethe spontaneous abortion, and she did not have a checkup in that period. In consultation with an anesthesiologist, in a short intravenous anesthesia, vacuum aspiration, andcurettage were performed. The patient regained consciousness immediately after the intervention and reached full orientation and cooperativeness within few minutes. The post-intervention period remained uneventful and the neurological and psychological symptoms returned to the pre-exacerbation status. In laboratory findings porphyrin derivatives (delta aminolevulinic acid 7.76 mg / dU- (reference range 1.5-7.5) and porphobilinogen 16.84 mg / dU- (reference range 0-3.4) were elevated. The therapy of glucose solution was administrated after which the patient’s condition stabilized. Porphyria markers decreased within the next four weeks. Seven years ago, the patient was admitted due to vomiting, severe intermittent pain in the abdomen, frequent urination, blood in the urine, and elevated body temperature. The last four months the patient was on oral contraceptives (0.035 mg ethinyl estradiol and 2.0 mg cyproteronacetat) due to irregular menstrual cycles. During hospitalization, at the time of the first day of menstruation, the patient developed grand mal seizures and expressed agitation. Seizures reached the epileptic status. Epileptic status cannot be ceased by maximal dose of diazepam, but only short intravenous anesthesia (midazolam maleate). The patient was in a state of high psychomotor agitation after the epileptic status. The brain CT pointed atthe left parietal paramedian hypodense area 16 mm in diameter. The MRI of the brain described the bilateral symmetric lesions of cortico-subcortical distribution, parieto occipital and frontal, which according to MRI characteristics primarily refer to posterior reversible encephalopathy within the metabolic disorder. In laboratory findings, pronounced hyponatremia, hypokalemia, hypomagnesemia, and hypocalcaemia were verified. Biochemical was proven of AIP, high positive variability of total porphyrins (700 μg / dU- reference interval <220), uroporphyrin (185 mg / dU), copro-porphyrin (515 mg / dU), delta amino levulinic acid (19.50 mg / dU) and porphobilinogen (98 mg / dU)). During hospitalization, the patient ceased to take harmful drugs and she was given haem arginate, glucose and symptomatic drugs, and she recovered completely.', 'Case report:': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Her therapy was dydrogesterone. In consultation with an anesthesiologist, a short intravenous anesthesia, vacuum aspiration, and curettage were performed.During hospitalization, the patient ceased to take harmful drugs and she was given haemarginate, glucose and symptomatic drugs, and she recovered completely.'}
|
Genitourinary-System
|
GU
|
[
"dark colour of urine",
"frequent urination, blood in the urine",
"irregular menstrual cycles",
"pronounced hyponatremia, hypokalemia, hypomagnesemia, and hypocalcaemia",
"dark colour of urine"
] |
test-2133
|
7296395
|
{'Declaration of patient consent:': 'The authors certify that they have obtained all appropriate patient consent forms.', 'Gynecological issues': 'The first attack in our patient was most probably provoked by taking hormonal contraception. The progesterone and estrogen levels modified heme biosynthesis in subjects with AIP during menstrual cycle. Increased levels of progesterone were considered more important than estrogen in precipitating AIP attacks ( 2, 4 ). The clinical evidence suggests that hormonal oral contraceptives can lead to a manifestation of AIP in 25% of the women with AIP, in most cases can lead to their first attack ( 2 ). If, for any reason, e.g. irregular menstrual bleeding or threatened spontaneous abortion, oral hormonal contraceptives or gestagenes are used, monitoring of porphyrin precursor levels is recommended during the first month, in order to be able to interrupt the treatment should it increase concentrations ( 2, 4 ). The AIP gene carriers are advised to refrain from using oral contraceptives, in line with European recommendations ( 4 ). AIP is usually manifested in adult women, which means that it is seldom developed before puberty and after menopause the frequency of attacks declines ( 4 ).', 'Anaesthesiological considerations': 'Patients with AIP are at particular risk from general anaesthesia as most of the intravenous agents including barbiturates and volatile agents are contraindicated. Asymptomatic patients can benefit from local and regional anesthesia with bupivacaine for both labour analgesia and caesarean section ( 8, 9 ), but for symptomatic patients, or patients in crisis, we should rather choose general anaesthesia for caesarean section. Several clinical reports suggest that the hypnotic agent of choice for both induction and maintenance of such anaesthesia is propofol ( 8, 9 ). In our case short intravenous anaesthesia was induced with a bolus of propofol, alfentanil and diasepam. AIP may also trigger posterior reversible encephalopathy syndrome (PRES), a rare condition that is characterized by acute neurological symptoms, like in our case. The clinical and radiological symptoms usually disappear through the elimination of PRES-triggering factors and appropriate treatment ( 10 ).', 'CASE REPORT': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Previously, she had had a seizure attack at home. Her therapy was dydrogesterone 10 mg, three times per day, during two weeks. In her personal history she stated to have had a porphyria. The last acute attack happened 7 years beforethe spontaneous abortion, and she did not have a checkup in that period. In consultation with an anesthesiologist, in a short intravenous anesthesia, vacuum aspiration, andcurettage were performed. The patient regained consciousness immediately after the intervention and reached full orientation and cooperativeness within few minutes. The post-intervention period remained uneventful and the neurological and psychological symptoms returned to the pre-exacerbation status. In laboratory findings porphyrin derivatives (delta aminolevulinic acid 7.76 mg / dU- (reference range 1.5-7.5) and porphobilinogen 16.84 mg / dU- (reference range 0-3.4) were elevated. The therapy of glucose solution was administrated after which the patient’s condition stabilized. Porphyria markers decreased within the next four weeks. Seven years ago, the patient was admitted due to vomiting, severe intermittent pain in the abdomen, frequent urination, blood in the urine, and elevated body temperature. The last four months the patient was on oral contraceptives (0.035 mg ethinyl estradiol and 2.0 mg cyproteronacetat) due to irregular menstrual cycles. During hospitalization, at the time of the first day of menstruation, the patient developed grand mal seizures and expressed agitation. Seizures reached the epileptic status. Epileptic status cannot be ceased by maximal dose of diazepam, but only short intravenous anesthesia (midazolam maleate). The patient was in a state of high psychomotor agitation after the epileptic status. The brain CT pointed atthe left parietal paramedian hypodense area 16 mm in diameter. The MRI of the brain described the bilateral symmetric lesions of cortico-subcortical distribution, parieto occipital and frontal, which according to MRI characteristics primarily refer to posterior reversible encephalopathy within the metabolic disorder. In laboratory findings, pronounced hyponatremia, hypokalemia, hypomagnesemia, and hypocalcaemia were verified. Biochemical was proven of AIP, high positive variability of total porphyrins (700 μg / dU- reference interval <220), uroporphyrin (185 mg / dU), copro-porphyrin (515 mg / dU), delta amino levulinic acid (19.50 mg / dU) and porphobilinogen (98 mg / dU)). During hospitalization, the patient ceased to take harmful drugs and she was given haem arginate, glucose and symptomatic drugs, and she recovered completely.', 'Case report:': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Her therapy was dydrogesterone. In consultation with an anesthesiologist, a short intravenous anesthesia, vacuum aspiration, and curettage were performed.During hospitalization, the patient ceased to take harmful drugs and she was given haemarginate, glucose and symptomatic drugs, and she recovered completely.'}
|
{'Declaration of patient consent:': 'The authors certify that they have obtained all appropriate patient consent forms.', 'Gynecological issues': 'The first attack in our patient was most probably provoked by taking hormonal contraception. The progesterone and estrogen levels modified heme biosynthesis in subjects with AIP during menstrual cycle. Increased levels of progesterone were considered more important than estrogen in precipitating AIP attacks ( 2, 4 ). The clinical evidence suggests that hormonal oral contraceptives can lead to a manifestation of AIP in 25% of the women with AIP, in most cases can lead to their first attack ( 2 ). If, for any reason, e.g. irregular menstrual bleeding or threatened spontaneous abortion, oral hormonal contraceptives or gestagenes are used, monitoring of porphyrin precursor levels is recommended during the first month, in order to be able to interrupt the treatment should it increase concentrations ( 2, 4 ). The AIP gene carriers are advised to refrain from using oral contraceptives, in line with European recommendations ( 4 ). AIP is usually manifested in adult women, which means that it is seldom developed before puberty and after menopause the frequency of attacks declines ( 4 ).', 'Anaesthesiological considerations': 'Patients with AIP are at particular risk from general anaesthesia as most of the intravenous agents including barbiturates and volatile agents are contraindicated. Asymptomatic patients can benefit from local and regional anesthesia with bupivacaine for both labour analgesia and caesarean section ( 8, 9 ), but for symptomatic patients, or patients in crisis, we should rather choose general anaesthesia for caesarean section. Several clinical reports suggest that the hypnotic agent of choice for both induction and maintenance of such anaesthesia is propofol ( 8, 9 ). In our case short intravenous anaesthesia was induced with a bolus of propofol, alfentanil and diasepam. AIP may also trigger posterior reversible encephalopathy syndrome (PRES), a rare condition that is characterized by acute neurological symptoms, like in our case. The clinical and radiological symptoms usually disappear through the elimination of PRES-triggering factors and appropriate treatment ( 10 ).', 'CASE REPORT': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Previously, she had had a seizure attack at home. Her therapy was dydrogesterone 10 mg, three times per day, during two weeks. In her personal history she stated to have had a porphyria. The last acute attack happened 7 years beforethe spontaneous abortion, and she did not have a checkup in that period. In consultation with an anesthesiologist, in a short intravenous anesthesia, vacuum aspiration, andcurettage were performed. The patient regained consciousness immediately after the intervention and reached full orientation and cooperativeness within few minutes. The post-intervention period remained uneventful and the neurological and psychological symptoms returned to the pre-exacerbation status. In laboratory findings porphyrin derivatives (delta aminolevulinic acid 7.76 mg / dU- (reference range 1.5-7.5) and porphobilinogen 16.84 mg / dU- (reference range 0-3.4) were elevated. The therapy of glucose solution was administrated after which the patient’s condition stabilized. Porphyria markers decreased within the next four weeks. Seven years ago, the patient was admitted due to vomiting, severe intermittent pain in the abdomen, frequent urination, blood in the urine, and elevated body temperature. The last four months the patient was on oral contraceptives (0.035 mg ethinyl estradiol and 2.0 mg cyproteronacetat) due to irregular menstrual cycles. During hospitalization, at the time of the first day of menstruation, the patient developed grand mal seizures and expressed agitation. Seizures reached the epileptic status. Epileptic status cannot be ceased by maximal dose of diazepam, but only short intravenous anesthesia (midazolam maleate). The patient was in a state of high psychomotor agitation after the epileptic status. The brain CT pointed atthe left parietal paramedian hypodense area 16 mm in diameter. The MRI of the brain described the bilateral symmetric lesions of cortico-subcortical distribution, parieto occipital and frontal, which according to MRI characteristics primarily refer to posterior reversible encephalopathy within the metabolic disorder. In laboratory findings, pronounced hyponatremia, hypokalemia, hypomagnesemia, and hypocalcaemia were verified. Biochemical was proven of AIP, high positive variability of total porphyrins (700 μg / dU- reference interval <220), uroporphyrin (185 mg / dU), copro-porphyrin (515 mg / dU), delta amino levulinic acid (19.50 mg / dU) and porphobilinogen (98 mg / dU)). During hospitalization, the patient ceased to take harmful drugs and she was given haem arginate, glucose and symptomatic drugs, and she recovered completely.', 'Case report:': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Her therapy was dydrogesterone. In consultation with an anesthesiologist, a short intravenous anesthesia, vacuum aspiration, and curettage were performed.During hospitalization, the patient ceased to take harmful drugs and she was given haemarginate, glucose and symptomatic drugs, and she recovered completely.'}
|
Respiratory-System
|
RESP
|
[] |
test-2134
|
7296395
|
{'Declaration of patient consent:': 'The authors certify that they have obtained all appropriate patient consent forms.', 'Gynecological issues': 'The first attack in our patient was most probably provoked by taking hormonal contraception. The progesterone and estrogen levels modified heme biosynthesis in subjects with AIP during menstrual cycle. Increased levels of progesterone were considered more important than estrogen in precipitating AIP attacks ( 2, 4 ). The clinical evidence suggests that hormonal oral contraceptives can lead to a manifestation of AIP in 25% of the women with AIP, in most cases can lead to their first attack ( 2 ). If, for any reason, e.g. irregular menstrual bleeding or threatened spontaneous abortion, oral hormonal contraceptives or gestagenes are used, monitoring of porphyrin precursor levels is recommended during the first month, in order to be able to interrupt the treatment should it increase concentrations ( 2, 4 ). The AIP gene carriers are advised to refrain from using oral contraceptives, in line with European recommendations ( 4 ). AIP is usually manifested in adult women, which means that it is seldom developed before puberty and after menopause the frequency of attacks declines ( 4 ).', 'Anaesthesiological considerations': 'Patients with AIP are at particular risk from general anaesthesia as most of the intravenous agents including barbiturates and volatile agents are contraindicated. Asymptomatic patients can benefit from local and regional anesthesia with bupivacaine for both labour analgesia and caesarean section ( 8, 9 ), but for symptomatic patients, or patients in crisis, we should rather choose general anaesthesia for caesarean section. Several clinical reports suggest that the hypnotic agent of choice for both induction and maintenance of such anaesthesia is propofol ( 8, 9 ). In our case short intravenous anaesthesia was induced with a bolus of propofol, alfentanil and diasepam. AIP may also trigger posterior reversible encephalopathy syndrome (PRES), a rare condition that is characterized by acute neurological symptoms, like in our case. The clinical and radiological symptoms usually disappear through the elimination of PRES-triggering factors and appropriate treatment ( 10 ).', 'CASE REPORT': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Previously, she had had a seizure attack at home. Her therapy was dydrogesterone 10 mg, three times per day, during two weeks. In her personal history she stated to have had a porphyria. The last acute attack happened 7 years beforethe spontaneous abortion, and she did not have a checkup in that period. In consultation with an anesthesiologist, in a short intravenous anesthesia, vacuum aspiration, andcurettage were performed. The patient regained consciousness immediately after the intervention and reached full orientation and cooperativeness within few minutes. The post-intervention period remained uneventful and the neurological and psychological symptoms returned to the pre-exacerbation status. In laboratory findings porphyrin derivatives (delta aminolevulinic acid 7.76 mg / dU- (reference range 1.5-7.5) and porphobilinogen 16.84 mg / dU- (reference range 0-3.4) were elevated. The therapy of glucose solution was administrated after which the patient’s condition stabilized. Porphyria markers decreased within the next four weeks. Seven years ago, the patient was admitted due to vomiting, severe intermittent pain in the abdomen, frequent urination, blood in the urine, and elevated body temperature. The last four months the patient was on oral contraceptives (0.035 mg ethinyl estradiol and 2.0 mg cyproteronacetat) due to irregular menstrual cycles. During hospitalization, at the time of the first day of menstruation, the patient developed grand mal seizures and expressed agitation. Seizures reached the epileptic status. Epileptic status cannot be ceased by maximal dose of diazepam, but only short intravenous anesthesia (midazolam maleate). The patient was in a state of high psychomotor agitation after the epileptic status. The brain CT pointed atthe left parietal paramedian hypodense area 16 mm in diameter. The MRI of the brain described the bilateral symmetric lesions of cortico-subcortical distribution, parieto occipital and frontal, which according to MRI characteristics primarily refer to posterior reversible encephalopathy within the metabolic disorder. In laboratory findings, pronounced hyponatremia, hypokalemia, hypomagnesemia, and hypocalcaemia were verified. Biochemical was proven of AIP, high positive variability of total porphyrins (700 μg / dU- reference interval <220), uroporphyrin (185 mg / dU), copro-porphyrin (515 mg / dU), delta amino levulinic acid (19.50 mg / dU) and porphobilinogen (98 mg / dU)). During hospitalization, the patient ceased to take harmful drugs and she was given haem arginate, glucose and symptomatic drugs, and she recovered completely.', 'Case report:': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Her therapy was dydrogesterone. In consultation with an anesthesiologist, a short intravenous anesthesia, vacuum aspiration, and curettage were performed.During hospitalization, the patient ceased to take harmful drugs and she was given haemarginate, glucose and symptomatic drugs, and she recovered completely.'}
|
{'Declaration of patient consent:': 'The authors certify that they have obtained all appropriate patient consent forms.', 'Gynecological issues': 'The first attack in our patient was most probably provoked by taking hormonal contraception. The progesterone and estrogen levels modified heme biosynthesis in subjects with AIP during menstrual cycle. Increased levels of progesterone were considered more important than estrogen in precipitating AIP attacks ( 2, 4 ). The clinical evidence suggests that hormonal oral contraceptives can lead to a manifestation of AIP in 25% of the women with AIP, in most cases can lead to their first attack ( 2 ). If, for any reason, e.g. irregular menstrual bleeding or threatened spontaneous abortion, oral hormonal contraceptives or gestagenes are used, monitoring of porphyrin precursor levels is recommended during the first month, in order to be able to interrupt the treatment should it increase concentrations ( 2, 4 ). The AIP gene carriers are advised to refrain from using oral contraceptives, in line with European recommendations ( 4 ). AIP is usually manifested in adult women, which means that it is seldom developed before puberty and after menopause the frequency of attacks declines ( 4 ).', 'Anaesthesiological considerations': 'Patients with AIP are at particular risk from general anaesthesia as most of the intravenous agents including barbiturates and volatile agents are contraindicated. Asymptomatic patients can benefit from local and regional anesthesia with bupivacaine for both labour analgesia and caesarean section ( 8, 9 ), but for symptomatic patients, or patients in crisis, we should rather choose general anaesthesia for caesarean section. Several clinical reports suggest that the hypnotic agent of choice for both induction and maintenance of such anaesthesia is propofol ( 8, 9 ). In our case short intravenous anaesthesia was induced with a bolus of propofol, alfentanil and diasepam. AIP may also trigger posterior reversible encephalopathy syndrome (PRES), a rare condition that is characterized by acute neurological symptoms, like in our case. The clinical and radiological symptoms usually disappear through the elimination of PRES-triggering factors and appropriate treatment ( 10 ).', 'CASE REPORT': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Previously, she had had a seizure attack at home. Her therapy was dydrogesterone 10 mg, three times per day, during two weeks. In her personal history she stated to have had a porphyria. The last acute attack happened 7 years beforethe spontaneous abortion, and she did not have a checkup in that period. In consultation with an anesthesiologist, in a short intravenous anesthesia, vacuum aspiration, andcurettage were performed. The patient regained consciousness immediately after the intervention and reached full orientation and cooperativeness within few minutes. The post-intervention period remained uneventful and the neurological and psychological symptoms returned to the pre-exacerbation status. In laboratory findings porphyrin derivatives (delta aminolevulinic acid 7.76 mg / dU- (reference range 1.5-7.5) and porphobilinogen 16.84 mg / dU- (reference range 0-3.4) were elevated. The therapy of glucose solution was administrated after which the patient’s condition stabilized. Porphyria markers decreased within the next four weeks. Seven years ago, the patient was admitted due to vomiting, severe intermittent pain in the abdomen, frequent urination, blood in the urine, and elevated body temperature. The last four months the patient was on oral contraceptives (0.035 mg ethinyl estradiol and 2.0 mg cyproteronacetat) due to irregular menstrual cycles. During hospitalization, at the time of the first day of menstruation, the patient developed grand mal seizures and expressed agitation. Seizures reached the epileptic status. Epileptic status cannot be ceased by maximal dose of diazepam, but only short intravenous anesthesia (midazolam maleate). The patient was in a state of high psychomotor agitation after the epileptic status. The brain CT pointed atthe left parietal paramedian hypodense area 16 mm in diameter. The MRI of the brain described the bilateral symmetric lesions of cortico-subcortical distribution, parieto occipital and frontal, which according to MRI characteristics primarily refer to posterior reversible encephalopathy within the metabolic disorder. In laboratory findings, pronounced hyponatremia, hypokalemia, hypomagnesemia, and hypocalcaemia were verified. Biochemical was proven of AIP, high positive variability of total porphyrins (700 μg / dU- reference interval <220), uroporphyrin (185 mg / dU), copro-porphyrin (515 mg / dU), delta amino levulinic acid (19.50 mg / dU) and porphobilinogen (98 mg / dU)). During hospitalization, the patient ceased to take harmful drugs and she was given haem arginate, glucose and symptomatic drugs, and she recovered completely.', 'Case report:': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Her therapy was dydrogesterone. In consultation with an anesthesiologist, a short intravenous anesthesia, vacuum aspiration, and curettage were performed.During hospitalization, the patient ceased to take harmful drugs and she was given haemarginate, glucose and symptomatic drugs, and she recovered completely.'}
|
Musculoskeletal-System
|
MSK
|
[
"muscle weakness",
"muscle weakness"
] |
test-2135
|
7296395
|
{'Declaration of patient consent:': 'The authors certify that they have obtained all appropriate patient consent forms.', 'Gynecological issues': 'The first attack in our patient was most probably provoked by taking hormonal contraception. The progesterone and estrogen levels modified heme biosynthesis in subjects with AIP during menstrual cycle. Increased levels of progesterone were considered more important than estrogen in precipitating AIP attacks ( 2, 4 ). The clinical evidence suggests that hormonal oral contraceptives can lead to a manifestation of AIP in 25% of the women with AIP, in most cases can lead to their first attack ( 2 ). If, for any reason, e.g. irregular menstrual bleeding or threatened spontaneous abortion, oral hormonal contraceptives or gestagenes are used, monitoring of porphyrin precursor levels is recommended during the first month, in order to be able to interrupt the treatment should it increase concentrations ( 2, 4 ). The AIP gene carriers are advised to refrain from using oral contraceptives, in line with European recommendations ( 4 ). AIP is usually manifested in adult women, which means that it is seldom developed before puberty and after menopause the frequency of attacks declines ( 4 ).', 'Anaesthesiological considerations': 'Patients with AIP are at particular risk from general anaesthesia as most of the intravenous agents including barbiturates and volatile agents are contraindicated. Asymptomatic patients can benefit from local and regional anesthesia with bupivacaine for both labour analgesia and caesarean section ( 8, 9 ), but for symptomatic patients, or patients in crisis, we should rather choose general anaesthesia for caesarean section. Several clinical reports suggest that the hypnotic agent of choice for both induction and maintenance of such anaesthesia is propofol ( 8, 9 ). In our case short intravenous anaesthesia was induced with a bolus of propofol, alfentanil and diasepam. AIP may also trigger posterior reversible encephalopathy syndrome (PRES), a rare condition that is characterized by acute neurological symptoms, like in our case. The clinical and radiological symptoms usually disappear through the elimination of PRES-triggering factors and appropriate treatment ( 10 ).', 'CASE REPORT': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Previously, she had had a seizure attack at home. Her therapy was dydrogesterone 10 mg, three times per day, during two weeks. In her personal history she stated to have had a porphyria. The last acute attack happened 7 years beforethe spontaneous abortion, and she did not have a checkup in that period. In consultation with an anesthesiologist, in a short intravenous anesthesia, vacuum aspiration, andcurettage were performed. The patient regained consciousness immediately after the intervention and reached full orientation and cooperativeness within few minutes. The post-intervention period remained uneventful and the neurological and psychological symptoms returned to the pre-exacerbation status. In laboratory findings porphyrin derivatives (delta aminolevulinic acid 7.76 mg / dU- (reference range 1.5-7.5) and porphobilinogen 16.84 mg / dU- (reference range 0-3.4) were elevated. The therapy of glucose solution was administrated after which the patient’s condition stabilized. Porphyria markers decreased within the next four weeks. Seven years ago, the patient was admitted due to vomiting, severe intermittent pain in the abdomen, frequent urination, blood in the urine, and elevated body temperature. The last four months the patient was on oral contraceptives (0.035 mg ethinyl estradiol and 2.0 mg cyproteronacetat) due to irregular menstrual cycles. During hospitalization, at the time of the first day of menstruation, the patient developed grand mal seizures and expressed agitation. Seizures reached the epileptic status. Epileptic status cannot be ceased by maximal dose of diazepam, but only short intravenous anesthesia (midazolam maleate). The patient was in a state of high psychomotor agitation after the epileptic status. The brain CT pointed atthe left parietal paramedian hypodense area 16 mm in diameter. The MRI of the brain described the bilateral symmetric lesions of cortico-subcortical distribution, parieto occipital and frontal, which according to MRI characteristics primarily refer to posterior reversible encephalopathy within the metabolic disorder. In laboratory findings, pronounced hyponatremia, hypokalemia, hypomagnesemia, and hypocalcaemia were verified. Biochemical was proven of AIP, high positive variability of total porphyrins (700 μg / dU- reference interval <220), uroporphyrin (185 mg / dU), copro-porphyrin (515 mg / dU), delta amino levulinic acid (19.50 mg / dU) and porphobilinogen (98 mg / dU)). During hospitalization, the patient ceased to take harmful drugs and she was given haem arginate, glucose and symptomatic drugs, and she recovered completely.', 'Case report:': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Her therapy was dydrogesterone. In consultation with an anesthesiologist, a short intravenous anesthesia, vacuum aspiration, and curettage were performed.During hospitalization, the patient ceased to take harmful drugs and she was given haemarginate, glucose and symptomatic drugs, and she recovered completely.'}
|
{'Declaration of patient consent:': 'The authors certify that they have obtained all appropriate patient consent forms.', 'Gynecological issues': 'The first attack in our patient was most probably provoked by taking hormonal contraception. The progesterone and estrogen levels modified heme biosynthesis in subjects with AIP during menstrual cycle. Increased levels of progesterone were considered more important than estrogen in precipitating AIP attacks ( 2, 4 ). The clinical evidence suggests that hormonal oral contraceptives can lead to a manifestation of AIP in 25% of the women with AIP, in most cases can lead to their first attack ( 2 ). If, for any reason, e.g. irregular menstrual bleeding or threatened spontaneous abortion, oral hormonal contraceptives or gestagenes are used, monitoring of porphyrin precursor levels is recommended during the first month, in order to be able to interrupt the treatment should it increase concentrations ( 2, 4 ). The AIP gene carriers are advised to refrain from using oral contraceptives, in line with European recommendations ( 4 ). AIP is usually manifested in adult women, which means that it is seldom developed before puberty and after menopause the frequency of attacks declines ( 4 ).', 'Anaesthesiological considerations': 'Patients with AIP are at particular risk from general anaesthesia as most of the intravenous agents including barbiturates and volatile agents are contraindicated. Asymptomatic patients can benefit from local and regional anesthesia with bupivacaine for both labour analgesia and caesarean section ( 8, 9 ), but for symptomatic patients, or patients in crisis, we should rather choose general anaesthesia for caesarean section. Several clinical reports suggest that the hypnotic agent of choice for both induction and maintenance of such anaesthesia is propofol ( 8, 9 ). In our case short intravenous anaesthesia was induced with a bolus of propofol, alfentanil and diasepam. AIP may also trigger posterior reversible encephalopathy syndrome (PRES), a rare condition that is characterized by acute neurological symptoms, like in our case. The clinical and radiological symptoms usually disappear through the elimination of PRES-triggering factors and appropriate treatment ( 10 ).', 'CASE REPORT': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Previously, she had had a seizure attack at home. Her therapy was dydrogesterone 10 mg, three times per day, during two weeks. In her personal history she stated to have had a porphyria. The last acute attack happened 7 years beforethe spontaneous abortion, and she did not have a checkup in that period. In consultation with an anesthesiologist, in a short intravenous anesthesia, vacuum aspiration, andcurettage were performed. The patient regained consciousness immediately after the intervention and reached full orientation and cooperativeness within few minutes. The post-intervention period remained uneventful and the neurological and psychological symptoms returned to the pre-exacerbation status. In laboratory findings porphyrin derivatives (delta aminolevulinic acid 7.76 mg / dU- (reference range 1.5-7.5) and porphobilinogen 16.84 mg / dU- (reference range 0-3.4) were elevated. The therapy of glucose solution was administrated after which the patient’s condition stabilized. Porphyria markers decreased within the next four weeks. Seven years ago, the patient was admitted due to vomiting, severe intermittent pain in the abdomen, frequent urination, blood in the urine, and elevated body temperature. The last four months the patient was on oral contraceptives (0.035 mg ethinyl estradiol and 2.0 mg cyproteronacetat) due to irregular menstrual cycles. During hospitalization, at the time of the first day of menstruation, the patient developed grand mal seizures and expressed agitation. Seizures reached the epileptic status. Epileptic status cannot be ceased by maximal dose of diazepam, but only short intravenous anesthesia (midazolam maleate). The patient was in a state of high psychomotor agitation after the epileptic status. The brain CT pointed atthe left parietal paramedian hypodense area 16 mm in diameter. The MRI of the brain described the bilateral symmetric lesions of cortico-subcortical distribution, parieto occipital and frontal, which according to MRI characteristics primarily refer to posterior reversible encephalopathy within the metabolic disorder. In laboratory findings, pronounced hyponatremia, hypokalemia, hypomagnesemia, and hypocalcaemia were verified. Biochemical was proven of AIP, high positive variability of total porphyrins (700 μg / dU- reference interval <220), uroporphyrin (185 mg / dU), copro-porphyrin (515 mg / dU), delta amino levulinic acid (19.50 mg / dU) and porphobilinogen (98 mg / dU)). During hospitalization, the patient ceased to take harmful drugs and she was given haem arginate, glucose and symptomatic drugs, and she recovered completely.', 'Case report:': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Her therapy was dydrogesterone. In consultation with an anesthesiologist, a short intravenous anesthesia, vacuum aspiration, and curettage were performed.During hospitalization, the patient ceased to take harmful drugs and she was given haemarginate, glucose and symptomatic drugs, and she recovered completely.'}
|
Eyes-Ears-Nose-Throat
|
EENT
|
[] |
test-2136
|
7296395
|
{'Declaration of patient consent:': 'The authors certify that they have obtained all appropriate patient consent forms.', 'Gynecological issues': 'The first attack in our patient was most probably provoked by taking hormonal contraception. The progesterone and estrogen levels modified heme biosynthesis in subjects with AIP during menstrual cycle. Increased levels of progesterone were considered more important than estrogen in precipitating AIP attacks ( 2, 4 ). The clinical evidence suggests that hormonal oral contraceptives can lead to a manifestation of AIP in 25% of the women with AIP, in most cases can lead to their first attack ( 2 ). If, for any reason, e.g. irregular menstrual bleeding or threatened spontaneous abortion, oral hormonal contraceptives or gestagenes are used, monitoring of porphyrin precursor levels is recommended during the first month, in order to be able to interrupt the treatment should it increase concentrations ( 2, 4 ). The AIP gene carriers are advised to refrain from using oral contraceptives, in line with European recommendations ( 4 ). AIP is usually manifested in adult women, which means that it is seldom developed before puberty and after menopause the frequency of attacks declines ( 4 ).', 'Anaesthesiological considerations': 'Patients with AIP are at particular risk from general anaesthesia as most of the intravenous agents including barbiturates and volatile agents are contraindicated. Asymptomatic patients can benefit from local and regional anesthesia with bupivacaine for both labour analgesia and caesarean section ( 8, 9 ), but for symptomatic patients, or patients in crisis, we should rather choose general anaesthesia for caesarean section. Several clinical reports suggest that the hypnotic agent of choice for both induction and maintenance of such anaesthesia is propofol ( 8, 9 ). In our case short intravenous anaesthesia was induced with a bolus of propofol, alfentanil and diasepam. AIP may also trigger posterior reversible encephalopathy syndrome (PRES), a rare condition that is characterized by acute neurological symptoms, like in our case. The clinical and radiological symptoms usually disappear through the elimination of PRES-triggering factors and appropriate treatment ( 10 ).', 'CASE REPORT': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Previously, she had had a seizure attack at home. Her therapy was dydrogesterone 10 mg, three times per day, during two weeks. In her personal history she stated to have had a porphyria. The last acute attack happened 7 years beforethe spontaneous abortion, and she did not have a checkup in that period. In consultation with an anesthesiologist, in a short intravenous anesthesia, vacuum aspiration, andcurettage were performed. The patient regained consciousness immediately after the intervention and reached full orientation and cooperativeness within few minutes. The post-intervention period remained uneventful and the neurological and psychological symptoms returned to the pre-exacerbation status. In laboratory findings porphyrin derivatives (delta aminolevulinic acid 7.76 mg / dU- (reference range 1.5-7.5) and porphobilinogen 16.84 mg / dU- (reference range 0-3.4) were elevated. The therapy of glucose solution was administrated after which the patient’s condition stabilized. Porphyria markers decreased within the next four weeks. Seven years ago, the patient was admitted due to vomiting, severe intermittent pain in the abdomen, frequent urination, blood in the urine, and elevated body temperature. The last four months the patient was on oral contraceptives (0.035 mg ethinyl estradiol and 2.0 mg cyproteronacetat) due to irregular menstrual cycles. During hospitalization, at the time of the first day of menstruation, the patient developed grand mal seizures and expressed agitation. Seizures reached the epileptic status. Epileptic status cannot be ceased by maximal dose of diazepam, but only short intravenous anesthesia (midazolam maleate). The patient was in a state of high psychomotor agitation after the epileptic status. The brain CT pointed atthe left parietal paramedian hypodense area 16 mm in diameter. The MRI of the brain described the bilateral symmetric lesions of cortico-subcortical distribution, parieto occipital and frontal, which according to MRI characteristics primarily refer to posterior reversible encephalopathy within the metabolic disorder. In laboratory findings, pronounced hyponatremia, hypokalemia, hypomagnesemia, and hypocalcaemia were verified. Biochemical was proven of AIP, high positive variability of total porphyrins (700 μg / dU- reference interval <220), uroporphyrin (185 mg / dU), copro-porphyrin (515 mg / dU), delta amino levulinic acid (19.50 mg / dU) and porphobilinogen (98 mg / dU)). During hospitalization, the patient ceased to take harmful drugs and she was given haem arginate, glucose and symptomatic drugs, and she recovered completely.', 'Case report:': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Her therapy was dydrogesterone. In consultation with an anesthesiologist, a short intravenous anesthesia, vacuum aspiration, and curettage were performed.During hospitalization, the patient ceased to take harmful drugs and she was given haemarginate, glucose and symptomatic drugs, and she recovered completely.'}
|
{'Declaration of patient consent:': 'The authors certify that they have obtained all appropriate patient consent forms.', 'Gynecological issues': 'The first attack in our patient was most probably provoked by taking hormonal contraception. The progesterone and estrogen levels modified heme biosynthesis in subjects with AIP during menstrual cycle. Increased levels of progesterone were considered more important than estrogen in precipitating AIP attacks ( 2, 4 ). The clinical evidence suggests that hormonal oral contraceptives can lead to a manifestation of AIP in 25% of the women with AIP, in most cases can lead to their first attack ( 2 ). If, for any reason, e.g. irregular menstrual bleeding or threatened spontaneous abortion, oral hormonal contraceptives or gestagenes are used, monitoring of porphyrin precursor levels is recommended during the first month, in order to be able to interrupt the treatment should it increase concentrations ( 2, 4 ). The AIP gene carriers are advised to refrain from using oral contraceptives, in line with European recommendations ( 4 ). AIP is usually manifested in adult women, which means that it is seldom developed before puberty and after menopause the frequency of attacks declines ( 4 ).', 'Anaesthesiological considerations': 'Patients with AIP are at particular risk from general anaesthesia as most of the intravenous agents including barbiturates and volatile agents are contraindicated. Asymptomatic patients can benefit from local and regional anesthesia with bupivacaine for both labour analgesia and caesarean section ( 8, 9 ), but for symptomatic patients, or patients in crisis, we should rather choose general anaesthesia for caesarean section. Several clinical reports suggest that the hypnotic agent of choice for both induction and maintenance of such anaesthesia is propofol ( 8, 9 ). In our case short intravenous anaesthesia was induced with a bolus of propofol, alfentanil and diasepam. AIP may also trigger posterior reversible encephalopathy syndrome (PRES), a rare condition that is characterized by acute neurological symptoms, like in our case. The clinical and radiological symptoms usually disappear through the elimination of PRES-triggering factors and appropriate treatment ( 10 ).', 'CASE REPORT': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Previously, she had had a seizure attack at home. Her therapy was dydrogesterone 10 mg, three times per day, during two weeks. In her personal history she stated to have had a porphyria. The last acute attack happened 7 years beforethe spontaneous abortion, and she did not have a checkup in that period. In consultation with an anesthesiologist, in a short intravenous anesthesia, vacuum aspiration, andcurettage were performed. The patient regained consciousness immediately after the intervention and reached full orientation and cooperativeness within few minutes. The post-intervention period remained uneventful and the neurological and psychological symptoms returned to the pre-exacerbation status. In laboratory findings porphyrin derivatives (delta aminolevulinic acid 7.76 mg / dU- (reference range 1.5-7.5) and porphobilinogen 16.84 mg / dU- (reference range 0-3.4) were elevated. The therapy of glucose solution was administrated after which the patient’s condition stabilized. Porphyria markers decreased within the next four weeks. Seven years ago, the patient was admitted due to vomiting, severe intermittent pain in the abdomen, frequent urination, blood in the urine, and elevated body temperature. The last four months the patient was on oral contraceptives (0.035 mg ethinyl estradiol and 2.0 mg cyproteronacetat) due to irregular menstrual cycles. During hospitalization, at the time of the first day of menstruation, the patient developed grand mal seizures and expressed agitation. Seizures reached the epileptic status. Epileptic status cannot be ceased by maximal dose of diazepam, but only short intravenous anesthesia (midazolam maleate). The patient was in a state of high psychomotor agitation after the epileptic status. The brain CT pointed atthe left parietal paramedian hypodense area 16 mm in diameter. The MRI of the brain described the bilateral symmetric lesions of cortico-subcortical distribution, parieto occipital and frontal, which according to MRI characteristics primarily refer to posterior reversible encephalopathy within the metabolic disorder. In laboratory findings, pronounced hyponatremia, hypokalemia, hypomagnesemia, and hypocalcaemia were verified. Biochemical was proven of AIP, high positive variability of total porphyrins (700 μg / dU- reference interval <220), uroporphyrin (185 mg / dU), copro-porphyrin (515 mg / dU), delta amino levulinic acid (19.50 mg / dU) and porphobilinogen (98 mg / dU)). During hospitalization, the patient ceased to take harmful drugs and she was given haem arginate, glucose and symptomatic drugs, and she recovered completely.', 'Case report:': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Her therapy was dydrogesterone. In consultation with an anesthesiologist, a short intravenous anesthesia, vacuum aspiration, and curettage were performed.During hospitalization, the patient ceased to take harmful drugs and she was given haemarginate, glucose and symptomatic drugs, and she recovered completely.'}
|
Dermatology
|
DERM
|
[] |
test-2137
|
7296395
|
{'Declaration of patient consent:': 'The authors certify that they have obtained all appropriate patient consent forms.', 'Gynecological issues': 'The first attack in our patient was most probably provoked by taking hormonal contraception. The progesterone and estrogen levels modified heme biosynthesis in subjects with AIP during menstrual cycle. Increased levels of progesterone were considered more important than estrogen in precipitating AIP attacks ( 2, 4 ). The clinical evidence suggests that hormonal oral contraceptives can lead to a manifestation of AIP in 25% of the women with AIP, in most cases can lead to their first attack ( 2 ). If, for any reason, e.g. irregular menstrual bleeding or threatened spontaneous abortion, oral hormonal contraceptives or gestagenes are used, monitoring of porphyrin precursor levels is recommended during the first month, in order to be able to interrupt the treatment should it increase concentrations ( 2, 4 ). The AIP gene carriers are advised to refrain from using oral contraceptives, in line with European recommendations ( 4 ). AIP is usually manifested in adult women, which means that it is seldom developed before puberty and after menopause the frequency of attacks declines ( 4 ).', 'Anaesthesiological considerations': 'Patients with AIP are at particular risk from general anaesthesia as most of the intravenous agents including barbiturates and volatile agents are contraindicated. Asymptomatic patients can benefit from local and regional anesthesia with bupivacaine for both labour analgesia and caesarean section ( 8, 9 ), but for symptomatic patients, or patients in crisis, we should rather choose general anaesthesia for caesarean section. Several clinical reports suggest that the hypnotic agent of choice for both induction and maintenance of such anaesthesia is propofol ( 8, 9 ). In our case short intravenous anaesthesia was induced with a bolus of propofol, alfentanil and diasepam. AIP may also trigger posterior reversible encephalopathy syndrome (PRES), a rare condition that is characterized by acute neurological symptoms, like in our case. The clinical and radiological symptoms usually disappear through the elimination of PRES-triggering factors and appropriate treatment ( 10 ).', 'CASE REPORT': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Previously, she had had a seizure attack at home. Her therapy was dydrogesterone 10 mg, three times per day, during two weeks. In her personal history she stated to have had a porphyria. The last acute attack happened 7 years beforethe spontaneous abortion, and she did not have a checkup in that period. In consultation with an anesthesiologist, in a short intravenous anesthesia, vacuum aspiration, andcurettage were performed. The patient regained consciousness immediately after the intervention and reached full orientation and cooperativeness within few minutes. The post-intervention period remained uneventful and the neurological and psychological symptoms returned to the pre-exacerbation status. In laboratory findings porphyrin derivatives (delta aminolevulinic acid 7.76 mg / dU- (reference range 1.5-7.5) and porphobilinogen 16.84 mg / dU- (reference range 0-3.4) were elevated. The therapy of glucose solution was administrated after which the patient’s condition stabilized. Porphyria markers decreased within the next four weeks. Seven years ago, the patient was admitted due to vomiting, severe intermittent pain in the abdomen, frequent urination, blood in the urine, and elevated body temperature. The last four months the patient was on oral contraceptives (0.035 mg ethinyl estradiol and 2.0 mg cyproteronacetat) due to irregular menstrual cycles. During hospitalization, at the time of the first day of menstruation, the patient developed grand mal seizures and expressed agitation. Seizures reached the epileptic status. Epileptic status cannot be ceased by maximal dose of diazepam, but only short intravenous anesthesia (midazolam maleate). The patient was in a state of high psychomotor agitation after the epileptic status. The brain CT pointed atthe left parietal paramedian hypodense area 16 mm in diameter. The MRI of the brain described the bilateral symmetric lesions of cortico-subcortical distribution, parieto occipital and frontal, which according to MRI characteristics primarily refer to posterior reversible encephalopathy within the metabolic disorder. In laboratory findings, pronounced hyponatremia, hypokalemia, hypomagnesemia, and hypocalcaemia were verified. Biochemical was proven of AIP, high positive variability of total porphyrins (700 μg / dU- reference interval <220), uroporphyrin (185 mg / dU), copro-porphyrin (515 mg / dU), delta amino levulinic acid (19.50 mg / dU) and porphobilinogen (98 mg / dU)). During hospitalization, the patient ceased to take harmful drugs and she was given haem arginate, glucose and symptomatic drugs, and she recovered completely.', 'Case report:': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Her therapy was dydrogesterone. In consultation with an anesthesiologist, a short intravenous anesthesia, vacuum aspiration, and curettage were performed.During hospitalization, the patient ceased to take harmful drugs and she was given haemarginate, glucose and symptomatic drugs, and she recovered completely.'}
|
{'Declaration of patient consent:': 'The authors certify that they have obtained all appropriate patient consent forms.', 'Gynecological issues': 'The first attack in our patient was most probably provoked by taking hormonal contraception. The progesterone and estrogen levels modified heme biosynthesis in subjects with AIP during menstrual cycle. Increased levels of progesterone were considered more important than estrogen in precipitating AIP attacks ( 2, 4 ). The clinical evidence suggests that hormonal oral contraceptives can lead to a manifestation of AIP in 25% of the women with AIP, in most cases can lead to their first attack ( 2 ). If, for any reason, e.g. irregular menstrual bleeding or threatened spontaneous abortion, oral hormonal contraceptives or gestagenes are used, monitoring of porphyrin precursor levels is recommended during the first month, in order to be able to interrupt the treatment should it increase concentrations ( 2, 4 ). The AIP gene carriers are advised to refrain from using oral contraceptives, in line with European recommendations ( 4 ). AIP is usually manifested in adult women, which means that it is seldom developed before puberty and after menopause the frequency of attacks declines ( 4 ).', 'Anaesthesiological considerations': 'Patients with AIP are at particular risk from general anaesthesia as most of the intravenous agents including barbiturates and volatile agents are contraindicated. Asymptomatic patients can benefit from local and regional anesthesia with bupivacaine for both labour analgesia and caesarean section ( 8, 9 ), but for symptomatic patients, or patients in crisis, we should rather choose general anaesthesia for caesarean section. Several clinical reports suggest that the hypnotic agent of choice for both induction and maintenance of such anaesthesia is propofol ( 8, 9 ). In our case short intravenous anaesthesia was induced with a bolus of propofol, alfentanil and diasepam. AIP may also trigger posterior reversible encephalopathy syndrome (PRES), a rare condition that is characterized by acute neurological symptoms, like in our case. The clinical and radiological symptoms usually disappear through the elimination of PRES-triggering factors and appropriate treatment ( 10 ).', 'CASE REPORT': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Previously, she had had a seizure attack at home. Her therapy was dydrogesterone 10 mg, three times per day, during two weeks. In her personal history she stated to have had a porphyria. The last acute attack happened 7 years beforethe spontaneous abortion, and she did not have a checkup in that period. In consultation with an anesthesiologist, in a short intravenous anesthesia, vacuum aspiration, andcurettage were performed. The patient regained consciousness immediately after the intervention and reached full orientation and cooperativeness within few minutes. The post-intervention period remained uneventful and the neurological and psychological symptoms returned to the pre-exacerbation status. In laboratory findings porphyrin derivatives (delta aminolevulinic acid 7.76 mg / dU- (reference range 1.5-7.5) and porphobilinogen 16.84 mg / dU- (reference range 0-3.4) were elevated. The therapy of glucose solution was administrated after which the patient’s condition stabilized. Porphyria markers decreased within the next four weeks. Seven years ago, the patient was admitted due to vomiting, severe intermittent pain in the abdomen, frequent urination, blood in the urine, and elevated body temperature. The last four months the patient was on oral contraceptives (0.035 mg ethinyl estradiol and 2.0 mg cyproteronacetat) due to irregular menstrual cycles. During hospitalization, at the time of the first day of menstruation, the patient developed grand mal seizures and expressed agitation. Seizures reached the epileptic status. Epileptic status cannot be ceased by maximal dose of diazepam, but only short intravenous anesthesia (midazolam maleate). The patient was in a state of high psychomotor agitation after the epileptic status. The brain CT pointed atthe left parietal paramedian hypodense area 16 mm in diameter. The MRI of the brain described the bilateral symmetric lesions of cortico-subcortical distribution, parieto occipital and frontal, which according to MRI characteristics primarily refer to posterior reversible encephalopathy within the metabolic disorder. In laboratory findings, pronounced hyponatremia, hypokalemia, hypomagnesemia, and hypocalcaemia were verified. Biochemical was proven of AIP, high positive variability of total porphyrins (700 μg / dU- reference interval <220), uroporphyrin (185 mg / dU), copro-porphyrin (515 mg / dU), delta amino levulinic acid (19.50 mg / dU) and porphobilinogen (98 mg / dU)). During hospitalization, the patient ceased to take harmful drugs and she was given haem arginate, glucose and symptomatic drugs, and she recovered completely.', 'Case report:': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Her therapy was dydrogesterone. In consultation with an anesthesiologist, a short intravenous anesthesia, vacuum aspiration, and curettage were performed.During hospitalization, the patient ceased to take harmful drugs and she was given haemarginate, glucose and symptomatic drugs, and she recovered completely.'}
|
Pregnancy
|
Pregnancy
|
[
"8th week of gestation, due to initial spontaneous abortion, abdominal pain",
"8th week of gestation, due to initial spontaneous abortion, abdominal pain,"
] |
test-2138
|
7296395
|
{'Declaration of patient consent:': 'The authors certify that they have obtained all appropriate patient consent forms.', 'Gynecological issues': 'The first attack in our patient was most probably provoked by taking hormonal contraception. The progesterone and estrogen levels modified heme biosynthesis in subjects with AIP during menstrual cycle. Increased levels of progesterone were considered more important than estrogen in precipitating AIP attacks ( 2, 4 ). The clinical evidence suggests that hormonal oral contraceptives can lead to a manifestation of AIP in 25% of the women with AIP, in most cases can lead to their first attack ( 2 ). If, for any reason, e.g. irregular menstrual bleeding or threatened spontaneous abortion, oral hormonal contraceptives or gestagenes are used, monitoring of porphyrin precursor levels is recommended during the first month, in order to be able to interrupt the treatment should it increase concentrations ( 2, 4 ). The AIP gene carriers are advised to refrain from using oral contraceptives, in line with European recommendations ( 4 ). AIP is usually manifested in adult women, which means that it is seldom developed before puberty and after menopause the frequency of attacks declines ( 4 ).', 'Anaesthesiological considerations': 'Patients with AIP are at particular risk from general anaesthesia as most of the intravenous agents including barbiturates and volatile agents are contraindicated. Asymptomatic patients can benefit from local and regional anesthesia with bupivacaine for both labour analgesia and caesarean section ( 8, 9 ), but for symptomatic patients, or patients in crisis, we should rather choose general anaesthesia for caesarean section. Several clinical reports suggest that the hypnotic agent of choice for both induction and maintenance of such anaesthesia is propofol ( 8, 9 ). In our case short intravenous anaesthesia was induced with a bolus of propofol, alfentanil and diasepam. AIP may also trigger posterior reversible encephalopathy syndrome (PRES), a rare condition that is characterized by acute neurological symptoms, like in our case. The clinical and radiological symptoms usually disappear through the elimination of PRES-triggering factors and appropriate treatment ( 10 ).', 'CASE REPORT': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Previously, she had had a seizure attack at home. Her therapy was dydrogesterone 10 mg, three times per day, during two weeks. In her personal history she stated to have had a porphyria. The last acute attack happened 7 years beforethe spontaneous abortion, and she did not have a checkup in that period. In consultation with an anesthesiologist, in a short intravenous anesthesia, vacuum aspiration, andcurettage were performed. The patient regained consciousness immediately after the intervention and reached full orientation and cooperativeness within few minutes. The post-intervention period remained uneventful and the neurological and psychological symptoms returned to the pre-exacerbation status. In laboratory findings porphyrin derivatives (delta aminolevulinic acid 7.76 mg / dU- (reference range 1.5-7.5) and porphobilinogen 16.84 mg / dU- (reference range 0-3.4) were elevated. The therapy of glucose solution was administrated after which the patient’s condition stabilized. Porphyria markers decreased within the next four weeks. Seven years ago, the patient was admitted due to vomiting, severe intermittent pain in the abdomen, frequent urination, blood in the urine, and elevated body temperature. The last four months the patient was on oral contraceptives (0.035 mg ethinyl estradiol and 2.0 mg cyproteronacetat) due to irregular menstrual cycles. During hospitalization, at the time of the first day of menstruation, the patient developed grand mal seizures and expressed agitation. Seizures reached the epileptic status. Epileptic status cannot be ceased by maximal dose of diazepam, but only short intravenous anesthesia (midazolam maleate). The patient was in a state of high psychomotor agitation after the epileptic status. The brain CT pointed atthe left parietal paramedian hypodense area 16 mm in diameter. The MRI of the brain described the bilateral symmetric lesions of cortico-subcortical distribution, parieto occipital and frontal, which according to MRI characteristics primarily refer to posterior reversible encephalopathy within the metabolic disorder. In laboratory findings, pronounced hyponatremia, hypokalemia, hypomagnesemia, and hypocalcaemia were verified. Biochemical was proven of AIP, high positive variability of total porphyrins (700 μg / dU- reference interval <220), uroporphyrin (185 mg / dU), copro-porphyrin (515 mg / dU), delta amino levulinic acid (19.50 mg / dU) and porphobilinogen (98 mg / dU)). During hospitalization, the patient ceased to take harmful drugs and she was given haem arginate, glucose and symptomatic drugs, and she recovered completely.', 'Case report:': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Her therapy was dydrogesterone. In consultation with an anesthesiologist, a short intravenous anesthesia, vacuum aspiration, and curettage were performed.During hospitalization, the patient ceased to take harmful drugs and she was given haemarginate, glucose and symptomatic drugs, and she recovered completely.'}
|
{'Declaration of patient consent:': 'The authors certify that they have obtained all appropriate patient consent forms.', 'Gynecological issues': 'The first attack in our patient was most probably provoked by taking hormonal contraception. The progesterone and estrogen levels modified heme biosynthesis in subjects with AIP during menstrual cycle. Increased levels of progesterone were considered more important than estrogen in precipitating AIP attacks ( 2, 4 ). The clinical evidence suggests that hormonal oral contraceptives can lead to a manifestation of AIP in 25% of the women with AIP, in most cases can lead to their first attack ( 2 ). If, for any reason, e.g. irregular menstrual bleeding or threatened spontaneous abortion, oral hormonal contraceptives or gestagenes are used, monitoring of porphyrin precursor levels is recommended during the first month, in order to be able to interrupt the treatment should it increase concentrations ( 2, 4 ). The AIP gene carriers are advised to refrain from using oral contraceptives, in line with European recommendations ( 4 ). AIP is usually manifested in adult women, which means that it is seldom developed before puberty and after menopause the frequency of attacks declines ( 4 ).', 'Anaesthesiological considerations': 'Patients with AIP are at particular risk from general anaesthesia as most of the intravenous agents including barbiturates and volatile agents are contraindicated. Asymptomatic patients can benefit from local and regional anesthesia with bupivacaine for both labour analgesia and caesarean section ( 8, 9 ), but for symptomatic patients, or patients in crisis, we should rather choose general anaesthesia for caesarean section. Several clinical reports suggest that the hypnotic agent of choice for both induction and maintenance of such anaesthesia is propofol ( 8, 9 ). In our case short intravenous anaesthesia was induced with a bolus of propofol, alfentanil and diasepam. AIP may also trigger posterior reversible encephalopathy syndrome (PRES), a rare condition that is characterized by acute neurological symptoms, like in our case. The clinical and radiological symptoms usually disappear through the elimination of PRES-triggering factors and appropriate treatment ( 10 ).', 'CASE REPORT': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Previously, she had had a seizure attack at home. Her therapy was dydrogesterone 10 mg, three times per day, during two weeks. In her personal history she stated to have had a porphyria. The last acute attack happened 7 years beforethe spontaneous abortion, and she did not have a checkup in that period. In consultation with an anesthesiologist, in a short intravenous anesthesia, vacuum aspiration, andcurettage were performed. The patient regained consciousness immediately after the intervention and reached full orientation and cooperativeness within few minutes. The post-intervention period remained uneventful and the neurological and psychological symptoms returned to the pre-exacerbation status. In laboratory findings porphyrin derivatives (delta aminolevulinic acid 7.76 mg / dU- (reference range 1.5-7.5) and porphobilinogen 16.84 mg / dU- (reference range 0-3.4) were elevated. The therapy of glucose solution was administrated after which the patient’s condition stabilized. Porphyria markers decreased within the next four weeks. Seven years ago, the patient was admitted due to vomiting, severe intermittent pain in the abdomen, frequent urination, blood in the urine, and elevated body temperature. The last four months the patient was on oral contraceptives (0.035 mg ethinyl estradiol and 2.0 mg cyproteronacetat) due to irregular menstrual cycles. During hospitalization, at the time of the first day of menstruation, the patient developed grand mal seizures and expressed agitation. Seizures reached the epileptic status. Epileptic status cannot be ceased by maximal dose of diazepam, but only short intravenous anesthesia (midazolam maleate). The patient was in a state of high psychomotor agitation after the epileptic status. The brain CT pointed atthe left parietal paramedian hypodense area 16 mm in diameter. The MRI of the brain described the bilateral symmetric lesions of cortico-subcortical distribution, parieto occipital and frontal, which according to MRI characteristics primarily refer to posterior reversible encephalopathy within the metabolic disorder. In laboratory findings, pronounced hyponatremia, hypokalemia, hypomagnesemia, and hypocalcaemia were verified. Biochemical was proven of AIP, high positive variability of total porphyrins (700 μg / dU- reference interval <220), uroporphyrin (185 mg / dU), copro-porphyrin (515 mg / dU), delta amino levulinic acid (19.50 mg / dU) and porphobilinogen (98 mg / dU)). During hospitalization, the patient ceased to take harmful drugs and she was given haem arginate, glucose and symptomatic drugs, and she recovered completely.', 'Case report:': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Her therapy was dydrogesterone. In consultation with an anesthesiologist, a short intravenous anesthesia, vacuum aspiration, and curettage were performed.During hospitalization, the patient ceased to take harmful drugs and she was given haemarginate, glucose and symptomatic drugs, and she recovered completely.'}
|
Lymphatic-System
|
LYMPH
|
[] |
test-2139
|
7296395
|
{'Declaration of patient consent:': 'The authors certify that they have obtained all appropriate patient consent forms.', 'Gynecological issues': 'The first attack in our patient was most probably provoked by taking hormonal contraception. The progesterone and estrogen levels modified heme biosynthesis in subjects with AIP during menstrual cycle. Increased levels of progesterone were considered more important than estrogen in precipitating AIP attacks ( 2, 4 ). The clinical evidence suggests that hormonal oral contraceptives can lead to a manifestation of AIP in 25% of the women with AIP, in most cases can lead to their first attack ( 2 ). If, for any reason, e.g. irregular menstrual bleeding or threatened spontaneous abortion, oral hormonal contraceptives or gestagenes are used, monitoring of porphyrin precursor levels is recommended during the first month, in order to be able to interrupt the treatment should it increase concentrations ( 2, 4 ). The AIP gene carriers are advised to refrain from using oral contraceptives, in line with European recommendations ( 4 ). AIP is usually manifested in adult women, which means that it is seldom developed before puberty and after menopause the frequency of attacks declines ( 4 ).', 'Anaesthesiological considerations': 'Patients with AIP are at particular risk from general anaesthesia as most of the intravenous agents including barbiturates and volatile agents are contraindicated. Asymptomatic patients can benefit from local and regional anesthesia with bupivacaine for both labour analgesia and caesarean section ( 8, 9 ), but for symptomatic patients, or patients in crisis, we should rather choose general anaesthesia for caesarean section. Several clinical reports suggest that the hypnotic agent of choice for both induction and maintenance of such anaesthesia is propofol ( 8, 9 ). In our case short intravenous anaesthesia was induced with a bolus of propofol, alfentanil and diasepam. AIP may also trigger posterior reversible encephalopathy syndrome (PRES), a rare condition that is characterized by acute neurological symptoms, like in our case. The clinical and radiological symptoms usually disappear through the elimination of PRES-triggering factors and appropriate treatment ( 10 ).', 'CASE REPORT': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Previously, she had had a seizure attack at home. Her therapy was dydrogesterone 10 mg, three times per day, during two weeks. In her personal history she stated to have had a porphyria. The last acute attack happened 7 years beforethe spontaneous abortion, and she did not have a checkup in that period. In consultation with an anesthesiologist, in a short intravenous anesthesia, vacuum aspiration, andcurettage were performed. The patient regained consciousness immediately after the intervention and reached full orientation and cooperativeness within few minutes. The post-intervention period remained uneventful and the neurological and psychological symptoms returned to the pre-exacerbation status. In laboratory findings porphyrin derivatives (delta aminolevulinic acid 7.76 mg / dU- (reference range 1.5-7.5) and porphobilinogen 16.84 mg / dU- (reference range 0-3.4) were elevated. The therapy of glucose solution was administrated after which the patient’s condition stabilized. Porphyria markers decreased within the next four weeks. Seven years ago, the patient was admitted due to vomiting, severe intermittent pain in the abdomen, frequent urination, blood in the urine, and elevated body temperature. The last four months the patient was on oral contraceptives (0.035 mg ethinyl estradiol and 2.0 mg cyproteronacetat) due to irregular menstrual cycles. During hospitalization, at the time of the first day of menstruation, the patient developed grand mal seizures and expressed agitation. Seizures reached the epileptic status. Epileptic status cannot be ceased by maximal dose of diazepam, but only short intravenous anesthesia (midazolam maleate). The patient was in a state of high psychomotor agitation after the epileptic status. The brain CT pointed atthe left parietal paramedian hypodense area 16 mm in diameter. The MRI of the brain described the bilateral symmetric lesions of cortico-subcortical distribution, parieto occipital and frontal, which according to MRI characteristics primarily refer to posterior reversible encephalopathy within the metabolic disorder. In laboratory findings, pronounced hyponatremia, hypokalemia, hypomagnesemia, and hypocalcaemia were verified. Biochemical was proven of AIP, high positive variability of total porphyrins (700 μg / dU- reference interval <220), uroporphyrin (185 mg / dU), copro-porphyrin (515 mg / dU), delta amino levulinic acid (19.50 mg / dU) and porphobilinogen (98 mg / dU)). During hospitalization, the patient ceased to take harmful drugs and she was given haem arginate, glucose and symptomatic drugs, and she recovered completely.', 'Case report:': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Her therapy was dydrogesterone. In consultation with an anesthesiologist, a short intravenous anesthesia, vacuum aspiration, and curettage were performed.During hospitalization, the patient ceased to take harmful drugs and she was given haemarginate, glucose and symptomatic drugs, and she recovered completely.'}
|
{'Declaration of patient consent:': 'The authors certify that they have obtained all appropriate patient consent forms.', 'Gynecological issues': 'The first attack in our patient was most probably provoked by taking hormonal contraception. The progesterone and estrogen levels modified heme biosynthesis in subjects with AIP during menstrual cycle. Increased levels of progesterone were considered more important than estrogen in precipitating AIP attacks ( 2, 4 ). The clinical evidence suggests that hormonal oral contraceptives can lead to a manifestation of AIP in 25% of the women with AIP, in most cases can lead to their first attack ( 2 ). If, for any reason, e.g. irregular menstrual bleeding or threatened spontaneous abortion, oral hormonal contraceptives or gestagenes are used, monitoring of porphyrin precursor levels is recommended during the first month, in order to be able to interrupt the treatment should it increase concentrations ( 2, 4 ). The AIP gene carriers are advised to refrain from using oral contraceptives, in line with European recommendations ( 4 ). AIP is usually manifested in adult women, which means that it is seldom developed before puberty and after menopause the frequency of attacks declines ( 4 ).', 'Anaesthesiological considerations': 'Patients with AIP are at particular risk from general anaesthesia as most of the intravenous agents including barbiturates and volatile agents are contraindicated. Asymptomatic patients can benefit from local and regional anesthesia with bupivacaine for both labour analgesia and caesarean section ( 8, 9 ), but for symptomatic patients, or patients in crisis, we should rather choose general anaesthesia for caesarean section. Several clinical reports suggest that the hypnotic agent of choice for both induction and maintenance of such anaesthesia is propofol ( 8, 9 ). In our case short intravenous anaesthesia was induced with a bolus of propofol, alfentanil and diasepam. AIP may also trigger posterior reversible encephalopathy syndrome (PRES), a rare condition that is characterized by acute neurological symptoms, like in our case. The clinical and radiological symptoms usually disappear through the elimination of PRES-triggering factors and appropriate treatment ( 10 ).', 'CASE REPORT': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Previously, she had had a seizure attack at home. Her therapy was dydrogesterone 10 mg, three times per day, during two weeks. In her personal history she stated to have had a porphyria. The last acute attack happened 7 years beforethe spontaneous abortion, and she did not have a checkup in that period. In consultation with an anesthesiologist, in a short intravenous anesthesia, vacuum aspiration, andcurettage were performed. The patient regained consciousness immediately after the intervention and reached full orientation and cooperativeness within few minutes. The post-intervention period remained uneventful and the neurological and psychological symptoms returned to the pre-exacerbation status. In laboratory findings porphyrin derivatives (delta aminolevulinic acid 7.76 mg / dU- (reference range 1.5-7.5) and porphobilinogen 16.84 mg / dU- (reference range 0-3.4) were elevated. The therapy of glucose solution was administrated after which the patient’s condition stabilized. Porphyria markers decreased within the next four weeks. Seven years ago, the patient was admitted due to vomiting, severe intermittent pain in the abdomen, frequent urination, blood in the urine, and elevated body temperature. The last four months the patient was on oral contraceptives (0.035 mg ethinyl estradiol and 2.0 mg cyproteronacetat) due to irregular menstrual cycles. During hospitalization, at the time of the first day of menstruation, the patient developed grand mal seizures and expressed agitation. Seizures reached the epileptic status. Epileptic status cannot be ceased by maximal dose of diazepam, but only short intravenous anesthesia (midazolam maleate). The patient was in a state of high psychomotor agitation after the epileptic status. The brain CT pointed atthe left parietal paramedian hypodense area 16 mm in diameter. The MRI of the brain described the bilateral symmetric lesions of cortico-subcortical distribution, parieto occipital and frontal, which according to MRI characteristics primarily refer to posterior reversible encephalopathy within the metabolic disorder. In laboratory findings, pronounced hyponatremia, hypokalemia, hypomagnesemia, and hypocalcaemia were verified. Biochemical was proven of AIP, high positive variability of total porphyrins (700 μg / dU- reference interval <220), uroporphyrin (185 mg / dU), copro-porphyrin (515 mg / dU), delta amino levulinic acid (19.50 mg / dU) and porphobilinogen (98 mg / dU)). During hospitalization, the patient ceased to take harmful drugs and she was given haem arginate, glucose and symptomatic drugs, and she recovered completely.', 'Case report:': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Her therapy was dydrogesterone. In consultation with an anesthesiologist, a short intravenous anesthesia, vacuum aspiration, and curettage were performed.During hospitalization, the patient ceased to take harmful drugs and she was given haemarginate, glucose and symptomatic drugs, and she recovered completely.'}
|
Age-at-Presentation
|
Age (at case presentation)
|
[
"26 - year - old patient",
"26 - year - old"
] |
test-2140
|
7296395
|
{'Declaration of patient consent:': 'The authors certify that they have obtained all appropriate patient consent forms.', 'Gynecological issues': 'The first attack in our patient was most probably provoked by taking hormonal contraception. The progesterone and estrogen levels modified heme biosynthesis in subjects with AIP during menstrual cycle. Increased levels of progesterone were considered more important than estrogen in precipitating AIP attacks ( 2, 4 ). The clinical evidence suggests that hormonal oral contraceptives can lead to a manifestation of AIP in 25% of the women with AIP, in most cases can lead to their first attack ( 2 ). If, for any reason, e.g. irregular menstrual bleeding or threatened spontaneous abortion, oral hormonal contraceptives or gestagenes are used, monitoring of porphyrin precursor levels is recommended during the first month, in order to be able to interrupt the treatment should it increase concentrations ( 2, 4 ). The AIP gene carriers are advised to refrain from using oral contraceptives, in line with European recommendations ( 4 ). AIP is usually manifested in adult women, which means that it is seldom developed before puberty and after menopause the frequency of attacks declines ( 4 ).', 'Anaesthesiological considerations': 'Patients with AIP are at particular risk from general anaesthesia as most of the intravenous agents including barbiturates and volatile agents are contraindicated. Asymptomatic patients can benefit from local and regional anesthesia with bupivacaine for both labour analgesia and caesarean section ( 8, 9 ), but for symptomatic patients, or patients in crisis, we should rather choose general anaesthesia for caesarean section. Several clinical reports suggest that the hypnotic agent of choice for both induction and maintenance of such anaesthesia is propofol ( 8, 9 ). In our case short intravenous anaesthesia was induced with a bolus of propofol, alfentanil and diasepam. AIP may also trigger posterior reversible encephalopathy syndrome (PRES), a rare condition that is characterized by acute neurological symptoms, like in our case. The clinical and radiological symptoms usually disappear through the elimination of PRES-triggering factors and appropriate treatment ( 10 ).', 'CASE REPORT': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Previously, she had had a seizure attack at home. Her therapy was dydrogesterone 10 mg, three times per day, during two weeks. In her personal history she stated to have had a porphyria. The last acute attack happened 7 years beforethe spontaneous abortion, and she did not have a checkup in that period. In consultation with an anesthesiologist, in a short intravenous anesthesia, vacuum aspiration, andcurettage were performed. The patient regained consciousness immediately after the intervention and reached full orientation and cooperativeness within few minutes. The post-intervention period remained uneventful and the neurological and psychological symptoms returned to the pre-exacerbation status. In laboratory findings porphyrin derivatives (delta aminolevulinic acid 7.76 mg / dU- (reference range 1.5-7.5) and porphobilinogen 16.84 mg / dU- (reference range 0-3.4) were elevated. The therapy of glucose solution was administrated after which the patient’s condition stabilized. Porphyria markers decreased within the next four weeks. Seven years ago, the patient was admitted due to vomiting, severe intermittent pain in the abdomen, frequent urination, blood in the urine, and elevated body temperature. The last four months the patient was on oral contraceptives (0.035 mg ethinyl estradiol and 2.0 mg cyproteronacetat) due to irregular menstrual cycles. During hospitalization, at the time of the first day of menstruation, the patient developed grand mal seizures and expressed agitation. Seizures reached the epileptic status. Epileptic status cannot be ceased by maximal dose of diazepam, but only short intravenous anesthesia (midazolam maleate). The patient was in a state of high psychomotor agitation after the epileptic status. The brain CT pointed atthe left parietal paramedian hypodense area 16 mm in diameter. The MRI of the brain described the bilateral symmetric lesions of cortico-subcortical distribution, parieto occipital and frontal, which according to MRI characteristics primarily refer to posterior reversible encephalopathy within the metabolic disorder. In laboratory findings, pronounced hyponatremia, hypokalemia, hypomagnesemia, and hypocalcaemia were verified. Biochemical was proven of AIP, high positive variability of total porphyrins (700 μg / dU- reference interval <220), uroporphyrin (185 mg / dU), copro-porphyrin (515 mg / dU), delta amino levulinic acid (19.50 mg / dU) and porphobilinogen (98 mg / dU)). During hospitalization, the patient ceased to take harmful drugs and she was given haem arginate, glucose and symptomatic drugs, and she recovered completely.', 'Case report:': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Her therapy was dydrogesterone. In consultation with an anesthesiologist, a short intravenous anesthesia, vacuum aspiration, and curettage were performed.During hospitalization, the patient ceased to take harmful drugs and she was given haemarginate, glucose and symptomatic drugs, and she recovered completely.'}
|
{'Declaration of patient consent:': 'The authors certify that they have obtained all appropriate patient consent forms.', 'Gynecological issues': 'The first attack in our patient was most probably provoked by taking hormonal contraception. The progesterone and estrogen levels modified heme biosynthesis in subjects with AIP during menstrual cycle. Increased levels of progesterone were considered more important than estrogen in precipitating AIP attacks ( 2, 4 ). The clinical evidence suggests that hormonal oral contraceptives can lead to a manifestation of AIP in 25% of the women with AIP, in most cases can lead to their first attack ( 2 ). If, for any reason, e.g. irregular menstrual bleeding or threatened spontaneous abortion, oral hormonal contraceptives or gestagenes are used, monitoring of porphyrin precursor levels is recommended during the first month, in order to be able to interrupt the treatment should it increase concentrations ( 2, 4 ). The AIP gene carriers are advised to refrain from using oral contraceptives, in line with European recommendations ( 4 ). AIP is usually manifested in adult women, which means that it is seldom developed before puberty and after menopause the frequency of attacks declines ( 4 ).', 'Anaesthesiological considerations': 'Patients with AIP are at particular risk from general anaesthesia as most of the intravenous agents including barbiturates and volatile agents are contraindicated. Asymptomatic patients can benefit from local and regional anesthesia with bupivacaine for both labour analgesia and caesarean section ( 8, 9 ), but for symptomatic patients, or patients in crisis, we should rather choose general anaesthesia for caesarean section. Several clinical reports suggest that the hypnotic agent of choice for both induction and maintenance of such anaesthesia is propofol ( 8, 9 ). In our case short intravenous anaesthesia was induced with a bolus of propofol, alfentanil and diasepam. AIP may also trigger posterior reversible encephalopathy syndrome (PRES), a rare condition that is characterized by acute neurological symptoms, like in our case. The clinical and radiological symptoms usually disappear through the elimination of PRES-triggering factors and appropriate treatment ( 10 ).', 'CASE REPORT': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Previously, she had had a seizure attack at home. Her therapy was dydrogesterone 10 mg, three times per day, during two weeks. In her personal history she stated to have had a porphyria. The last acute attack happened 7 years beforethe spontaneous abortion, and she did not have a checkup in that period. In consultation with an anesthesiologist, in a short intravenous anesthesia, vacuum aspiration, andcurettage were performed. The patient regained consciousness immediately after the intervention and reached full orientation and cooperativeness within few minutes. The post-intervention period remained uneventful and the neurological and psychological symptoms returned to the pre-exacerbation status. In laboratory findings porphyrin derivatives (delta aminolevulinic acid 7.76 mg / dU- (reference range 1.5-7.5) and porphobilinogen 16.84 mg / dU- (reference range 0-3.4) were elevated. The therapy of glucose solution was administrated after which the patient’s condition stabilized. Porphyria markers decreased within the next four weeks. Seven years ago, the patient was admitted due to vomiting, severe intermittent pain in the abdomen, frequent urination, blood in the urine, and elevated body temperature. The last four months the patient was on oral contraceptives (0.035 mg ethinyl estradiol and 2.0 mg cyproteronacetat) due to irregular menstrual cycles. During hospitalization, at the time of the first day of menstruation, the patient developed grand mal seizures and expressed agitation. Seizures reached the epileptic status. Epileptic status cannot be ceased by maximal dose of diazepam, but only short intravenous anesthesia (midazolam maleate). The patient was in a state of high psychomotor agitation after the epileptic status. The brain CT pointed atthe left parietal paramedian hypodense area 16 mm in diameter. The MRI of the brain described the bilateral symmetric lesions of cortico-subcortical distribution, parieto occipital and frontal, which according to MRI characteristics primarily refer to posterior reversible encephalopathy within the metabolic disorder. In laboratory findings, pronounced hyponatremia, hypokalemia, hypomagnesemia, and hypocalcaemia were verified. Biochemical was proven of AIP, high positive variability of total porphyrins (700 μg / dU- reference interval <220), uroporphyrin (185 mg / dU), copro-porphyrin (515 mg / dU), delta amino levulinic acid (19.50 mg / dU) and porphobilinogen (98 mg / dU)). During hospitalization, the patient ceased to take harmful drugs and she was given haem arginate, glucose and symptomatic drugs, and she recovered completely.', 'Case report:': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Her therapy was dydrogesterone. In consultation with an anesthesiologist, a short intravenous anesthesia, vacuum aspiration, and curettage were performed.During hospitalization, the patient ceased to take harmful drugs and she was given haemarginate, glucose and symptomatic drugs, and she recovered completely.'}
|
Age-of-Onset
|
Age (of onset)
|
[] |
test-2141
|
7296395
|
{'Declaration of patient consent:': 'The authors certify that they have obtained all appropriate patient consent forms.', 'Gynecological issues': 'The first attack in our patient was most probably provoked by taking hormonal contraception. The progesterone and estrogen levels modified heme biosynthesis in subjects with AIP during menstrual cycle. Increased levels of progesterone were considered more important than estrogen in precipitating AIP attacks ( 2, 4 ). The clinical evidence suggests that hormonal oral contraceptives can lead to a manifestation of AIP in 25% of the women with AIP, in most cases can lead to their first attack ( 2 ). If, for any reason, e.g. irregular menstrual bleeding or threatened spontaneous abortion, oral hormonal contraceptives or gestagenes are used, monitoring of porphyrin precursor levels is recommended during the first month, in order to be able to interrupt the treatment should it increase concentrations ( 2, 4 ). The AIP gene carriers are advised to refrain from using oral contraceptives, in line with European recommendations ( 4 ). AIP is usually manifested in adult women, which means that it is seldom developed before puberty and after menopause the frequency of attacks declines ( 4 ).', 'Anaesthesiological considerations': 'Patients with AIP are at particular risk from general anaesthesia as most of the intravenous agents including barbiturates and volatile agents are contraindicated. Asymptomatic patients can benefit from local and regional anesthesia with bupivacaine for both labour analgesia and caesarean section ( 8, 9 ), but for symptomatic patients, or patients in crisis, we should rather choose general anaesthesia for caesarean section. Several clinical reports suggest that the hypnotic agent of choice for both induction and maintenance of such anaesthesia is propofol ( 8, 9 ). In our case short intravenous anaesthesia was induced with a bolus of propofol, alfentanil and diasepam. AIP may also trigger posterior reversible encephalopathy syndrome (PRES), a rare condition that is characterized by acute neurological symptoms, like in our case. The clinical and radiological symptoms usually disappear through the elimination of PRES-triggering factors and appropriate treatment ( 10 ).', 'CASE REPORT': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Previously, she had had a seizure attack at home. Her therapy was dydrogesterone 10 mg, three times per day, during two weeks. In her personal history she stated to have had a porphyria. The last acute attack happened 7 years beforethe spontaneous abortion, and she did not have a checkup in that period. In consultation with an anesthesiologist, in a short intravenous anesthesia, vacuum aspiration, andcurettage were performed. The patient regained consciousness immediately after the intervention and reached full orientation and cooperativeness within few minutes. The post-intervention period remained uneventful and the neurological and psychological symptoms returned to the pre-exacerbation status. In laboratory findings porphyrin derivatives (delta aminolevulinic acid 7.76 mg / dU- (reference range 1.5-7.5) and porphobilinogen 16.84 mg / dU- (reference range 0-3.4) were elevated. The therapy of glucose solution was administrated after which the patient’s condition stabilized. Porphyria markers decreased within the next four weeks. Seven years ago, the patient was admitted due to vomiting, severe intermittent pain in the abdomen, frequent urination, blood in the urine, and elevated body temperature. The last four months the patient was on oral contraceptives (0.035 mg ethinyl estradiol and 2.0 mg cyproteronacetat) due to irregular menstrual cycles. During hospitalization, at the time of the first day of menstruation, the patient developed grand mal seizures and expressed agitation. Seizures reached the epileptic status. Epileptic status cannot be ceased by maximal dose of diazepam, but only short intravenous anesthesia (midazolam maleate). The patient was in a state of high psychomotor agitation after the epileptic status. The brain CT pointed atthe left parietal paramedian hypodense area 16 mm in diameter. The MRI of the brain described the bilateral symmetric lesions of cortico-subcortical distribution, parieto occipital and frontal, which according to MRI characteristics primarily refer to posterior reversible encephalopathy within the metabolic disorder. In laboratory findings, pronounced hyponatremia, hypokalemia, hypomagnesemia, and hypocalcaemia were verified. Biochemical was proven of AIP, high positive variability of total porphyrins (700 μg / dU- reference interval <220), uroporphyrin (185 mg / dU), copro-porphyrin (515 mg / dU), delta amino levulinic acid (19.50 mg / dU) and porphobilinogen (98 mg / dU)). During hospitalization, the patient ceased to take harmful drugs and she was given haem arginate, glucose and symptomatic drugs, and she recovered completely.', 'Case report:': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Her therapy was dydrogesterone. In consultation with an anesthesiologist, a short intravenous anesthesia, vacuum aspiration, and curettage were performed.During hospitalization, the patient ceased to take harmful drugs and she was given haemarginate, glucose and symptomatic drugs, and she recovered completely.'}
|
{'Declaration of patient consent:': 'The authors certify that they have obtained all appropriate patient consent forms.', 'Gynecological issues': 'The first attack in our patient was most probably provoked by taking hormonal contraception. The progesterone and estrogen levels modified heme biosynthesis in subjects with AIP during menstrual cycle. Increased levels of progesterone were considered more important than estrogen in precipitating AIP attacks ( 2, 4 ). The clinical evidence suggests that hormonal oral contraceptives can lead to a manifestation of AIP in 25% of the women with AIP, in most cases can lead to their first attack ( 2 ). If, for any reason, e.g. irregular menstrual bleeding or threatened spontaneous abortion, oral hormonal contraceptives or gestagenes are used, monitoring of porphyrin precursor levels is recommended during the first month, in order to be able to interrupt the treatment should it increase concentrations ( 2, 4 ). The AIP gene carriers are advised to refrain from using oral contraceptives, in line with European recommendations ( 4 ). AIP is usually manifested in adult women, which means that it is seldom developed before puberty and after menopause the frequency of attacks declines ( 4 ).', 'Anaesthesiological considerations': 'Patients with AIP are at particular risk from general anaesthesia as most of the intravenous agents including barbiturates and volatile agents are contraindicated. Asymptomatic patients can benefit from local and regional anesthesia with bupivacaine for both labour analgesia and caesarean section ( 8, 9 ), but for symptomatic patients, or patients in crisis, we should rather choose general anaesthesia for caesarean section. Several clinical reports suggest that the hypnotic agent of choice for both induction and maintenance of such anaesthesia is propofol ( 8, 9 ). In our case short intravenous anaesthesia was induced with a bolus of propofol, alfentanil and diasepam. AIP may also trigger posterior reversible encephalopathy syndrome (PRES), a rare condition that is characterized by acute neurological symptoms, like in our case. The clinical and radiological symptoms usually disappear through the elimination of PRES-triggering factors and appropriate treatment ( 10 ).', 'CASE REPORT': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Previously, she had had a seizure attack at home. Her therapy was dydrogesterone 10 mg, three times per day, during two weeks. In her personal history she stated to have had a porphyria. The last acute attack happened 7 years beforethe spontaneous abortion, and she did not have a checkup in that period. In consultation with an anesthesiologist, in a short intravenous anesthesia, vacuum aspiration, andcurettage were performed. The patient regained consciousness immediately after the intervention and reached full orientation and cooperativeness within few minutes. The post-intervention period remained uneventful and the neurological and psychological symptoms returned to the pre-exacerbation status. In laboratory findings porphyrin derivatives (delta aminolevulinic acid 7.76 mg / dU- (reference range 1.5-7.5) and porphobilinogen 16.84 mg / dU- (reference range 0-3.4) were elevated. The therapy of glucose solution was administrated after which the patient’s condition stabilized. Porphyria markers decreased within the next four weeks. Seven years ago, the patient was admitted due to vomiting, severe intermittent pain in the abdomen, frequent urination, blood in the urine, and elevated body temperature. The last four months the patient was on oral contraceptives (0.035 mg ethinyl estradiol and 2.0 mg cyproteronacetat) due to irregular menstrual cycles. During hospitalization, at the time of the first day of menstruation, the patient developed grand mal seizures and expressed agitation. Seizures reached the epileptic status. Epileptic status cannot be ceased by maximal dose of diazepam, but only short intravenous anesthesia (midazolam maleate). The patient was in a state of high psychomotor agitation after the epileptic status. The brain CT pointed atthe left parietal paramedian hypodense area 16 mm in diameter. The MRI of the brain described the bilateral symmetric lesions of cortico-subcortical distribution, parieto occipital and frontal, which according to MRI characteristics primarily refer to posterior reversible encephalopathy within the metabolic disorder. In laboratory findings, pronounced hyponatremia, hypokalemia, hypomagnesemia, and hypocalcaemia were verified. Biochemical was proven of AIP, high positive variability of total porphyrins (700 μg / dU- reference interval <220), uroporphyrin (185 mg / dU), copro-porphyrin (515 mg / dU), delta amino levulinic acid (19.50 mg / dU) and porphobilinogen (98 mg / dU)). During hospitalization, the patient ceased to take harmful drugs and she was given haem arginate, glucose and symptomatic drugs, and she recovered completely.', 'Case report:': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Her therapy was dydrogesterone. In consultation with an anesthesiologist, a short intravenous anesthesia, vacuum aspiration, and curettage were performed.During hospitalization, the patient ceased to take harmful drugs and she was given haemarginate, glucose and symptomatic drugs, and she recovered completely.'}
|
Confirmed-Diagnosis-IEM
|
Confirmed_Diagnosis(IEM)
|
[
"AIP"
] |
test-2142
|
7296395
|
{'Declaration of patient consent:': 'The authors certify that they have obtained all appropriate patient consent forms.', 'Gynecological issues': 'The first attack in our patient was most probably provoked by taking hormonal contraception. The progesterone and estrogen levels modified heme biosynthesis in subjects with AIP during menstrual cycle. Increased levels of progesterone were considered more important than estrogen in precipitating AIP attacks ( 2, 4 ). The clinical evidence suggests that hormonal oral contraceptives can lead to a manifestation of AIP in 25% of the women with AIP, in most cases can lead to their first attack ( 2 ). If, for any reason, e.g. irregular menstrual bleeding or threatened spontaneous abortion, oral hormonal contraceptives or gestagenes are used, monitoring of porphyrin precursor levels is recommended during the first month, in order to be able to interrupt the treatment should it increase concentrations ( 2, 4 ). The AIP gene carriers are advised to refrain from using oral contraceptives, in line with European recommendations ( 4 ). AIP is usually manifested in adult women, which means that it is seldom developed before puberty and after menopause the frequency of attacks declines ( 4 ).', 'Anaesthesiological considerations': 'Patients with AIP are at particular risk from general anaesthesia as most of the intravenous agents including barbiturates and volatile agents are contraindicated. Asymptomatic patients can benefit from local and regional anesthesia with bupivacaine for both labour analgesia and caesarean section ( 8, 9 ), but for symptomatic patients, or patients in crisis, we should rather choose general anaesthesia for caesarean section. Several clinical reports suggest that the hypnotic agent of choice for both induction and maintenance of such anaesthesia is propofol ( 8, 9 ). In our case short intravenous anaesthesia was induced with a bolus of propofol, alfentanil and diasepam. AIP may also trigger posterior reversible encephalopathy syndrome (PRES), a rare condition that is characterized by acute neurological symptoms, like in our case. The clinical and radiological symptoms usually disappear through the elimination of PRES-triggering factors and appropriate treatment ( 10 ).', 'CASE REPORT': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Previously, she had had a seizure attack at home. Her therapy was dydrogesterone 10 mg, three times per day, during two weeks. In her personal history she stated to have had a porphyria. The last acute attack happened 7 years beforethe spontaneous abortion, and she did not have a checkup in that period. In consultation with an anesthesiologist, in a short intravenous anesthesia, vacuum aspiration, andcurettage were performed. The patient regained consciousness immediately after the intervention and reached full orientation and cooperativeness within few minutes. The post-intervention period remained uneventful and the neurological and psychological symptoms returned to the pre-exacerbation status. In laboratory findings porphyrin derivatives (delta aminolevulinic acid 7.76 mg / dU- (reference range 1.5-7.5) and porphobilinogen 16.84 mg / dU- (reference range 0-3.4) were elevated. The therapy of glucose solution was administrated after which the patient’s condition stabilized. Porphyria markers decreased within the next four weeks. Seven years ago, the patient was admitted due to vomiting, severe intermittent pain in the abdomen, frequent urination, blood in the urine, and elevated body temperature. The last four months the patient was on oral contraceptives (0.035 mg ethinyl estradiol and 2.0 mg cyproteronacetat) due to irregular menstrual cycles. During hospitalization, at the time of the first day of menstruation, the patient developed grand mal seizures and expressed agitation. Seizures reached the epileptic status. Epileptic status cannot be ceased by maximal dose of diazepam, but only short intravenous anesthesia (midazolam maleate). The patient was in a state of high psychomotor agitation after the epileptic status. The brain CT pointed atthe left parietal paramedian hypodense area 16 mm in diameter. The MRI of the brain described the bilateral symmetric lesions of cortico-subcortical distribution, parieto occipital and frontal, which according to MRI characteristics primarily refer to posterior reversible encephalopathy within the metabolic disorder. In laboratory findings, pronounced hyponatremia, hypokalemia, hypomagnesemia, and hypocalcaemia were verified. Biochemical was proven of AIP, high positive variability of total porphyrins (700 μg / dU- reference interval <220), uroporphyrin (185 mg / dU), copro-porphyrin (515 mg / dU), delta amino levulinic acid (19.50 mg / dU) and porphobilinogen (98 mg / dU)). During hospitalization, the patient ceased to take harmful drugs and she was given haem arginate, glucose and symptomatic drugs, and she recovered completely.', 'Case report:': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Her therapy was dydrogesterone. In consultation with an anesthesiologist, a short intravenous anesthesia, vacuum aspiration, and curettage were performed.During hospitalization, the patient ceased to take harmful drugs and she was given haemarginate, glucose and symptomatic drugs, and she recovered completely.'}
|
{'Declaration of patient consent:': 'The authors certify that they have obtained all appropriate patient consent forms.', 'Gynecological issues': 'The first attack in our patient was most probably provoked by taking hormonal contraception. The progesterone and estrogen levels modified heme biosynthesis in subjects with AIP during menstrual cycle. Increased levels of progesterone were considered more important than estrogen in precipitating AIP attacks ( 2, 4 ). The clinical evidence suggests that hormonal oral contraceptives can lead to a manifestation of AIP in 25% of the women with AIP, in most cases can lead to their first attack ( 2 ). If, for any reason, e.g. irregular menstrual bleeding or threatened spontaneous abortion, oral hormonal contraceptives or gestagenes are used, monitoring of porphyrin precursor levels is recommended during the first month, in order to be able to interrupt the treatment should it increase concentrations ( 2, 4 ). The AIP gene carriers are advised to refrain from using oral contraceptives, in line with European recommendations ( 4 ). AIP is usually manifested in adult women, which means that it is seldom developed before puberty and after menopause the frequency of attacks declines ( 4 ).', 'Anaesthesiological considerations': 'Patients with AIP are at particular risk from general anaesthesia as most of the intravenous agents including barbiturates and volatile agents are contraindicated. Asymptomatic patients can benefit from local and regional anesthesia with bupivacaine for both labour analgesia and caesarean section ( 8, 9 ), but for symptomatic patients, or patients in crisis, we should rather choose general anaesthesia for caesarean section. Several clinical reports suggest that the hypnotic agent of choice for both induction and maintenance of such anaesthesia is propofol ( 8, 9 ). In our case short intravenous anaesthesia was induced with a bolus of propofol, alfentanil and diasepam. AIP may also trigger posterior reversible encephalopathy syndrome (PRES), a rare condition that is characterized by acute neurological symptoms, like in our case. The clinical and radiological symptoms usually disappear through the elimination of PRES-triggering factors and appropriate treatment ( 10 ).', 'CASE REPORT': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Previously, she had had a seizure attack at home. Her therapy was dydrogesterone 10 mg, three times per day, during two weeks. In her personal history she stated to have had a porphyria. The last acute attack happened 7 years beforethe spontaneous abortion, and she did not have a checkup in that period. In consultation with an anesthesiologist, in a short intravenous anesthesia, vacuum aspiration, andcurettage were performed. The patient regained consciousness immediately after the intervention and reached full orientation and cooperativeness within few minutes. The post-intervention period remained uneventful and the neurological and psychological symptoms returned to the pre-exacerbation status. In laboratory findings porphyrin derivatives (delta aminolevulinic acid 7.76 mg / dU- (reference range 1.5-7.5) and porphobilinogen 16.84 mg / dU- (reference range 0-3.4) were elevated. The therapy of glucose solution was administrated after which the patient’s condition stabilized. Porphyria markers decreased within the next four weeks. Seven years ago, the patient was admitted due to vomiting, severe intermittent pain in the abdomen, frequent urination, blood in the urine, and elevated body temperature. The last four months the patient was on oral contraceptives (0.035 mg ethinyl estradiol and 2.0 mg cyproteronacetat) due to irregular menstrual cycles. During hospitalization, at the time of the first day of menstruation, the patient developed grand mal seizures and expressed agitation. Seizures reached the epileptic status. Epileptic status cannot be ceased by maximal dose of diazepam, but only short intravenous anesthesia (midazolam maleate). The patient was in a state of high psychomotor agitation after the epileptic status. The brain CT pointed atthe left parietal paramedian hypodense area 16 mm in diameter. The MRI of the brain described the bilateral symmetric lesions of cortico-subcortical distribution, parieto occipital and frontal, which according to MRI characteristics primarily refer to posterior reversible encephalopathy within the metabolic disorder. In laboratory findings, pronounced hyponatremia, hypokalemia, hypomagnesemia, and hypocalcaemia were verified. Biochemical was proven of AIP, high positive variability of total porphyrins (700 μg / dU- reference interval <220), uroporphyrin (185 mg / dU), copro-porphyrin (515 mg / dU), delta amino levulinic acid (19.50 mg / dU) and porphobilinogen (98 mg / dU)). During hospitalization, the patient ceased to take harmful drugs and she was given haem arginate, glucose and symptomatic drugs, and she recovered completely.', 'Case report:': 'A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Her therapy was dydrogesterone. In consultation with an anesthesiologist, a short intravenous anesthesia, vacuum aspiration, and curettage were performed.During hospitalization, the patient ceased to take harmful drugs and she was given haemarginate, glucose and symptomatic drugs, and she recovered completely.'}
|
IEM-Treatment
|
IEM_Treatment
|
[
"she was given haem arginate , glucose and symptomatic drugs , and she recovered completely",
"she was given haemarginate , glucose"
] |
test-2143
|
8022107
|
{'Case 2': 'The older sister of case patient 1 presented at the age of 18 years with photoinduced skin blistering of the face and extremities since her sixth day of life. She had associated progressive deformities of her bilateral hands and feet, bilateral ears, and nose. She reported having had photophobia and diminished vision in the right eye since early childhood. Examination revealed sclerodermatous changes and hypopigmented and hyperpigmented scars over the face and extremities ( Fig 2, A ); partial absorption of both ears; and brownish-pink-colored teeth. Hypertrichosis over the face and arms was present, and the bilateral extremities showed sclerodermatous contracture and acro-osteolysis ( Fig 2, B ). Ectropion and bilateral keratoconjunctivitis were apparent. She had mild anemia and splenomegaly. Porphyrin profiling and genetic analysis were not performed because of the unavailability of laboratory facilities at that time. She died at the age of 24 from a secondary infection. Fig 2 A, Sclerodermatous changes and hypopigmented and hyperpigmented scars over the face. B, Acro-osteolysis and contracture of the bilateral hands.', 'Case 3': "A 35-year-old woman, born to phenotypically normal parents, presented with progressive bilateral deformities of the hands and photoblistering since birth, with resulting dyspigmentation, scarring, and sclerodermatous changes of the face and distal extremities ( Fig 3 ) and progressive deformities of both hands. She had a history of recurrent keratoconjunctivitis and complications requiring enucleation of her left eye ( Fig 3 ). Facial hypertrichosis, microstomia ( Fig 3 ), erythrodontia, and mutilations of both hands were evident on examination. Laboratory reports revealed a normal complete blood count but an abnormal porphyrin profile ( Table I ). Fig 3 Dyspigmentation, scarring, and sclerodermatous changes over the face with enucleation of the left eye. Wood's lamp examination revealed pink-red fluorescence of the urine and teeth in all 3 patients. In case patients 1 and 3, sequencing of the UROS gene, exons 1 to 10 including flanking intronic regions, showed a homozygous transversion of T to G at nucleotide 416 in exon 7 (c.416T>G) leading to an L139R protein substitution at the terminal of the β6 protein chain. The patients were advised to use strict photoprotection, emollients, and vitamin D supplementation. They were also counseled about the disease, the need for long-term follow-up, wound care, and lifestyle modifications.", 'Case 1': 'A 17-year-old female (now 37 years old), born from a nonconsanguineous marriage, presented with a history of spontaneous blistering over photoexposed areas, starting in the first few days of her life. The lesions healed with scarring that led to progressive deformities of her hands, ears, and nose by 18 years of age. Her mother reported a red discharge in her diaper and redness and matting of both eyes since early childhood. She gradually developed deformities of her eyelids, making it difficult to close them fully. Three of her 7 siblings were similarly affected. Two of the affected siblings died shortly after birth, and a third, her older sister (case 2), died at the age of 24. Both parents were phenotypically normal. Examination revealed thickened skin, hypopigmentation and hyperpigmentation, and scarring at photoexposed sites ( Fig 1, A ); facial hypertrichosis; and reddish-brown tooth discoloration and disfiguration of the nose, ears, and fingertips bilaterally to the proximal interphalangeal joints. Eye examination revealed severe ectropion, trichiasis, and scleral melting ( Fig 1, B ). Abdominal examination revealed an enlarged spleen 4 cm below the left costal margin. Blood investigation showed pancytopenia, elevated erythrocyte sedimentation rate, positive creatinine-reactive protein, a normal serum iron profile, and an abnormal porphyrin profile ( Table I ). Fig 1 A, Thickened skin with hypopigmentation and hyperpigmentation and scarring over photoexposed sites, facial hypertrichosis, and reddish-brownish discoloration of the teeth. B, Severe ectropion, trichiasis, and scleral melting. Table I Results of laboratory investigations Parameter (normal range) Case 1 Case 2 Case 3 Urine total porphyrin (25-144 nmol/L) 11,986 nmol/L NA 13,269 nmol/L Fecal porphyrin (10-200 nmol/g) 5569 nmol/g NA 1797 nmol/g Plasma porphyrin (<11.2 nmol/L) NA NA 1120.5 nmol/L Plasma porphyrin peak 618 nm NA 618 nm Erythrocyte porphyrin (0.4-1.7 μmol/L) 35.8 μmol/L NA 26.2 μmol/L Total white blood cell count (4000-11,000/mm 3 ) 1700/mm 3 3600/mm 3 4500/mm 3 Platelets (150,000-450,000/mm 3 ) 107,000/mm 3 150,000/mm 3 175,000/mm 3 Hemoglobin (female: 12.0-15.5 g/dL) 9.4 g/dL 8.7 g/dL 12 g/dL'}
|
{'Case 2': 'The older sister of case patient 1 presented at the age of 18 years with photoinduced skin blistering of the face and extremities since her sixth day of life. She had associated progressive deformities of her bilateral hands and feet, bilateral ears, and nose. She reported having had photophobia and diminished vision in the right eye since early childhood. Examination revealed sclerodermatous changes and hypopigmented and hyperpigmented scars over the face and extremities ( Fig 2, A ); partial absorption of both ears; and brownish-pink-colored teeth. Hypertrichosis over the face and arms was present, and the bilateral extremities showed sclerodermatous contracture and acro-osteolysis ( Fig 2, B ). Ectropion and bilateral keratoconjunctivitis were apparent. She had mild anemia and splenomegaly. Porphyrin profiling and genetic analysis were not performed because of the unavailability of laboratory facilities at that time. She died at the age of 24 from a secondary infection. Fig 2 A, Sclerodermatous changes and hypopigmented and hyperpigmented scars over the face. B, Acro-osteolysis and contracture of the bilateral hands.', 'Case 3': "A 35-year-old woman, born to phenotypically normal parents, presented with progressive bilateral deformities of the hands and photoblistering since birth, with resulting dyspigmentation, scarring, and sclerodermatous changes of the face and distal extremities ( Fig 3 ) and progressive deformities of both hands. She had a history of recurrent keratoconjunctivitis and complications requiring enucleation of her left eye ( Fig 3 ). Facial hypertrichosis, microstomia ( Fig 3 ), erythrodontia, and mutilations of both hands were evident on examination. Laboratory reports revealed a normal complete blood count but an abnormal porphyrin profile ( Table I ). Fig 3 Dyspigmentation, scarring, and sclerodermatous changes over the face with enucleation of the left eye. Wood's lamp examination revealed pink-red fluorescence of the urine and teeth in all 3 patients. In case patients 1 and 3, sequencing of the UROS gene, exons 1 to 10 including flanking intronic regions, showed a homozygous transversion of T to G at nucleotide 416 in exon 7 (c.416T>G) leading to an L139R protein substitution at the terminal of the β6 protein chain. The patients were advised to use strict photoprotection, emollients, and vitamin D supplementation. They were also counseled about the disease, the need for long-term follow-up, wound care, and lifestyle modifications.", 'Case 1': 'A 17-year-old female (now 37 years old), born from a nonconsanguineous marriage, presented with a history of spontaneous blistering over photoexposed areas, starting in the first few days of her life. The lesions healed with scarring that led to progressive deformities of her hands, ears, and nose by 18 years of age. Her mother reported a red discharge in her diaper and redness and matting of both eyes since early childhood. She gradually developed deformities of her eyelids, making it difficult to close them fully. Three of her 7 siblings were similarly affected. Two of the affected siblings died shortly after birth, and a third, her older sister (case 2), died at the age of 24. Both parents were phenotypically normal. Examination revealed thickened skin, hypopigmentation and hyperpigmentation, and scarring at photoexposed sites ( Fig 1, A ); facial hypertrichosis; and reddish-brown tooth discoloration and disfiguration of the nose, ears, and fingertips bilaterally to the proximal interphalangeal joints. Eye examination revealed severe ectropion, trichiasis, and scleral melting ( Fig 1, B ). Abdominal examination revealed an enlarged spleen 4 cm below the left costal margin. Blood investigation showed pancytopenia, elevated erythrocyte sedimentation rate, positive creatinine-reactive protein, a normal serum iron profile, and an abnormal porphyrin profile ( Table I ). Fig 1 A, Thickened skin with hypopigmentation and hyperpigmentation and scarring over photoexposed sites, facial hypertrichosis, and reddish-brownish discoloration of the teeth. B, Severe ectropion, trichiasis, and scleral melting. Table I Results of laboratory investigations Parameter (normal range) Case 1 Case 2 Case 3 Urine total porphyrin (25-144 nmol/L) 11,986 nmol/L NA 13,269 nmol/L Fecal porphyrin (10-200 nmol/g) 5569 nmol/g NA 1797 nmol/g Plasma porphyrin (<11.2 nmol/L) NA NA 1120.5 nmol/L Plasma porphyrin peak 618 nm NA 618 nm Erythrocyte porphyrin (0.4-1.7 μmol/L) 35.8 μmol/L NA 26.2 μmol/L Total white blood cell count (4000-11,000/mm 3 ) 1700/mm 3 3600/mm 3 4500/mm 3 Platelets (150,000-450,000/mm 3 ) 107,000/mm 3 150,000/mm 3 175,000/mm 3 Hemoglobin (female: 12.0-15.5 g/dL) 9.4 g/dL 8.7 g/dL 12 g/dL'}
|
Vitals-and-Hematology
|
Vitals_Hema
|
[
"mild anemia and splenomegaly",
"normal complete blood count",
"enlarged spleen 4 cm below the left costal margin. Blood investigation showed pancytopenia",
"normal serum iron profile",
"Total white blood cell count ( 4000 - 11,000 / mm 3 ) 1700 / mm 3 3600 / mm 3 4500 / mm 3 Platelets ( 150,000 - 450,000 / mm 3 ) 107,000 / mm 3 150,000 / mm 3 175,000 / mm 3 Hemoglobin ( female : 12.0 - 15.5 g / dL ) 9.4 g / dL 8.7 g / dL 12 g / dL '"
] |
test-2144
|
8022107
|
{'Case 2': 'The older sister of case patient 1 presented at the age of 18 years with photoinduced skin blistering of the face and extremities since her sixth day of life. She had associated progressive deformities of her bilateral hands and feet, bilateral ears, and nose. She reported having had photophobia and diminished vision in the right eye since early childhood. Examination revealed sclerodermatous changes and hypopigmented and hyperpigmented scars over the face and extremities ( Fig 2, A ); partial absorption of both ears; and brownish-pink-colored teeth. Hypertrichosis over the face and arms was present, and the bilateral extremities showed sclerodermatous contracture and acro-osteolysis ( Fig 2, B ). Ectropion and bilateral keratoconjunctivitis were apparent. She had mild anemia and splenomegaly. Porphyrin profiling and genetic analysis were not performed because of the unavailability of laboratory facilities at that time. She died at the age of 24 from a secondary infection. Fig 2 A, Sclerodermatous changes and hypopigmented and hyperpigmented scars over the face. B, Acro-osteolysis and contracture of the bilateral hands.', 'Case 3': "A 35-year-old woman, born to phenotypically normal parents, presented with progressive bilateral deformities of the hands and photoblistering since birth, with resulting dyspigmentation, scarring, and sclerodermatous changes of the face and distal extremities ( Fig 3 ) and progressive deformities of both hands. She had a history of recurrent keratoconjunctivitis and complications requiring enucleation of her left eye ( Fig 3 ). Facial hypertrichosis, microstomia ( Fig 3 ), erythrodontia, and mutilations of both hands were evident on examination. Laboratory reports revealed a normal complete blood count but an abnormal porphyrin profile ( Table I ). Fig 3 Dyspigmentation, scarring, and sclerodermatous changes over the face with enucleation of the left eye. Wood's lamp examination revealed pink-red fluorescence of the urine and teeth in all 3 patients. In case patients 1 and 3, sequencing of the UROS gene, exons 1 to 10 including flanking intronic regions, showed a homozygous transversion of T to G at nucleotide 416 in exon 7 (c.416T>G) leading to an L139R protein substitution at the terminal of the β6 protein chain. The patients were advised to use strict photoprotection, emollients, and vitamin D supplementation. They were also counseled about the disease, the need for long-term follow-up, wound care, and lifestyle modifications.", 'Case 1': 'A 17-year-old female (now 37 years old), born from a nonconsanguineous marriage, presented with a history of spontaneous blistering over photoexposed areas, starting in the first few days of her life. The lesions healed with scarring that led to progressive deformities of her hands, ears, and nose by 18 years of age. Her mother reported a red discharge in her diaper and redness and matting of both eyes since early childhood. She gradually developed deformities of her eyelids, making it difficult to close them fully. Three of her 7 siblings were similarly affected. Two of the affected siblings died shortly after birth, and a third, her older sister (case 2), died at the age of 24. Both parents were phenotypically normal. Examination revealed thickened skin, hypopigmentation and hyperpigmentation, and scarring at photoexposed sites ( Fig 1, A ); facial hypertrichosis; and reddish-brown tooth discoloration and disfiguration of the nose, ears, and fingertips bilaterally to the proximal interphalangeal joints. Eye examination revealed severe ectropion, trichiasis, and scleral melting ( Fig 1, B ). Abdominal examination revealed an enlarged spleen 4 cm below the left costal margin. Blood investigation showed pancytopenia, elevated erythrocyte sedimentation rate, positive creatinine-reactive protein, a normal serum iron profile, and an abnormal porphyrin profile ( Table I ). Fig 1 A, Thickened skin with hypopigmentation and hyperpigmentation and scarring over photoexposed sites, facial hypertrichosis, and reddish-brownish discoloration of the teeth. B, Severe ectropion, trichiasis, and scleral melting. Table I Results of laboratory investigations Parameter (normal range) Case 1 Case 2 Case 3 Urine total porphyrin (25-144 nmol/L) 11,986 nmol/L NA 13,269 nmol/L Fecal porphyrin (10-200 nmol/g) 5569 nmol/g NA 1797 nmol/g Plasma porphyrin (<11.2 nmol/L) NA NA 1120.5 nmol/L Plasma porphyrin peak 618 nm NA 618 nm Erythrocyte porphyrin (0.4-1.7 μmol/L) 35.8 μmol/L NA 26.2 μmol/L Total white blood cell count (4000-11,000/mm 3 ) 1700/mm 3 3600/mm 3 4500/mm 3 Platelets (150,000-450,000/mm 3 ) 107,000/mm 3 150,000/mm 3 175,000/mm 3 Hemoglobin (female: 12.0-15.5 g/dL) 9.4 g/dL 8.7 g/dL 12 g/dL'}
|
{'Case 2': 'The older sister of case patient 1 presented at the age of 18 years with photoinduced skin blistering of the face and extremities since her sixth day of life. She had associated progressive deformities of her bilateral hands and feet, bilateral ears, and nose. She reported having had photophobia and diminished vision in the right eye since early childhood. Examination revealed sclerodermatous changes and hypopigmented and hyperpigmented scars over the face and extremities ( Fig 2, A ); partial absorption of both ears; and brownish-pink-colored teeth. Hypertrichosis over the face and arms was present, and the bilateral extremities showed sclerodermatous contracture and acro-osteolysis ( Fig 2, B ). Ectropion and bilateral keratoconjunctivitis were apparent. She had mild anemia and splenomegaly. Porphyrin profiling and genetic analysis were not performed because of the unavailability of laboratory facilities at that time. She died at the age of 24 from a secondary infection. Fig 2 A, Sclerodermatous changes and hypopigmented and hyperpigmented scars over the face. B, Acro-osteolysis and contracture of the bilateral hands.', 'Case 3': "A 35-year-old woman, born to phenotypically normal parents, presented with progressive bilateral deformities of the hands and photoblistering since birth, with resulting dyspigmentation, scarring, and sclerodermatous changes of the face and distal extremities ( Fig 3 ) and progressive deformities of both hands. She had a history of recurrent keratoconjunctivitis and complications requiring enucleation of her left eye ( Fig 3 ). Facial hypertrichosis, microstomia ( Fig 3 ), erythrodontia, and mutilations of both hands were evident on examination. Laboratory reports revealed a normal complete blood count but an abnormal porphyrin profile ( Table I ). Fig 3 Dyspigmentation, scarring, and sclerodermatous changes over the face with enucleation of the left eye. Wood's lamp examination revealed pink-red fluorescence of the urine and teeth in all 3 patients. In case patients 1 and 3, sequencing of the UROS gene, exons 1 to 10 including flanking intronic regions, showed a homozygous transversion of T to G at nucleotide 416 in exon 7 (c.416T>G) leading to an L139R protein substitution at the terminal of the β6 protein chain. The patients were advised to use strict photoprotection, emollients, and vitamin D supplementation. They were also counseled about the disease, the need for long-term follow-up, wound care, and lifestyle modifications.", 'Case 1': 'A 17-year-old female (now 37 years old), born from a nonconsanguineous marriage, presented with a history of spontaneous blistering over photoexposed areas, starting in the first few days of her life. The lesions healed with scarring that led to progressive deformities of her hands, ears, and nose by 18 years of age. Her mother reported a red discharge in her diaper and redness and matting of both eyes since early childhood. She gradually developed deformities of her eyelids, making it difficult to close them fully. Three of her 7 siblings were similarly affected. Two of the affected siblings died shortly after birth, and a third, her older sister (case 2), died at the age of 24. Both parents were phenotypically normal. Examination revealed thickened skin, hypopigmentation and hyperpigmentation, and scarring at photoexposed sites ( Fig 1, A ); facial hypertrichosis; and reddish-brown tooth discoloration and disfiguration of the nose, ears, and fingertips bilaterally to the proximal interphalangeal joints. Eye examination revealed severe ectropion, trichiasis, and scleral melting ( Fig 1, B ). Abdominal examination revealed an enlarged spleen 4 cm below the left costal margin. Blood investigation showed pancytopenia, elevated erythrocyte sedimentation rate, positive creatinine-reactive protein, a normal serum iron profile, and an abnormal porphyrin profile ( Table I ). Fig 1 A, Thickened skin with hypopigmentation and hyperpigmentation and scarring over photoexposed sites, facial hypertrichosis, and reddish-brownish discoloration of the teeth. B, Severe ectropion, trichiasis, and scleral melting. Table I Results of laboratory investigations Parameter (normal range) Case 1 Case 2 Case 3 Urine total porphyrin (25-144 nmol/L) 11,986 nmol/L NA 13,269 nmol/L Fecal porphyrin (10-200 nmol/g) 5569 nmol/g NA 1797 nmol/g Plasma porphyrin (<11.2 nmol/L) NA NA 1120.5 nmol/L Plasma porphyrin peak 618 nm NA 618 nm Erythrocyte porphyrin (0.4-1.7 μmol/L) 35.8 μmol/L NA 26.2 μmol/L Total white blood cell count (4000-11,000/mm 3 ) 1700/mm 3 3600/mm 3 4500/mm 3 Platelets (150,000-450,000/mm 3 ) 107,000/mm 3 150,000/mm 3 175,000/mm 3 Hemoglobin (female: 12.0-15.5 g/dL) 9.4 g/dL 8.7 g/dL 12 g/dL'}
|
Gastrointestinal-System
|
GI
|
[] |
test-2145
|
8022107
|
{'Case 2': 'The older sister of case patient 1 presented at the age of 18 years with photoinduced skin blistering of the face and extremities since her sixth day of life. She had associated progressive deformities of her bilateral hands and feet, bilateral ears, and nose. She reported having had photophobia and diminished vision in the right eye since early childhood. Examination revealed sclerodermatous changes and hypopigmented and hyperpigmented scars over the face and extremities ( Fig 2, A ); partial absorption of both ears; and brownish-pink-colored teeth. Hypertrichosis over the face and arms was present, and the bilateral extremities showed sclerodermatous contracture and acro-osteolysis ( Fig 2, B ). Ectropion and bilateral keratoconjunctivitis were apparent. She had mild anemia and splenomegaly. Porphyrin profiling and genetic analysis were not performed because of the unavailability of laboratory facilities at that time. She died at the age of 24 from a secondary infection. Fig 2 A, Sclerodermatous changes and hypopigmented and hyperpigmented scars over the face. B, Acro-osteolysis and contracture of the bilateral hands.', 'Case 3': "A 35-year-old woman, born to phenotypically normal parents, presented with progressive bilateral deformities of the hands and photoblistering since birth, with resulting dyspigmentation, scarring, and sclerodermatous changes of the face and distal extremities ( Fig 3 ) and progressive deformities of both hands. She had a history of recurrent keratoconjunctivitis and complications requiring enucleation of her left eye ( Fig 3 ). Facial hypertrichosis, microstomia ( Fig 3 ), erythrodontia, and mutilations of both hands were evident on examination. Laboratory reports revealed a normal complete blood count but an abnormal porphyrin profile ( Table I ). Fig 3 Dyspigmentation, scarring, and sclerodermatous changes over the face with enucleation of the left eye. Wood's lamp examination revealed pink-red fluorescence of the urine and teeth in all 3 patients. In case patients 1 and 3, sequencing of the UROS gene, exons 1 to 10 including flanking intronic regions, showed a homozygous transversion of T to G at nucleotide 416 in exon 7 (c.416T>G) leading to an L139R protein substitution at the terminal of the β6 protein chain. The patients were advised to use strict photoprotection, emollients, and vitamin D supplementation. They were also counseled about the disease, the need for long-term follow-up, wound care, and lifestyle modifications.", 'Case 1': 'A 17-year-old female (now 37 years old), born from a nonconsanguineous marriage, presented with a history of spontaneous blistering over photoexposed areas, starting in the first few days of her life. The lesions healed with scarring that led to progressive deformities of her hands, ears, and nose by 18 years of age. Her mother reported a red discharge in her diaper and redness and matting of both eyes since early childhood. She gradually developed deformities of her eyelids, making it difficult to close them fully. Three of her 7 siblings were similarly affected. Two of the affected siblings died shortly after birth, and a third, her older sister (case 2), died at the age of 24. Both parents were phenotypically normal. Examination revealed thickened skin, hypopigmentation and hyperpigmentation, and scarring at photoexposed sites ( Fig 1, A ); facial hypertrichosis; and reddish-brown tooth discoloration and disfiguration of the nose, ears, and fingertips bilaterally to the proximal interphalangeal joints. Eye examination revealed severe ectropion, trichiasis, and scleral melting ( Fig 1, B ). Abdominal examination revealed an enlarged spleen 4 cm below the left costal margin. Blood investigation showed pancytopenia, elevated erythrocyte sedimentation rate, positive creatinine-reactive protein, a normal serum iron profile, and an abnormal porphyrin profile ( Table I ). Fig 1 A, Thickened skin with hypopigmentation and hyperpigmentation and scarring over photoexposed sites, facial hypertrichosis, and reddish-brownish discoloration of the teeth. B, Severe ectropion, trichiasis, and scleral melting. Table I Results of laboratory investigations Parameter (normal range) Case 1 Case 2 Case 3 Urine total porphyrin (25-144 nmol/L) 11,986 nmol/L NA 13,269 nmol/L Fecal porphyrin (10-200 nmol/g) 5569 nmol/g NA 1797 nmol/g Plasma porphyrin (<11.2 nmol/L) NA NA 1120.5 nmol/L Plasma porphyrin peak 618 nm NA 618 nm Erythrocyte porphyrin (0.4-1.7 μmol/L) 35.8 μmol/L NA 26.2 μmol/L Total white blood cell count (4000-11,000/mm 3 ) 1700/mm 3 3600/mm 3 4500/mm 3 Platelets (150,000-450,000/mm 3 ) 107,000/mm 3 150,000/mm 3 175,000/mm 3 Hemoglobin (female: 12.0-15.5 g/dL) 9.4 g/dL 8.7 g/dL 12 g/dL'}
|
{'Case 2': 'The older sister of case patient 1 presented at the age of 18 years with photoinduced skin blistering of the face and extremities since her sixth day of life. She had associated progressive deformities of her bilateral hands and feet, bilateral ears, and nose. She reported having had photophobia and diminished vision in the right eye since early childhood. Examination revealed sclerodermatous changes and hypopigmented and hyperpigmented scars over the face and extremities ( Fig 2, A ); partial absorption of both ears; and brownish-pink-colored teeth. Hypertrichosis over the face and arms was present, and the bilateral extremities showed sclerodermatous contracture and acro-osteolysis ( Fig 2, B ). Ectropion and bilateral keratoconjunctivitis were apparent. She had mild anemia and splenomegaly. Porphyrin profiling and genetic analysis were not performed because of the unavailability of laboratory facilities at that time. She died at the age of 24 from a secondary infection. Fig 2 A, Sclerodermatous changes and hypopigmented and hyperpigmented scars over the face. B, Acro-osteolysis and contracture of the bilateral hands.', 'Case 3': "A 35-year-old woman, born to phenotypically normal parents, presented with progressive bilateral deformities of the hands and photoblistering since birth, with resulting dyspigmentation, scarring, and sclerodermatous changes of the face and distal extremities ( Fig 3 ) and progressive deformities of both hands. She had a history of recurrent keratoconjunctivitis and complications requiring enucleation of her left eye ( Fig 3 ). Facial hypertrichosis, microstomia ( Fig 3 ), erythrodontia, and mutilations of both hands were evident on examination. Laboratory reports revealed a normal complete blood count but an abnormal porphyrin profile ( Table I ). Fig 3 Dyspigmentation, scarring, and sclerodermatous changes over the face with enucleation of the left eye. Wood's lamp examination revealed pink-red fluorescence of the urine and teeth in all 3 patients. In case patients 1 and 3, sequencing of the UROS gene, exons 1 to 10 including flanking intronic regions, showed a homozygous transversion of T to G at nucleotide 416 in exon 7 (c.416T>G) leading to an L139R protein substitution at the terminal of the β6 protein chain. The patients were advised to use strict photoprotection, emollients, and vitamin D supplementation. They were also counseled about the disease, the need for long-term follow-up, wound care, and lifestyle modifications.", 'Case 1': 'A 17-year-old female (now 37 years old), born from a nonconsanguineous marriage, presented with a history of spontaneous blistering over photoexposed areas, starting in the first few days of her life. The lesions healed with scarring that led to progressive deformities of her hands, ears, and nose by 18 years of age. Her mother reported a red discharge in her diaper and redness and matting of both eyes since early childhood. She gradually developed deformities of her eyelids, making it difficult to close them fully. Three of her 7 siblings were similarly affected. Two of the affected siblings died shortly after birth, and a third, her older sister (case 2), died at the age of 24. Both parents were phenotypically normal. Examination revealed thickened skin, hypopigmentation and hyperpigmentation, and scarring at photoexposed sites ( Fig 1, A ); facial hypertrichosis; and reddish-brown tooth discoloration and disfiguration of the nose, ears, and fingertips bilaterally to the proximal interphalangeal joints. Eye examination revealed severe ectropion, trichiasis, and scleral melting ( Fig 1, B ). Abdominal examination revealed an enlarged spleen 4 cm below the left costal margin. Blood investigation showed pancytopenia, elevated erythrocyte sedimentation rate, positive creatinine-reactive protein, a normal serum iron profile, and an abnormal porphyrin profile ( Table I ). Fig 1 A, Thickened skin with hypopigmentation and hyperpigmentation and scarring over photoexposed sites, facial hypertrichosis, and reddish-brownish discoloration of the teeth. B, Severe ectropion, trichiasis, and scleral melting. Table I Results of laboratory investigations Parameter (normal range) Case 1 Case 2 Case 3 Urine total porphyrin (25-144 nmol/L) 11,986 nmol/L NA 13,269 nmol/L Fecal porphyrin (10-200 nmol/g) 5569 nmol/g NA 1797 nmol/g Plasma porphyrin (<11.2 nmol/L) NA NA 1120.5 nmol/L Plasma porphyrin peak 618 nm NA 618 nm Erythrocyte porphyrin (0.4-1.7 μmol/L) 35.8 μmol/L NA 26.2 μmol/L Total white blood cell count (4000-11,000/mm 3 ) 1700/mm 3 3600/mm 3 4500/mm 3 Platelets (150,000-450,000/mm 3 ) 107,000/mm 3 150,000/mm 3 175,000/mm 3 Hemoglobin (female: 12.0-15.5 g/dL) 9.4 g/dL 8.7 g/dL 12 g/dL'}
|
Patient-History
|
History
|
[
"presented at the age of 18 years with photoinduced skin blistering of the face and extremities since her sixth day of life. She had associated progressive deformities of her bilateral hands and feet, bilateral ears, and nose",
"She died at the age of 24 from a secondary infection",
"A 35 - year - old woman, born to phenotypically normal parents, presented with progressive bilateral deformities of the hands and photoblistering since birth, with resulting dyspigmentation, scarring, and sclerodermatous changes of the face and distal extremities ( Fig 3 ) and progressive deformities of both hands. She had a history of recurrent keratoconjunctivitis and complications requiring enucleation of her left eye",
"enucleation of the left eye",
"A 17 - year - old female ( now 37 years old ), born from a nonconsanguineous marriage, presented with a history of spontaneous blistering over photoexposed areas, starting in the first few days of her life. The lesions healed with scarring that led to progressive deformities of her hands, ears, and nose by 18 years of age.",
"Three of her 7 siblings were similarly affected. Two of the affected siblings died shortly after birth, and a third, her older sister ( case 2 ), died at the age of 24. Both parents were phenotypically normal."
] |
test-2146
|
8022107
|
{'Case 2': 'The older sister of case patient 1 presented at the age of 18 years with photoinduced skin blistering of the face and extremities since her sixth day of life. She had associated progressive deformities of her bilateral hands and feet, bilateral ears, and nose. She reported having had photophobia and diminished vision in the right eye since early childhood. Examination revealed sclerodermatous changes and hypopigmented and hyperpigmented scars over the face and extremities ( Fig 2, A ); partial absorption of both ears; and brownish-pink-colored teeth. Hypertrichosis over the face and arms was present, and the bilateral extremities showed sclerodermatous contracture and acro-osteolysis ( Fig 2, B ). Ectropion and bilateral keratoconjunctivitis were apparent. She had mild anemia and splenomegaly. Porphyrin profiling and genetic analysis were not performed because of the unavailability of laboratory facilities at that time. She died at the age of 24 from a secondary infection. Fig 2 A, Sclerodermatous changes and hypopigmented and hyperpigmented scars over the face. B, Acro-osteolysis and contracture of the bilateral hands.', 'Case 3': "A 35-year-old woman, born to phenotypically normal parents, presented with progressive bilateral deformities of the hands and photoblistering since birth, with resulting dyspigmentation, scarring, and sclerodermatous changes of the face and distal extremities ( Fig 3 ) and progressive deformities of both hands. She had a history of recurrent keratoconjunctivitis and complications requiring enucleation of her left eye ( Fig 3 ). Facial hypertrichosis, microstomia ( Fig 3 ), erythrodontia, and mutilations of both hands were evident on examination. Laboratory reports revealed a normal complete blood count but an abnormal porphyrin profile ( Table I ). Fig 3 Dyspigmentation, scarring, and sclerodermatous changes over the face with enucleation of the left eye. Wood's lamp examination revealed pink-red fluorescence of the urine and teeth in all 3 patients. In case patients 1 and 3, sequencing of the UROS gene, exons 1 to 10 including flanking intronic regions, showed a homozygous transversion of T to G at nucleotide 416 in exon 7 (c.416T>G) leading to an L139R protein substitution at the terminal of the β6 protein chain. The patients were advised to use strict photoprotection, emollients, and vitamin D supplementation. They were also counseled about the disease, the need for long-term follow-up, wound care, and lifestyle modifications.", 'Case 1': 'A 17-year-old female (now 37 years old), born from a nonconsanguineous marriage, presented with a history of spontaneous blistering over photoexposed areas, starting in the first few days of her life. The lesions healed with scarring that led to progressive deformities of her hands, ears, and nose by 18 years of age. Her mother reported a red discharge in her diaper and redness and matting of both eyes since early childhood. She gradually developed deformities of her eyelids, making it difficult to close them fully. Three of her 7 siblings were similarly affected. Two of the affected siblings died shortly after birth, and a third, her older sister (case 2), died at the age of 24. Both parents were phenotypically normal. Examination revealed thickened skin, hypopigmentation and hyperpigmentation, and scarring at photoexposed sites ( Fig 1, A ); facial hypertrichosis; and reddish-brown tooth discoloration and disfiguration of the nose, ears, and fingertips bilaterally to the proximal interphalangeal joints. Eye examination revealed severe ectropion, trichiasis, and scleral melting ( Fig 1, B ). Abdominal examination revealed an enlarged spleen 4 cm below the left costal margin. Blood investigation showed pancytopenia, elevated erythrocyte sedimentation rate, positive creatinine-reactive protein, a normal serum iron profile, and an abnormal porphyrin profile ( Table I ). Fig 1 A, Thickened skin with hypopigmentation and hyperpigmentation and scarring over photoexposed sites, facial hypertrichosis, and reddish-brownish discoloration of the teeth. B, Severe ectropion, trichiasis, and scleral melting. Table I Results of laboratory investigations Parameter (normal range) Case 1 Case 2 Case 3 Urine total porphyrin (25-144 nmol/L) 11,986 nmol/L NA 13,269 nmol/L Fecal porphyrin (10-200 nmol/g) 5569 nmol/g NA 1797 nmol/g Plasma porphyrin (<11.2 nmol/L) NA NA 1120.5 nmol/L Plasma porphyrin peak 618 nm NA 618 nm Erythrocyte porphyrin (0.4-1.7 μmol/L) 35.8 μmol/L NA 26.2 μmol/L Total white blood cell count (4000-11,000/mm 3 ) 1700/mm 3 3600/mm 3 4500/mm 3 Platelets (150,000-450,000/mm 3 ) 107,000/mm 3 150,000/mm 3 175,000/mm 3 Hemoglobin (female: 12.0-15.5 g/dL) 9.4 g/dL 8.7 g/dL 12 g/dL'}
|
{'Case 2': 'The older sister of case patient 1 presented at the age of 18 years with photoinduced skin blistering of the face and extremities since her sixth day of life. She had associated progressive deformities of her bilateral hands and feet, bilateral ears, and nose. She reported having had photophobia and diminished vision in the right eye since early childhood. Examination revealed sclerodermatous changes and hypopigmented and hyperpigmented scars over the face and extremities ( Fig 2, A ); partial absorption of both ears; and brownish-pink-colored teeth. Hypertrichosis over the face and arms was present, and the bilateral extremities showed sclerodermatous contracture and acro-osteolysis ( Fig 2, B ). Ectropion and bilateral keratoconjunctivitis were apparent. She had mild anemia and splenomegaly. Porphyrin profiling and genetic analysis were not performed because of the unavailability of laboratory facilities at that time. She died at the age of 24 from a secondary infection. Fig 2 A, Sclerodermatous changes and hypopigmented and hyperpigmented scars over the face. B, Acro-osteolysis and contracture of the bilateral hands.', 'Case 3': "A 35-year-old woman, born to phenotypically normal parents, presented with progressive bilateral deformities of the hands and photoblistering since birth, with resulting dyspigmentation, scarring, and sclerodermatous changes of the face and distal extremities ( Fig 3 ) and progressive deformities of both hands. She had a history of recurrent keratoconjunctivitis and complications requiring enucleation of her left eye ( Fig 3 ). Facial hypertrichosis, microstomia ( Fig 3 ), erythrodontia, and mutilations of both hands were evident on examination. Laboratory reports revealed a normal complete blood count but an abnormal porphyrin profile ( Table I ). Fig 3 Dyspigmentation, scarring, and sclerodermatous changes over the face with enucleation of the left eye. Wood's lamp examination revealed pink-red fluorescence of the urine and teeth in all 3 patients. In case patients 1 and 3, sequencing of the UROS gene, exons 1 to 10 including flanking intronic regions, showed a homozygous transversion of T to G at nucleotide 416 in exon 7 (c.416T>G) leading to an L139R protein substitution at the terminal of the β6 protein chain. The patients were advised to use strict photoprotection, emollients, and vitamin D supplementation. They were also counseled about the disease, the need for long-term follow-up, wound care, and lifestyle modifications.", 'Case 1': 'A 17-year-old female (now 37 years old), born from a nonconsanguineous marriage, presented with a history of spontaneous blistering over photoexposed areas, starting in the first few days of her life. The lesions healed with scarring that led to progressive deformities of her hands, ears, and nose by 18 years of age. Her mother reported a red discharge in her diaper and redness and matting of both eyes since early childhood. She gradually developed deformities of her eyelids, making it difficult to close them fully. Three of her 7 siblings were similarly affected. Two of the affected siblings died shortly after birth, and a third, her older sister (case 2), died at the age of 24. Both parents were phenotypically normal. Examination revealed thickened skin, hypopigmentation and hyperpigmentation, and scarring at photoexposed sites ( Fig 1, A ); facial hypertrichosis; and reddish-brown tooth discoloration and disfiguration of the nose, ears, and fingertips bilaterally to the proximal interphalangeal joints. Eye examination revealed severe ectropion, trichiasis, and scleral melting ( Fig 1, B ). Abdominal examination revealed an enlarged spleen 4 cm below the left costal margin. Blood investigation showed pancytopenia, elevated erythrocyte sedimentation rate, positive creatinine-reactive protein, a normal serum iron profile, and an abnormal porphyrin profile ( Table I ). Fig 1 A, Thickened skin with hypopigmentation and hyperpigmentation and scarring over photoexposed sites, facial hypertrichosis, and reddish-brownish discoloration of the teeth. B, Severe ectropion, trichiasis, and scleral melting. Table I Results of laboratory investigations Parameter (normal range) Case 1 Case 2 Case 3 Urine total porphyrin (25-144 nmol/L) 11,986 nmol/L NA 13,269 nmol/L Fecal porphyrin (10-200 nmol/g) 5569 nmol/g NA 1797 nmol/g Plasma porphyrin (<11.2 nmol/L) NA NA 1120.5 nmol/L Plasma porphyrin peak 618 nm NA 618 nm Erythrocyte porphyrin (0.4-1.7 μmol/L) 35.8 μmol/L NA 26.2 μmol/L Total white blood cell count (4000-11,000/mm 3 ) 1700/mm 3 3600/mm 3 4500/mm 3 Platelets (150,000-450,000/mm 3 ) 107,000/mm 3 150,000/mm 3 175,000/mm 3 Hemoglobin (female: 12.0-15.5 g/dL) 9.4 g/dL 8.7 g/dL 12 g/dL'}
|
Neurology
|
Neuro
|
[] |
test-2147
|
8022107
|
{'Case 2': 'The older sister of case patient 1 presented at the age of 18 years with photoinduced skin blistering of the face and extremities since her sixth day of life. She had associated progressive deformities of her bilateral hands and feet, bilateral ears, and nose. She reported having had photophobia and diminished vision in the right eye since early childhood. Examination revealed sclerodermatous changes and hypopigmented and hyperpigmented scars over the face and extremities ( Fig 2, A ); partial absorption of both ears; and brownish-pink-colored teeth. Hypertrichosis over the face and arms was present, and the bilateral extremities showed sclerodermatous contracture and acro-osteolysis ( Fig 2, B ). Ectropion and bilateral keratoconjunctivitis were apparent. She had mild anemia and splenomegaly. Porphyrin profiling and genetic analysis were not performed because of the unavailability of laboratory facilities at that time. She died at the age of 24 from a secondary infection. Fig 2 A, Sclerodermatous changes and hypopigmented and hyperpigmented scars over the face. B, Acro-osteolysis and contracture of the bilateral hands.', 'Case 3': "A 35-year-old woman, born to phenotypically normal parents, presented with progressive bilateral deformities of the hands and photoblistering since birth, with resulting dyspigmentation, scarring, and sclerodermatous changes of the face and distal extremities ( Fig 3 ) and progressive deformities of both hands. She had a history of recurrent keratoconjunctivitis and complications requiring enucleation of her left eye ( Fig 3 ). Facial hypertrichosis, microstomia ( Fig 3 ), erythrodontia, and mutilations of both hands were evident on examination. Laboratory reports revealed a normal complete blood count but an abnormal porphyrin profile ( Table I ). Fig 3 Dyspigmentation, scarring, and sclerodermatous changes over the face with enucleation of the left eye. Wood's lamp examination revealed pink-red fluorescence of the urine and teeth in all 3 patients. In case patients 1 and 3, sequencing of the UROS gene, exons 1 to 10 including flanking intronic regions, showed a homozygous transversion of T to G at nucleotide 416 in exon 7 (c.416T>G) leading to an L139R protein substitution at the terminal of the β6 protein chain. The patients were advised to use strict photoprotection, emollients, and vitamin D supplementation. They were also counseled about the disease, the need for long-term follow-up, wound care, and lifestyle modifications.", 'Case 1': 'A 17-year-old female (now 37 years old), born from a nonconsanguineous marriage, presented with a history of spontaneous blistering over photoexposed areas, starting in the first few days of her life. The lesions healed with scarring that led to progressive deformities of her hands, ears, and nose by 18 years of age. Her mother reported a red discharge in her diaper and redness and matting of both eyes since early childhood. She gradually developed deformities of her eyelids, making it difficult to close them fully. Three of her 7 siblings were similarly affected. Two of the affected siblings died shortly after birth, and a third, her older sister (case 2), died at the age of 24. Both parents were phenotypically normal. Examination revealed thickened skin, hypopigmentation and hyperpigmentation, and scarring at photoexposed sites ( Fig 1, A ); facial hypertrichosis; and reddish-brown tooth discoloration and disfiguration of the nose, ears, and fingertips bilaterally to the proximal interphalangeal joints. Eye examination revealed severe ectropion, trichiasis, and scleral melting ( Fig 1, B ). Abdominal examination revealed an enlarged spleen 4 cm below the left costal margin. Blood investigation showed pancytopenia, elevated erythrocyte sedimentation rate, positive creatinine-reactive protein, a normal serum iron profile, and an abnormal porphyrin profile ( Table I ). Fig 1 A, Thickened skin with hypopigmentation and hyperpigmentation and scarring over photoexposed sites, facial hypertrichosis, and reddish-brownish discoloration of the teeth. B, Severe ectropion, trichiasis, and scleral melting. Table I Results of laboratory investigations Parameter (normal range) Case 1 Case 2 Case 3 Urine total porphyrin (25-144 nmol/L) 11,986 nmol/L NA 13,269 nmol/L Fecal porphyrin (10-200 nmol/g) 5569 nmol/g NA 1797 nmol/g Plasma porphyrin (<11.2 nmol/L) NA NA 1120.5 nmol/L Plasma porphyrin peak 618 nm NA 618 nm Erythrocyte porphyrin (0.4-1.7 μmol/L) 35.8 μmol/L NA 26.2 μmol/L Total white blood cell count (4000-11,000/mm 3 ) 1700/mm 3 3600/mm 3 4500/mm 3 Platelets (150,000-450,000/mm 3 ) 107,000/mm 3 150,000/mm 3 175,000/mm 3 Hemoglobin (female: 12.0-15.5 g/dL) 9.4 g/dL 8.7 g/dL 12 g/dL'}
|
{'Case 2': 'The older sister of case patient 1 presented at the age of 18 years with photoinduced skin blistering of the face and extremities since her sixth day of life. She had associated progressive deformities of her bilateral hands and feet, bilateral ears, and nose. She reported having had photophobia and diminished vision in the right eye since early childhood. Examination revealed sclerodermatous changes and hypopigmented and hyperpigmented scars over the face and extremities ( Fig 2, A ); partial absorption of both ears; and brownish-pink-colored teeth. Hypertrichosis over the face and arms was present, and the bilateral extremities showed sclerodermatous contracture and acro-osteolysis ( Fig 2, B ). Ectropion and bilateral keratoconjunctivitis were apparent. She had mild anemia and splenomegaly. Porphyrin profiling and genetic analysis were not performed because of the unavailability of laboratory facilities at that time. She died at the age of 24 from a secondary infection. Fig 2 A, Sclerodermatous changes and hypopigmented and hyperpigmented scars over the face. B, Acro-osteolysis and contracture of the bilateral hands.', 'Case 3': "A 35-year-old woman, born to phenotypically normal parents, presented with progressive bilateral deformities of the hands and photoblistering since birth, with resulting dyspigmentation, scarring, and sclerodermatous changes of the face and distal extremities ( Fig 3 ) and progressive deformities of both hands. She had a history of recurrent keratoconjunctivitis and complications requiring enucleation of her left eye ( Fig 3 ). Facial hypertrichosis, microstomia ( Fig 3 ), erythrodontia, and mutilations of both hands were evident on examination. Laboratory reports revealed a normal complete blood count but an abnormal porphyrin profile ( Table I ). Fig 3 Dyspigmentation, scarring, and sclerodermatous changes over the face with enucleation of the left eye. Wood's lamp examination revealed pink-red fluorescence of the urine and teeth in all 3 patients. In case patients 1 and 3, sequencing of the UROS gene, exons 1 to 10 including flanking intronic regions, showed a homozygous transversion of T to G at nucleotide 416 in exon 7 (c.416T>G) leading to an L139R protein substitution at the terminal of the β6 protein chain. The patients were advised to use strict photoprotection, emollients, and vitamin D supplementation. They were also counseled about the disease, the need for long-term follow-up, wound care, and lifestyle modifications.", 'Case 1': 'A 17-year-old female (now 37 years old), born from a nonconsanguineous marriage, presented with a history of spontaneous blistering over photoexposed areas, starting in the first few days of her life. The lesions healed with scarring that led to progressive deformities of her hands, ears, and nose by 18 years of age. Her mother reported a red discharge in her diaper and redness and matting of both eyes since early childhood. She gradually developed deformities of her eyelids, making it difficult to close them fully. Three of her 7 siblings were similarly affected. Two of the affected siblings died shortly after birth, and a third, her older sister (case 2), died at the age of 24. Both parents were phenotypically normal. Examination revealed thickened skin, hypopigmentation and hyperpigmentation, and scarring at photoexposed sites ( Fig 1, A ); facial hypertrichosis; and reddish-brown tooth discoloration and disfiguration of the nose, ears, and fingertips bilaterally to the proximal interphalangeal joints. Eye examination revealed severe ectropion, trichiasis, and scleral melting ( Fig 1, B ). Abdominal examination revealed an enlarged spleen 4 cm below the left costal margin. Blood investigation showed pancytopenia, elevated erythrocyte sedimentation rate, positive creatinine-reactive protein, a normal serum iron profile, and an abnormal porphyrin profile ( Table I ). Fig 1 A, Thickened skin with hypopigmentation and hyperpigmentation and scarring over photoexposed sites, facial hypertrichosis, and reddish-brownish discoloration of the teeth. B, Severe ectropion, trichiasis, and scleral melting. Table I Results of laboratory investigations Parameter (normal range) Case 1 Case 2 Case 3 Urine total porphyrin (25-144 nmol/L) 11,986 nmol/L NA 13,269 nmol/L Fecal porphyrin (10-200 nmol/g) 5569 nmol/g NA 1797 nmol/g Plasma porphyrin (<11.2 nmol/L) NA NA 1120.5 nmol/L Plasma porphyrin peak 618 nm NA 618 nm Erythrocyte porphyrin (0.4-1.7 μmol/L) 35.8 μmol/L NA 26.2 μmol/L Total white blood cell count (4000-11,000/mm 3 ) 1700/mm 3 3600/mm 3 4500/mm 3 Platelets (150,000-450,000/mm 3 ) 107,000/mm 3 150,000/mm 3 175,000/mm 3 Hemoglobin (female: 12.0-15.5 g/dL) 9.4 g/dL 8.7 g/dL 12 g/dL'}
|
Laboratory-and-Imaging
|
Lab_Image
|
[
"Laboratory reports revealed a normal complete blood count but an abnormal porphyrin profile",
"In case patients 1 and 3, sequencing of the UROS gene, exons 1 to 10 including flanking intronic regions, showed a homozygous transversion of T to G at nucleotide 416 in exon 7 ( c.416T > G ) leading to an L139R protein substitution at the terminal of the β6 protein chain.",
"Blood investigation showed pancytopenia, elevated erythrocyte sedimentation rate, positive creatinine - reactive protein, a normal serum iron profile, and an abnormal porphyrin profile",
"Urine total porphyrin ( 25 - 144 nmol / L ) 11,986 nmol / L NA 13,269 nmol / L Fecal porphyrin ( 10 - 200 nmol / g ) 5569 nmol / g NA 1797 nmol / g Plasma porphyrin ( < 11.2 nmol / L ) NA NA 1120.5 nmol / L Plasma porphyrin peak 618 nm NA 618 nm Erythrocyte porphyrin ( 0.4 - 1.7 μmol / L ) 35.8 μmol / L NA 26.2 μmol / L Total white blood cell count ( 4000 - 11,000 / mm 3 ) 1700 / mm 3 3600 / mm 3 4500 / mm 3 Platelets ( 150,000 - 450,000 / mm 3 ) 107,000 / mm 3 150,000 / mm 3 175,000 / mm 3 Hemoglobin ( female : 12.0 - 15.5 g / dL ) 9.4 g / dL 8.7 g / dL 12 g / dL ' }"
] |
test-2148
|
8022107
|
{'Case 2': 'The older sister of case patient 1 presented at the age of 18 years with photoinduced skin blistering of the face and extremities since her sixth day of life. She had associated progressive deformities of her bilateral hands and feet, bilateral ears, and nose. She reported having had photophobia and diminished vision in the right eye since early childhood. Examination revealed sclerodermatous changes and hypopigmented and hyperpigmented scars over the face and extremities ( Fig 2, A ); partial absorption of both ears; and brownish-pink-colored teeth. Hypertrichosis over the face and arms was present, and the bilateral extremities showed sclerodermatous contracture and acro-osteolysis ( Fig 2, B ). Ectropion and bilateral keratoconjunctivitis were apparent. She had mild anemia and splenomegaly. Porphyrin profiling and genetic analysis were not performed because of the unavailability of laboratory facilities at that time. She died at the age of 24 from a secondary infection. Fig 2 A, Sclerodermatous changes and hypopigmented and hyperpigmented scars over the face. B, Acro-osteolysis and contracture of the bilateral hands.', 'Case 3': "A 35-year-old woman, born to phenotypically normal parents, presented with progressive bilateral deformities of the hands and photoblistering since birth, with resulting dyspigmentation, scarring, and sclerodermatous changes of the face and distal extremities ( Fig 3 ) and progressive deformities of both hands. She had a history of recurrent keratoconjunctivitis and complications requiring enucleation of her left eye ( Fig 3 ). Facial hypertrichosis, microstomia ( Fig 3 ), erythrodontia, and mutilations of both hands were evident on examination. Laboratory reports revealed a normal complete blood count but an abnormal porphyrin profile ( Table I ). Fig 3 Dyspigmentation, scarring, and sclerodermatous changes over the face with enucleation of the left eye. Wood's lamp examination revealed pink-red fluorescence of the urine and teeth in all 3 patients. In case patients 1 and 3, sequencing of the UROS gene, exons 1 to 10 including flanking intronic regions, showed a homozygous transversion of T to G at nucleotide 416 in exon 7 (c.416T>G) leading to an L139R protein substitution at the terminal of the β6 protein chain. The patients were advised to use strict photoprotection, emollients, and vitamin D supplementation. They were also counseled about the disease, the need for long-term follow-up, wound care, and lifestyle modifications.", 'Case 1': 'A 17-year-old female (now 37 years old), born from a nonconsanguineous marriage, presented with a history of spontaneous blistering over photoexposed areas, starting in the first few days of her life. The lesions healed with scarring that led to progressive deformities of her hands, ears, and nose by 18 years of age. Her mother reported a red discharge in her diaper and redness and matting of both eyes since early childhood. She gradually developed deformities of her eyelids, making it difficult to close them fully. Three of her 7 siblings were similarly affected. Two of the affected siblings died shortly after birth, and a third, her older sister (case 2), died at the age of 24. Both parents were phenotypically normal. Examination revealed thickened skin, hypopigmentation and hyperpigmentation, and scarring at photoexposed sites ( Fig 1, A ); facial hypertrichosis; and reddish-brown tooth discoloration and disfiguration of the nose, ears, and fingertips bilaterally to the proximal interphalangeal joints. Eye examination revealed severe ectropion, trichiasis, and scleral melting ( Fig 1, B ). Abdominal examination revealed an enlarged spleen 4 cm below the left costal margin. Blood investigation showed pancytopenia, elevated erythrocyte sedimentation rate, positive creatinine-reactive protein, a normal serum iron profile, and an abnormal porphyrin profile ( Table I ). Fig 1 A, Thickened skin with hypopigmentation and hyperpigmentation and scarring over photoexposed sites, facial hypertrichosis, and reddish-brownish discoloration of the teeth. B, Severe ectropion, trichiasis, and scleral melting. Table I Results of laboratory investigations Parameter (normal range) Case 1 Case 2 Case 3 Urine total porphyrin (25-144 nmol/L) 11,986 nmol/L NA 13,269 nmol/L Fecal porphyrin (10-200 nmol/g) 5569 nmol/g NA 1797 nmol/g Plasma porphyrin (<11.2 nmol/L) NA NA 1120.5 nmol/L Plasma porphyrin peak 618 nm NA 618 nm Erythrocyte porphyrin (0.4-1.7 μmol/L) 35.8 μmol/L NA 26.2 μmol/L Total white blood cell count (4000-11,000/mm 3 ) 1700/mm 3 3600/mm 3 4500/mm 3 Platelets (150,000-450,000/mm 3 ) 107,000/mm 3 150,000/mm 3 175,000/mm 3 Hemoglobin (female: 12.0-15.5 g/dL) 9.4 g/dL 8.7 g/dL 12 g/dL'}
|
{'Case 2': 'The older sister of case patient 1 presented at the age of 18 years with photoinduced skin blistering of the face and extremities since her sixth day of life. She had associated progressive deformities of her bilateral hands and feet, bilateral ears, and nose. She reported having had photophobia and diminished vision in the right eye since early childhood. Examination revealed sclerodermatous changes and hypopigmented and hyperpigmented scars over the face and extremities ( Fig 2, A ); partial absorption of both ears; and brownish-pink-colored teeth. Hypertrichosis over the face and arms was present, and the bilateral extremities showed sclerodermatous contracture and acro-osteolysis ( Fig 2, B ). Ectropion and bilateral keratoconjunctivitis were apparent. She had mild anemia and splenomegaly. Porphyrin profiling and genetic analysis were not performed because of the unavailability of laboratory facilities at that time. She died at the age of 24 from a secondary infection. Fig 2 A, Sclerodermatous changes and hypopigmented and hyperpigmented scars over the face. B, Acro-osteolysis and contracture of the bilateral hands.', 'Case 3': "A 35-year-old woman, born to phenotypically normal parents, presented with progressive bilateral deformities of the hands and photoblistering since birth, with resulting dyspigmentation, scarring, and sclerodermatous changes of the face and distal extremities ( Fig 3 ) and progressive deformities of both hands. She had a history of recurrent keratoconjunctivitis and complications requiring enucleation of her left eye ( Fig 3 ). Facial hypertrichosis, microstomia ( Fig 3 ), erythrodontia, and mutilations of both hands were evident on examination. Laboratory reports revealed a normal complete blood count but an abnormal porphyrin profile ( Table I ). Fig 3 Dyspigmentation, scarring, and sclerodermatous changes over the face with enucleation of the left eye. Wood's lamp examination revealed pink-red fluorescence of the urine and teeth in all 3 patients. In case patients 1 and 3, sequencing of the UROS gene, exons 1 to 10 including flanking intronic regions, showed a homozygous transversion of T to G at nucleotide 416 in exon 7 (c.416T>G) leading to an L139R protein substitution at the terminal of the β6 protein chain. The patients were advised to use strict photoprotection, emollients, and vitamin D supplementation. They were also counseled about the disease, the need for long-term follow-up, wound care, and lifestyle modifications.", 'Case 1': 'A 17-year-old female (now 37 years old), born from a nonconsanguineous marriage, presented with a history of spontaneous blistering over photoexposed areas, starting in the first few days of her life. The lesions healed with scarring that led to progressive deformities of her hands, ears, and nose by 18 years of age. Her mother reported a red discharge in her diaper and redness and matting of both eyes since early childhood. She gradually developed deformities of her eyelids, making it difficult to close them fully. Three of her 7 siblings were similarly affected. Two of the affected siblings died shortly after birth, and a third, her older sister (case 2), died at the age of 24. Both parents were phenotypically normal. Examination revealed thickened skin, hypopigmentation and hyperpigmentation, and scarring at photoexposed sites ( Fig 1, A ); facial hypertrichosis; and reddish-brown tooth discoloration and disfiguration of the nose, ears, and fingertips bilaterally to the proximal interphalangeal joints. Eye examination revealed severe ectropion, trichiasis, and scleral melting ( Fig 1, B ). Abdominal examination revealed an enlarged spleen 4 cm below the left costal margin. Blood investigation showed pancytopenia, elevated erythrocyte sedimentation rate, positive creatinine-reactive protein, a normal serum iron profile, and an abnormal porphyrin profile ( Table I ). Fig 1 A, Thickened skin with hypopigmentation and hyperpigmentation and scarring over photoexposed sites, facial hypertrichosis, and reddish-brownish discoloration of the teeth. B, Severe ectropion, trichiasis, and scleral melting. Table I Results of laboratory investigations Parameter (normal range) Case 1 Case 2 Case 3 Urine total porphyrin (25-144 nmol/L) 11,986 nmol/L NA 13,269 nmol/L Fecal porphyrin (10-200 nmol/g) 5569 nmol/g NA 1797 nmol/g Plasma porphyrin (<11.2 nmol/L) NA NA 1120.5 nmol/L Plasma porphyrin peak 618 nm NA 618 nm Erythrocyte porphyrin (0.4-1.7 μmol/L) 35.8 μmol/L NA 26.2 μmol/L Total white blood cell count (4000-11,000/mm 3 ) 1700/mm 3 3600/mm 3 4500/mm 3 Platelets (150,000-450,000/mm 3 ) 107,000/mm 3 150,000/mm 3 175,000/mm 3 Hemoglobin (female: 12.0-15.5 g/dL) 9.4 g/dL 8.7 g/dL 12 g/dL'}
|
Cardiovascular-System
|
CVS
|
[] |
test-2149
|
8022107
|
{'Case 2': 'The older sister of case patient 1 presented at the age of 18 years with photoinduced skin blistering of the face and extremities since her sixth day of life. She had associated progressive deformities of her bilateral hands and feet, bilateral ears, and nose. She reported having had photophobia and diminished vision in the right eye since early childhood. Examination revealed sclerodermatous changes and hypopigmented and hyperpigmented scars over the face and extremities ( Fig 2, A ); partial absorption of both ears; and brownish-pink-colored teeth. Hypertrichosis over the face and arms was present, and the bilateral extremities showed sclerodermatous contracture and acro-osteolysis ( Fig 2, B ). Ectropion and bilateral keratoconjunctivitis were apparent. She had mild anemia and splenomegaly. Porphyrin profiling and genetic analysis were not performed because of the unavailability of laboratory facilities at that time. She died at the age of 24 from a secondary infection. Fig 2 A, Sclerodermatous changes and hypopigmented and hyperpigmented scars over the face. B, Acro-osteolysis and contracture of the bilateral hands.', 'Case 3': "A 35-year-old woman, born to phenotypically normal parents, presented with progressive bilateral deformities of the hands and photoblistering since birth, with resulting dyspigmentation, scarring, and sclerodermatous changes of the face and distal extremities ( Fig 3 ) and progressive deformities of both hands. She had a history of recurrent keratoconjunctivitis and complications requiring enucleation of her left eye ( Fig 3 ). Facial hypertrichosis, microstomia ( Fig 3 ), erythrodontia, and mutilations of both hands were evident on examination. Laboratory reports revealed a normal complete blood count but an abnormal porphyrin profile ( Table I ). Fig 3 Dyspigmentation, scarring, and sclerodermatous changes over the face with enucleation of the left eye. Wood's lamp examination revealed pink-red fluorescence of the urine and teeth in all 3 patients. In case patients 1 and 3, sequencing of the UROS gene, exons 1 to 10 including flanking intronic regions, showed a homozygous transversion of T to G at nucleotide 416 in exon 7 (c.416T>G) leading to an L139R protein substitution at the terminal of the β6 protein chain. The patients were advised to use strict photoprotection, emollients, and vitamin D supplementation. They were also counseled about the disease, the need for long-term follow-up, wound care, and lifestyle modifications.", 'Case 1': 'A 17-year-old female (now 37 years old), born from a nonconsanguineous marriage, presented with a history of spontaneous blistering over photoexposed areas, starting in the first few days of her life. The lesions healed with scarring that led to progressive deformities of her hands, ears, and nose by 18 years of age. Her mother reported a red discharge in her diaper and redness and matting of both eyes since early childhood. She gradually developed deformities of her eyelids, making it difficult to close them fully. Three of her 7 siblings were similarly affected. Two of the affected siblings died shortly after birth, and a third, her older sister (case 2), died at the age of 24. Both parents were phenotypically normal. Examination revealed thickened skin, hypopigmentation and hyperpigmentation, and scarring at photoexposed sites ( Fig 1, A ); facial hypertrichosis; and reddish-brown tooth discoloration and disfiguration of the nose, ears, and fingertips bilaterally to the proximal interphalangeal joints. Eye examination revealed severe ectropion, trichiasis, and scleral melting ( Fig 1, B ). Abdominal examination revealed an enlarged spleen 4 cm below the left costal margin. Blood investigation showed pancytopenia, elevated erythrocyte sedimentation rate, positive creatinine-reactive protein, a normal serum iron profile, and an abnormal porphyrin profile ( Table I ). Fig 1 A, Thickened skin with hypopigmentation and hyperpigmentation and scarring over photoexposed sites, facial hypertrichosis, and reddish-brownish discoloration of the teeth. B, Severe ectropion, trichiasis, and scleral melting. Table I Results of laboratory investigations Parameter (normal range) Case 1 Case 2 Case 3 Urine total porphyrin (25-144 nmol/L) 11,986 nmol/L NA 13,269 nmol/L Fecal porphyrin (10-200 nmol/g) 5569 nmol/g NA 1797 nmol/g Plasma porphyrin (<11.2 nmol/L) NA NA 1120.5 nmol/L Plasma porphyrin peak 618 nm NA 618 nm Erythrocyte porphyrin (0.4-1.7 μmol/L) 35.8 μmol/L NA 26.2 μmol/L Total white blood cell count (4000-11,000/mm 3 ) 1700/mm 3 3600/mm 3 4500/mm 3 Platelets (150,000-450,000/mm 3 ) 107,000/mm 3 150,000/mm 3 175,000/mm 3 Hemoglobin (female: 12.0-15.5 g/dL) 9.4 g/dL 8.7 g/dL 12 g/dL'}
|
{'Case 2': 'The older sister of case patient 1 presented at the age of 18 years with photoinduced skin blistering of the face and extremities since her sixth day of life. She had associated progressive deformities of her bilateral hands and feet, bilateral ears, and nose. She reported having had photophobia and diminished vision in the right eye since early childhood. Examination revealed sclerodermatous changes and hypopigmented and hyperpigmented scars over the face and extremities ( Fig 2, A ); partial absorption of both ears; and brownish-pink-colored teeth. Hypertrichosis over the face and arms was present, and the bilateral extremities showed sclerodermatous contracture and acro-osteolysis ( Fig 2, B ). Ectropion and bilateral keratoconjunctivitis were apparent. She had mild anemia and splenomegaly. Porphyrin profiling and genetic analysis were not performed because of the unavailability of laboratory facilities at that time. She died at the age of 24 from a secondary infection. Fig 2 A, Sclerodermatous changes and hypopigmented and hyperpigmented scars over the face. B, Acro-osteolysis and contracture of the bilateral hands.', 'Case 3': "A 35-year-old woman, born to phenotypically normal parents, presented with progressive bilateral deformities of the hands and photoblistering since birth, with resulting dyspigmentation, scarring, and sclerodermatous changes of the face and distal extremities ( Fig 3 ) and progressive deformities of both hands. She had a history of recurrent keratoconjunctivitis and complications requiring enucleation of her left eye ( Fig 3 ). Facial hypertrichosis, microstomia ( Fig 3 ), erythrodontia, and mutilations of both hands were evident on examination. Laboratory reports revealed a normal complete blood count but an abnormal porphyrin profile ( Table I ). Fig 3 Dyspigmentation, scarring, and sclerodermatous changes over the face with enucleation of the left eye. Wood's lamp examination revealed pink-red fluorescence of the urine and teeth in all 3 patients. In case patients 1 and 3, sequencing of the UROS gene, exons 1 to 10 including flanking intronic regions, showed a homozygous transversion of T to G at nucleotide 416 in exon 7 (c.416T>G) leading to an L139R protein substitution at the terminal of the β6 protein chain. The patients were advised to use strict photoprotection, emollients, and vitamin D supplementation. They were also counseled about the disease, the need for long-term follow-up, wound care, and lifestyle modifications.", 'Case 1': 'A 17-year-old female (now 37 years old), born from a nonconsanguineous marriage, presented with a history of spontaneous blistering over photoexposed areas, starting in the first few days of her life. The lesions healed with scarring that led to progressive deformities of her hands, ears, and nose by 18 years of age. Her mother reported a red discharge in her diaper and redness and matting of both eyes since early childhood. She gradually developed deformities of her eyelids, making it difficult to close them fully. Three of her 7 siblings were similarly affected. Two of the affected siblings died shortly after birth, and a third, her older sister (case 2), died at the age of 24. Both parents were phenotypically normal. Examination revealed thickened skin, hypopigmentation and hyperpigmentation, and scarring at photoexposed sites ( Fig 1, A ); facial hypertrichosis; and reddish-brown tooth discoloration and disfiguration of the nose, ears, and fingertips bilaterally to the proximal interphalangeal joints. Eye examination revealed severe ectropion, trichiasis, and scleral melting ( Fig 1, B ). Abdominal examination revealed an enlarged spleen 4 cm below the left costal margin. Blood investigation showed pancytopenia, elevated erythrocyte sedimentation rate, positive creatinine-reactive protein, a normal serum iron profile, and an abnormal porphyrin profile ( Table I ). Fig 1 A, Thickened skin with hypopigmentation and hyperpigmentation and scarring over photoexposed sites, facial hypertrichosis, and reddish-brownish discoloration of the teeth. B, Severe ectropion, trichiasis, and scleral melting. Table I Results of laboratory investigations Parameter (normal range) Case 1 Case 2 Case 3 Urine total porphyrin (25-144 nmol/L) 11,986 nmol/L NA 13,269 nmol/L Fecal porphyrin (10-200 nmol/g) 5569 nmol/g NA 1797 nmol/g Plasma porphyrin (<11.2 nmol/L) NA NA 1120.5 nmol/L Plasma porphyrin peak 618 nm NA 618 nm Erythrocyte porphyrin (0.4-1.7 μmol/L) 35.8 μmol/L NA 26.2 μmol/L Total white blood cell count (4000-11,000/mm 3 ) 1700/mm 3 3600/mm 3 4500/mm 3 Platelets (150,000-450,000/mm 3 ) 107,000/mm 3 150,000/mm 3 175,000/mm 3 Hemoglobin (female: 12.0-15.5 g/dL) 9.4 g/dL 8.7 g/dL 12 g/dL'}
|
Endocrinology
|
ENDO
|
[] |
test-2150
|
8022107
|
{'Case 2': 'The older sister of case patient 1 presented at the age of 18 years with photoinduced skin blistering of the face and extremities since her sixth day of life. She had associated progressive deformities of her bilateral hands and feet, bilateral ears, and nose. She reported having had photophobia and diminished vision in the right eye since early childhood. Examination revealed sclerodermatous changes and hypopigmented and hyperpigmented scars over the face and extremities ( Fig 2, A ); partial absorption of both ears; and brownish-pink-colored teeth. Hypertrichosis over the face and arms was present, and the bilateral extremities showed sclerodermatous contracture and acro-osteolysis ( Fig 2, B ). Ectropion and bilateral keratoconjunctivitis were apparent. She had mild anemia and splenomegaly. Porphyrin profiling and genetic analysis were not performed because of the unavailability of laboratory facilities at that time. She died at the age of 24 from a secondary infection. Fig 2 A, Sclerodermatous changes and hypopigmented and hyperpigmented scars over the face. B, Acro-osteolysis and contracture of the bilateral hands.', 'Case 3': "A 35-year-old woman, born to phenotypically normal parents, presented with progressive bilateral deformities of the hands and photoblistering since birth, with resulting dyspigmentation, scarring, and sclerodermatous changes of the face and distal extremities ( Fig 3 ) and progressive deformities of both hands. She had a history of recurrent keratoconjunctivitis and complications requiring enucleation of her left eye ( Fig 3 ). Facial hypertrichosis, microstomia ( Fig 3 ), erythrodontia, and mutilations of both hands were evident on examination. Laboratory reports revealed a normal complete blood count but an abnormal porphyrin profile ( Table I ). Fig 3 Dyspigmentation, scarring, and sclerodermatous changes over the face with enucleation of the left eye. Wood's lamp examination revealed pink-red fluorescence of the urine and teeth in all 3 patients. In case patients 1 and 3, sequencing of the UROS gene, exons 1 to 10 including flanking intronic regions, showed a homozygous transversion of T to G at nucleotide 416 in exon 7 (c.416T>G) leading to an L139R protein substitution at the terminal of the β6 protein chain. The patients were advised to use strict photoprotection, emollients, and vitamin D supplementation. They were also counseled about the disease, the need for long-term follow-up, wound care, and lifestyle modifications.", 'Case 1': 'A 17-year-old female (now 37 years old), born from a nonconsanguineous marriage, presented with a history of spontaneous blistering over photoexposed areas, starting in the first few days of her life. The lesions healed with scarring that led to progressive deformities of her hands, ears, and nose by 18 years of age. Her mother reported a red discharge in her diaper and redness and matting of both eyes since early childhood. She gradually developed deformities of her eyelids, making it difficult to close them fully. Three of her 7 siblings were similarly affected. Two of the affected siblings died shortly after birth, and a third, her older sister (case 2), died at the age of 24. Both parents were phenotypically normal. Examination revealed thickened skin, hypopigmentation and hyperpigmentation, and scarring at photoexposed sites ( Fig 1, A ); facial hypertrichosis; and reddish-brown tooth discoloration and disfiguration of the nose, ears, and fingertips bilaterally to the proximal interphalangeal joints. Eye examination revealed severe ectropion, trichiasis, and scleral melting ( Fig 1, B ). Abdominal examination revealed an enlarged spleen 4 cm below the left costal margin. Blood investigation showed pancytopenia, elevated erythrocyte sedimentation rate, positive creatinine-reactive protein, a normal serum iron profile, and an abnormal porphyrin profile ( Table I ). Fig 1 A, Thickened skin with hypopigmentation and hyperpigmentation and scarring over photoexposed sites, facial hypertrichosis, and reddish-brownish discoloration of the teeth. B, Severe ectropion, trichiasis, and scleral melting. Table I Results of laboratory investigations Parameter (normal range) Case 1 Case 2 Case 3 Urine total porphyrin (25-144 nmol/L) 11,986 nmol/L NA 13,269 nmol/L Fecal porphyrin (10-200 nmol/g) 5569 nmol/g NA 1797 nmol/g Plasma porphyrin (<11.2 nmol/L) NA NA 1120.5 nmol/L Plasma porphyrin peak 618 nm NA 618 nm Erythrocyte porphyrin (0.4-1.7 μmol/L) 35.8 μmol/L NA 26.2 μmol/L Total white blood cell count (4000-11,000/mm 3 ) 1700/mm 3 3600/mm 3 4500/mm 3 Platelets (150,000-450,000/mm 3 ) 107,000/mm 3 150,000/mm 3 175,000/mm 3 Hemoglobin (female: 12.0-15.5 g/dL) 9.4 g/dL 8.7 g/dL 12 g/dL'}
|
{'Case 2': 'The older sister of case patient 1 presented at the age of 18 years with photoinduced skin blistering of the face and extremities since her sixth day of life. She had associated progressive deformities of her bilateral hands and feet, bilateral ears, and nose. She reported having had photophobia and diminished vision in the right eye since early childhood. Examination revealed sclerodermatous changes and hypopigmented and hyperpigmented scars over the face and extremities ( Fig 2, A ); partial absorption of both ears; and brownish-pink-colored teeth. Hypertrichosis over the face and arms was present, and the bilateral extremities showed sclerodermatous contracture and acro-osteolysis ( Fig 2, B ). Ectropion and bilateral keratoconjunctivitis were apparent. She had mild anemia and splenomegaly. Porphyrin profiling and genetic analysis were not performed because of the unavailability of laboratory facilities at that time. She died at the age of 24 from a secondary infection. Fig 2 A, Sclerodermatous changes and hypopigmented and hyperpigmented scars over the face. B, Acro-osteolysis and contracture of the bilateral hands.', 'Case 3': "A 35-year-old woman, born to phenotypically normal parents, presented with progressive bilateral deformities of the hands and photoblistering since birth, with resulting dyspigmentation, scarring, and sclerodermatous changes of the face and distal extremities ( Fig 3 ) and progressive deformities of both hands. She had a history of recurrent keratoconjunctivitis and complications requiring enucleation of her left eye ( Fig 3 ). Facial hypertrichosis, microstomia ( Fig 3 ), erythrodontia, and mutilations of both hands were evident on examination. Laboratory reports revealed a normal complete blood count but an abnormal porphyrin profile ( Table I ). Fig 3 Dyspigmentation, scarring, and sclerodermatous changes over the face with enucleation of the left eye. Wood's lamp examination revealed pink-red fluorescence of the urine and teeth in all 3 patients. In case patients 1 and 3, sequencing of the UROS gene, exons 1 to 10 including flanking intronic regions, showed a homozygous transversion of T to G at nucleotide 416 in exon 7 (c.416T>G) leading to an L139R protein substitution at the terminal of the β6 protein chain. The patients were advised to use strict photoprotection, emollients, and vitamin D supplementation. They were also counseled about the disease, the need for long-term follow-up, wound care, and lifestyle modifications.", 'Case 1': 'A 17-year-old female (now 37 years old), born from a nonconsanguineous marriage, presented with a history of spontaneous blistering over photoexposed areas, starting in the first few days of her life. The lesions healed with scarring that led to progressive deformities of her hands, ears, and nose by 18 years of age. Her mother reported a red discharge in her diaper and redness and matting of both eyes since early childhood. She gradually developed deformities of her eyelids, making it difficult to close them fully. Three of her 7 siblings were similarly affected. Two of the affected siblings died shortly after birth, and a third, her older sister (case 2), died at the age of 24. Both parents were phenotypically normal. Examination revealed thickened skin, hypopigmentation and hyperpigmentation, and scarring at photoexposed sites ( Fig 1, A ); facial hypertrichosis; and reddish-brown tooth discoloration and disfiguration of the nose, ears, and fingertips bilaterally to the proximal interphalangeal joints. Eye examination revealed severe ectropion, trichiasis, and scleral melting ( Fig 1, B ). Abdominal examination revealed an enlarged spleen 4 cm below the left costal margin. Blood investigation showed pancytopenia, elevated erythrocyte sedimentation rate, positive creatinine-reactive protein, a normal serum iron profile, and an abnormal porphyrin profile ( Table I ). Fig 1 A, Thickened skin with hypopigmentation and hyperpigmentation and scarring over photoexposed sites, facial hypertrichosis, and reddish-brownish discoloration of the teeth. B, Severe ectropion, trichiasis, and scleral melting. Table I Results of laboratory investigations Parameter (normal range) Case 1 Case 2 Case 3 Urine total porphyrin (25-144 nmol/L) 11,986 nmol/L NA 13,269 nmol/L Fecal porphyrin (10-200 nmol/g) 5569 nmol/g NA 1797 nmol/g Plasma porphyrin (<11.2 nmol/L) NA NA 1120.5 nmol/L Plasma porphyrin peak 618 nm NA 618 nm Erythrocyte porphyrin (0.4-1.7 μmol/L) 35.8 μmol/L NA 26.2 μmol/L Total white blood cell count (4000-11,000/mm 3 ) 1700/mm 3 3600/mm 3 4500/mm 3 Platelets (150,000-450,000/mm 3 ) 107,000/mm 3 150,000/mm 3 175,000/mm 3 Hemoglobin (female: 12.0-15.5 g/dL) 9.4 g/dL 8.7 g/dL 12 g/dL'}
|
Genitourinary-System
|
GU
|
[
"Wood 's lamp examination revealed pink - red fluorescence of the urine",
"red discharge in her diaper"
] |
test-2151
|
8022107
|
{'Case 2': 'The older sister of case patient 1 presented at the age of 18 years with photoinduced skin blistering of the face and extremities since her sixth day of life. She had associated progressive deformities of her bilateral hands and feet, bilateral ears, and nose. She reported having had photophobia and diminished vision in the right eye since early childhood. Examination revealed sclerodermatous changes and hypopigmented and hyperpigmented scars over the face and extremities ( Fig 2, A ); partial absorption of both ears; and brownish-pink-colored teeth. Hypertrichosis over the face and arms was present, and the bilateral extremities showed sclerodermatous contracture and acro-osteolysis ( Fig 2, B ). Ectropion and bilateral keratoconjunctivitis were apparent. She had mild anemia and splenomegaly. Porphyrin profiling and genetic analysis were not performed because of the unavailability of laboratory facilities at that time. She died at the age of 24 from a secondary infection. Fig 2 A, Sclerodermatous changes and hypopigmented and hyperpigmented scars over the face. B, Acro-osteolysis and contracture of the bilateral hands.', 'Case 3': "A 35-year-old woman, born to phenotypically normal parents, presented with progressive bilateral deformities of the hands and photoblistering since birth, with resulting dyspigmentation, scarring, and sclerodermatous changes of the face and distal extremities ( Fig 3 ) and progressive deformities of both hands. She had a history of recurrent keratoconjunctivitis and complications requiring enucleation of her left eye ( Fig 3 ). Facial hypertrichosis, microstomia ( Fig 3 ), erythrodontia, and mutilations of both hands were evident on examination. Laboratory reports revealed a normal complete blood count but an abnormal porphyrin profile ( Table I ). Fig 3 Dyspigmentation, scarring, and sclerodermatous changes over the face with enucleation of the left eye. Wood's lamp examination revealed pink-red fluorescence of the urine and teeth in all 3 patients. In case patients 1 and 3, sequencing of the UROS gene, exons 1 to 10 including flanking intronic regions, showed a homozygous transversion of T to G at nucleotide 416 in exon 7 (c.416T>G) leading to an L139R protein substitution at the terminal of the β6 protein chain. The patients were advised to use strict photoprotection, emollients, and vitamin D supplementation. They were also counseled about the disease, the need for long-term follow-up, wound care, and lifestyle modifications.", 'Case 1': 'A 17-year-old female (now 37 years old), born from a nonconsanguineous marriage, presented with a history of spontaneous blistering over photoexposed areas, starting in the first few days of her life. The lesions healed with scarring that led to progressive deformities of her hands, ears, and nose by 18 years of age. Her mother reported a red discharge in her diaper and redness and matting of both eyes since early childhood. She gradually developed deformities of her eyelids, making it difficult to close them fully. Three of her 7 siblings were similarly affected. Two of the affected siblings died shortly after birth, and a third, her older sister (case 2), died at the age of 24. Both parents were phenotypically normal. Examination revealed thickened skin, hypopigmentation and hyperpigmentation, and scarring at photoexposed sites ( Fig 1, A ); facial hypertrichosis; and reddish-brown tooth discoloration and disfiguration of the nose, ears, and fingertips bilaterally to the proximal interphalangeal joints. Eye examination revealed severe ectropion, trichiasis, and scleral melting ( Fig 1, B ). Abdominal examination revealed an enlarged spleen 4 cm below the left costal margin. Blood investigation showed pancytopenia, elevated erythrocyte sedimentation rate, positive creatinine-reactive protein, a normal serum iron profile, and an abnormal porphyrin profile ( Table I ). Fig 1 A, Thickened skin with hypopigmentation and hyperpigmentation and scarring over photoexposed sites, facial hypertrichosis, and reddish-brownish discoloration of the teeth. B, Severe ectropion, trichiasis, and scleral melting. Table I Results of laboratory investigations Parameter (normal range) Case 1 Case 2 Case 3 Urine total porphyrin (25-144 nmol/L) 11,986 nmol/L NA 13,269 nmol/L Fecal porphyrin (10-200 nmol/g) 5569 nmol/g NA 1797 nmol/g Plasma porphyrin (<11.2 nmol/L) NA NA 1120.5 nmol/L Plasma porphyrin peak 618 nm NA 618 nm Erythrocyte porphyrin (0.4-1.7 μmol/L) 35.8 μmol/L NA 26.2 μmol/L Total white blood cell count (4000-11,000/mm 3 ) 1700/mm 3 3600/mm 3 4500/mm 3 Platelets (150,000-450,000/mm 3 ) 107,000/mm 3 150,000/mm 3 175,000/mm 3 Hemoglobin (female: 12.0-15.5 g/dL) 9.4 g/dL 8.7 g/dL 12 g/dL'}
|
{'Case 2': 'The older sister of case patient 1 presented at the age of 18 years with photoinduced skin blistering of the face and extremities since her sixth day of life. She had associated progressive deformities of her bilateral hands and feet, bilateral ears, and nose. She reported having had photophobia and diminished vision in the right eye since early childhood. Examination revealed sclerodermatous changes and hypopigmented and hyperpigmented scars over the face and extremities ( Fig 2, A ); partial absorption of both ears; and brownish-pink-colored teeth. Hypertrichosis over the face and arms was present, and the bilateral extremities showed sclerodermatous contracture and acro-osteolysis ( Fig 2, B ). Ectropion and bilateral keratoconjunctivitis were apparent. She had mild anemia and splenomegaly. Porphyrin profiling and genetic analysis were not performed because of the unavailability of laboratory facilities at that time. She died at the age of 24 from a secondary infection. Fig 2 A, Sclerodermatous changes and hypopigmented and hyperpigmented scars over the face. B, Acro-osteolysis and contracture of the bilateral hands.', 'Case 3': "A 35-year-old woman, born to phenotypically normal parents, presented with progressive bilateral deformities of the hands and photoblistering since birth, with resulting dyspigmentation, scarring, and sclerodermatous changes of the face and distal extremities ( Fig 3 ) and progressive deformities of both hands. She had a history of recurrent keratoconjunctivitis and complications requiring enucleation of her left eye ( Fig 3 ). Facial hypertrichosis, microstomia ( Fig 3 ), erythrodontia, and mutilations of both hands were evident on examination. Laboratory reports revealed a normal complete blood count but an abnormal porphyrin profile ( Table I ). Fig 3 Dyspigmentation, scarring, and sclerodermatous changes over the face with enucleation of the left eye. Wood's lamp examination revealed pink-red fluorescence of the urine and teeth in all 3 patients. In case patients 1 and 3, sequencing of the UROS gene, exons 1 to 10 including flanking intronic regions, showed a homozygous transversion of T to G at nucleotide 416 in exon 7 (c.416T>G) leading to an L139R protein substitution at the terminal of the β6 protein chain. The patients were advised to use strict photoprotection, emollients, and vitamin D supplementation. They were also counseled about the disease, the need for long-term follow-up, wound care, and lifestyle modifications.", 'Case 1': 'A 17-year-old female (now 37 years old), born from a nonconsanguineous marriage, presented with a history of spontaneous blistering over photoexposed areas, starting in the first few days of her life. The lesions healed with scarring that led to progressive deformities of her hands, ears, and nose by 18 years of age. Her mother reported a red discharge in her diaper and redness and matting of both eyes since early childhood. She gradually developed deformities of her eyelids, making it difficult to close them fully. Three of her 7 siblings were similarly affected. Two of the affected siblings died shortly after birth, and a third, her older sister (case 2), died at the age of 24. Both parents were phenotypically normal. Examination revealed thickened skin, hypopigmentation and hyperpigmentation, and scarring at photoexposed sites ( Fig 1, A ); facial hypertrichosis; and reddish-brown tooth discoloration and disfiguration of the nose, ears, and fingertips bilaterally to the proximal interphalangeal joints. Eye examination revealed severe ectropion, trichiasis, and scleral melting ( Fig 1, B ). Abdominal examination revealed an enlarged spleen 4 cm below the left costal margin. Blood investigation showed pancytopenia, elevated erythrocyte sedimentation rate, positive creatinine-reactive protein, a normal serum iron profile, and an abnormal porphyrin profile ( Table I ). Fig 1 A, Thickened skin with hypopigmentation and hyperpigmentation and scarring over photoexposed sites, facial hypertrichosis, and reddish-brownish discoloration of the teeth. B, Severe ectropion, trichiasis, and scleral melting. Table I Results of laboratory investigations Parameter (normal range) Case 1 Case 2 Case 3 Urine total porphyrin (25-144 nmol/L) 11,986 nmol/L NA 13,269 nmol/L Fecal porphyrin (10-200 nmol/g) 5569 nmol/g NA 1797 nmol/g Plasma porphyrin (<11.2 nmol/L) NA NA 1120.5 nmol/L Plasma porphyrin peak 618 nm NA 618 nm Erythrocyte porphyrin (0.4-1.7 μmol/L) 35.8 μmol/L NA 26.2 μmol/L Total white blood cell count (4000-11,000/mm 3 ) 1700/mm 3 3600/mm 3 4500/mm 3 Platelets (150,000-450,000/mm 3 ) 107,000/mm 3 150,000/mm 3 175,000/mm 3 Hemoglobin (female: 12.0-15.5 g/dL) 9.4 g/dL 8.7 g/dL 12 g/dL'}
|
Respiratory-System
|
RESP
|
[] |
test-2152
|
8022107
|
{'Case 2': 'The older sister of case patient 1 presented at the age of 18 years with photoinduced skin blistering of the face and extremities since her sixth day of life. She had associated progressive deformities of her bilateral hands and feet, bilateral ears, and nose. She reported having had photophobia and diminished vision in the right eye since early childhood. Examination revealed sclerodermatous changes and hypopigmented and hyperpigmented scars over the face and extremities ( Fig 2, A ); partial absorption of both ears; and brownish-pink-colored teeth. Hypertrichosis over the face and arms was present, and the bilateral extremities showed sclerodermatous contracture and acro-osteolysis ( Fig 2, B ). Ectropion and bilateral keratoconjunctivitis were apparent. She had mild anemia and splenomegaly. Porphyrin profiling and genetic analysis were not performed because of the unavailability of laboratory facilities at that time. She died at the age of 24 from a secondary infection. Fig 2 A, Sclerodermatous changes and hypopigmented and hyperpigmented scars over the face. B, Acro-osteolysis and contracture of the bilateral hands.', 'Case 3': "A 35-year-old woman, born to phenotypically normal parents, presented with progressive bilateral deformities of the hands and photoblistering since birth, with resulting dyspigmentation, scarring, and sclerodermatous changes of the face and distal extremities ( Fig 3 ) and progressive deformities of both hands. She had a history of recurrent keratoconjunctivitis and complications requiring enucleation of her left eye ( Fig 3 ). Facial hypertrichosis, microstomia ( Fig 3 ), erythrodontia, and mutilations of both hands were evident on examination. Laboratory reports revealed a normal complete blood count but an abnormal porphyrin profile ( Table I ). Fig 3 Dyspigmentation, scarring, and sclerodermatous changes over the face with enucleation of the left eye. Wood's lamp examination revealed pink-red fluorescence of the urine and teeth in all 3 patients. In case patients 1 and 3, sequencing of the UROS gene, exons 1 to 10 including flanking intronic regions, showed a homozygous transversion of T to G at nucleotide 416 in exon 7 (c.416T>G) leading to an L139R protein substitution at the terminal of the β6 protein chain. The patients were advised to use strict photoprotection, emollients, and vitamin D supplementation. They were also counseled about the disease, the need for long-term follow-up, wound care, and lifestyle modifications.", 'Case 1': 'A 17-year-old female (now 37 years old), born from a nonconsanguineous marriage, presented with a history of spontaneous blistering over photoexposed areas, starting in the first few days of her life. The lesions healed with scarring that led to progressive deformities of her hands, ears, and nose by 18 years of age. Her mother reported a red discharge in her diaper and redness and matting of both eyes since early childhood. She gradually developed deformities of her eyelids, making it difficult to close them fully. Three of her 7 siblings were similarly affected. Two of the affected siblings died shortly after birth, and a third, her older sister (case 2), died at the age of 24. Both parents were phenotypically normal. Examination revealed thickened skin, hypopigmentation and hyperpigmentation, and scarring at photoexposed sites ( Fig 1, A ); facial hypertrichosis; and reddish-brown tooth discoloration and disfiguration of the nose, ears, and fingertips bilaterally to the proximal interphalangeal joints. Eye examination revealed severe ectropion, trichiasis, and scleral melting ( Fig 1, B ). Abdominal examination revealed an enlarged spleen 4 cm below the left costal margin. Blood investigation showed pancytopenia, elevated erythrocyte sedimentation rate, positive creatinine-reactive protein, a normal serum iron profile, and an abnormal porphyrin profile ( Table I ). Fig 1 A, Thickened skin with hypopigmentation and hyperpigmentation and scarring over photoexposed sites, facial hypertrichosis, and reddish-brownish discoloration of the teeth. B, Severe ectropion, trichiasis, and scleral melting. Table I Results of laboratory investigations Parameter (normal range) Case 1 Case 2 Case 3 Urine total porphyrin (25-144 nmol/L) 11,986 nmol/L NA 13,269 nmol/L Fecal porphyrin (10-200 nmol/g) 5569 nmol/g NA 1797 nmol/g Plasma porphyrin (<11.2 nmol/L) NA NA 1120.5 nmol/L Plasma porphyrin peak 618 nm NA 618 nm Erythrocyte porphyrin (0.4-1.7 μmol/L) 35.8 μmol/L NA 26.2 μmol/L Total white blood cell count (4000-11,000/mm 3 ) 1700/mm 3 3600/mm 3 4500/mm 3 Platelets (150,000-450,000/mm 3 ) 107,000/mm 3 150,000/mm 3 175,000/mm 3 Hemoglobin (female: 12.0-15.5 g/dL) 9.4 g/dL 8.7 g/dL 12 g/dL'}
|
{'Case 2': 'The older sister of case patient 1 presented at the age of 18 years with photoinduced skin blistering of the face and extremities since her sixth day of life. She had associated progressive deformities of her bilateral hands and feet, bilateral ears, and nose. She reported having had photophobia and diminished vision in the right eye since early childhood. Examination revealed sclerodermatous changes and hypopigmented and hyperpigmented scars over the face and extremities ( Fig 2, A ); partial absorption of both ears; and brownish-pink-colored teeth. Hypertrichosis over the face and arms was present, and the bilateral extremities showed sclerodermatous contracture and acro-osteolysis ( Fig 2, B ). Ectropion and bilateral keratoconjunctivitis were apparent. She had mild anemia and splenomegaly. Porphyrin profiling and genetic analysis were not performed because of the unavailability of laboratory facilities at that time. She died at the age of 24 from a secondary infection. Fig 2 A, Sclerodermatous changes and hypopigmented and hyperpigmented scars over the face. B, Acro-osteolysis and contracture of the bilateral hands.', 'Case 3': "A 35-year-old woman, born to phenotypically normal parents, presented with progressive bilateral deformities of the hands and photoblistering since birth, with resulting dyspigmentation, scarring, and sclerodermatous changes of the face and distal extremities ( Fig 3 ) and progressive deformities of both hands. She had a history of recurrent keratoconjunctivitis and complications requiring enucleation of her left eye ( Fig 3 ). Facial hypertrichosis, microstomia ( Fig 3 ), erythrodontia, and mutilations of both hands were evident on examination. Laboratory reports revealed a normal complete blood count but an abnormal porphyrin profile ( Table I ). Fig 3 Dyspigmentation, scarring, and sclerodermatous changes over the face with enucleation of the left eye. Wood's lamp examination revealed pink-red fluorescence of the urine and teeth in all 3 patients. In case patients 1 and 3, sequencing of the UROS gene, exons 1 to 10 including flanking intronic regions, showed a homozygous transversion of T to G at nucleotide 416 in exon 7 (c.416T>G) leading to an L139R protein substitution at the terminal of the β6 protein chain. The patients were advised to use strict photoprotection, emollients, and vitamin D supplementation. They were also counseled about the disease, the need for long-term follow-up, wound care, and lifestyle modifications.", 'Case 1': 'A 17-year-old female (now 37 years old), born from a nonconsanguineous marriage, presented with a history of spontaneous blistering over photoexposed areas, starting in the first few days of her life. The lesions healed with scarring that led to progressive deformities of her hands, ears, and nose by 18 years of age. Her mother reported a red discharge in her diaper and redness and matting of both eyes since early childhood. She gradually developed deformities of her eyelids, making it difficult to close them fully. Three of her 7 siblings were similarly affected. Two of the affected siblings died shortly after birth, and a third, her older sister (case 2), died at the age of 24. Both parents were phenotypically normal. Examination revealed thickened skin, hypopigmentation and hyperpigmentation, and scarring at photoexposed sites ( Fig 1, A ); facial hypertrichosis; and reddish-brown tooth discoloration and disfiguration of the nose, ears, and fingertips bilaterally to the proximal interphalangeal joints. Eye examination revealed severe ectropion, trichiasis, and scleral melting ( Fig 1, B ). Abdominal examination revealed an enlarged spleen 4 cm below the left costal margin. Blood investigation showed pancytopenia, elevated erythrocyte sedimentation rate, positive creatinine-reactive protein, a normal serum iron profile, and an abnormal porphyrin profile ( Table I ). Fig 1 A, Thickened skin with hypopigmentation and hyperpigmentation and scarring over photoexposed sites, facial hypertrichosis, and reddish-brownish discoloration of the teeth. B, Severe ectropion, trichiasis, and scleral melting. Table I Results of laboratory investigations Parameter (normal range) Case 1 Case 2 Case 3 Urine total porphyrin (25-144 nmol/L) 11,986 nmol/L NA 13,269 nmol/L Fecal porphyrin (10-200 nmol/g) 5569 nmol/g NA 1797 nmol/g Plasma porphyrin (<11.2 nmol/L) NA NA 1120.5 nmol/L Plasma porphyrin peak 618 nm NA 618 nm Erythrocyte porphyrin (0.4-1.7 μmol/L) 35.8 μmol/L NA 26.2 μmol/L Total white blood cell count (4000-11,000/mm 3 ) 1700/mm 3 3600/mm 3 4500/mm 3 Platelets (150,000-450,000/mm 3 ) 107,000/mm 3 150,000/mm 3 175,000/mm 3 Hemoglobin (female: 12.0-15.5 g/dL) 9.4 g/dL 8.7 g/dL 12 g/dL'}
|
Musculoskeletal-System
|
MSK
|
[
"bilateral extremities showed sclerodermatous contracture and acro - osteolysis",
"Acro - osteolysis and contracture of the bilateral hands",
"progressive bilateral deformities of the hands",
"progressive deformities of both hands",
"mutilations of both hands",
"progressive deformities of her hands",
"disfiguration of the nose, ears, and fingertips bilaterally to the proximal interphalangeal joints"
] |
test-2153
|
8022107
|
{'Case 2': 'The older sister of case patient 1 presented at the age of 18 years with photoinduced skin blistering of the face and extremities since her sixth day of life. She had associated progressive deformities of her bilateral hands and feet, bilateral ears, and nose. She reported having had photophobia and diminished vision in the right eye since early childhood. Examination revealed sclerodermatous changes and hypopigmented and hyperpigmented scars over the face and extremities ( Fig 2, A ); partial absorption of both ears; and brownish-pink-colored teeth. Hypertrichosis over the face and arms was present, and the bilateral extremities showed sclerodermatous contracture and acro-osteolysis ( Fig 2, B ). Ectropion and bilateral keratoconjunctivitis were apparent. She had mild anemia and splenomegaly. Porphyrin profiling and genetic analysis were not performed because of the unavailability of laboratory facilities at that time. She died at the age of 24 from a secondary infection. Fig 2 A, Sclerodermatous changes and hypopigmented and hyperpigmented scars over the face. B, Acro-osteolysis and contracture of the bilateral hands.', 'Case 3': "A 35-year-old woman, born to phenotypically normal parents, presented with progressive bilateral deformities of the hands and photoblistering since birth, with resulting dyspigmentation, scarring, and sclerodermatous changes of the face and distal extremities ( Fig 3 ) and progressive deformities of both hands. She had a history of recurrent keratoconjunctivitis and complications requiring enucleation of her left eye ( Fig 3 ). Facial hypertrichosis, microstomia ( Fig 3 ), erythrodontia, and mutilations of both hands were evident on examination. Laboratory reports revealed a normal complete blood count but an abnormal porphyrin profile ( Table I ). Fig 3 Dyspigmentation, scarring, and sclerodermatous changes over the face with enucleation of the left eye. Wood's lamp examination revealed pink-red fluorescence of the urine and teeth in all 3 patients. In case patients 1 and 3, sequencing of the UROS gene, exons 1 to 10 including flanking intronic regions, showed a homozygous transversion of T to G at nucleotide 416 in exon 7 (c.416T>G) leading to an L139R protein substitution at the terminal of the β6 protein chain. The patients were advised to use strict photoprotection, emollients, and vitamin D supplementation. They were also counseled about the disease, the need for long-term follow-up, wound care, and lifestyle modifications.", 'Case 1': 'A 17-year-old female (now 37 years old), born from a nonconsanguineous marriage, presented with a history of spontaneous blistering over photoexposed areas, starting in the first few days of her life. The lesions healed with scarring that led to progressive deformities of her hands, ears, and nose by 18 years of age. Her mother reported a red discharge in her diaper and redness and matting of both eyes since early childhood. She gradually developed deformities of her eyelids, making it difficult to close them fully. Three of her 7 siblings were similarly affected. Two of the affected siblings died shortly after birth, and a third, her older sister (case 2), died at the age of 24. Both parents were phenotypically normal. Examination revealed thickened skin, hypopigmentation and hyperpigmentation, and scarring at photoexposed sites ( Fig 1, A ); facial hypertrichosis; and reddish-brown tooth discoloration and disfiguration of the nose, ears, and fingertips bilaterally to the proximal interphalangeal joints. Eye examination revealed severe ectropion, trichiasis, and scleral melting ( Fig 1, B ). Abdominal examination revealed an enlarged spleen 4 cm below the left costal margin. Blood investigation showed pancytopenia, elevated erythrocyte sedimentation rate, positive creatinine-reactive protein, a normal serum iron profile, and an abnormal porphyrin profile ( Table I ). Fig 1 A, Thickened skin with hypopigmentation and hyperpigmentation and scarring over photoexposed sites, facial hypertrichosis, and reddish-brownish discoloration of the teeth. B, Severe ectropion, trichiasis, and scleral melting. Table I Results of laboratory investigations Parameter (normal range) Case 1 Case 2 Case 3 Urine total porphyrin (25-144 nmol/L) 11,986 nmol/L NA 13,269 nmol/L Fecal porphyrin (10-200 nmol/g) 5569 nmol/g NA 1797 nmol/g Plasma porphyrin (<11.2 nmol/L) NA NA 1120.5 nmol/L Plasma porphyrin peak 618 nm NA 618 nm Erythrocyte porphyrin (0.4-1.7 μmol/L) 35.8 μmol/L NA 26.2 μmol/L Total white blood cell count (4000-11,000/mm 3 ) 1700/mm 3 3600/mm 3 4500/mm 3 Platelets (150,000-450,000/mm 3 ) 107,000/mm 3 150,000/mm 3 175,000/mm 3 Hemoglobin (female: 12.0-15.5 g/dL) 9.4 g/dL 8.7 g/dL 12 g/dL'}
|
{'Case 2': 'The older sister of case patient 1 presented at the age of 18 years with photoinduced skin blistering of the face and extremities since her sixth day of life. She had associated progressive deformities of her bilateral hands and feet, bilateral ears, and nose. She reported having had photophobia and diminished vision in the right eye since early childhood. Examination revealed sclerodermatous changes and hypopigmented and hyperpigmented scars over the face and extremities ( Fig 2, A ); partial absorption of both ears; and brownish-pink-colored teeth. Hypertrichosis over the face and arms was present, and the bilateral extremities showed sclerodermatous contracture and acro-osteolysis ( Fig 2, B ). Ectropion and bilateral keratoconjunctivitis were apparent. She had mild anemia and splenomegaly. Porphyrin profiling and genetic analysis were not performed because of the unavailability of laboratory facilities at that time. She died at the age of 24 from a secondary infection. Fig 2 A, Sclerodermatous changes and hypopigmented and hyperpigmented scars over the face. B, Acro-osteolysis and contracture of the bilateral hands.', 'Case 3': "A 35-year-old woman, born to phenotypically normal parents, presented with progressive bilateral deformities of the hands and photoblistering since birth, with resulting dyspigmentation, scarring, and sclerodermatous changes of the face and distal extremities ( Fig 3 ) and progressive deformities of both hands. She had a history of recurrent keratoconjunctivitis and complications requiring enucleation of her left eye ( Fig 3 ). Facial hypertrichosis, microstomia ( Fig 3 ), erythrodontia, and mutilations of both hands were evident on examination. Laboratory reports revealed a normal complete blood count but an abnormal porphyrin profile ( Table I ). Fig 3 Dyspigmentation, scarring, and sclerodermatous changes over the face with enucleation of the left eye. Wood's lamp examination revealed pink-red fluorescence of the urine and teeth in all 3 patients. In case patients 1 and 3, sequencing of the UROS gene, exons 1 to 10 including flanking intronic regions, showed a homozygous transversion of T to G at nucleotide 416 in exon 7 (c.416T>G) leading to an L139R protein substitution at the terminal of the β6 protein chain. The patients were advised to use strict photoprotection, emollients, and vitamin D supplementation. They were also counseled about the disease, the need for long-term follow-up, wound care, and lifestyle modifications.", 'Case 1': 'A 17-year-old female (now 37 years old), born from a nonconsanguineous marriage, presented with a history of spontaneous blistering over photoexposed areas, starting in the first few days of her life. The lesions healed with scarring that led to progressive deformities of her hands, ears, and nose by 18 years of age. Her mother reported a red discharge in her diaper and redness and matting of both eyes since early childhood. She gradually developed deformities of her eyelids, making it difficult to close them fully. Three of her 7 siblings were similarly affected. Two of the affected siblings died shortly after birth, and a third, her older sister (case 2), died at the age of 24. Both parents were phenotypically normal. Examination revealed thickened skin, hypopigmentation and hyperpigmentation, and scarring at photoexposed sites ( Fig 1, A ); facial hypertrichosis; and reddish-brown tooth discoloration and disfiguration of the nose, ears, and fingertips bilaterally to the proximal interphalangeal joints. Eye examination revealed severe ectropion, trichiasis, and scleral melting ( Fig 1, B ). Abdominal examination revealed an enlarged spleen 4 cm below the left costal margin. Blood investigation showed pancytopenia, elevated erythrocyte sedimentation rate, positive creatinine-reactive protein, a normal serum iron profile, and an abnormal porphyrin profile ( Table I ). Fig 1 A, Thickened skin with hypopigmentation and hyperpigmentation and scarring over photoexposed sites, facial hypertrichosis, and reddish-brownish discoloration of the teeth. B, Severe ectropion, trichiasis, and scleral melting. Table I Results of laboratory investigations Parameter (normal range) Case 1 Case 2 Case 3 Urine total porphyrin (25-144 nmol/L) 11,986 nmol/L NA 13,269 nmol/L Fecal porphyrin (10-200 nmol/g) 5569 nmol/g NA 1797 nmol/g Plasma porphyrin (<11.2 nmol/L) NA NA 1120.5 nmol/L Plasma porphyrin peak 618 nm NA 618 nm Erythrocyte porphyrin (0.4-1.7 μmol/L) 35.8 μmol/L NA 26.2 μmol/L Total white blood cell count (4000-11,000/mm 3 ) 1700/mm 3 3600/mm 3 4500/mm 3 Platelets (150,000-450,000/mm 3 ) 107,000/mm 3 150,000/mm 3 175,000/mm 3 Hemoglobin (female: 12.0-15.5 g/dL) 9.4 g/dL 8.7 g/dL 12 g/dL'}
|
Eyes-Ears-Nose-Throat
|
EENT
|
[
"having had photophobia and diminished vision in the right eye",
"partial absorption of both ears; and brownish - pink - colored teeth",
"Ectropion and bilateral keratoconjunctivitis were apparent",
"recurrent keratoconjunctivitis and complications",
"microstomia ( Fig 3 ), erythrodontia",
"Wood 's lamp examination revealed pink - red fluorescence of the urine and teeth",
"redness and matting of both eyes",
"deformities of her eyelids, making it difficult to close them fully",
"reddish - brown tooth discoloration and disfiguration of the nose, ears",
"Eye examination revealed severe ectropion, trichiasis, and scleral melting",
"reddish - brownish discoloration of the teeth. B, Severe ectropion, trichiasis, and scleral melting"
] |
test-2154
|
8022107
|
{'Case 2': 'The older sister of case patient 1 presented at the age of 18 years with photoinduced skin blistering of the face and extremities since her sixth day of life. She had associated progressive deformities of her bilateral hands and feet, bilateral ears, and nose. She reported having had photophobia and diminished vision in the right eye since early childhood. Examination revealed sclerodermatous changes and hypopigmented and hyperpigmented scars over the face and extremities ( Fig 2, A ); partial absorption of both ears; and brownish-pink-colored teeth. Hypertrichosis over the face and arms was present, and the bilateral extremities showed sclerodermatous contracture and acro-osteolysis ( Fig 2, B ). Ectropion and bilateral keratoconjunctivitis were apparent. She had mild anemia and splenomegaly. Porphyrin profiling and genetic analysis were not performed because of the unavailability of laboratory facilities at that time. She died at the age of 24 from a secondary infection. Fig 2 A, Sclerodermatous changes and hypopigmented and hyperpigmented scars over the face. B, Acro-osteolysis and contracture of the bilateral hands.', 'Case 3': "A 35-year-old woman, born to phenotypically normal parents, presented with progressive bilateral deformities of the hands and photoblistering since birth, with resulting dyspigmentation, scarring, and sclerodermatous changes of the face and distal extremities ( Fig 3 ) and progressive deformities of both hands. She had a history of recurrent keratoconjunctivitis and complications requiring enucleation of her left eye ( Fig 3 ). Facial hypertrichosis, microstomia ( Fig 3 ), erythrodontia, and mutilations of both hands were evident on examination. Laboratory reports revealed a normal complete blood count but an abnormal porphyrin profile ( Table I ). Fig 3 Dyspigmentation, scarring, and sclerodermatous changes over the face with enucleation of the left eye. Wood's lamp examination revealed pink-red fluorescence of the urine and teeth in all 3 patients. In case patients 1 and 3, sequencing of the UROS gene, exons 1 to 10 including flanking intronic regions, showed a homozygous transversion of T to G at nucleotide 416 in exon 7 (c.416T>G) leading to an L139R protein substitution at the terminal of the β6 protein chain. The patients were advised to use strict photoprotection, emollients, and vitamin D supplementation. They were also counseled about the disease, the need for long-term follow-up, wound care, and lifestyle modifications.", 'Case 1': 'A 17-year-old female (now 37 years old), born from a nonconsanguineous marriage, presented with a history of spontaneous blistering over photoexposed areas, starting in the first few days of her life. The lesions healed with scarring that led to progressive deformities of her hands, ears, and nose by 18 years of age. Her mother reported a red discharge in her diaper and redness and matting of both eyes since early childhood. She gradually developed deformities of her eyelids, making it difficult to close them fully. Three of her 7 siblings were similarly affected. Two of the affected siblings died shortly after birth, and a third, her older sister (case 2), died at the age of 24. Both parents were phenotypically normal. Examination revealed thickened skin, hypopigmentation and hyperpigmentation, and scarring at photoexposed sites ( Fig 1, A ); facial hypertrichosis; and reddish-brown tooth discoloration and disfiguration of the nose, ears, and fingertips bilaterally to the proximal interphalangeal joints. Eye examination revealed severe ectropion, trichiasis, and scleral melting ( Fig 1, B ). Abdominal examination revealed an enlarged spleen 4 cm below the left costal margin. Blood investigation showed pancytopenia, elevated erythrocyte sedimentation rate, positive creatinine-reactive protein, a normal serum iron profile, and an abnormal porphyrin profile ( Table I ). Fig 1 A, Thickened skin with hypopigmentation and hyperpigmentation and scarring over photoexposed sites, facial hypertrichosis, and reddish-brownish discoloration of the teeth. B, Severe ectropion, trichiasis, and scleral melting. Table I Results of laboratory investigations Parameter (normal range) Case 1 Case 2 Case 3 Urine total porphyrin (25-144 nmol/L) 11,986 nmol/L NA 13,269 nmol/L Fecal porphyrin (10-200 nmol/g) 5569 nmol/g NA 1797 nmol/g Plasma porphyrin (<11.2 nmol/L) NA NA 1120.5 nmol/L Plasma porphyrin peak 618 nm NA 618 nm Erythrocyte porphyrin (0.4-1.7 μmol/L) 35.8 μmol/L NA 26.2 μmol/L Total white blood cell count (4000-11,000/mm 3 ) 1700/mm 3 3600/mm 3 4500/mm 3 Platelets (150,000-450,000/mm 3 ) 107,000/mm 3 150,000/mm 3 175,000/mm 3 Hemoglobin (female: 12.0-15.5 g/dL) 9.4 g/dL 8.7 g/dL 12 g/dL'}
|
{'Case 2': 'The older sister of case patient 1 presented at the age of 18 years with photoinduced skin blistering of the face and extremities since her sixth day of life. She had associated progressive deformities of her bilateral hands and feet, bilateral ears, and nose. She reported having had photophobia and diminished vision in the right eye since early childhood. Examination revealed sclerodermatous changes and hypopigmented and hyperpigmented scars over the face and extremities ( Fig 2, A ); partial absorption of both ears; and brownish-pink-colored teeth. Hypertrichosis over the face and arms was present, and the bilateral extremities showed sclerodermatous contracture and acro-osteolysis ( Fig 2, B ). Ectropion and bilateral keratoconjunctivitis were apparent. She had mild anemia and splenomegaly. Porphyrin profiling and genetic analysis were not performed because of the unavailability of laboratory facilities at that time. She died at the age of 24 from a secondary infection. Fig 2 A, Sclerodermatous changes and hypopigmented and hyperpigmented scars over the face. B, Acro-osteolysis and contracture of the bilateral hands.', 'Case 3': "A 35-year-old woman, born to phenotypically normal parents, presented with progressive bilateral deformities of the hands and photoblistering since birth, with resulting dyspigmentation, scarring, and sclerodermatous changes of the face and distal extremities ( Fig 3 ) and progressive deformities of both hands. She had a history of recurrent keratoconjunctivitis and complications requiring enucleation of her left eye ( Fig 3 ). Facial hypertrichosis, microstomia ( Fig 3 ), erythrodontia, and mutilations of both hands were evident on examination. Laboratory reports revealed a normal complete blood count but an abnormal porphyrin profile ( Table I ). Fig 3 Dyspigmentation, scarring, and sclerodermatous changes over the face with enucleation of the left eye. Wood's lamp examination revealed pink-red fluorescence of the urine and teeth in all 3 patients. In case patients 1 and 3, sequencing of the UROS gene, exons 1 to 10 including flanking intronic regions, showed a homozygous transversion of T to G at nucleotide 416 in exon 7 (c.416T>G) leading to an L139R protein substitution at the terminal of the β6 protein chain. The patients were advised to use strict photoprotection, emollients, and vitamin D supplementation. They were also counseled about the disease, the need for long-term follow-up, wound care, and lifestyle modifications.", 'Case 1': 'A 17-year-old female (now 37 years old), born from a nonconsanguineous marriage, presented with a history of spontaneous blistering over photoexposed areas, starting in the first few days of her life. The lesions healed with scarring that led to progressive deformities of her hands, ears, and nose by 18 years of age. Her mother reported a red discharge in her diaper and redness and matting of both eyes since early childhood. She gradually developed deformities of her eyelids, making it difficult to close them fully. Three of her 7 siblings were similarly affected. Two of the affected siblings died shortly after birth, and a third, her older sister (case 2), died at the age of 24. Both parents were phenotypically normal. Examination revealed thickened skin, hypopigmentation and hyperpigmentation, and scarring at photoexposed sites ( Fig 1, A ); facial hypertrichosis; and reddish-brown tooth discoloration and disfiguration of the nose, ears, and fingertips bilaterally to the proximal interphalangeal joints. Eye examination revealed severe ectropion, trichiasis, and scleral melting ( Fig 1, B ). Abdominal examination revealed an enlarged spleen 4 cm below the left costal margin. Blood investigation showed pancytopenia, elevated erythrocyte sedimentation rate, positive creatinine-reactive protein, a normal serum iron profile, and an abnormal porphyrin profile ( Table I ). Fig 1 A, Thickened skin with hypopigmentation and hyperpigmentation and scarring over photoexposed sites, facial hypertrichosis, and reddish-brownish discoloration of the teeth. B, Severe ectropion, trichiasis, and scleral melting. Table I Results of laboratory investigations Parameter (normal range) Case 1 Case 2 Case 3 Urine total porphyrin (25-144 nmol/L) 11,986 nmol/L NA 13,269 nmol/L Fecal porphyrin (10-200 nmol/g) 5569 nmol/g NA 1797 nmol/g Plasma porphyrin (<11.2 nmol/L) NA NA 1120.5 nmol/L Plasma porphyrin peak 618 nm NA 618 nm Erythrocyte porphyrin (0.4-1.7 μmol/L) 35.8 μmol/L NA 26.2 μmol/L Total white blood cell count (4000-11,000/mm 3 ) 1700/mm 3 3600/mm 3 4500/mm 3 Platelets (150,000-450,000/mm 3 ) 107,000/mm 3 150,000/mm 3 175,000/mm 3 Hemoglobin (female: 12.0-15.5 g/dL) 9.4 g/dL 8.7 g/dL 12 g/dL'}
|
Dermatology
|
DERM
|
[
"photoinduced skin blistering of the face and extremities",
"associated progressive deformities of her bilateral hands and feet, bilateral ears, and nose",
"sclerodermatous changes and hypopigmented and hyperpigmented scars over the face and extremities ( Fig 2, A ); partial absorption of both ears",
"Hypertrichosis over the face and arms was present, and the bilateral extremities showed sclerodermatous contracture and acro - osteolysis",
"Sclerodermatous changes and hypopigmented and hyperpigmented scars over the face",
"progressive bilateral deformities of the hands and photoblistering since birth, with resulting dyspigmentation, scarring, and sclerodermatous changes of the face and distal extremities",
"Facial hypertrichosis, microstomia",
"mutilations of both hands",
"Dyspigmentation, scarring, and sclerodermatous changes over the face",
"spontaneous blistering over photoexposed areas",
"lesions healed with scarring that led to progressive deformities of her hands, ears, and nose",
"thickened skin, hypopigmentation and hyperpigmentation, and scarring at photoexposed sites ( Fig 1, A ); facial hypertrichosis",
"Thickened skin with hypopigmentation and hyperpigmentation and scarring over photoexposed sites, facial hypertrichosis"
] |
test-2155
|
8022107
|
{'Case 2': 'The older sister of case patient 1 presented at the age of 18 years with photoinduced skin blistering of the face and extremities since her sixth day of life. She had associated progressive deformities of her bilateral hands and feet, bilateral ears, and nose. She reported having had photophobia and diminished vision in the right eye since early childhood. Examination revealed sclerodermatous changes and hypopigmented and hyperpigmented scars over the face and extremities ( Fig 2, A ); partial absorption of both ears; and brownish-pink-colored teeth. Hypertrichosis over the face and arms was present, and the bilateral extremities showed sclerodermatous contracture and acro-osteolysis ( Fig 2, B ). Ectropion and bilateral keratoconjunctivitis were apparent. She had mild anemia and splenomegaly. Porphyrin profiling and genetic analysis were not performed because of the unavailability of laboratory facilities at that time. She died at the age of 24 from a secondary infection. Fig 2 A, Sclerodermatous changes and hypopigmented and hyperpigmented scars over the face. B, Acro-osteolysis and contracture of the bilateral hands.', 'Case 3': "A 35-year-old woman, born to phenotypically normal parents, presented with progressive bilateral deformities of the hands and photoblistering since birth, with resulting dyspigmentation, scarring, and sclerodermatous changes of the face and distal extremities ( Fig 3 ) and progressive deformities of both hands. She had a history of recurrent keratoconjunctivitis and complications requiring enucleation of her left eye ( Fig 3 ). Facial hypertrichosis, microstomia ( Fig 3 ), erythrodontia, and mutilations of both hands were evident on examination. Laboratory reports revealed a normal complete blood count but an abnormal porphyrin profile ( Table I ). Fig 3 Dyspigmentation, scarring, and sclerodermatous changes over the face with enucleation of the left eye. Wood's lamp examination revealed pink-red fluorescence of the urine and teeth in all 3 patients. In case patients 1 and 3, sequencing of the UROS gene, exons 1 to 10 including flanking intronic regions, showed a homozygous transversion of T to G at nucleotide 416 in exon 7 (c.416T>G) leading to an L139R protein substitution at the terminal of the β6 protein chain. The patients were advised to use strict photoprotection, emollients, and vitamin D supplementation. They were also counseled about the disease, the need for long-term follow-up, wound care, and lifestyle modifications.", 'Case 1': 'A 17-year-old female (now 37 years old), born from a nonconsanguineous marriage, presented with a history of spontaneous blistering over photoexposed areas, starting in the first few days of her life. The lesions healed with scarring that led to progressive deformities of her hands, ears, and nose by 18 years of age. Her mother reported a red discharge in her diaper and redness and matting of both eyes since early childhood. She gradually developed deformities of her eyelids, making it difficult to close them fully. Three of her 7 siblings were similarly affected. Two of the affected siblings died shortly after birth, and a third, her older sister (case 2), died at the age of 24. Both parents were phenotypically normal. Examination revealed thickened skin, hypopigmentation and hyperpigmentation, and scarring at photoexposed sites ( Fig 1, A ); facial hypertrichosis; and reddish-brown tooth discoloration and disfiguration of the nose, ears, and fingertips bilaterally to the proximal interphalangeal joints. Eye examination revealed severe ectropion, trichiasis, and scleral melting ( Fig 1, B ). Abdominal examination revealed an enlarged spleen 4 cm below the left costal margin. Blood investigation showed pancytopenia, elevated erythrocyte sedimentation rate, positive creatinine-reactive protein, a normal serum iron profile, and an abnormal porphyrin profile ( Table I ). Fig 1 A, Thickened skin with hypopigmentation and hyperpigmentation and scarring over photoexposed sites, facial hypertrichosis, and reddish-brownish discoloration of the teeth. B, Severe ectropion, trichiasis, and scleral melting. Table I Results of laboratory investigations Parameter (normal range) Case 1 Case 2 Case 3 Urine total porphyrin (25-144 nmol/L) 11,986 nmol/L NA 13,269 nmol/L Fecal porphyrin (10-200 nmol/g) 5569 nmol/g NA 1797 nmol/g Plasma porphyrin (<11.2 nmol/L) NA NA 1120.5 nmol/L Plasma porphyrin peak 618 nm NA 618 nm Erythrocyte porphyrin (0.4-1.7 μmol/L) 35.8 μmol/L NA 26.2 μmol/L Total white blood cell count (4000-11,000/mm 3 ) 1700/mm 3 3600/mm 3 4500/mm 3 Platelets (150,000-450,000/mm 3 ) 107,000/mm 3 150,000/mm 3 175,000/mm 3 Hemoglobin (female: 12.0-15.5 g/dL) 9.4 g/dL 8.7 g/dL 12 g/dL'}
|
{'Case 2': 'The older sister of case patient 1 presented at the age of 18 years with photoinduced skin blistering of the face and extremities since her sixth day of life. She had associated progressive deformities of her bilateral hands and feet, bilateral ears, and nose. She reported having had photophobia and diminished vision in the right eye since early childhood. Examination revealed sclerodermatous changes and hypopigmented and hyperpigmented scars over the face and extremities ( Fig 2, A ); partial absorption of both ears; and brownish-pink-colored teeth. Hypertrichosis over the face and arms was present, and the bilateral extremities showed sclerodermatous contracture and acro-osteolysis ( Fig 2, B ). Ectropion and bilateral keratoconjunctivitis were apparent. She had mild anemia and splenomegaly. Porphyrin profiling and genetic analysis were not performed because of the unavailability of laboratory facilities at that time. She died at the age of 24 from a secondary infection. Fig 2 A, Sclerodermatous changes and hypopigmented and hyperpigmented scars over the face. B, Acro-osteolysis and contracture of the bilateral hands.', 'Case 3': "A 35-year-old woman, born to phenotypically normal parents, presented with progressive bilateral deformities of the hands and photoblistering since birth, with resulting dyspigmentation, scarring, and sclerodermatous changes of the face and distal extremities ( Fig 3 ) and progressive deformities of both hands. She had a history of recurrent keratoconjunctivitis and complications requiring enucleation of her left eye ( Fig 3 ). Facial hypertrichosis, microstomia ( Fig 3 ), erythrodontia, and mutilations of both hands were evident on examination. Laboratory reports revealed a normal complete blood count but an abnormal porphyrin profile ( Table I ). Fig 3 Dyspigmentation, scarring, and sclerodermatous changes over the face with enucleation of the left eye. Wood's lamp examination revealed pink-red fluorescence of the urine and teeth in all 3 patients. In case patients 1 and 3, sequencing of the UROS gene, exons 1 to 10 including flanking intronic regions, showed a homozygous transversion of T to G at nucleotide 416 in exon 7 (c.416T>G) leading to an L139R protein substitution at the terminal of the β6 protein chain. The patients were advised to use strict photoprotection, emollients, and vitamin D supplementation. They were also counseled about the disease, the need for long-term follow-up, wound care, and lifestyle modifications.", 'Case 1': 'A 17-year-old female (now 37 years old), born from a nonconsanguineous marriage, presented with a history of spontaneous blistering over photoexposed areas, starting in the first few days of her life. The lesions healed with scarring that led to progressive deformities of her hands, ears, and nose by 18 years of age. Her mother reported a red discharge in her diaper and redness and matting of both eyes since early childhood. She gradually developed deformities of her eyelids, making it difficult to close them fully. Three of her 7 siblings were similarly affected. Two of the affected siblings died shortly after birth, and a third, her older sister (case 2), died at the age of 24. Both parents were phenotypically normal. Examination revealed thickened skin, hypopigmentation and hyperpigmentation, and scarring at photoexposed sites ( Fig 1, A ); facial hypertrichosis; and reddish-brown tooth discoloration and disfiguration of the nose, ears, and fingertips bilaterally to the proximal interphalangeal joints. Eye examination revealed severe ectropion, trichiasis, and scleral melting ( Fig 1, B ). Abdominal examination revealed an enlarged spleen 4 cm below the left costal margin. Blood investigation showed pancytopenia, elevated erythrocyte sedimentation rate, positive creatinine-reactive protein, a normal serum iron profile, and an abnormal porphyrin profile ( Table I ). Fig 1 A, Thickened skin with hypopigmentation and hyperpigmentation and scarring over photoexposed sites, facial hypertrichosis, and reddish-brownish discoloration of the teeth. B, Severe ectropion, trichiasis, and scleral melting. Table I Results of laboratory investigations Parameter (normal range) Case 1 Case 2 Case 3 Urine total porphyrin (25-144 nmol/L) 11,986 nmol/L NA 13,269 nmol/L Fecal porphyrin (10-200 nmol/g) 5569 nmol/g NA 1797 nmol/g Plasma porphyrin (<11.2 nmol/L) NA NA 1120.5 nmol/L Plasma porphyrin peak 618 nm NA 618 nm Erythrocyte porphyrin (0.4-1.7 μmol/L) 35.8 μmol/L NA 26.2 μmol/L Total white blood cell count (4000-11,000/mm 3 ) 1700/mm 3 3600/mm 3 4500/mm 3 Platelets (150,000-450,000/mm 3 ) 107,000/mm 3 150,000/mm 3 175,000/mm 3 Hemoglobin (female: 12.0-15.5 g/dL) 9.4 g/dL 8.7 g/dL 12 g/dL'}
|
Pregnancy
|
Pregnancy
|
[] |
test-2156
|
8022107
|
{'Case 2': 'The older sister of case patient 1 presented at the age of 18 years with photoinduced skin blistering of the face and extremities since her sixth day of life. She had associated progressive deformities of her bilateral hands and feet, bilateral ears, and nose. She reported having had photophobia and diminished vision in the right eye since early childhood. Examination revealed sclerodermatous changes and hypopigmented and hyperpigmented scars over the face and extremities ( Fig 2, A ); partial absorption of both ears; and brownish-pink-colored teeth. Hypertrichosis over the face and arms was present, and the bilateral extremities showed sclerodermatous contracture and acro-osteolysis ( Fig 2, B ). Ectropion and bilateral keratoconjunctivitis were apparent. She had mild anemia and splenomegaly. Porphyrin profiling and genetic analysis were not performed because of the unavailability of laboratory facilities at that time. She died at the age of 24 from a secondary infection. Fig 2 A, Sclerodermatous changes and hypopigmented and hyperpigmented scars over the face. B, Acro-osteolysis and contracture of the bilateral hands.', 'Case 3': "A 35-year-old woman, born to phenotypically normal parents, presented with progressive bilateral deformities of the hands and photoblistering since birth, with resulting dyspigmentation, scarring, and sclerodermatous changes of the face and distal extremities ( Fig 3 ) and progressive deformities of both hands. She had a history of recurrent keratoconjunctivitis and complications requiring enucleation of her left eye ( Fig 3 ). Facial hypertrichosis, microstomia ( Fig 3 ), erythrodontia, and mutilations of both hands were evident on examination. Laboratory reports revealed a normal complete blood count but an abnormal porphyrin profile ( Table I ). Fig 3 Dyspigmentation, scarring, and sclerodermatous changes over the face with enucleation of the left eye. Wood's lamp examination revealed pink-red fluorescence of the urine and teeth in all 3 patients. In case patients 1 and 3, sequencing of the UROS gene, exons 1 to 10 including flanking intronic regions, showed a homozygous transversion of T to G at nucleotide 416 in exon 7 (c.416T>G) leading to an L139R protein substitution at the terminal of the β6 protein chain. The patients were advised to use strict photoprotection, emollients, and vitamin D supplementation. They were also counseled about the disease, the need for long-term follow-up, wound care, and lifestyle modifications.", 'Case 1': 'A 17-year-old female (now 37 years old), born from a nonconsanguineous marriage, presented with a history of spontaneous blistering over photoexposed areas, starting in the first few days of her life. The lesions healed with scarring that led to progressive deformities of her hands, ears, and nose by 18 years of age. Her mother reported a red discharge in her diaper and redness and matting of both eyes since early childhood. She gradually developed deformities of her eyelids, making it difficult to close them fully. Three of her 7 siblings were similarly affected. Two of the affected siblings died shortly after birth, and a third, her older sister (case 2), died at the age of 24. Both parents were phenotypically normal. Examination revealed thickened skin, hypopigmentation and hyperpigmentation, and scarring at photoexposed sites ( Fig 1, A ); facial hypertrichosis; and reddish-brown tooth discoloration and disfiguration of the nose, ears, and fingertips bilaterally to the proximal interphalangeal joints. Eye examination revealed severe ectropion, trichiasis, and scleral melting ( Fig 1, B ). Abdominal examination revealed an enlarged spleen 4 cm below the left costal margin. Blood investigation showed pancytopenia, elevated erythrocyte sedimentation rate, positive creatinine-reactive protein, a normal serum iron profile, and an abnormal porphyrin profile ( Table I ). Fig 1 A, Thickened skin with hypopigmentation and hyperpigmentation and scarring over photoexposed sites, facial hypertrichosis, and reddish-brownish discoloration of the teeth. B, Severe ectropion, trichiasis, and scleral melting. Table I Results of laboratory investigations Parameter (normal range) Case 1 Case 2 Case 3 Urine total porphyrin (25-144 nmol/L) 11,986 nmol/L NA 13,269 nmol/L Fecal porphyrin (10-200 nmol/g) 5569 nmol/g NA 1797 nmol/g Plasma porphyrin (<11.2 nmol/L) NA NA 1120.5 nmol/L Plasma porphyrin peak 618 nm NA 618 nm Erythrocyte porphyrin (0.4-1.7 μmol/L) 35.8 μmol/L NA 26.2 μmol/L Total white blood cell count (4000-11,000/mm 3 ) 1700/mm 3 3600/mm 3 4500/mm 3 Platelets (150,000-450,000/mm 3 ) 107,000/mm 3 150,000/mm 3 175,000/mm 3 Hemoglobin (female: 12.0-15.5 g/dL) 9.4 g/dL 8.7 g/dL 12 g/dL'}
|
{'Case 2': 'The older sister of case patient 1 presented at the age of 18 years with photoinduced skin blistering of the face and extremities since her sixth day of life. She had associated progressive deformities of her bilateral hands and feet, bilateral ears, and nose. She reported having had photophobia and diminished vision in the right eye since early childhood. Examination revealed sclerodermatous changes and hypopigmented and hyperpigmented scars over the face and extremities ( Fig 2, A ); partial absorption of both ears; and brownish-pink-colored teeth. Hypertrichosis over the face and arms was present, and the bilateral extremities showed sclerodermatous contracture and acro-osteolysis ( Fig 2, B ). Ectropion and bilateral keratoconjunctivitis were apparent. She had mild anemia and splenomegaly. Porphyrin profiling and genetic analysis were not performed because of the unavailability of laboratory facilities at that time. She died at the age of 24 from a secondary infection. Fig 2 A, Sclerodermatous changes and hypopigmented and hyperpigmented scars over the face. B, Acro-osteolysis and contracture of the bilateral hands.', 'Case 3': "A 35-year-old woman, born to phenotypically normal parents, presented with progressive bilateral deformities of the hands and photoblistering since birth, with resulting dyspigmentation, scarring, and sclerodermatous changes of the face and distal extremities ( Fig 3 ) and progressive deformities of both hands. She had a history of recurrent keratoconjunctivitis and complications requiring enucleation of her left eye ( Fig 3 ). Facial hypertrichosis, microstomia ( Fig 3 ), erythrodontia, and mutilations of both hands were evident on examination. Laboratory reports revealed a normal complete blood count but an abnormal porphyrin profile ( Table I ). Fig 3 Dyspigmentation, scarring, and sclerodermatous changes over the face with enucleation of the left eye. Wood's lamp examination revealed pink-red fluorescence of the urine and teeth in all 3 patients. In case patients 1 and 3, sequencing of the UROS gene, exons 1 to 10 including flanking intronic regions, showed a homozygous transversion of T to G at nucleotide 416 in exon 7 (c.416T>G) leading to an L139R protein substitution at the terminal of the β6 protein chain. The patients were advised to use strict photoprotection, emollients, and vitamin D supplementation. They were also counseled about the disease, the need for long-term follow-up, wound care, and lifestyle modifications.", 'Case 1': 'A 17-year-old female (now 37 years old), born from a nonconsanguineous marriage, presented with a history of spontaneous blistering over photoexposed areas, starting in the first few days of her life. The lesions healed with scarring that led to progressive deformities of her hands, ears, and nose by 18 years of age. Her mother reported a red discharge in her diaper and redness and matting of both eyes since early childhood. She gradually developed deformities of her eyelids, making it difficult to close them fully. Three of her 7 siblings were similarly affected. Two of the affected siblings died shortly after birth, and a third, her older sister (case 2), died at the age of 24. Both parents were phenotypically normal. Examination revealed thickened skin, hypopigmentation and hyperpigmentation, and scarring at photoexposed sites ( Fig 1, A ); facial hypertrichosis; and reddish-brown tooth discoloration and disfiguration of the nose, ears, and fingertips bilaterally to the proximal interphalangeal joints. Eye examination revealed severe ectropion, trichiasis, and scleral melting ( Fig 1, B ). Abdominal examination revealed an enlarged spleen 4 cm below the left costal margin. Blood investigation showed pancytopenia, elevated erythrocyte sedimentation rate, positive creatinine-reactive protein, a normal serum iron profile, and an abnormal porphyrin profile ( Table I ). Fig 1 A, Thickened skin with hypopigmentation and hyperpigmentation and scarring over photoexposed sites, facial hypertrichosis, and reddish-brownish discoloration of the teeth. B, Severe ectropion, trichiasis, and scleral melting. Table I Results of laboratory investigations Parameter (normal range) Case 1 Case 2 Case 3 Urine total porphyrin (25-144 nmol/L) 11,986 nmol/L NA 13,269 nmol/L Fecal porphyrin (10-200 nmol/g) 5569 nmol/g NA 1797 nmol/g Plasma porphyrin (<11.2 nmol/L) NA NA 1120.5 nmol/L Plasma porphyrin peak 618 nm NA 618 nm Erythrocyte porphyrin (0.4-1.7 μmol/L) 35.8 μmol/L NA 26.2 μmol/L Total white blood cell count (4000-11,000/mm 3 ) 1700/mm 3 3600/mm 3 4500/mm 3 Platelets (150,000-450,000/mm 3 ) 107,000/mm 3 150,000/mm 3 175,000/mm 3 Hemoglobin (female: 12.0-15.5 g/dL) 9.4 g/dL 8.7 g/dL 12 g/dL'}
|
Lymphatic-System
|
LYMPH
|
[] |
test-2157
|
8022107
|
{'Case 2': 'The older sister of case patient 1 presented at the age of 18 years with photoinduced skin blistering of the face and extremities since her sixth day of life. She had associated progressive deformities of her bilateral hands and feet, bilateral ears, and nose. She reported having had photophobia and diminished vision in the right eye since early childhood. Examination revealed sclerodermatous changes and hypopigmented and hyperpigmented scars over the face and extremities ( Fig 2, A ); partial absorption of both ears; and brownish-pink-colored teeth. Hypertrichosis over the face and arms was present, and the bilateral extremities showed sclerodermatous contracture and acro-osteolysis ( Fig 2, B ). Ectropion and bilateral keratoconjunctivitis were apparent. She had mild anemia and splenomegaly. Porphyrin profiling and genetic analysis were not performed because of the unavailability of laboratory facilities at that time. She died at the age of 24 from a secondary infection. Fig 2 A, Sclerodermatous changes and hypopigmented and hyperpigmented scars over the face. B, Acro-osteolysis and contracture of the bilateral hands.', 'Case 3': "A 35-year-old woman, born to phenotypically normal parents, presented with progressive bilateral deformities of the hands and photoblistering since birth, with resulting dyspigmentation, scarring, and sclerodermatous changes of the face and distal extremities ( Fig 3 ) and progressive deformities of both hands. She had a history of recurrent keratoconjunctivitis and complications requiring enucleation of her left eye ( Fig 3 ). Facial hypertrichosis, microstomia ( Fig 3 ), erythrodontia, and mutilations of both hands were evident on examination. Laboratory reports revealed a normal complete blood count but an abnormal porphyrin profile ( Table I ). Fig 3 Dyspigmentation, scarring, and sclerodermatous changes over the face with enucleation of the left eye. Wood's lamp examination revealed pink-red fluorescence of the urine and teeth in all 3 patients. In case patients 1 and 3, sequencing of the UROS gene, exons 1 to 10 including flanking intronic regions, showed a homozygous transversion of T to G at nucleotide 416 in exon 7 (c.416T>G) leading to an L139R protein substitution at the terminal of the β6 protein chain. The patients were advised to use strict photoprotection, emollients, and vitamin D supplementation. They were also counseled about the disease, the need for long-term follow-up, wound care, and lifestyle modifications.", 'Case 1': 'A 17-year-old female (now 37 years old), born from a nonconsanguineous marriage, presented with a history of spontaneous blistering over photoexposed areas, starting in the first few days of her life. The lesions healed with scarring that led to progressive deformities of her hands, ears, and nose by 18 years of age. Her mother reported a red discharge in her diaper and redness and matting of both eyes since early childhood. She gradually developed deformities of her eyelids, making it difficult to close them fully. Three of her 7 siblings were similarly affected. Two of the affected siblings died shortly after birth, and a third, her older sister (case 2), died at the age of 24. Both parents were phenotypically normal. Examination revealed thickened skin, hypopigmentation and hyperpigmentation, and scarring at photoexposed sites ( Fig 1, A ); facial hypertrichosis; and reddish-brown tooth discoloration and disfiguration of the nose, ears, and fingertips bilaterally to the proximal interphalangeal joints. Eye examination revealed severe ectropion, trichiasis, and scleral melting ( Fig 1, B ). Abdominal examination revealed an enlarged spleen 4 cm below the left costal margin. Blood investigation showed pancytopenia, elevated erythrocyte sedimentation rate, positive creatinine-reactive protein, a normal serum iron profile, and an abnormal porphyrin profile ( Table I ). Fig 1 A, Thickened skin with hypopigmentation and hyperpigmentation and scarring over photoexposed sites, facial hypertrichosis, and reddish-brownish discoloration of the teeth. B, Severe ectropion, trichiasis, and scleral melting. Table I Results of laboratory investigations Parameter (normal range) Case 1 Case 2 Case 3 Urine total porphyrin (25-144 nmol/L) 11,986 nmol/L NA 13,269 nmol/L Fecal porphyrin (10-200 nmol/g) 5569 nmol/g NA 1797 nmol/g Plasma porphyrin (<11.2 nmol/L) NA NA 1120.5 nmol/L Plasma porphyrin peak 618 nm NA 618 nm Erythrocyte porphyrin (0.4-1.7 μmol/L) 35.8 μmol/L NA 26.2 μmol/L Total white blood cell count (4000-11,000/mm 3 ) 1700/mm 3 3600/mm 3 4500/mm 3 Platelets (150,000-450,000/mm 3 ) 107,000/mm 3 150,000/mm 3 175,000/mm 3 Hemoglobin (female: 12.0-15.5 g/dL) 9.4 g/dL 8.7 g/dL 12 g/dL'}
|
{'Case 2': 'The older sister of case patient 1 presented at the age of 18 years with photoinduced skin blistering of the face and extremities since her sixth day of life. She had associated progressive deformities of her bilateral hands and feet, bilateral ears, and nose. She reported having had photophobia and diminished vision in the right eye since early childhood. Examination revealed sclerodermatous changes and hypopigmented and hyperpigmented scars over the face and extremities ( Fig 2, A ); partial absorption of both ears; and brownish-pink-colored teeth. Hypertrichosis over the face and arms was present, and the bilateral extremities showed sclerodermatous contracture and acro-osteolysis ( Fig 2, B ). Ectropion and bilateral keratoconjunctivitis were apparent. She had mild anemia and splenomegaly. Porphyrin profiling and genetic analysis were not performed because of the unavailability of laboratory facilities at that time. She died at the age of 24 from a secondary infection. Fig 2 A, Sclerodermatous changes and hypopigmented and hyperpigmented scars over the face. B, Acro-osteolysis and contracture of the bilateral hands.', 'Case 3': "A 35-year-old woman, born to phenotypically normal parents, presented with progressive bilateral deformities of the hands and photoblistering since birth, with resulting dyspigmentation, scarring, and sclerodermatous changes of the face and distal extremities ( Fig 3 ) and progressive deformities of both hands. She had a history of recurrent keratoconjunctivitis and complications requiring enucleation of her left eye ( Fig 3 ). Facial hypertrichosis, microstomia ( Fig 3 ), erythrodontia, and mutilations of both hands were evident on examination. Laboratory reports revealed a normal complete blood count but an abnormal porphyrin profile ( Table I ). Fig 3 Dyspigmentation, scarring, and sclerodermatous changes over the face with enucleation of the left eye. Wood's lamp examination revealed pink-red fluorescence of the urine and teeth in all 3 patients. In case patients 1 and 3, sequencing of the UROS gene, exons 1 to 10 including flanking intronic regions, showed a homozygous transversion of T to G at nucleotide 416 in exon 7 (c.416T>G) leading to an L139R protein substitution at the terminal of the β6 protein chain. The patients were advised to use strict photoprotection, emollients, and vitamin D supplementation. They were also counseled about the disease, the need for long-term follow-up, wound care, and lifestyle modifications.", 'Case 1': 'A 17-year-old female (now 37 years old), born from a nonconsanguineous marriage, presented with a history of spontaneous blistering over photoexposed areas, starting in the first few days of her life. The lesions healed with scarring that led to progressive deformities of her hands, ears, and nose by 18 years of age. Her mother reported a red discharge in her diaper and redness and matting of both eyes since early childhood. She gradually developed deformities of her eyelids, making it difficult to close them fully. Three of her 7 siblings were similarly affected. Two of the affected siblings died shortly after birth, and a third, her older sister (case 2), died at the age of 24. Both parents were phenotypically normal. Examination revealed thickened skin, hypopigmentation and hyperpigmentation, and scarring at photoexposed sites ( Fig 1, A ); facial hypertrichosis; and reddish-brown tooth discoloration and disfiguration of the nose, ears, and fingertips bilaterally to the proximal interphalangeal joints. Eye examination revealed severe ectropion, trichiasis, and scleral melting ( Fig 1, B ). Abdominal examination revealed an enlarged spleen 4 cm below the left costal margin. Blood investigation showed pancytopenia, elevated erythrocyte sedimentation rate, positive creatinine-reactive protein, a normal serum iron profile, and an abnormal porphyrin profile ( Table I ). Fig 1 A, Thickened skin with hypopigmentation and hyperpigmentation and scarring over photoexposed sites, facial hypertrichosis, and reddish-brownish discoloration of the teeth. B, Severe ectropion, trichiasis, and scleral melting. Table I Results of laboratory investigations Parameter (normal range) Case 1 Case 2 Case 3 Urine total porphyrin (25-144 nmol/L) 11,986 nmol/L NA 13,269 nmol/L Fecal porphyrin (10-200 nmol/g) 5569 nmol/g NA 1797 nmol/g Plasma porphyrin (<11.2 nmol/L) NA NA 1120.5 nmol/L Plasma porphyrin peak 618 nm NA 618 nm Erythrocyte porphyrin (0.4-1.7 μmol/L) 35.8 μmol/L NA 26.2 μmol/L Total white blood cell count (4000-11,000/mm 3 ) 1700/mm 3 3600/mm 3 4500/mm 3 Platelets (150,000-450,000/mm 3 ) 107,000/mm 3 150,000/mm 3 175,000/mm 3 Hemoglobin (female: 12.0-15.5 g/dL) 9.4 g/dL 8.7 g/dL 12 g/dL'}
|
Age-at-Presentation
|
Age (at case presentation)
|
[
"35 - year - old",
"17 - year - old"
] |
test-2158
|
8022107
|
{'Case 2': 'The older sister of case patient 1 presented at the age of 18 years with photoinduced skin blistering of the face and extremities since her sixth day of life. She had associated progressive deformities of her bilateral hands and feet, bilateral ears, and nose. She reported having had photophobia and diminished vision in the right eye since early childhood. Examination revealed sclerodermatous changes and hypopigmented and hyperpigmented scars over the face and extremities ( Fig 2, A ); partial absorption of both ears; and brownish-pink-colored teeth. Hypertrichosis over the face and arms was present, and the bilateral extremities showed sclerodermatous contracture and acro-osteolysis ( Fig 2, B ). Ectropion and bilateral keratoconjunctivitis were apparent. She had mild anemia and splenomegaly. Porphyrin profiling and genetic analysis were not performed because of the unavailability of laboratory facilities at that time. She died at the age of 24 from a secondary infection. Fig 2 A, Sclerodermatous changes and hypopigmented and hyperpigmented scars over the face. B, Acro-osteolysis and contracture of the bilateral hands.', 'Case 3': "A 35-year-old woman, born to phenotypically normal parents, presented with progressive bilateral deformities of the hands and photoblistering since birth, with resulting dyspigmentation, scarring, and sclerodermatous changes of the face and distal extremities ( Fig 3 ) and progressive deformities of both hands. She had a history of recurrent keratoconjunctivitis and complications requiring enucleation of her left eye ( Fig 3 ). Facial hypertrichosis, microstomia ( Fig 3 ), erythrodontia, and mutilations of both hands were evident on examination. Laboratory reports revealed a normal complete blood count but an abnormal porphyrin profile ( Table I ). Fig 3 Dyspigmentation, scarring, and sclerodermatous changes over the face with enucleation of the left eye. Wood's lamp examination revealed pink-red fluorescence of the urine and teeth in all 3 patients. In case patients 1 and 3, sequencing of the UROS gene, exons 1 to 10 including flanking intronic regions, showed a homozygous transversion of T to G at nucleotide 416 in exon 7 (c.416T>G) leading to an L139R protein substitution at the terminal of the β6 protein chain. The patients were advised to use strict photoprotection, emollients, and vitamin D supplementation. They were also counseled about the disease, the need for long-term follow-up, wound care, and lifestyle modifications.", 'Case 1': 'A 17-year-old female (now 37 years old), born from a nonconsanguineous marriage, presented with a history of spontaneous blistering over photoexposed areas, starting in the first few days of her life. The lesions healed with scarring that led to progressive deformities of her hands, ears, and nose by 18 years of age. Her mother reported a red discharge in her diaper and redness and matting of both eyes since early childhood. She gradually developed deformities of her eyelids, making it difficult to close them fully. Three of her 7 siblings were similarly affected. Two of the affected siblings died shortly after birth, and a third, her older sister (case 2), died at the age of 24. Both parents were phenotypically normal. Examination revealed thickened skin, hypopigmentation and hyperpigmentation, and scarring at photoexposed sites ( Fig 1, A ); facial hypertrichosis; and reddish-brown tooth discoloration and disfiguration of the nose, ears, and fingertips bilaterally to the proximal interphalangeal joints. Eye examination revealed severe ectropion, trichiasis, and scleral melting ( Fig 1, B ). Abdominal examination revealed an enlarged spleen 4 cm below the left costal margin. Blood investigation showed pancytopenia, elevated erythrocyte sedimentation rate, positive creatinine-reactive protein, a normal serum iron profile, and an abnormal porphyrin profile ( Table I ). Fig 1 A, Thickened skin with hypopigmentation and hyperpigmentation and scarring over photoexposed sites, facial hypertrichosis, and reddish-brownish discoloration of the teeth. B, Severe ectropion, trichiasis, and scleral melting. Table I Results of laboratory investigations Parameter (normal range) Case 1 Case 2 Case 3 Urine total porphyrin (25-144 nmol/L) 11,986 nmol/L NA 13,269 nmol/L Fecal porphyrin (10-200 nmol/g) 5569 nmol/g NA 1797 nmol/g Plasma porphyrin (<11.2 nmol/L) NA NA 1120.5 nmol/L Plasma porphyrin peak 618 nm NA 618 nm Erythrocyte porphyrin (0.4-1.7 μmol/L) 35.8 μmol/L NA 26.2 μmol/L Total white blood cell count (4000-11,000/mm 3 ) 1700/mm 3 3600/mm 3 4500/mm 3 Platelets (150,000-450,000/mm 3 ) 107,000/mm 3 150,000/mm 3 175,000/mm 3 Hemoglobin (female: 12.0-15.5 g/dL) 9.4 g/dL 8.7 g/dL 12 g/dL'}
|
{'Case 2': 'The older sister of case patient 1 presented at the age of 18 years with photoinduced skin blistering of the face and extremities since her sixth day of life. She had associated progressive deformities of her bilateral hands and feet, bilateral ears, and nose. She reported having had photophobia and diminished vision in the right eye since early childhood. Examination revealed sclerodermatous changes and hypopigmented and hyperpigmented scars over the face and extremities ( Fig 2, A ); partial absorption of both ears; and brownish-pink-colored teeth. Hypertrichosis over the face and arms was present, and the bilateral extremities showed sclerodermatous contracture and acro-osteolysis ( Fig 2, B ). Ectropion and bilateral keratoconjunctivitis were apparent. She had mild anemia and splenomegaly. Porphyrin profiling and genetic analysis were not performed because of the unavailability of laboratory facilities at that time. She died at the age of 24 from a secondary infection. Fig 2 A, Sclerodermatous changes and hypopigmented and hyperpigmented scars over the face. B, Acro-osteolysis and contracture of the bilateral hands.', 'Case 3': "A 35-year-old woman, born to phenotypically normal parents, presented with progressive bilateral deformities of the hands and photoblistering since birth, with resulting dyspigmentation, scarring, and sclerodermatous changes of the face and distal extremities ( Fig 3 ) and progressive deformities of both hands. She had a history of recurrent keratoconjunctivitis and complications requiring enucleation of her left eye ( Fig 3 ). Facial hypertrichosis, microstomia ( Fig 3 ), erythrodontia, and mutilations of both hands were evident on examination. Laboratory reports revealed a normal complete blood count but an abnormal porphyrin profile ( Table I ). Fig 3 Dyspigmentation, scarring, and sclerodermatous changes over the face with enucleation of the left eye. Wood's lamp examination revealed pink-red fluorescence of the urine and teeth in all 3 patients. In case patients 1 and 3, sequencing of the UROS gene, exons 1 to 10 including flanking intronic regions, showed a homozygous transversion of T to G at nucleotide 416 in exon 7 (c.416T>G) leading to an L139R protein substitution at the terminal of the β6 protein chain. The patients were advised to use strict photoprotection, emollients, and vitamin D supplementation. They were also counseled about the disease, the need for long-term follow-up, wound care, and lifestyle modifications.", 'Case 1': 'A 17-year-old female (now 37 years old), born from a nonconsanguineous marriage, presented with a history of spontaneous blistering over photoexposed areas, starting in the first few days of her life. The lesions healed with scarring that led to progressive deformities of her hands, ears, and nose by 18 years of age. Her mother reported a red discharge in her diaper and redness and matting of both eyes since early childhood. She gradually developed deformities of her eyelids, making it difficult to close them fully. Three of her 7 siblings were similarly affected. Two of the affected siblings died shortly after birth, and a third, her older sister (case 2), died at the age of 24. Both parents were phenotypically normal. Examination revealed thickened skin, hypopigmentation and hyperpigmentation, and scarring at photoexposed sites ( Fig 1, A ); facial hypertrichosis; and reddish-brown tooth discoloration and disfiguration of the nose, ears, and fingertips bilaterally to the proximal interphalangeal joints. Eye examination revealed severe ectropion, trichiasis, and scleral melting ( Fig 1, B ). Abdominal examination revealed an enlarged spleen 4 cm below the left costal margin. Blood investigation showed pancytopenia, elevated erythrocyte sedimentation rate, positive creatinine-reactive protein, a normal serum iron profile, and an abnormal porphyrin profile ( Table I ). Fig 1 A, Thickened skin with hypopigmentation and hyperpigmentation and scarring over photoexposed sites, facial hypertrichosis, and reddish-brownish discoloration of the teeth. B, Severe ectropion, trichiasis, and scleral melting. Table I Results of laboratory investigations Parameter (normal range) Case 1 Case 2 Case 3 Urine total porphyrin (25-144 nmol/L) 11,986 nmol/L NA 13,269 nmol/L Fecal porphyrin (10-200 nmol/g) 5569 nmol/g NA 1797 nmol/g Plasma porphyrin (<11.2 nmol/L) NA NA 1120.5 nmol/L Plasma porphyrin peak 618 nm NA 618 nm Erythrocyte porphyrin (0.4-1.7 μmol/L) 35.8 μmol/L NA 26.2 μmol/L Total white blood cell count (4000-11,000/mm 3 ) 1700/mm 3 3600/mm 3 4500/mm 3 Platelets (150,000-450,000/mm 3 ) 107,000/mm 3 150,000/mm 3 175,000/mm 3 Hemoglobin (female: 12.0-15.5 g/dL) 9.4 g/dL 8.7 g/dL 12 g/dL'}
|
Age-of-Onset
|
Age (of onset)
|
[
"presented at the age of 18 years",
"birth"
] |
test-2159
|
8022107
|
{'Case 2': 'The older sister of case patient 1 presented at the age of 18 years with photoinduced skin blistering of the face and extremities since her sixth day of life. She had associated progressive deformities of her bilateral hands and feet, bilateral ears, and nose. She reported having had photophobia and diminished vision in the right eye since early childhood. Examination revealed sclerodermatous changes and hypopigmented and hyperpigmented scars over the face and extremities ( Fig 2, A ); partial absorption of both ears; and brownish-pink-colored teeth. Hypertrichosis over the face and arms was present, and the bilateral extremities showed sclerodermatous contracture and acro-osteolysis ( Fig 2, B ). Ectropion and bilateral keratoconjunctivitis were apparent. She had mild anemia and splenomegaly. Porphyrin profiling and genetic analysis were not performed because of the unavailability of laboratory facilities at that time. She died at the age of 24 from a secondary infection. Fig 2 A, Sclerodermatous changes and hypopigmented and hyperpigmented scars over the face. B, Acro-osteolysis and contracture of the bilateral hands.', 'Case 3': "A 35-year-old woman, born to phenotypically normal parents, presented with progressive bilateral deformities of the hands and photoblistering since birth, with resulting dyspigmentation, scarring, and sclerodermatous changes of the face and distal extremities ( Fig 3 ) and progressive deformities of both hands. She had a history of recurrent keratoconjunctivitis and complications requiring enucleation of her left eye ( Fig 3 ). Facial hypertrichosis, microstomia ( Fig 3 ), erythrodontia, and mutilations of both hands were evident on examination. Laboratory reports revealed a normal complete blood count but an abnormal porphyrin profile ( Table I ). Fig 3 Dyspigmentation, scarring, and sclerodermatous changes over the face with enucleation of the left eye. Wood's lamp examination revealed pink-red fluorescence of the urine and teeth in all 3 patients. In case patients 1 and 3, sequencing of the UROS gene, exons 1 to 10 including flanking intronic regions, showed a homozygous transversion of T to G at nucleotide 416 in exon 7 (c.416T>G) leading to an L139R protein substitution at the terminal of the β6 protein chain. The patients were advised to use strict photoprotection, emollients, and vitamin D supplementation. They were also counseled about the disease, the need for long-term follow-up, wound care, and lifestyle modifications.", 'Case 1': 'A 17-year-old female (now 37 years old), born from a nonconsanguineous marriage, presented with a history of spontaneous blistering over photoexposed areas, starting in the first few days of her life. The lesions healed with scarring that led to progressive deformities of her hands, ears, and nose by 18 years of age. Her mother reported a red discharge in her diaper and redness and matting of both eyes since early childhood. She gradually developed deformities of her eyelids, making it difficult to close them fully. Three of her 7 siblings were similarly affected. Two of the affected siblings died shortly after birth, and a third, her older sister (case 2), died at the age of 24. Both parents were phenotypically normal. Examination revealed thickened skin, hypopigmentation and hyperpigmentation, and scarring at photoexposed sites ( Fig 1, A ); facial hypertrichosis; and reddish-brown tooth discoloration and disfiguration of the nose, ears, and fingertips bilaterally to the proximal interphalangeal joints. Eye examination revealed severe ectropion, trichiasis, and scleral melting ( Fig 1, B ). Abdominal examination revealed an enlarged spleen 4 cm below the left costal margin. Blood investigation showed pancytopenia, elevated erythrocyte sedimentation rate, positive creatinine-reactive protein, a normal serum iron profile, and an abnormal porphyrin profile ( Table I ). Fig 1 A, Thickened skin with hypopigmentation and hyperpigmentation and scarring over photoexposed sites, facial hypertrichosis, and reddish-brownish discoloration of the teeth. B, Severe ectropion, trichiasis, and scleral melting. Table I Results of laboratory investigations Parameter (normal range) Case 1 Case 2 Case 3 Urine total porphyrin (25-144 nmol/L) 11,986 nmol/L NA 13,269 nmol/L Fecal porphyrin (10-200 nmol/g) 5569 nmol/g NA 1797 nmol/g Plasma porphyrin (<11.2 nmol/L) NA NA 1120.5 nmol/L Plasma porphyrin peak 618 nm NA 618 nm Erythrocyte porphyrin (0.4-1.7 μmol/L) 35.8 μmol/L NA 26.2 μmol/L Total white blood cell count (4000-11,000/mm 3 ) 1700/mm 3 3600/mm 3 4500/mm 3 Platelets (150,000-450,000/mm 3 ) 107,000/mm 3 150,000/mm 3 175,000/mm 3 Hemoglobin (female: 12.0-15.5 g/dL) 9.4 g/dL 8.7 g/dL 12 g/dL'}
|
{'Case 2': 'The older sister of case patient 1 presented at the age of 18 years with photoinduced skin blistering of the face and extremities since her sixth day of life. She had associated progressive deformities of her bilateral hands and feet, bilateral ears, and nose. She reported having had photophobia and diminished vision in the right eye since early childhood. Examination revealed sclerodermatous changes and hypopigmented and hyperpigmented scars over the face and extremities ( Fig 2, A ); partial absorption of both ears; and brownish-pink-colored teeth. Hypertrichosis over the face and arms was present, and the bilateral extremities showed sclerodermatous contracture and acro-osteolysis ( Fig 2, B ). Ectropion and bilateral keratoconjunctivitis were apparent. She had mild anemia and splenomegaly. Porphyrin profiling and genetic analysis were not performed because of the unavailability of laboratory facilities at that time. She died at the age of 24 from a secondary infection. Fig 2 A, Sclerodermatous changes and hypopigmented and hyperpigmented scars over the face. B, Acro-osteolysis and contracture of the bilateral hands.', 'Case 3': "A 35-year-old woman, born to phenotypically normal parents, presented with progressive bilateral deformities of the hands and photoblistering since birth, with resulting dyspigmentation, scarring, and sclerodermatous changes of the face and distal extremities ( Fig 3 ) and progressive deformities of both hands. She had a history of recurrent keratoconjunctivitis and complications requiring enucleation of her left eye ( Fig 3 ). Facial hypertrichosis, microstomia ( Fig 3 ), erythrodontia, and mutilations of both hands were evident on examination. Laboratory reports revealed a normal complete blood count but an abnormal porphyrin profile ( Table I ). Fig 3 Dyspigmentation, scarring, and sclerodermatous changes over the face with enucleation of the left eye. Wood's lamp examination revealed pink-red fluorescence of the urine and teeth in all 3 patients. In case patients 1 and 3, sequencing of the UROS gene, exons 1 to 10 including flanking intronic regions, showed a homozygous transversion of T to G at nucleotide 416 in exon 7 (c.416T>G) leading to an L139R protein substitution at the terminal of the β6 protein chain. The patients were advised to use strict photoprotection, emollients, and vitamin D supplementation. They were also counseled about the disease, the need for long-term follow-up, wound care, and lifestyle modifications.", 'Case 1': 'A 17-year-old female (now 37 years old), born from a nonconsanguineous marriage, presented with a history of spontaneous blistering over photoexposed areas, starting in the first few days of her life. The lesions healed with scarring that led to progressive deformities of her hands, ears, and nose by 18 years of age. Her mother reported a red discharge in her diaper and redness and matting of both eyes since early childhood. She gradually developed deformities of her eyelids, making it difficult to close them fully. Three of her 7 siblings were similarly affected. Two of the affected siblings died shortly after birth, and a third, her older sister (case 2), died at the age of 24. Both parents were phenotypically normal. Examination revealed thickened skin, hypopigmentation and hyperpigmentation, and scarring at photoexposed sites ( Fig 1, A ); facial hypertrichosis; and reddish-brown tooth discoloration and disfiguration of the nose, ears, and fingertips bilaterally to the proximal interphalangeal joints. Eye examination revealed severe ectropion, trichiasis, and scleral melting ( Fig 1, B ). Abdominal examination revealed an enlarged spleen 4 cm below the left costal margin. Blood investigation showed pancytopenia, elevated erythrocyte sedimentation rate, positive creatinine-reactive protein, a normal serum iron profile, and an abnormal porphyrin profile ( Table I ). Fig 1 A, Thickened skin with hypopigmentation and hyperpigmentation and scarring over photoexposed sites, facial hypertrichosis, and reddish-brownish discoloration of the teeth. B, Severe ectropion, trichiasis, and scleral melting. Table I Results of laboratory investigations Parameter (normal range) Case 1 Case 2 Case 3 Urine total porphyrin (25-144 nmol/L) 11,986 nmol/L NA 13,269 nmol/L Fecal porphyrin (10-200 nmol/g) 5569 nmol/g NA 1797 nmol/g Plasma porphyrin (<11.2 nmol/L) NA NA 1120.5 nmol/L Plasma porphyrin peak 618 nm NA 618 nm Erythrocyte porphyrin (0.4-1.7 μmol/L) 35.8 μmol/L NA 26.2 μmol/L Total white blood cell count (4000-11,000/mm 3 ) 1700/mm 3 3600/mm 3 4500/mm 3 Platelets (150,000-450,000/mm 3 ) 107,000/mm 3 150,000/mm 3 175,000/mm 3 Hemoglobin (female: 12.0-15.5 g/dL) 9.4 g/dL 8.7 g/dL 12 g/dL'}
|
Confirmed-Diagnosis-IEM
|
Confirmed_Diagnosis(IEM)
|
[] |
test-2160
|
8022107
|
{'Case 2': 'The older sister of case patient 1 presented at the age of 18 years with photoinduced skin blistering of the face and extremities since her sixth day of life. She had associated progressive deformities of her bilateral hands and feet, bilateral ears, and nose. She reported having had photophobia and diminished vision in the right eye since early childhood. Examination revealed sclerodermatous changes and hypopigmented and hyperpigmented scars over the face and extremities ( Fig 2, A ); partial absorption of both ears; and brownish-pink-colored teeth. Hypertrichosis over the face and arms was present, and the bilateral extremities showed sclerodermatous contracture and acro-osteolysis ( Fig 2, B ). Ectropion and bilateral keratoconjunctivitis were apparent. She had mild anemia and splenomegaly. Porphyrin profiling and genetic analysis were not performed because of the unavailability of laboratory facilities at that time. She died at the age of 24 from a secondary infection. Fig 2 A, Sclerodermatous changes and hypopigmented and hyperpigmented scars over the face. B, Acro-osteolysis and contracture of the bilateral hands.', 'Case 3': "A 35-year-old woman, born to phenotypically normal parents, presented with progressive bilateral deformities of the hands and photoblistering since birth, with resulting dyspigmentation, scarring, and sclerodermatous changes of the face and distal extremities ( Fig 3 ) and progressive deformities of both hands. She had a history of recurrent keratoconjunctivitis and complications requiring enucleation of her left eye ( Fig 3 ). Facial hypertrichosis, microstomia ( Fig 3 ), erythrodontia, and mutilations of both hands were evident on examination. Laboratory reports revealed a normal complete blood count but an abnormal porphyrin profile ( Table I ). Fig 3 Dyspigmentation, scarring, and sclerodermatous changes over the face with enucleation of the left eye. Wood's lamp examination revealed pink-red fluorescence of the urine and teeth in all 3 patients. In case patients 1 and 3, sequencing of the UROS gene, exons 1 to 10 including flanking intronic regions, showed a homozygous transversion of T to G at nucleotide 416 in exon 7 (c.416T>G) leading to an L139R protein substitution at the terminal of the β6 protein chain. The patients were advised to use strict photoprotection, emollients, and vitamin D supplementation. They were also counseled about the disease, the need for long-term follow-up, wound care, and lifestyle modifications.", 'Case 1': 'A 17-year-old female (now 37 years old), born from a nonconsanguineous marriage, presented with a history of spontaneous blistering over photoexposed areas, starting in the first few days of her life. The lesions healed with scarring that led to progressive deformities of her hands, ears, and nose by 18 years of age. Her mother reported a red discharge in her diaper and redness and matting of both eyes since early childhood. She gradually developed deformities of her eyelids, making it difficult to close them fully. Three of her 7 siblings were similarly affected. Two of the affected siblings died shortly after birth, and a third, her older sister (case 2), died at the age of 24. Both parents were phenotypically normal. Examination revealed thickened skin, hypopigmentation and hyperpigmentation, and scarring at photoexposed sites ( Fig 1, A ); facial hypertrichosis; and reddish-brown tooth discoloration and disfiguration of the nose, ears, and fingertips bilaterally to the proximal interphalangeal joints. Eye examination revealed severe ectropion, trichiasis, and scleral melting ( Fig 1, B ). Abdominal examination revealed an enlarged spleen 4 cm below the left costal margin. Blood investigation showed pancytopenia, elevated erythrocyte sedimentation rate, positive creatinine-reactive protein, a normal serum iron profile, and an abnormal porphyrin profile ( Table I ). Fig 1 A, Thickened skin with hypopigmentation and hyperpigmentation and scarring over photoexposed sites, facial hypertrichosis, and reddish-brownish discoloration of the teeth. B, Severe ectropion, trichiasis, and scleral melting. Table I Results of laboratory investigations Parameter (normal range) Case 1 Case 2 Case 3 Urine total porphyrin (25-144 nmol/L) 11,986 nmol/L NA 13,269 nmol/L Fecal porphyrin (10-200 nmol/g) 5569 nmol/g NA 1797 nmol/g Plasma porphyrin (<11.2 nmol/L) NA NA 1120.5 nmol/L Plasma porphyrin peak 618 nm NA 618 nm Erythrocyte porphyrin (0.4-1.7 μmol/L) 35.8 μmol/L NA 26.2 μmol/L Total white blood cell count (4000-11,000/mm 3 ) 1700/mm 3 3600/mm 3 4500/mm 3 Platelets (150,000-450,000/mm 3 ) 107,000/mm 3 150,000/mm 3 175,000/mm 3 Hemoglobin (female: 12.0-15.5 g/dL) 9.4 g/dL 8.7 g/dL 12 g/dL'}
|
{'Case 2': 'The older sister of case patient 1 presented at the age of 18 years with photoinduced skin blistering of the face and extremities since her sixth day of life. She had associated progressive deformities of her bilateral hands and feet, bilateral ears, and nose. She reported having had photophobia and diminished vision in the right eye since early childhood. Examination revealed sclerodermatous changes and hypopigmented and hyperpigmented scars over the face and extremities ( Fig 2, A ); partial absorption of both ears; and brownish-pink-colored teeth. Hypertrichosis over the face and arms was present, and the bilateral extremities showed sclerodermatous contracture and acro-osteolysis ( Fig 2, B ). Ectropion and bilateral keratoconjunctivitis were apparent. She had mild anemia and splenomegaly. Porphyrin profiling and genetic analysis were not performed because of the unavailability of laboratory facilities at that time. She died at the age of 24 from a secondary infection. Fig 2 A, Sclerodermatous changes and hypopigmented and hyperpigmented scars over the face. B, Acro-osteolysis and contracture of the bilateral hands.', 'Case 3': "A 35-year-old woman, born to phenotypically normal parents, presented with progressive bilateral deformities of the hands and photoblistering since birth, with resulting dyspigmentation, scarring, and sclerodermatous changes of the face and distal extremities ( Fig 3 ) and progressive deformities of both hands. She had a history of recurrent keratoconjunctivitis and complications requiring enucleation of her left eye ( Fig 3 ). Facial hypertrichosis, microstomia ( Fig 3 ), erythrodontia, and mutilations of both hands were evident on examination. Laboratory reports revealed a normal complete blood count but an abnormal porphyrin profile ( Table I ). Fig 3 Dyspigmentation, scarring, and sclerodermatous changes over the face with enucleation of the left eye. Wood's lamp examination revealed pink-red fluorescence of the urine and teeth in all 3 patients. In case patients 1 and 3, sequencing of the UROS gene, exons 1 to 10 including flanking intronic regions, showed a homozygous transversion of T to G at nucleotide 416 in exon 7 (c.416T>G) leading to an L139R protein substitution at the terminal of the β6 protein chain. The patients were advised to use strict photoprotection, emollients, and vitamin D supplementation. They were also counseled about the disease, the need for long-term follow-up, wound care, and lifestyle modifications.", 'Case 1': 'A 17-year-old female (now 37 years old), born from a nonconsanguineous marriage, presented with a history of spontaneous blistering over photoexposed areas, starting in the first few days of her life. The lesions healed with scarring that led to progressive deformities of her hands, ears, and nose by 18 years of age. Her mother reported a red discharge in her diaper and redness and matting of both eyes since early childhood. She gradually developed deformities of her eyelids, making it difficult to close them fully. Three of her 7 siblings were similarly affected. Two of the affected siblings died shortly after birth, and a third, her older sister (case 2), died at the age of 24. Both parents were phenotypically normal. Examination revealed thickened skin, hypopigmentation and hyperpigmentation, and scarring at photoexposed sites ( Fig 1, A ); facial hypertrichosis; and reddish-brown tooth discoloration and disfiguration of the nose, ears, and fingertips bilaterally to the proximal interphalangeal joints. Eye examination revealed severe ectropion, trichiasis, and scleral melting ( Fig 1, B ). Abdominal examination revealed an enlarged spleen 4 cm below the left costal margin. Blood investigation showed pancytopenia, elevated erythrocyte sedimentation rate, positive creatinine-reactive protein, a normal serum iron profile, and an abnormal porphyrin profile ( Table I ). Fig 1 A, Thickened skin with hypopigmentation and hyperpigmentation and scarring over photoexposed sites, facial hypertrichosis, and reddish-brownish discoloration of the teeth. B, Severe ectropion, trichiasis, and scleral melting. Table I Results of laboratory investigations Parameter (normal range) Case 1 Case 2 Case 3 Urine total porphyrin (25-144 nmol/L) 11,986 nmol/L NA 13,269 nmol/L Fecal porphyrin (10-200 nmol/g) 5569 nmol/g NA 1797 nmol/g Plasma porphyrin (<11.2 nmol/L) NA NA 1120.5 nmol/L Plasma porphyrin peak 618 nm NA 618 nm Erythrocyte porphyrin (0.4-1.7 μmol/L) 35.8 μmol/L NA 26.2 μmol/L Total white blood cell count (4000-11,000/mm 3 ) 1700/mm 3 3600/mm 3 4500/mm 3 Platelets (150,000-450,000/mm 3 ) 107,000/mm 3 150,000/mm 3 175,000/mm 3 Hemoglobin (female: 12.0-15.5 g/dL) 9.4 g/dL 8.7 g/dL 12 g/dL'}
|
IEM-Treatment
|
IEM_Treatment
|
[
"The patients were advised to use strict photoprotection"
] |
test-2161
|
8114284
|
{'History, Clinical Examination, and Hormonal Laboratory Findings': 'The proband was born full-term to nonconsanguineous parents by spontaneous vaginal delivery following an uncomplicated gestation. On the day of delivery, he was found to have persistent hypoglycemia with blood glucoses of 20 to 30s mg/dL. Initial physical examination was notable for bilateral descended testes and a fused scrotum with a small phallus (1.5 cm × 0.08 cm). Laboratory evaluation showed low cortisol at <0.2 µg/dL (both at time of hypoglycemia and following 1 µg adrenocorticotropic hormone stimulation test, with normal for these being ≥18 µg/dL), and he was started on hydrocortisone for adrenal insufficiency. At 10 days of life, he developed hyponatremia (sodium 130 mmol/L) and hyperkalemia (potassium 7.2 mmol/L). Fludrocortisone was added with resultant normalization of electrolytes. Additional neonatal evaluation included normal newborn screen (although undetectable 17-hydroxyprogesterone), normal pituitary on brain magnetic resonance imaging, normal chromosomal microarray, and 46,XY karyotype. He had an elevated ACTH >1250 pg/mL (normal 0-46), elevated plasma renin activity 193 ng/mL/h (normal 2-37), and low aldosterone 3 ng/dL (normal 6-179) indicative of primary adrenal insufficiency. Serum 17-hydroxyprogesterone was also undetectable at <10 ng/dL. At 2 months of age, during the minipuberty of infancy, he had an elevated luteinizing hormone 17.5 mIU/mL (normal 0.02-7.0) and follicle-stimulating hormone 7.9 mIU/mL (normal 0.16-4.1), and low total testosterone 5.6 ng/dL (normal 60-400) consistent with hypergonadotropic hypogonadism. He received testosterone 25 mg intramuscularly every 28 days for 4 doses, to replace the absent testosterone surge during the minipuberty of infancy.', 'Genetic Analysis': 'The patient underwent genetic testing at a commercial laboratory. The testing included sequencing of exonic regions and at least 10 bases of flanking intronic regions for 69 genes associated with differences in sex development. Initial sequencing and copy number variant detection was done using standard methods for next-generation (short read) sequencing. Read depth was at least 20× for all regions included on the panel. Potential pathogenic variants were confirmed using Sanger sequencing, also using standard methods. Results revealed a heterozygous novel variant in STAR at c.65-2A>C, confirming a diagnosis of LCAH. Targeted variant testing was negative for the variant in both parents, confirming a de novo pathogenic variant in the proband. No other potential pathogenic variants were detected in genes associated with a difference of sex development.'}
|
{'History, Clinical Examination, and Hormonal Laboratory Findings': 'The proband was born full-term to nonconsanguineous parents by spontaneous vaginal delivery following an uncomplicated gestation. On the day of delivery, he was found to have persistent hypoglycemia with blood glucoses of 20 to 30s mg/dL. Initial physical examination was notable for bilateral descended testes and a fused scrotum with a small phallus (1.5 cm × 0.08 cm). Laboratory evaluation showed low cortisol at <0.2 µg/dL (both at time of hypoglycemia and following 1 µg adrenocorticotropic hormone stimulation test, with normal for these being ≥18 µg/dL), and he was started on hydrocortisone for adrenal insufficiency. At 10 days of life, he developed hyponatremia (sodium 130 mmol/L) and hyperkalemia (potassium 7.2 mmol/L). Fludrocortisone was added with resultant normalization of electrolytes. Additional neonatal evaluation included normal newborn screen (although undetectable 17-hydroxyprogesterone), normal pituitary on brain magnetic resonance imaging, normal chromosomal microarray, and 46,XY karyotype. He had an elevated ACTH >1250 pg/mL (normal 0-46), elevated plasma renin activity 193 ng/mL/h (normal 2-37), and low aldosterone 3 ng/dL (normal 6-179) indicative of primary adrenal insufficiency. Serum 17-hydroxyprogesterone was also undetectable at <10 ng/dL. At 2 months of age, during the minipuberty of infancy, he had an elevated luteinizing hormone 17.5 mIU/mL (normal 0.02-7.0) and follicle-stimulating hormone 7.9 mIU/mL (normal 0.16-4.1), and low total testosterone 5.6 ng/dL (normal 60-400) consistent with hypergonadotropic hypogonadism. He received testosterone 25 mg intramuscularly every 28 days for 4 doses, to replace the absent testosterone surge during the minipuberty of infancy.', 'Genetic Analysis': 'The patient underwent genetic testing at a commercial laboratory. The testing included sequencing of exonic regions and at least 10 bases of flanking intronic regions for 69 genes associated with differences in sex development. Initial sequencing and copy number variant detection was done using standard methods for next-generation (short read) sequencing. Read depth was at least 20× for all regions included on the panel. Potential pathogenic variants were confirmed using Sanger sequencing, also using standard methods. Results revealed a heterozygous novel variant in STAR at c.65-2A>C, confirming a diagnosis of LCAH. Targeted variant testing was negative for the variant in both parents, confirming a de novo pathogenic variant in the proband. No other potential pathogenic variants were detected in genes associated with a difference of sex development.'}
|
Vitals-and-Hematology
|
Vitals_Hema
|
[] |
test-2162
|
8114284
|
{'History, Clinical Examination, and Hormonal Laboratory Findings': 'The proband was born full-term to nonconsanguineous parents by spontaneous vaginal delivery following an uncomplicated gestation. On the day of delivery, he was found to have persistent hypoglycemia with blood glucoses of 20 to 30s mg/dL. Initial physical examination was notable for bilateral descended testes and a fused scrotum with a small phallus (1.5 cm × 0.08 cm). Laboratory evaluation showed low cortisol at <0.2 µg/dL (both at time of hypoglycemia and following 1 µg adrenocorticotropic hormone stimulation test, with normal for these being ≥18 µg/dL), and he was started on hydrocortisone for adrenal insufficiency. At 10 days of life, he developed hyponatremia (sodium 130 mmol/L) and hyperkalemia (potassium 7.2 mmol/L). Fludrocortisone was added with resultant normalization of electrolytes. Additional neonatal evaluation included normal newborn screen (although undetectable 17-hydroxyprogesterone), normal pituitary on brain magnetic resonance imaging, normal chromosomal microarray, and 46,XY karyotype. He had an elevated ACTH >1250 pg/mL (normal 0-46), elevated plasma renin activity 193 ng/mL/h (normal 2-37), and low aldosterone 3 ng/dL (normal 6-179) indicative of primary adrenal insufficiency. Serum 17-hydroxyprogesterone was also undetectable at <10 ng/dL. At 2 months of age, during the minipuberty of infancy, he had an elevated luteinizing hormone 17.5 mIU/mL (normal 0.02-7.0) and follicle-stimulating hormone 7.9 mIU/mL (normal 0.16-4.1), and low total testosterone 5.6 ng/dL (normal 60-400) consistent with hypergonadotropic hypogonadism. He received testosterone 25 mg intramuscularly every 28 days for 4 doses, to replace the absent testosterone surge during the minipuberty of infancy.', 'Genetic Analysis': 'The patient underwent genetic testing at a commercial laboratory. The testing included sequencing of exonic regions and at least 10 bases of flanking intronic regions for 69 genes associated with differences in sex development. Initial sequencing and copy number variant detection was done using standard methods for next-generation (short read) sequencing. Read depth was at least 20× for all regions included on the panel. Potential pathogenic variants were confirmed using Sanger sequencing, also using standard methods. Results revealed a heterozygous novel variant in STAR at c.65-2A>C, confirming a diagnosis of LCAH. Targeted variant testing was negative for the variant in both parents, confirming a de novo pathogenic variant in the proband. No other potential pathogenic variants were detected in genes associated with a difference of sex development.'}
|
{'History, Clinical Examination, and Hormonal Laboratory Findings': 'The proband was born full-term to nonconsanguineous parents by spontaneous vaginal delivery following an uncomplicated gestation. On the day of delivery, he was found to have persistent hypoglycemia with blood glucoses of 20 to 30s mg/dL. Initial physical examination was notable for bilateral descended testes and a fused scrotum with a small phallus (1.5 cm × 0.08 cm). Laboratory evaluation showed low cortisol at <0.2 µg/dL (both at time of hypoglycemia and following 1 µg adrenocorticotropic hormone stimulation test, with normal for these being ≥18 µg/dL), and he was started on hydrocortisone for adrenal insufficiency. At 10 days of life, he developed hyponatremia (sodium 130 mmol/L) and hyperkalemia (potassium 7.2 mmol/L). Fludrocortisone was added with resultant normalization of electrolytes. Additional neonatal evaluation included normal newborn screen (although undetectable 17-hydroxyprogesterone), normal pituitary on brain magnetic resonance imaging, normal chromosomal microarray, and 46,XY karyotype. He had an elevated ACTH >1250 pg/mL (normal 0-46), elevated plasma renin activity 193 ng/mL/h (normal 2-37), and low aldosterone 3 ng/dL (normal 6-179) indicative of primary adrenal insufficiency. Serum 17-hydroxyprogesterone was also undetectable at <10 ng/dL. At 2 months of age, during the minipuberty of infancy, he had an elevated luteinizing hormone 17.5 mIU/mL (normal 0.02-7.0) and follicle-stimulating hormone 7.9 mIU/mL (normal 0.16-4.1), and low total testosterone 5.6 ng/dL (normal 60-400) consistent with hypergonadotropic hypogonadism. He received testosterone 25 mg intramuscularly every 28 days for 4 doses, to replace the absent testosterone surge during the minipuberty of infancy.', 'Genetic Analysis': 'The patient underwent genetic testing at a commercial laboratory. The testing included sequencing of exonic regions and at least 10 bases of flanking intronic regions for 69 genes associated with differences in sex development. Initial sequencing and copy number variant detection was done using standard methods for next-generation (short read) sequencing. Read depth was at least 20× for all regions included on the panel. Potential pathogenic variants were confirmed using Sanger sequencing, also using standard methods. Results revealed a heterozygous novel variant in STAR at c.65-2A>C, confirming a diagnosis of LCAH. Targeted variant testing was negative for the variant in both parents, confirming a de novo pathogenic variant in the proband. No other potential pathogenic variants were detected in genes associated with a difference of sex development.'}
|
Gastrointestinal-System
|
GI
|
[] |
test-2163
|
8114284
|
{'History, Clinical Examination, and Hormonal Laboratory Findings': 'The proband was born full-term to nonconsanguineous parents by spontaneous vaginal delivery following an uncomplicated gestation. On the day of delivery, he was found to have persistent hypoglycemia with blood glucoses of 20 to 30s mg/dL. Initial physical examination was notable for bilateral descended testes and a fused scrotum with a small phallus (1.5 cm × 0.08 cm). Laboratory evaluation showed low cortisol at <0.2 µg/dL (both at time of hypoglycemia and following 1 µg adrenocorticotropic hormone stimulation test, with normal for these being ≥18 µg/dL), and he was started on hydrocortisone for adrenal insufficiency. At 10 days of life, he developed hyponatremia (sodium 130 mmol/L) and hyperkalemia (potassium 7.2 mmol/L). Fludrocortisone was added with resultant normalization of electrolytes. Additional neonatal evaluation included normal newborn screen (although undetectable 17-hydroxyprogesterone), normal pituitary on brain magnetic resonance imaging, normal chromosomal microarray, and 46,XY karyotype. He had an elevated ACTH >1250 pg/mL (normal 0-46), elevated plasma renin activity 193 ng/mL/h (normal 2-37), and low aldosterone 3 ng/dL (normal 6-179) indicative of primary adrenal insufficiency. Serum 17-hydroxyprogesterone was also undetectable at <10 ng/dL. At 2 months of age, during the minipuberty of infancy, he had an elevated luteinizing hormone 17.5 mIU/mL (normal 0.02-7.0) and follicle-stimulating hormone 7.9 mIU/mL (normal 0.16-4.1), and low total testosterone 5.6 ng/dL (normal 60-400) consistent with hypergonadotropic hypogonadism. He received testosterone 25 mg intramuscularly every 28 days for 4 doses, to replace the absent testosterone surge during the minipuberty of infancy.', 'Genetic Analysis': 'The patient underwent genetic testing at a commercial laboratory. The testing included sequencing of exonic regions and at least 10 bases of flanking intronic regions for 69 genes associated with differences in sex development. Initial sequencing and copy number variant detection was done using standard methods for next-generation (short read) sequencing. Read depth was at least 20× for all regions included on the panel. Potential pathogenic variants were confirmed using Sanger sequencing, also using standard methods. Results revealed a heterozygous novel variant in STAR at c.65-2A>C, confirming a diagnosis of LCAH. Targeted variant testing was negative for the variant in both parents, confirming a de novo pathogenic variant in the proband. No other potential pathogenic variants were detected in genes associated with a difference of sex development.'}
|
{'History, Clinical Examination, and Hormonal Laboratory Findings': 'The proband was born full-term to nonconsanguineous parents by spontaneous vaginal delivery following an uncomplicated gestation. On the day of delivery, he was found to have persistent hypoglycemia with blood glucoses of 20 to 30s mg/dL. Initial physical examination was notable for bilateral descended testes and a fused scrotum with a small phallus (1.5 cm × 0.08 cm). Laboratory evaluation showed low cortisol at <0.2 µg/dL (both at time of hypoglycemia and following 1 µg adrenocorticotropic hormone stimulation test, with normal for these being ≥18 µg/dL), and he was started on hydrocortisone for adrenal insufficiency. At 10 days of life, he developed hyponatremia (sodium 130 mmol/L) and hyperkalemia (potassium 7.2 mmol/L). Fludrocortisone was added with resultant normalization of electrolytes. Additional neonatal evaluation included normal newborn screen (although undetectable 17-hydroxyprogesterone), normal pituitary on brain magnetic resonance imaging, normal chromosomal microarray, and 46,XY karyotype. He had an elevated ACTH >1250 pg/mL (normal 0-46), elevated plasma renin activity 193 ng/mL/h (normal 2-37), and low aldosterone 3 ng/dL (normal 6-179) indicative of primary adrenal insufficiency. Serum 17-hydroxyprogesterone was also undetectable at <10 ng/dL. At 2 months of age, during the minipuberty of infancy, he had an elevated luteinizing hormone 17.5 mIU/mL (normal 0.02-7.0) and follicle-stimulating hormone 7.9 mIU/mL (normal 0.16-4.1), and low total testosterone 5.6 ng/dL (normal 60-400) consistent with hypergonadotropic hypogonadism. He received testosterone 25 mg intramuscularly every 28 days for 4 doses, to replace the absent testosterone surge during the minipuberty of infancy.', 'Genetic Analysis': 'The patient underwent genetic testing at a commercial laboratory. The testing included sequencing of exonic regions and at least 10 bases of flanking intronic regions for 69 genes associated with differences in sex development. Initial sequencing and copy number variant detection was done using standard methods for next-generation (short read) sequencing. Read depth was at least 20× for all regions included on the panel. Potential pathogenic variants were confirmed using Sanger sequencing, also using standard methods. Results revealed a heterozygous novel variant in STAR at c.65-2A>C, confirming a diagnosis of LCAH. Targeted variant testing was negative for the variant in both parents, confirming a de novo pathogenic variant in the proband. No other potential pathogenic variants were detected in genes associated with a difference of sex development.'}
|
Patient-History
|
History
|
[
"The proband was born full - term to nonconsanguineous parents by spontaneous vaginal delivery following an uncomplicated gestation. On the day of delivery, he was found to have persistent hypoglycemia with blood glucoses of 20 to 30s mg / dL."
] |
test-2164
|
8114284
|
{'History, Clinical Examination, and Hormonal Laboratory Findings': 'The proband was born full-term to nonconsanguineous parents by spontaneous vaginal delivery following an uncomplicated gestation. On the day of delivery, he was found to have persistent hypoglycemia with blood glucoses of 20 to 30s mg/dL. Initial physical examination was notable for bilateral descended testes and a fused scrotum with a small phallus (1.5 cm × 0.08 cm). Laboratory evaluation showed low cortisol at <0.2 µg/dL (both at time of hypoglycemia and following 1 µg adrenocorticotropic hormone stimulation test, with normal for these being ≥18 µg/dL), and he was started on hydrocortisone for adrenal insufficiency. At 10 days of life, he developed hyponatremia (sodium 130 mmol/L) and hyperkalemia (potassium 7.2 mmol/L). Fludrocortisone was added with resultant normalization of electrolytes. Additional neonatal evaluation included normal newborn screen (although undetectable 17-hydroxyprogesterone), normal pituitary on brain magnetic resonance imaging, normal chromosomal microarray, and 46,XY karyotype. He had an elevated ACTH >1250 pg/mL (normal 0-46), elevated plasma renin activity 193 ng/mL/h (normal 2-37), and low aldosterone 3 ng/dL (normal 6-179) indicative of primary adrenal insufficiency. Serum 17-hydroxyprogesterone was also undetectable at <10 ng/dL. At 2 months of age, during the minipuberty of infancy, he had an elevated luteinizing hormone 17.5 mIU/mL (normal 0.02-7.0) and follicle-stimulating hormone 7.9 mIU/mL (normal 0.16-4.1), and low total testosterone 5.6 ng/dL (normal 60-400) consistent with hypergonadotropic hypogonadism. He received testosterone 25 mg intramuscularly every 28 days for 4 doses, to replace the absent testosterone surge during the minipuberty of infancy.', 'Genetic Analysis': 'The patient underwent genetic testing at a commercial laboratory. The testing included sequencing of exonic regions and at least 10 bases of flanking intronic regions for 69 genes associated with differences in sex development. Initial sequencing and copy number variant detection was done using standard methods for next-generation (short read) sequencing. Read depth was at least 20× for all regions included on the panel. Potential pathogenic variants were confirmed using Sanger sequencing, also using standard methods. Results revealed a heterozygous novel variant in STAR at c.65-2A>C, confirming a diagnosis of LCAH. Targeted variant testing was negative for the variant in both parents, confirming a de novo pathogenic variant in the proband. No other potential pathogenic variants were detected in genes associated with a difference of sex development.'}
|
{'History, Clinical Examination, and Hormonal Laboratory Findings': 'The proband was born full-term to nonconsanguineous parents by spontaneous vaginal delivery following an uncomplicated gestation. On the day of delivery, he was found to have persistent hypoglycemia with blood glucoses of 20 to 30s mg/dL. Initial physical examination was notable for bilateral descended testes and a fused scrotum with a small phallus (1.5 cm × 0.08 cm). Laboratory evaluation showed low cortisol at <0.2 µg/dL (both at time of hypoglycemia and following 1 µg adrenocorticotropic hormone stimulation test, with normal for these being ≥18 µg/dL), and he was started on hydrocortisone for adrenal insufficiency. At 10 days of life, he developed hyponatremia (sodium 130 mmol/L) and hyperkalemia (potassium 7.2 mmol/L). Fludrocortisone was added with resultant normalization of electrolytes. Additional neonatal evaluation included normal newborn screen (although undetectable 17-hydroxyprogesterone), normal pituitary on brain magnetic resonance imaging, normal chromosomal microarray, and 46,XY karyotype. He had an elevated ACTH >1250 pg/mL (normal 0-46), elevated plasma renin activity 193 ng/mL/h (normal 2-37), and low aldosterone 3 ng/dL (normal 6-179) indicative of primary adrenal insufficiency. Serum 17-hydroxyprogesterone was also undetectable at <10 ng/dL. At 2 months of age, during the minipuberty of infancy, he had an elevated luteinizing hormone 17.5 mIU/mL (normal 0.02-7.0) and follicle-stimulating hormone 7.9 mIU/mL (normal 0.16-4.1), and low total testosterone 5.6 ng/dL (normal 60-400) consistent with hypergonadotropic hypogonadism. He received testosterone 25 mg intramuscularly every 28 days for 4 doses, to replace the absent testosterone surge during the minipuberty of infancy.', 'Genetic Analysis': 'The patient underwent genetic testing at a commercial laboratory. The testing included sequencing of exonic regions and at least 10 bases of flanking intronic regions for 69 genes associated with differences in sex development. Initial sequencing and copy number variant detection was done using standard methods for next-generation (short read) sequencing. Read depth was at least 20× for all regions included on the panel. Potential pathogenic variants were confirmed using Sanger sequencing, also using standard methods. Results revealed a heterozygous novel variant in STAR at c.65-2A>C, confirming a diagnosis of LCAH. Targeted variant testing was negative for the variant in both parents, confirming a de novo pathogenic variant in the proband. No other potential pathogenic variants were detected in genes associated with a difference of sex development.'}
|
Neurology
|
Neuro
|
[] |
test-2165
|
8114284
|
{'History, Clinical Examination, and Hormonal Laboratory Findings': 'The proband was born full-term to nonconsanguineous parents by spontaneous vaginal delivery following an uncomplicated gestation. On the day of delivery, he was found to have persistent hypoglycemia with blood glucoses of 20 to 30s mg/dL. Initial physical examination was notable for bilateral descended testes and a fused scrotum with a small phallus (1.5 cm × 0.08 cm). Laboratory evaluation showed low cortisol at <0.2 µg/dL (both at time of hypoglycemia and following 1 µg adrenocorticotropic hormone stimulation test, with normal for these being ≥18 µg/dL), and he was started on hydrocortisone for adrenal insufficiency. At 10 days of life, he developed hyponatremia (sodium 130 mmol/L) and hyperkalemia (potassium 7.2 mmol/L). Fludrocortisone was added with resultant normalization of electrolytes. Additional neonatal evaluation included normal newborn screen (although undetectable 17-hydroxyprogesterone), normal pituitary on brain magnetic resonance imaging, normal chromosomal microarray, and 46,XY karyotype. He had an elevated ACTH >1250 pg/mL (normal 0-46), elevated plasma renin activity 193 ng/mL/h (normal 2-37), and low aldosterone 3 ng/dL (normal 6-179) indicative of primary adrenal insufficiency. Serum 17-hydroxyprogesterone was also undetectable at <10 ng/dL. At 2 months of age, during the minipuberty of infancy, he had an elevated luteinizing hormone 17.5 mIU/mL (normal 0.02-7.0) and follicle-stimulating hormone 7.9 mIU/mL (normal 0.16-4.1), and low total testosterone 5.6 ng/dL (normal 60-400) consistent with hypergonadotropic hypogonadism. He received testosterone 25 mg intramuscularly every 28 days for 4 doses, to replace the absent testosterone surge during the minipuberty of infancy.', 'Genetic Analysis': 'The patient underwent genetic testing at a commercial laboratory. The testing included sequencing of exonic regions and at least 10 bases of flanking intronic regions for 69 genes associated with differences in sex development. Initial sequencing and copy number variant detection was done using standard methods for next-generation (short read) sequencing. Read depth was at least 20× for all regions included on the panel. Potential pathogenic variants were confirmed using Sanger sequencing, also using standard methods. Results revealed a heterozygous novel variant in STAR at c.65-2A>C, confirming a diagnosis of LCAH. Targeted variant testing was negative for the variant in both parents, confirming a de novo pathogenic variant in the proband. No other potential pathogenic variants were detected in genes associated with a difference of sex development.'}
|
{'History, Clinical Examination, and Hormonal Laboratory Findings': 'The proband was born full-term to nonconsanguineous parents by spontaneous vaginal delivery following an uncomplicated gestation. On the day of delivery, he was found to have persistent hypoglycemia with blood glucoses of 20 to 30s mg/dL. Initial physical examination was notable for bilateral descended testes and a fused scrotum with a small phallus (1.5 cm × 0.08 cm). Laboratory evaluation showed low cortisol at <0.2 µg/dL (both at time of hypoglycemia and following 1 µg adrenocorticotropic hormone stimulation test, with normal for these being ≥18 µg/dL), and he was started on hydrocortisone for adrenal insufficiency. At 10 days of life, he developed hyponatremia (sodium 130 mmol/L) and hyperkalemia (potassium 7.2 mmol/L). Fludrocortisone was added with resultant normalization of electrolytes. Additional neonatal evaluation included normal newborn screen (although undetectable 17-hydroxyprogesterone), normal pituitary on brain magnetic resonance imaging, normal chromosomal microarray, and 46,XY karyotype. He had an elevated ACTH >1250 pg/mL (normal 0-46), elevated plasma renin activity 193 ng/mL/h (normal 2-37), and low aldosterone 3 ng/dL (normal 6-179) indicative of primary adrenal insufficiency. Serum 17-hydroxyprogesterone was also undetectable at <10 ng/dL. At 2 months of age, during the minipuberty of infancy, he had an elevated luteinizing hormone 17.5 mIU/mL (normal 0.02-7.0) and follicle-stimulating hormone 7.9 mIU/mL (normal 0.16-4.1), and low total testosterone 5.6 ng/dL (normal 60-400) consistent with hypergonadotropic hypogonadism. He received testosterone 25 mg intramuscularly every 28 days for 4 doses, to replace the absent testosterone surge during the minipuberty of infancy.', 'Genetic Analysis': 'The patient underwent genetic testing at a commercial laboratory. The testing included sequencing of exonic regions and at least 10 bases of flanking intronic regions for 69 genes associated with differences in sex development. Initial sequencing and copy number variant detection was done using standard methods for next-generation (short read) sequencing. Read depth was at least 20× for all regions included on the panel. Potential pathogenic variants were confirmed using Sanger sequencing, also using standard methods. Results revealed a heterozygous novel variant in STAR at c.65-2A>C, confirming a diagnosis of LCAH. Targeted variant testing was negative for the variant in both parents, confirming a de novo pathogenic variant in the proband. No other potential pathogenic variants were detected in genes associated with a difference of sex development.'}
|
Laboratory-and-Imaging
|
Lab_Image
|
[
"Laboratory evaluation showed low cortisol at < 0.2 µg / dL ( both at time of hypoglycemia and following 1 µg adrenocorticotropic hormone stimulation test, with normal for these being ≥18 µg / dL )",
"he developed hyponatremia ( sodium 130 mmol / L ) and hyperkalemia ( potassium 7.2 mmol / L )",
"Additional neonatal evaluation included normal newborn screen ( although undetectable 17 - hydroxyprogesterone ), normal pituitary on brain magnetic resonance imaging, normal chromosomal microarray, and 46,XY karyotype. He had an elevated ACTH > 1250 pg / mL ( normal 0 - 46 ), elevated plasma renin activity 193 ng / mL / h ( normal 2 - 37 ), and low aldosterone 3 ng / dL ( normal 6 - 179 ) indicative of primary adrenal insufficiency. Serum 17 - hydroxyprogesterone was also undetectable at < 10 ng / dL. At 2 months of age, during the minipuberty of infancy, he had an elevated luteinizing hormone 17.5 mIU / mL ( normal 0.02 - 7.0 ) and follicle - stimulating hormone 7.9 mIU / mL ( normal 0.16 - 4.1 ), and low total testosterone 5.6 ng / dL ( normal 60 - 400 ) consistent with hypergonadotropic hypogonadism",
"Results revealed a heterozygous novel variant in STAR at c.65 - 2A > C",
"Targeted variant testing was negative for the variant in both parents, confirming a de novo pathogenic variant in the proband. No other potential pathogenic variants were detected in genes associated with a difference of sex development."
] |
test-2166
|
8114284
|
{'History, Clinical Examination, and Hormonal Laboratory Findings': 'The proband was born full-term to nonconsanguineous parents by spontaneous vaginal delivery following an uncomplicated gestation. On the day of delivery, he was found to have persistent hypoglycemia with blood glucoses of 20 to 30s mg/dL. Initial physical examination was notable for bilateral descended testes and a fused scrotum with a small phallus (1.5 cm × 0.08 cm). Laboratory evaluation showed low cortisol at <0.2 µg/dL (both at time of hypoglycemia and following 1 µg adrenocorticotropic hormone stimulation test, with normal for these being ≥18 µg/dL), and he was started on hydrocortisone for adrenal insufficiency. At 10 days of life, he developed hyponatremia (sodium 130 mmol/L) and hyperkalemia (potassium 7.2 mmol/L). Fludrocortisone was added with resultant normalization of electrolytes. Additional neonatal evaluation included normal newborn screen (although undetectable 17-hydroxyprogesterone), normal pituitary on brain magnetic resonance imaging, normal chromosomal microarray, and 46,XY karyotype. He had an elevated ACTH >1250 pg/mL (normal 0-46), elevated plasma renin activity 193 ng/mL/h (normal 2-37), and low aldosterone 3 ng/dL (normal 6-179) indicative of primary adrenal insufficiency. Serum 17-hydroxyprogesterone was also undetectable at <10 ng/dL. At 2 months of age, during the minipuberty of infancy, he had an elevated luteinizing hormone 17.5 mIU/mL (normal 0.02-7.0) and follicle-stimulating hormone 7.9 mIU/mL (normal 0.16-4.1), and low total testosterone 5.6 ng/dL (normal 60-400) consistent with hypergonadotropic hypogonadism. He received testosterone 25 mg intramuscularly every 28 days for 4 doses, to replace the absent testosterone surge during the minipuberty of infancy.', 'Genetic Analysis': 'The patient underwent genetic testing at a commercial laboratory. The testing included sequencing of exonic regions and at least 10 bases of flanking intronic regions for 69 genes associated with differences in sex development. Initial sequencing and copy number variant detection was done using standard methods for next-generation (short read) sequencing. Read depth was at least 20× for all regions included on the panel. Potential pathogenic variants were confirmed using Sanger sequencing, also using standard methods. Results revealed a heterozygous novel variant in STAR at c.65-2A>C, confirming a diagnosis of LCAH. Targeted variant testing was negative for the variant in both parents, confirming a de novo pathogenic variant in the proband. No other potential pathogenic variants were detected in genes associated with a difference of sex development.'}
|
{'History, Clinical Examination, and Hormonal Laboratory Findings': 'The proband was born full-term to nonconsanguineous parents by spontaneous vaginal delivery following an uncomplicated gestation. On the day of delivery, he was found to have persistent hypoglycemia with blood glucoses of 20 to 30s mg/dL. Initial physical examination was notable for bilateral descended testes and a fused scrotum with a small phallus (1.5 cm × 0.08 cm). Laboratory evaluation showed low cortisol at <0.2 µg/dL (both at time of hypoglycemia and following 1 µg adrenocorticotropic hormone stimulation test, with normal for these being ≥18 µg/dL), and he was started on hydrocortisone for adrenal insufficiency. At 10 days of life, he developed hyponatremia (sodium 130 mmol/L) and hyperkalemia (potassium 7.2 mmol/L). Fludrocortisone was added with resultant normalization of electrolytes. Additional neonatal evaluation included normal newborn screen (although undetectable 17-hydroxyprogesterone), normal pituitary on brain magnetic resonance imaging, normal chromosomal microarray, and 46,XY karyotype. He had an elevated ACTH >1250 pg/mL (normal 0-46), elevated plasma renin activity 193 ng/mL/h (normal 2-37), and low aldosterone 3 ng/dL (normal 6-179) indicative of primary adrenal insufficiency. Serum 17-hydroxyprogesterone was also undetectable at <10 ng/dL. At 2 months of age, during the minipuberty of infancy, he had an elevated luteinizing hormone 17.5 mIU/mL (normal 0.02-7.0) and follicle-stimulating hormone 7.9 mIU/mL (normal 0.16-4.1), and low total testosterone 5.6 ng/dL (normal 60-400) consistent with hypergonadotropic hypogonadism. He received testosterone 25 mg intramuscularly every 28 days for 4 doses, to replace the absent testosterone surge during the minipuberty of infancy.', 'Genetic Analysis': 'The patient underwent genetic testing at a commercial laboratory. The testing included sequencing of exonic regions and at least 10 bases of flanking intronic regions for 69 genes associated with differences in sex development. Initial sequencing and copy number variant detection was done using standard methods for next-generation (short read) sequencing. Read depth was at least 20× for all regions included on the panel. Potential pathogenic variants were confirmed using Sanger sequencing, also using standard methods. Results revealed a heterozygous novel variant in STAR at c.65-2A>C, confirming a diagnosis of LCAH. Targeted variant testing was negative for the variant in both parents, confirming a de novo pathogenic variant in the proband. No other potential pathogenic variants were detected in genes associated with a difference of sex development.'}
|
Cardiovascular-System
|
CVS
|
[] |
test-2167
|
8114284
|
{'History, Clinical Examination, and Hormonal Laboratory Findings': 'The proband was born full-term to nonconsanguineous parents by spontaneous vaginal delivery following an uncomplicated gestation. On the day of delivery, he was found to have persistent hypoglycemia with blood glucoses of 20 to 30s mg/dL. Initial physical examination was notable for bilateral descended testes and a fused scrotum with a small phallus (1.5 cm × 0.08 cm). Laboratory evaluation showed low cortisol at <0.2 µg/dL (both at time of hypoglycemia and following 1 µg adrenocorticotropic hormone stimulation test, with normal for these being ≥18 µg/dL), and he was started on hydrocortisone for adrenal insufficiency. At 10 days of life, he developed hyponatremia (sodium 130 mmol/L) and hyperkalemia (potassium 7.2 mmol/L). Fludrocortisone was added with resultant normalization of electrolytes. Additional neonatal evaluation included normal newborn screen (although undetectable 17-hydroxyprogesterone), normal pituitary on brain magnetic resonance imaging, normal chromosomal microarray, and 46,XY karyotype. He had an elevated ACTH >1250 pg/mL (normal 0-46), elevated plasma renin activity 193 ng/mL/h (normal 2-37), and low aldosterone 3 ng/dL (normal 6-179) indicative of primary adrenal insufficiency. Serum 17-hydroxyprogesterone was also undetectable at <10 ng/dL. At 2 months of age, during the minipuberty of infancy, he had an elevated luteinizing hormone 17.5 mIU/mL (normal 0.02-7.0) and follicle-stimulating hormone 7.9 mIU/mL (normal 0.16-4.1), and low total testosterone 5.6 ng/dL (normal 60-400) consistent with hypergonadotropic hypogonadism. He received testosterone 25 mg intramuscularly every 28 days for 4 doses, to replace the absent testosterone surge during the minipuberty of infancy.', 'Genetic Analysis': 'The patient underwent genetic testing at a commercial laboratory. The testing included sequencing of exonic regions and at least 10 bases of flanking intronic regions for 69 genes associated with differences in sex development. Initial sequencing and copy number variant detection was done using standard methods for next-generation (short read) sequencing. Read depth was at least 20× for all regions included on the panel. Potential pathogenic variants were confirmed using Sanger sequencing, also using standard methods. Results revealed a heterozygous novel variant in STAR at c.65-2A>C, confirming a diagnosis of LCAH. Targeted variant testing was negative for the variant in both parents, confirming a de novo pathogenic variant in the proband. No other potential pathogenic variants were detected in genes associated with a difference of sex development.'}
|
{'History, Clinical Examination, and Hormonal Laboratory Findings': 'The proband was born full-term to nonconsanguineous parents by spontaneous vaginal delivery following an uncomplicated gestation. On the day of delivery, he was found to have persistent hypoglycemia with blood glucoses of 20 to 30s mg/dL. Initial physical examination was notable for bilateral descended testes and a fused scrotum with a small phallus (1.5 cm × 0.08 cm). Laboratory evaluation showed low cortisol at <0.2 µg/dL (both at time of hypoglycemia and following 1 µg adrenocorticotropic hormone stimulation test, with normal for these being ≥18 µg/dL), and he was started on hydrocortisone for adrenal insufficiency. At 10 days of life, he developed hyponatremia (sodium 130 mmol/L) and hyperkalemia (potassium 7.2 mmol/L). Fludrocortisone was added with resultant normalization of electrolytes. Additional neonatal evaluation included normal newborn screen (although undetectable 17-hydroxyprogesterone), normal pituitary on brain magnetic resonance imaging, normal chromosomal microarray, and 46,XY karyotype. He had an elevated ACTH >1250 pg/mL (normal 0-46), elevated plasma renin activity 193 ng/mL/h (normal 2-37), and low aldosterone 3 ng/dL (normal 6-179) indicative of primary adrenal insufficiency. Serum 17-hydroxyprogesterone was also undetectable at <10 ng/dL. At 2 months of age, during the minipuberty of infancy, he had an elevated luteinizing hormone 17.5 mIU/mL (normal 0.02-7.0) and follicle-stimulating hormone 7.9 mIU/mL (normal 0.16-4.1), and low total testosterone 5.6 ng/dL (normal 60-400) consistent with hypergonadotropic hypogonadism. He received testosterone 25 mg intramuscularly every 28 days for 4 doses, to replace the absent testosterone surge during the minipuberty of infancy.', 'Genetic Analysis': 'The patient underwent genetic testing at a commercial laboratory. The testing included sequencing of exonic regions and at least 10 bases of flanking intronic regions for 69 genes associated with differences in sex development. Initial sequencing and copy number variant detection was done using standard methods for next-generation (short read) sequencing. Read depth was at least 20× for all regions included on the panel. Potential pathogenic variants were confirmed using Sanger sequencing, also using standard methods. Results revealed a heterozygous novel variant in STAR at c.65-2A>C, confirming a diagnosis of LCAH. Targeted variant testing was negative for the variant in both parents, confirming a de novo pathogenic variant in the proband. No other potential pathogenic variants were detected in genes associated with a difference of sex development.'}
|
Endocrinology
|
ENDO
|
[
"persistent hypoglycemia with blood glucoses of 20 to 30s mg / dL.",
"low cortisol at < 0.2 µg / dL ( both at time of hypoglycemia and following 1 µg adrenocorticotropic hormone stimulation test, with normal for these being ≥18 µg / dL ),",
"adrenal insufficiency",
"hyponatremia ( sodium 130 mmol / L ) and hyperkalemia ( potassium 7.2 mmol / L",
"undetectable 17 - hydroxyprogesterone ), normal pituitary on brain magnetic resonance imaging",
"He had an elevated ACTH > 1250 pg / mL ( normal 0 - 46 ), elevated plasma renin activity 193 ng / mL / h ( normal 2 - 37 ), and low aldosterone 3 ng / dL ( normal 6 - 179 ) indicative of primary adrenal insufficiency. Serum 17 - hydroxyprogesterone was also undetectable at < 10 ng / dL. At 2 months of age, during the minipuberty of infancy, he had an elevated luteinizing hormone 17.5 mIU / mL ( normal 0.02 - 7.0 ) and follicle - stimulating hormone 7.9 mIU / mL ( normal 0.16 - 4.1 ), and low total testosterone 5.6 ng / dL ( normal 60 - 400 ) consistent with hypergonadotropic hypogonadism."
] |
test-2168
|
8114284
|
{'History, Clinical Examination, and Hormonal Laboratory Findings': 'The proband was born full-term to nonconsanguineous parents by spontaneous vaginal delivery following an uncomplicated gestation. On the day of delivery, he was found to have persistent hypoglycemia with blood glucoses of 20 to 30s mg/dL. Initial physical examination was notable for bilateral descended testes and a fused scrotum with a small phallus (1.5 cm × 0.08 cm). Laboratory evaluation showed low cortisol at <0.2 µg/dL (both at time of hypoglycemia and following 1 µg adrenocorticotropic hormone stimulation test, with normal for these being ≥18 µg/dL), and he was started on hydrocortisone for adrenal insufficiency. At 10 days of life, he developed hyponatremia (sodium 130 mmol/L) and hyperkalemia (potassium 7.2 mmol/L). Fludrocortisone was added with resultant normalization of electrolytes. Additional neonatal evaluation included normal newborn screen (although undetectable 17-hydroxyprogesterone), normal pituitary on brain magnetic resonance imaging, normal chromosomal microarray, and 46,XY karyotype. He had an elevated ACTH >1250 pg/mL (normal 0-46), elevated plasma renin activity 193 ng/mL/h (normal 2-37), and low aldosterone 3 ng/dL (normal 6-179) indicative of primary adrenal insufficiency. Serum 17-hydroxyprogesterone was also undetectable at <10 ng/dL. At 2 months of age, during the minipuberty of infancy, he had an elevated luteinizing hormone 17.5 mIU/mL (normal 0.02-7.0) and follicle-stimulating hormone 7.9 mIU/mL (normal 0.16-4.1), and low total testosterone 5.6 ng/dL (normal 60-400) consistent with hypergonadotropic hypogonadism. He received testosterone 25 mg intramuscularly every 28 days for 4 doses, to replace the absent testosterone surge during the minipuberty of infancy.', 'Genetic Analysis': 'The patient underwent genetic testing at a commercial laboratory. The testing included sequencing of exonic regions and at least 10 bases of flanking intronic regions for 69 genes associated with differences in sex development. Initial sequencing and copy number variant detection was done using standard methods for next-generation (short read) sequencing. Read depth was at least 20× for all regions included on the panel. Potential pathogenic variants were confirmed using Sanger sequencing, also using standard methods. Results revealed a heterozygous novel variant in STAR at c.65-2A>C, confirming a diagnosis of LCAH. Targeted variant testing was negative for the variant in both parents, confirming a de novo pathogenic variant in the proband. No other potential pathogenic variants were detected in genes associated with a difference of sex development.'}
|
{'History, Clinical Examination, and Hormonal Laboratory Findings': 'The proband was born full-term to nonconsanguineous parents by spontaneous vaginal delivery following an uncomplicated gestation. On the day of delivery, he was found to have persistent hypoglycemia with blood glucoses of 20 to 30s mg/dL. Initial physical examination was notable for bilateral descended testes and a fused scrotum with a small phallus (1.5 cm × 0.08 cm). Laboratory evaluation showed low cortisol at <0.2 µg/dL (both at time of hypoglycemia and following 1 µg adrenocorticotropic hormone stimulation test, with normal for these being ≥18 µg/dL), and he was started on hydrocortisone for adrenal insufficiency. At 10 days of life, he developed hyponatremia (sodium 130 mmol/L) and hyperkalemia (potassium 7.2 mmol/L). Fludrocortisone was added with resultant normalization of electrolytes. Additional neonatal evaluation included normal newborn screen (although undetectable 17-hydroxyprogesterone), normal pituitary on brain magnetic resonance imaging, normal chromosomal microarray, and 46,XY karyotype. He had an elevated ACTH >1250 pg/mL (normal 0-46), elevated plasma renin activity 193 ng/mL/h (normal 2-37), and low aldosterone 3 ng/dL (normal 6-179) indicative of primary adrenal insufficiency. Serum 17-hydroxyprogesterone was also undetectable at <10 ng/dL. At 2 months of age, during the minipuberty of infancy, he had an elevated luteinizing hormone 17.5 mIU/mL (normal 0.02-7.0) and follicle-stimulating hormone 7.9 mIU/mL (normal 0.16-4.1), and low total testosterone 5.6 ng/dL (normal 60-400) consistent with hypergonadotropic hypogonadism. He received testosterone 25 mg intramuscularly every 28 days for 4 doses, to replace the absent testosterone surge during the minipuberty of infancy.', 'Genetic Analysis': 'The patient underwent genetic testing at a commercial laboratory. The testing included sequencing of exonic regions and at least 10 bases of flanking intronic regions for 69 genes associated with differences in sex development. Initial sequencing and copy number variant detection was done using standard methods for next-generation (short read) sequencing. Read depth was at least 20× for all regions included on the panel. Potential pathogenic variants were confirmed using Sanger sequencing, also using standard methods. Results revealed a heterozygous novel variant in STAR at c.65-2A>C, confirming a diagnosis of LCAH. Targeted variant testing was negative for the variant in both parents, confirming a de novo pathogenic variant in the proband. No other potential pathogenic variants were detected in genes associated with a difference of sex development.'}
|
Genitourinary-System
|
GU
|
[
"bilateral descended testes and a fused scrotum with a small phallus ( 1.5 cm × 0.08 cm )",
"hyponatremia ( sodium 130 mmol / L ) and hyperkalemia ( potassium 7.2 mmol / L"
] |
test-2169
|
8114284
|
{'History, Clinical Examination, and Hormonal Laboratory Findings': 'The proband was born full-term to nonconsanguineous parents by spontaneous vaginal delivery following an uncomplicated gestation. On the day of delivery, he was found to have persistent hypoglycemia with blood glucoses of 20 to 30s mg/dL. Initial physical examination was notable for bilateral descended testes and a fused scrotum with a small phallus (1.5 cm × 0.08 cm). Laboratory evaluation showed low cortisol at <0.2 µg/dL (both at time of hypoglycemia and following 1 µg adrenocorticotropic hormone stimulation test, with normal for these being ≥18 µg/dL), and he was started on hydrocortisone for adrenal insufficiency. At 10 days of life, he developed hyponatremia (sodium 130 mmol/L) and hyperkalemia (potassium 7.2 mmol/L). Fludrocortisone was added with resultant normalization of electrolytes. Additional neonatal evaluation included normal newborn screen (although undetectable 17-hydroxyprogesterone), normal pituitary on brain magnetic resonance imaging, normal chromosomal microarray, and 46,XY karyotype. He had an elevated ACTH >1250 pg/mL (normal 0-46), elevated plasma renin activity 193 ng/mL/h (normal 2-37), and low aldosterone 3 ng/dL (normal 6-179) indicative of primary adrenal insufficiency. Serum 17-hydroxyprogesterone was also undetectable at <10 ng/dL. At 2 months of age, during the minipuberty of infancy, he had an elevated luteinizing hormone 17.5 mIU/mL (normal 0.02-7.0) and follicle-stimulating hormone 7.9 mIU/mL (normal 0.16-4.1), and low total testosterone 5.6 ng/dL (normal 60-400) consistent with hypergonadotropic hypogonadism. He received testosterone 25 mg intramuscularly every 28 days for 4 doses, to replace the absent testosterone surge during the minipuberty of infancy.', 'Genetic Analysis': 'The patient underwent genetic testing at a commercial laboratory. The testing included sequencing of exonic regions and at least 10 bases of flanking intronic regions for 69 genes associated with differences in sex development. Initial sequencing and copy number variant detection was done using standard methods for next-generation (short read) sequencing. Read depth was at least 20× for all regions included on the panel. Potential pathogenic variants were confirmed using Sanger sequencing, also using standard methods. Results revealed a heterozygous novel variant in STAR at c.65-2A>C, confirming a diagnosis of LCAH. Targeted variant testing was negative for the variant in both parents, confirming a de novo pathogenic variant in the proband. No other potential pathogenic variants were detected in genes associated with a difference of sex development.'}
|
{'History, Clinical Examination, and Hormonal Laboratory Findings': 'The proband was born full-term to nonconsanguineous parents by spontaneous vaginal delivery following an uncomplicated gestation. On the day of delivery, he was found to have persistent hypoglycemia with blood glucoses of 20 to 30s mg/dL. Initial physical examination was notable for bilateral descended testes and a fused scrotum with a small phallus (1.5 cm × 0.08 cm). Laboratory evaluation showed low cortisol at <0.2 µg/dL (both at time of hypoglycemia and following 1 µg adrenocorticotropic hormone stimulation test, with normal for these being ≥18 µg/dL), and he was started on hydrocortisone for adrenal insufficiency. At 10 days of life, he developed hyponatremia (sodium 130 mmol/L) and hyperkalemia (potassium 7.2 mmol/L). Fludrocortisone was added with resultant normalization of electrolytes. Additional neonatal evaluation included normal newborn screen (although undetectable 17-hydroxyprogesterone), normal pituitary on brain magnetic resonance imaging, normal chromosomal microarray, and 46,XY karyotype. He had an elevated ACTH >1250 pg/mL (normal 0-46), elevated plasma renin activity 193 ng/mL/h (normal 2-37), and low aldosterone 3 ng/dL (normal 6-179) indicative of primary adrenal insufficiency. Serum 17-hydroxyprogesterone was also undetectable at <10 ng/dL. At 2 months of age, during the minipuberty of infancy, he had an elevated luteinizing hormone 17.5 mIU/mL (normal 0.02-7.0) and follicle-stimulating hormone 7.9 mIU/mL (normal 0.16-4.1), and low total testosterone 5.6 ng/dL (normal 60-400) consistent with hypergonadotropic hypogonadism. He received testosterone 25 mg intramuscularly every 28 days for 4 doses, to replace the absent testosterone surge during the minipuberty of infancy.', 'Genetic Analysis': 'The patient underwent genetic testing at a commercial laboratory. The testing included sequencing of exonic regions and at least 10 bases of flanking intronic regions for 69 genes associated with differences in sex development. Initial sequencing and copy number variant detection was done using standard methods for next-generation (short read) sequencing. Read depth was at least 20× for all regions included on the panel. Potential pathogenic variants were confirmed using Sanger sequencing, also using standard methods. Results revealed a heterozygous novel variant in STAR at c.65-2A>C, confirming a diagnosis of LCAH. Targeted variant testing was negative for the variant in both parents, confirming a de novo pathogenic variant in the proband. No other potential pathogenic variants were detected in genes associated with a difference of sex development.'}
|
Respiratory-System
|
RESP
|
[] |
test-2170
|
8114284
|
{'History, Clinical Examination, and Hormonal Laboratory Findings': 'The proband was born full-term to nonconsanguineous parents by spontaneous vaginal delivery following an uncomplicated gestation. On the day of delivery, he was found to have persistent hypoglycemia with blood glucoses of 20 to 30s mg/dL. Initial physical examination was notable for bilateral descended testes and a fused scrotum with a small phallus (1.5 cm × 0.08 cm). Laboratory evaluation showed low cortisol at <0.2 µg/dL (both at time of hypoglycemia and following 1 µg adrenocorticotropic hormone stimulation test, with normal for these being ≥18 µg/dL), and he was started on hydrocortisone for adrenal insufficiency. At 10 days of life, he developed hyponatremia (sodium 130 mmol/L) and hyperkalemia (potassium 7.2 mmol/L). Fludrocortisone was added with resultant normalization of electrolytes. Additional neonatal evaluation included normal newborn screen (although undetectable 17-hydroxyprogesterone), normal pituitary on brain magnetic resonance imaging, normal chromosomal microarray, and 46,XY karyotype. He had an elevated ACTH >1250 pg/mL (normal 0-46), elevated plasma renin activity 193 ng/mL/h (normal 2-37), and low aldosterone 3 ng/dL (normal 6-179) indicative of primary adrenal insufficiency. Serum 17-hydroxyprogesterone was also undetectable at <10 ng/dL. At 2 months of age, during the minipuberty of infancy, he had an elevated luteinizing hormone 17.5 mIU/mL (normal 0.02-7.0) and follicle-stimulating hormone 7.9 mIU/mL (normal 0.16-4.1), and low total testosterone 5.6 ng/dL (normal 60-400) consistent with hypergonadotropic hypogonadism. He received testosterone 25 mg intramuscularly every 28 days for 4 doses, to replace the absent testosterone surge during the minipuberty of infancy.', 'Genetic Analysis': 'The patient underwent genetic testing at a commercial laboratory. The testing included sequencing of exonic regions and at least 10 bases of flanking intronic regions for 69 genes associated with differences in sex development. Initial sequencing and copy number variant detection was done using standard methods for next-generation (short read) sequencing. Read depth was at least 20× for all regions included on the panel. Potential pathogenic variants were confirmed using Sanger sequencing, also using standard methods. Results revealed a heterozygous novel variant in STAR at c.65-2A>C, confirming a diagnosis of LCAH. Targeted variant testing was negative for the variant in both parents, confirming a de novo pathogenic variant in the proband. No other potential pathogenic variants were detected in genes associated with a difference of sex development.'}
|
{'History, Clinical Examination, and Hormonal Laboratory Findings': 'The proband was born full-term to nonconsanguineous parents by spontaneous vaginal delivery following an uncomplicated gestation. On the day of delivery, he was found to have persistent hypoglycemia with blood glucoses of 20 to 30s mg/dL. Initial physical examination was notable for bilateral descended testes and a fused scrotum with a small phallus (1.5 cm × 0.08 cm). Laboratory evaluation showed low cortisol at <0.2 µg/dL (both at time of hypoglycemia and following 1 µg adrenocorticotropic hormone stimulation test, with normal for these being ≥18 µg/dL), and he was started on hydrocortisone for adrenal insufficiency. At 10 days of life, he developed hyponatremia (sodium 130 mmol/L) and hyperkalemia (potassium 7.2 mmol/L). Fludrocortisone was added with resultant normalization of electrolytes. Additional neonatal evaluation included normal newborn screen (although undetectable 17-hydroxyprogesterone), normal pituitary on brain magnetic resonance imaging, normal chromosomal microarray, and 46,XY karyotype. He had an elevated ACTH >1250 pg/mL (normal 0-46), elevated plasma renin activity 193 ng/mL/h (normal 2-37), and low aldosterone 3 ng/dL (normal 6-179) indicative of primary adrenal insufficiency. Serum 17-hydroxyprogesterone was also undetectable at <10 ng/dL. At 2 months of age, during the minipuberty of infancy, he had an elevated luteinizing hormone 17.5 mIU/mL (normal 0.02-7.0) and follicle-stimulating hormone 7.9 mIU/mL (normal 0.16-4.1), and low total testosterone 5.6 ng/dL (normal 60-400) consistent with hypergonadotropic hypogonadism. He received testosterone 25 mg intramuscularly every 28 days for 4 doses, to replace the absent testosterone surge during the minipuberty of infancy.', 'Genetic Analysis': 'The patient underwent genetic testing at a commercial laboratory. The testing included sequencing of exonic regions and at least 10 bases of flanking intronic regions for 69 genes associated with differences in sex development. Initial sequencing and copy number variant detection was done using standard methods for next-generation (short read) sequencing. Read depth was at least 20× for all regions included on the panel. Potential pathogenic variants were confirmed using Sanger sequencing, also using standard methods. Results revealed a heterozygous novel variant in STAR at c.65-2A>C, confirming a diagnosis of LCAH. Targeted variant testing was negative for the variant in both parents, confirming a de novo pathogenic variant in the proband. No other potential pathogenic variants were detected in genes associated with a difference of sex development.'}
|
Musculoskeletal-System
|
MSK
|
[] |
test-2171
|
8114284
|
{'History, Clinical Examination, and Hormonal Laboratory Findings': 'The proband was born full-term to nonconsanguineous parents by spontaneous vaginal delivery following an uncomplicated gestation. On the day of delivery, he was found to have persistent hypoglycemia with blood glucoses of 20 to 30s mg/dL. Initial physical examination was notable for bilateral descended testes and a fused scrotum with a small phallus (1.5 cm × 0.08 cm). Laboratory evaluation showed low cortisol at <0.2 µg/dL (both at time of hypoglycemia and following 1 µg adrenocorticotropic hormone stimulation test, with normal for these being ≥18 µg/dL), and he was started on hydrocortisone for adrenal insufficiency. At 10 days of life, he developed hyponatremia (sodium 130 mmol/L) and hyperkalemia (potassium 7.2 mmol/L). Fludrocortisone was added with resultant normalization of electrolytes. Additional neonatal evaluation included normal newborn screen (although undetectable 17-hydroxyprogesterone), normal pituitary on brain magnetic resonance imaging, normal chromosomal microarray, and 46,XY karyotype. He had an elevated ACTH >1250 pg/mL (normal 0-46), elevated plasma renin activity 193 ng/mL/h (normal 2-37), and low aldosterone 3 ng/dL (normal 6-179) indicative of primary adrenal insufficiency. Serum 17-hydroxyprogesterone was also undetectable at <10 ng/dL. At 2 months of age, during the minipuberty of infancy, he had an elevated luteinizing hormone 17.5 mIU/mL (normal 0.02-7.0) and follicle-stimulating hormone 7.9 mIU/mL (normal 0.16-4.1), and low total testosterone 5.6 ng/dL (normal 60-400) consistent with hypergonadotropic hypogonadism. He received testosterone 25 mg intramuscularly every 28 days for 4 doses, to replace the absent testosterone surge during the minipuberty of infancy.', 'Genetic Analysis': 'The patient underwent genetic testing at a commercial laboratory. The testing included sequencing of exonic regions and at least 10 bases of flanking intronic regions for 69 genes associated with differences in sex development. Initial sequencing and copy number variant detection was done using standard methods for next-generation (short read) sequencing. Read depth was at least 20× for all regions included on the panel. Potential pathogenic variants were confirmed using Sanger sequencing, also using standard methods. Results revealed a heterozygous novel variant in STAR at c.65-2A>C, confirming a diagnosis of LCAH. Targeted variant testing was negative for the variant in both parents, confirming a de novo pathogenic variant in the proband. No other potential pathogenic variants were detected in genes associated with a difference of sex development.'}
|
{'History, Clinical Examination, and Hormonal Laboratory Findings': 'The proband was born full-term to nonconsanguineous parents by spontaneous vaginal delivery following an uncomplicated gestation. On the day of delivery, he was found to have persistent hypoglycemia with blood glucoses of 20 to 30s mg/dL. Initial physical examination was notable for bilateral descended testes and a fused scrotum with a small phallus (1.5 cm × 0.08 cm). Laboratory evaluation showed low cortisol at <0.2 µg/dL (both at time of hypoglycemia and following 1 µg adrenocorticotropic hormone stimulation test, with normal for these being ≥18 µg/dL), and he was started on hydrocortisone for adrenal insufficiency. At 10 days of life, he developed hyponatremia (sodium 130 mmol/L) and hyperkalemia (potassium 7.2 mmol/L). Fludrocortisone was added with resultant normalization of electrolytes. Additional neonatal evaluation included normal newborn screen (although undetectable 17-hydroxyprogesterone), normal pituitary on brain magnetic resonance imaging, normal chromosomal microarray, and 46,XY karyotype. He had an elevated ACTH >1250 pg/mL (normal 0-46), elevated plasma renin activity 193 ng/mL/h (normal 2-37), and low aldosterone 3 ng/dL (normal 6-179) indicative of primary adrenal insufficiency. Serum 17-hydroxyprogesterone was also undetectable at <10 ng/dL. At 2 months of age, during the minipuberty of infancy, he had an elevated luteinizing hormone 17.5 mIU/mL (normal 0.02-7.0) and follicle-stimulating hormone 7.9 mIU/mL (normal 0.16-4.1), and low total testosterone 5.6 ng/dL (normal 60-400) consistent with hypergonadotropic hypogonadism. He received testosterone 25 mg intramuscularly every 28 days for 4 doses, to replace the absent testosterone surge during the minipuberty of infancy.', 'Genetic Analysis': 'The patient underwent genetic testing at a commercial laboratory. The testing included sequencing of exonic regions and at least 10 bases of flanking intronic regions for 69 genes associated with differences in sex development. Initial sequencing and copy number variant detection was done using standard methods for next-generation (short read) sequencing. Read depth was at least 20× for all regions included on the panel. Potential pathogenic variants were confirmed using Sanger sequencing, also using standard methods. Results revealed a heterozygous novel variant in STAR at c.65-2A>C, confirming a diagnosis of LCAH. Targeted variant testing was negative for the variant in both parents, confirming a de novo pathogenic variant in the proband. No other potential pathogenic variants were detected in genes associated with a difference of sex development.'}
|
Eyes-Ears-Nose-Throat
|
EENT
|
[] |
test-2172
|
8114284
|
{'History, Clinical Examination, and Hormonal Laboratory Findings': 'The proband was born full-term to nonconsanguineous parents by spontaneous vaginal delivery following an uncomplicated gestation. On the day of delivery, he was found to have persistent hypoglycemia with blood glucoses of 20 to 30s mg/dL. Initial physical examination was notable for bilateral descended testes and a fused scrotum with a small phallus (1.5 cm × 0.08 cm). Laboratory evaluation showed low cortisol at <0.2 µg/dL (both at time of hypoglycemia and following 1 µg adrenocorticotropic hormone stimulation test, with normal for these being ≥18 µg/dL), and he was started on hydrocortisone for adrenal insufficiency. At 10 days of life, he developed hyponatremia (sodium 130 mmol/L) and hyperkalemia (potassium 7.2 mmol/L). Fludrocortisone was added with resultant normalization of electrolytes. Additional neonatal evaluation included normal newborn screen (although undetectable 17-hydroxyprogesterone), normal pituitary on brain magnetic resonance imaging, normal chromosomal microarray, and 46,XY karyotype. He had an elevated ACTH >1250 pg/mL (normal 0-46), elevated plasma renin activity 193 ng/mL/h (normal 2-37), and low aldosterone 3 ng/dL (normal 6-179) indicative of primary adrenal insufficiency. Serum 17-hydroxyprogesterone was also undetectable at <10 ng/dL. At 2 months of age, during the minipuberty of infancy, he had an elevated luteinizing hormone 17.5 mIU/mL (normal 0.02-7.0) and follicle-stimulating hormone 7.9 mIU/mL (normal 0.16-4.1), and low total testosterone 5.6 ng/dL (normal 60-400) consistent with hypergonadotropic hypogonadism. He received testosterone 25 mg intramuscularly every 28 days for 4 doses, to replace the absent testosterone surge during the minipuberty of infancy.', 'Genetic Analysis': 'The patient underwent genetic testing at a commercial laboratory. The testing included sequencing of exonic regions and at least 10 bases of flanking intronic regions for 69 genes associated with differences in sex development. Initial sequencing and copy number variant detection was done using standard methods for next-generation (short read) sequencing. Read depth was at least 20× for all regions included on the panel. Potential pathogenic variants were confirmed using Sanger sequencing, also using standard methods. Results revealed a heterozygous novel variant in STAR at c.65-2A>C, confirming a diagnosis of LCAH. Targeted variant testing was negative for the variant in both parents, confirming a de novo pathogenic variant in the proband. No other potential pathogenic variants were detected in genes associated with a difference of sex development.'}
|
{'History, Clinical Examination, and Hormonal Laboratory Findings': 'The proband was born full-term to nonconsanguineous parents by spontaneous vaginal delivery following an uncomplicated gestation. On the day of delivery, he was found to have persistent hypoglycemia with blood glucoses of 20 to 30s mg/dL. Initial physical examination was notable for bilateral descended testes and a fused scrotum with a small phallus (1.5 cm × 0.08 cm). Laboratory evaluation showed low cortisol at <0.2 µg/dL (both at time of hypoglycemia and following 1 µg adrenocorticotropic hormone stimulation test, with normal for these being ≥18 µg/dL), and he was started on hydrocortisone for adrenal insufficiency. At 10 days of life, he developed hyponatremia (sodium 130 mmol/L) and hyperkalemia (potassium 7.2 mmol/L). Fludrocortisone was added with resultant normalization of electrolytes. Additional neonatal evaluation included normal newborn screen (although undetectable 17-hydroxyprogesterone), normal pituitary on brain magnetic resonance imaging, normal chromosomal microarray, and 46,XY karyotype. He had an elevated ACTH >1250 pg/mL (normal 0-46), elevated plasma renin activity 193 ng/mL/h (normal 2-37), and low aldosterone 3 ng/dL (normal 6-179) indicative of primary adrenal insufficiency. Serum 17-hydroxyprogesterone was also undetectable at <10 ng/dL. At 2 months of age, during the minipuberty of infancy, he had an elevated luteinizing hormone 17.5 mIU/mL (normal 0.02-7.0) and follicle-stimulating hormone 7.9 mIU/mL (normal 0.16-4.1), and low total testosterone 5.6 ng/dL (normal 60-400) consistent with hypergonadotropic hypogonadism. He received testosterone 25 mg intramuscularly every 28 days for 4 doses, to replace the absent testosterone surge during the minipuberty of infancy.', 'Genetic Analysis': 'The patient underwent genetic testing at a commercial laboratory. The testing included sequencing of exonic regions and at least 10 bases of flanking intronic regions for 69 genes associated with differences in sex development. Initial sequencing and copy number variant detection was done using standard methods for next-generation (short read) sequencing. Read depth was at least 20× for all regions included on the panel. Potential pathogenic variants were confirmed using Sanger sequencing, also using standard methods. Results revealed a heterozygous novel variant in STAR at c.65-2A>C, confirming a diagnosis of LCAH. Targeted variant testing was negative for the variant in both parents, confirming a de novo pathogenic variant in the proband. No other potential pathogenic variants were detected in genes associated with a difference of sex development.'}
|
Dermatology
|
DERM
|
[] |
test-2173
|
8114284
|
{'History, Clinical Examination, and Hormonal Laboratory Findings': 'The proband was born full-term to nonconsanguineous parents by spontaneous vaginal delivery following an uncomplicated gestation. On the day of delivery, he was found to have persistent hypoglycemia with blood glucoses of 20 to 30s mg/dL. Initial physical examination was notable for bilateral descended testes and a fused scrotum with a small phallus (1.5 cm × 0.08 cm). Laboratory evaluation showed low cortisol at <0.2 µg/dL (both at time of hypoglycemia and following 1 µg adrenocorticotropic hormone stimulation test, with normal for these being ≥18 µg/dL), and he was started on hydrocortisone for adrenal insufficiency. At 10 days of life, he developed hyponatremia (sodium 130 mmol/L) and hyperkalemia (potassium 7.2 mmol/L). Fludrocortisone was added with resultant normalization of electrolytes. Additional neonatal evaluation included normal newborn screen (although undetectable 17-hydroxyprogesterone), normal pituitary on brain magnetic resonance imaging, normal chromosomal microarray, and 46,XY karyotype. He had an elevated ACTH >1250 pg/mL (normal 0-46), elevated plasma renin activity 193 ng/mL/h (normal 2-37), and low aldosterone 3 ng/dL (normal 6-179) indicative of primary adrenal insufficiency. Serum 17-hydroxyprogesterone was also undetectable at <10 ng/dL. At 2 months of age, during the minipuberty of infancy, he had an elevated luteinizing hormone 17.5 mIU/mL (normal 0.02-7.0) and follicle-stimulating hormone 7.9 mIU/mL (normal 0.16-4.1), and low total testosterone 5.6 ng/dL (normal 60-400) consistent with hypergonadotropic hypogonadism. He received testosterone 25 mg intramuscularly every 28 days for 4 doses, to replace the absent testosterone surge during the minipuberty of infancy.', 'Genetic Analysis': 'The patient underwent genetic testing at a commercial laboratory. The testing included sequencing of exonic regions and at least 10 bases of flanking intronic regions for 69 genes associated with differences in sex development. Initial sequencing and copy number variant detection was done using standard methods for next-generation (short read) sequencing. Read depth was at least 20× for all regions included on the panel. Potential pathogenic variants were confirmed using Sanger sequencing, also using standard methods. Results revealed a heterozygous novel variant in STAR at c.65-2A>C, confirming a diagnosis of LCAH. Targeted variant testing was negative for the variant in both parents, confirming a de novo pathogenic variant in the proband. No other potential pathogenic variants were detected in genes associated with a difference of sex development.'}
|
{'History, Clinical Examination, and Hormonal Laboratory Findings': 'The proband was born full-term to nonconsanguineous parents by spontaneous vaginal delivery following an uncomplicated gestation. On the day of delivery, he was found to have persistent hypoglycemia with blood glucoses of 20 to 30s mg/dL. Initial physical examination was notable for bilateral descended testes and a fused scrotum with a small phallus (1.5 cm × 0.08 cm). Laboratory evaluation showed low cortisol at <0.2 µg/dL (both at time of hypoglycemia and following 1 µg adrenocorticotropic hormone stimulation test, with normal for these being ≥18 µg/dL), and he was started on hydrocortisone for adrenal insufficiency. At 10 days of life, he developed hyponatremia (sodium 130 mmol/L) and hyperkalemia (potassium 7.2 mmol/L). Fludrocortisone was added with resultant normalization of electrolytes. Additional neonatal evaluation included normal newborn screen (although undetectable 17-hydroxyprogesterone), normal pituitary on brain magnetic resonance imaging, normal chromosomal microarray, and 46,XY karyotype. He had an elevated ACTH >1250 pg/mL (normal 0-46), elevated plasma renin activity 193 ng/mL/h (normal 2-37), and low aldosterone 3 ng/dL (normal 6-179) indicative of primary adrenal insufficiency. Serum 17-hydroxyprogesterone was also undetectable at <10 ng/dL. At 2 months of age, during the minipuberty of infancy, he had an elevated luteinizing hormone 17.5 mIU/mL (normal 0.02-7.0) and follicle-stimulating hormone 7.9 mIU/mL (normal 0.16-4.1), and low total testosterone 5.6 ng/dL (normal 60-400) consistent with hypergonadotropic hypogonadism. He received testosterone 25 mg intramuscularly every 28 days for 4 doses, to replace the absent testosterone surge during the minipuberty of infancy.', 'Genetic Analysis': 'The patient underwent genetic testing at a commercial laboratory. The testing included sequencing of exonic regions and at least 10 bases of flanking intronic regions for 69 genes associated with differences in sex development. Initial sequencing and copy number variant detection was done using standard methods for next-generation (short read) sequencing. Read depth was at least 20× for all regions included on the panel. Potential pathogenic variants were confirmed using Sanger sequencing, also using standard methods. Results revealed a heterozygous novel variant in STAR at c.65-2A>C, confirming a diagnosis of LCAH. Targeted variant testing was negative for the variant in both parents, confirming a de novo pathogenic variant in the proband. No other potential pathogenic variants were detected in genes associated with a difference of sex development.'}
|
Pregnancy
|
Pregnancy
|
[
"born full - term to nonconsanguineous parents by spontaneous vaginal delivery following an uncomplicated gestation. On the day of delivery, he was found to have persistent hypoglycemia with blood glucoses of 20 to 30s mg / dL."
] |
test-2174
|
8114284
|
{'History, Clinical Examination, and Hormonal Laboratory Findings': 'The proband was born full-term to nonconsanguineous parents by spontaneous vaginal delivery following an uncomplicated gestation. On the day of delivery, he was found to have persistent hypoglycemia with blood glucoses of 20 to 30s mg/dL. Initial physical examination was notable for bilateral descended testes and a fused scrotum with a small phallus (1.5 cm × 0.08 cm). Laboratory evaluation showed low cortisol at <0.2 µg/dL (both at time of hypoglycemia and following 1 µg adrenocorticotropic hormone stimulation test, with normal for these being ≥18 µg/dL), and he was started on hydrocortisone for adrenal insufficiency. At 10 days of life, he developed hyponatremia (sodium 130 mmol/L) and hyperkalemia (potassium 7.2 mmol/L). Fludrocortisone was added with resultant normalization of electrolytes. Additional neonatal evaluation included normal newborn screen (although undetectable 17-hydroxyprogesterone), normal pituitary on brain magnetic resonance imaging, normal chromosomal microarray, and 46,XY karyotype. He had an elevated ACTH >1250 pg/mL (normal 0-46), elevated plasma renin activity 193 ng/mL/h (normal 2-37), and low aldosterone 3 ng/dL (normal 6-179) indicative of primary adrenal insufficiency. Serum 17-hydroxyprogesterone was also undetectable at <10 ng/dL. At 2 months of age, during the minipuberty of infancy, he had an elevated luteinizing hormone 17.5 mIU/mL (normal 0.02-7.0) and follicle-stimulating hormone 7.9 mIU/mL (normal 0.16-4.1), and low total testosterone 5.6 ng/dL (normal 60-400) consistent with hypergonadotropic hypogonadism. He received testosterone 25 mg intramuscularly every 28 days for 4 doses, to replace the absent testosterone surge during the minipuberty of infancy.', 'Genetic Analysis': 'The patient underwent genetic testing at a commercial laboratory. The testing included sequencing of exonic regions and at least 10 bases of flanking intronic regions for 69 genes associated with differences in sex development. Initial sequencing and copy number variant detection was done using standard methods for next-generation (short read) sequencing. Read depth was at least 20× for all regions included on the panel. Potential pathogenic variants were confirmed using Sanger sequencing, also using standard methods. Results revealed a heterozygous novel variant in STAR at c.65-2A>C, confirming a diagnosis of LCAH. Targeted variant testing was negative for the variant in both parents, confirming a de novo pathogenic variant in the proband. No other potential pathogenic variants were detected in genes associated with a difference of sex development.'}
|
{'History, Clinical Examination, and Hormonal Laboratory Findings': 'The proband was born full-term to nonconsanguineous parents by spontaneous vaginal delivery following an uncomplicated gestation. On the day of delivery, he was found to have persistent hypoglycemia with blood glucoses of 20 to 30s mg/dL. Initial physical examination was notable for bilateral descended testes and a fused scrotum with a small phallus (1.5 cm × 0.08 cm). Laboratory evaluation showed low cortisol at <0.2 µg/dL (both at time of hypoglycemia and following 1 µg adrenocorticotropic hormone stimulation test, with normal for these being ≥18 µg/dL), and he was started on hydrocortisone for adrenal insufficiency. At 10 days of life, he developed hyponatremia (sodium 130 mmol/L) and hyperkalemia (potassium 7.2 mmol/L). Fludrocortisone was added with resultant normalization of electrolytes. Additional neonatal evaluation included normal newborn screen (although undetectable 17-hydroxyprogesterone), normal pituitary on brain magnetic resonance imaging, normal chromosomal microarray, and 46,XY karyotype. He had an elevated ACTH >1250 pg/mL (normal 0-46), elevated plasma renin activity 193 ng/mL/h (normal 2-37), and low aldosterone 3 ng/dL (normal 6-179) indicative of primary adrenal insufficiency. Serum 17-hydroxyprogesterone was also undetectable at <10 ng/dL. At 2 months of age, during the minipuberty of infancy, he had an elevated luteinizing hormone 17.5 mIU/mL (normal 0.02-7.0) and follicle-stimulating hormone 7.9 mIU/mL (normal 0.16-4.1), and low total testosterone 5.6 ng/dL (normal 60-400) consistent with hypergonadotropic hypogonadism. He received testosterone 25 mg intramuscularly every 28 days for 4 doses, to replace the absent testosterone surge during the minipuberty of infancy.', 'Genetic Analysis': 'The patient underwent genetic testing at a commercial laboratory. The testing included sequencing of exonic regions and at least 10 bases of flanking intronic regions for 69 genes associated with differences in sex development. Initial sequencing and copy number variant detection was done using standard methods for next-generation (short read) sequencing. Read depth was at least 20× for all regions included on the panel. Potential pathogenic variants were confirmed using Sanger sequencing, also using standard methods. Results revealed a heterozygous novel variant in STAR at c.65-2A>C, confirming a diagnosis of LCAH. Targeted variant testing was negative for the variant in both parents, confirming a de novo pathogenic variant in the proband. No other potential pathogenic variants were detected in genes associated with a difference of sex development.'}
|
Lymphatic-System
|
LYMPH
|
[] |
test-2175
|
8114284
|
{'History, Clinical Examination, and Hormonal Laboratory Findings': 'The proband was born full-term to nonconsanguineous parents by spontaneous vaginal delivery following an uncomplicated gestation. On the day of delivery, he was found to have persistent hypoglycemia with blood glucoses of 20 to 30s mg/dL. Initial physical examination was notable for bilateral descended testes and a fused scrotum with a small phallus (1.5 cm × 0.08 cm). Laboratory evaluation showed low cortisol at <0.2 µg/dL (both at time of hypoglycemia and following 1 µg adrenocorticotropic hormone stimulation test, with normal for these being ≥18 µg/dL), and he was started on hydrocortisone for adrenal insufficiency. At 10 days of life, he developed hyponatremia (sodium 130 mmol/L) and hyperkalemia (potassium 7.2 mmol/L). Fludrocortisone was added with resultant normalization of electrolytes. Additional neonatal evaluation included normal newborn screen (although undetectable 17-hydroxyprogesterone), normal pituitary on brain magnetic resonance imaging, normal chromosomal microarray, and 46,XY karyotype. He had an elevated ACTH >1250 pg/mL (normal 0-46), elevated plasma renin activity 193 ng/mL/h (normal 2-37), and low aldosterone 3 ng/dL (normal 6-179) indicative of primary adrenal insufficiency. Serum 17-hydroxyprogesterone was also undetectable at <10 ng/dL. At 2 months of age, during the minipuberty of infancy, he had an elevated luteinizing hormone 17.5 mIU/mL (normal 0.02-7.0) and follicle-stimulating hormone 7.9 mIU/mL (normal 0.16-4.1), and low total testosterone 5.6 ng/dL (normal 60-400) consistent with hypergonadotropic hypogonadism. He received testosterone 25 mg intramuscularly every 28 days for 4 doses, to replace the absent testosterone surge during the minipuberty of infancy.', 'Genetic Analysis': 'The patient underwent genetic testing at a commercial laboratory. The testing included sequencing of exonic regions and at least 10 bases of flanking intronic regions for 69 genes associated with differences in sex development. Initial sequencing and copy number variant detection was done using standard methods for next-generation (short read) sequencing. Read depth was at least 20× for all regions included on the panel. Potential pathogenic variants were confirmed using Sanger sequencing, also using standard methods. Results revealed a heterozygous novel variant in STAR at c.65-2A>C, confirming a diagnosis of LCAH. Targeted variant testing was negative for the variant in both parents, confirming a de novo pathogenic variant in the proband. No other potential pathogenic variants were detected in genes associated with a difference of sex development.'}
|
{'History, Clinical Examination, and Hormonal Laboratory Findings': 'The proband was born full-term to nonconsanguineous parents by spontaneous vaginal delivery following an uncomplicated gestation. On the day of delivery, he was found to have persistent hypoglycemia with blood glucoses of 20 to 30s mg/dL. Initial physical examination was notable for bilateral descended testes and a fused scrotum with a small phallus (1.5 cm × 0.08 cm). Laboratory evaluation showed low cortisol at <0.2 µg/dL (both at time of hypoglycemia and following 1 µg adrenocorticotropic hormone stimulation test, with normal for these being ≥18 µg/dL), and he was started on hydrocortisone for adrenal insufficiency. At 10 days of life, he developed hyponatremia (sodium 130 mmol/L) and hyperkalemia (potassium 7.2 mmol/L). Fludrocortisone was added with resultant normalization of electrolytes. Additional neonatal evaluation included normal newborn screen (although undetectable 17-hydroxyprogesterone), normal pituitary on brain magnetic resonance imaging, normal chromosomal microarray, and 46,XY karyotype. He had an elevated ACTH >1250 pg/mL (normal 0-46), elevated plasma renin activity 193 ng/mL/h (normal 2-37), and low aldosterone 3 ng/dL (normal 6-179) indicative of primary adrenal insufficiency. Serum 17-hydroxyprogesterone was also undetectable at <10 ng/dL. At 2 months of age, during the minipuberty of infancy, he had an elevated luteinizing hormone 17.5 mIU/mL (normal 0.02-7.0) and follicle-stimulating hormone 7.9 mIU/mL (normal 0.16-4.1), and low total testosterone 5.6 ng/dL (normal 60-400) consistent with hypergonadotropic hypogonadism. He received testosterone 25 mg intramuscularly every 28 days for 4 doses, to replace the absent testosterone surge during the minipuberty of infancy.', 'Genetic Analysis': 'The patient underwent genetic testing at a commercial laboratory. The testing included sequencing of exonic regions and at least 10 bases of flanking intronic regions for 69 genes associated with differences in sex development. Initial sequencing and copy number variant detection was done using standard methods for next-generation (short read) sequencing. Read depth was at least 20× for all regions included on the panel. Potential pathogenic variants were confirmed using Sanger sequencing, also using standard methods. Results revealed a heterozygous novel variant in STAR at c.65-2A>C, confirming a diagnosis of LCAH. Targeted variant testing was negative for the variant in both parents, confirming a de novo pathogenic variant in the proband. No other potential pathogenic variants were detected in genes associated with a difference of sex development.'}
|
Age-at-Presentation
|
Age (at case presentation)
|
[] |
test-2176
|
8114284
|
{'History, Clinical Examination, and Hormonal Laboratory Findings': 'The proband was born full-term to nonconsanguineous parents by spontaneous vaginal delivery following an uncomplicated gestation. On the day of delivery, he was found to have persistent hypoglycemia with blood glucoses of 20 to 30s mg/dL. Initial physical examination was notable for bilateral descended testes and a fused scrotum with a small phallus (1.5 cm × 0.08 cm). Laboratory evaluation showed low cortisol at <0.2 µg/dL (both at time of hypoglycemia and following 1 µg adrenocorticotropic hormone stimulation test, with normal for these being ≥18 µg/dL), and he was started on hydrocortisone for adrenal insufficiency. At 10 days of life, he developed hyponatremia (sodium 130 mmol/L) and hyperkalemia (potassium 7.2 mmol/L). Fludrocortisone was added with resultant normalization of electrolytes. Additional neonatal evaluation included normal newborn screen (although undetectable 17-hydroxyprogesterone), normal pituitary on brain magnetic resonance imaging, normal chromosomal microarray, and 46,XY karyotype. He had an elevated ACTH >1250 pg/mL (normal 0-46), elevated plasma renin activity 193 ng/mL/h (normal 2-37), and low aldosterone 3 ng/dL (normal 6-179) indicative of primary adrenal insufficiency. Serum 17-hydroxyprogesterone was also undetectable at <10 ng/dL. At 2 months of age, during the minipuberty of infancy, he had an elevated luteinizing hormone 17.5 mIU/mL (normal 0.02-7.0) and follicle-stimulating hormone 7.9 mIU/mL (normal 0.16-4.1), and low total testosterone 5.6 ng/dL (normal 60-400) consistent with hypergonadotropic hypogonadism. He received testosterone 25 mg intramuscularly every 28 days for 4 doses, to replace the absent testosterone surge during the minipuberty of infancy.', 'Genetic Analysis': 'The patient underwent genetic testing at a commercial laboratory. The testing included sequencing of exonic regions and at least 10 bases of flanking intronic regions for 69 genes associated with differences in sex development. Initial sequencing and copy number variant detection was done using standard methods for next-generation (short read) sequencing. Read depth was at least 20× for all regions included on the panel. Potential pathogenic variants were confirmed using Sanger sequencing, also using standard methods. Results revealed a heterozygous novel variant in STAR at c.65-2A>C, confirming a diagnosis of LCAH. Targeted variant testing was negative for the variant in both parents, confirming a de novo pathogenic variant in the proband. No other potential pathogenic variants were detected in genes associated with a difference of sex development.'}
|
{'History, Clinical Examination, and Hormonal Laboratory Findings': 'The proband was born full-term to nonconsanguineous parents by spontaneous vaginal delivery following an uncomplicated gestation. On the day of delivery, he was found to have persistent hypoglycemia with blood glucoses of 20 to 30s mg/dL. Initial physical examination was notable for bilateral descended testes and a fused scrotum with a small phallus (1.5 cm × 0.08 cm). Laboratory evaluation showed low cortisol at <0.2 µg/dL (both at time of hypoglycemia and following 1 µg adrenocorticotropic hormone stimulation test, with normal for these being ≥18 µg/dL), and he was started on hydrocortisone for adrenal insufficiency. At 10 days of life, he developed hyponatremia (sodium 130 mmol/L) and hyperkalemia (potassium 7.2 mmol/L). Fludrocortisone was added with resultant normalization of electrolytes. Additional neonatal evaluation included normal newborn screen (although undetectable 17-hydroxyprogesterone), normal pituitary on brain magnetic resonance imaging, normal chromosomal microarray, and 46,XY karyotype. He had an elevated ACTH >1250 pg/mL (normal 0-46), elevated plasma renin activity 193 ng/mL/h (normal 2-37), and low aldosterone 3 ng/dL (normal 6-179) indicative of primary adrenal insufficiency. Serum 17-hydroxyprogesterone was also undetectable at <10 ng/dL. At 2 months of age, during the minipuberty of infancy, he had an elevated luteinizing hormone 17.5 mIU/mL (normal 0.02-7.0) and follicle-stimulating hormone 7.9 mIU/mL (normal 0.16-4.1), and low total testosterone 5.6 ng/dL (normal 60-400) consistent with hypergonadotropic hypogonadism. He received testosterone 25 mg intramuscularly every 28 days for 4 doses, to replace the absent testosterone surge during the minipuberty of infancy.', 'Genetic Analysis': 'The patient underwent genetic testing at a commercial laboratory. The testing included sequencing of exonic regions and at least 10 bases of flanking intronic regions for 69 genes associated with differences in sex development. Initial sequencing and copy number variant detection was done using standard methods for next-generation (short read) sequencing. Read depth was at least 20× for all regions included on the panel. Potential pathogenic variants were confirmed using Sanger sequencing, also using standard methods. Results revealed a heterozygous novel variant in STAR at c.65-2A>C, confirming a diagnosis of LCAH. Targeted variant testing was negative for the variant in both parents, confirming a de novo pathogenic variant in the proband. No other potential pathogenic variants were detected in genes associated with a difference of sex development.'}
|
Age-of-Onset
|
Age (of onset)
|
[] |
test-2177
|
8114284
|
{'History, Clinical Examination, and Hormonal Laboratory Findings': 'The proband was born full-term to nonconsanguineous parents by spontaneous vaginal delivery following an uncomplicated gestation. On the day of delivery, he was found to have persistent hypoglycemia with blood glucoses of 20 to 30s mg/dL. Initial physical examination was notable for bilateral descended testes and a fused scrotum with a small phallus (1.5 cm × 0.08 cm). Laboratory evaluation showed low cortisol at <0.2 µg/dL (both at time of hypoglycemia and following 1 µg adrenocorticotropic hormone stimulation test, with normal for these being ≥18 µg/dL), and he was started on hydrocortisone for adrenal insufficiency. At 10 days of life, he developed hyponatremia (sodium 130 mmol/L) and hyperkalemia (potassium 7.2 mmol/L). Fludrocortisone was added with resultant normalization of electrolytes. Additional neonatal evaluation included normal newborn screen (although undetectable 17-hydroxyprogesterone), normal pituitary on brain magnetic resonance imaging, normal chromosomal microarray, and 46,XY karyotype. He had an elevated ACTH >1250 pg/mL (normal 0-46), elevated plasma renin activity 193 ng/mL/h (normal 2-37), and low aldosterone 3 ng/dL (normal 6-179) indicative of primary adrenal insufficiency. Serum 17-hydroxyprogesterone was also undetectable at <10 ng/dL. At 2 months of age, during the minipuberty of infancy, he had an elevated luteinizing hormone 17.5 mIU/mL (normal 0.02-7.0) and follicle-stimulating hormone 7.9 mIU/mL (normal 0.16-4.1), and low total testosterone 5.6 ng/dL (normal 60-400) consistent with hypergonadotropic hypogonadism. He received testosterone 25 mg intramuscularly every 28 days for 4 doses, to replace the absent testosterone surge during the minipuberty of infancy.', 'Genetic Analysis': 'The patient underwent genetic testing at a commercial laboratory. The testing included sequencing of exonic regions and at least 10 bases of flanking intronic regions for 69 genes associated with differences in sex development. Initial sequencing and copy number variant detection was done using standard methods for next-generation (short read) sequencing. Read depth was at least 20× for all regions included on the panel. Potential pathogenic variants were confirmed using Sanger sequencing, also using standard methods. Results revealed a heterozygous novel variant in STAR at c.65-2A>C, confirming a diagnosis of LCAH. Targeted variant testing was negative for the variant in both parents, confirming a de novo pathogenic variant in the proband. No other potential pathogenic variants were detected in genes associated with a difference of sex development.'}
|
{'History, Clinical Examination, and Hormonal Laboratory Findings': 'The proband was born full-term to nonconsanguineous parents by spontaneous vaginal delivery following an uncomplicated gestation. On the day of delivery, he was found to have persistent hypoglycemia with blood glucoses of 20 to 30s mg/dL. Initial physical examination was notable for bilateral descended testes and a fused scrotum with a small phallus (1.5 cm × 0.08 cm). Laboratory evaluation showed low cortisol at <0.2 µg/dL (both at time of hypoglycemia and following 1 µg adrenocorticotropic hormone stimulation test, with normal for these being ≥18 µg/dL), and he was started on hydrocortisone for adrenal insufficiency. At 10 days of life, he developed hyponatremia (sodium 130 mmol/L) and hyperkalemia (potassium 7.2 mmol/L). Fludrocortisone was added with resultant normalization of electrolytes. Additional neonatal evaluation included normal newborn screen (although undetectable 17-hydroxyprogesterone), normal pituitary on brain magnetic resonance imaging, normal chromosomal microarray, and 46,XY karyotype. He had an elevated ACTH >1250 pg/mL (normal 0-46), elevated plasma renin activity 193 ng/mL/h (normal 2-37), and low aldosterone 3 ng/dL (normal 6-179) indicative of primary adrenal insufficiency. Serum 17-hydroxyprogesterone was also undetectable at <10 ng/dL. At 2 months of age, during the minipuberty of infancy, he had an elevated luteinizing hormone 17.5 mIU/mL (normal 0.02-7.0) and follicle-stimulating hormone 7.9 mIU/mL (normal 0.16-4.1), and low total testosterone 5.6 ng/dL (normal 60-400) consistent with hypergonadotropic hypogonadism. He received testosterone 25 mg intramuscularly every 28 days for 4 doses, to replace the absent testosterone surge during the minipuberty of infancy.', 'Genetic Analysis': 'The patient underwent genetic testing at a commercial laboratory. The testing included sequencing of exonic regions and at least 10 bases of flanking intronic regions for 69 genes associated with differences in sex development. Initial sequencing and copy number variant detection was done using standard methods for next-generation (short read) sequencing. Read depth was at least 20× for all regions included on the panel. Potential pathogenic variants were confirmed using Sanger sequencing, also using standard methods. Results revealed a heterozygous novel variant in STAR at c.65-2A>C, confirming a diagnosis of LCAH. Targeted variant testing was negative for the variant in both parents, confirming a de novo pathogenic variant in the proband. No other potential pathogenic variants were detected in genes associated with a difference of sex development.'}
|
Confirmed-Diagnosis-IEM
|
Confirmed_Diagnosis(IEM)
|
[
"confirming a diagnosis of LCAH ."
] |
test-2178
|
8114284
|
{'History, Clinical Examination, and Hormonal Laboratory Findings': 'The proband was born full-term to nonconsanguineous parents by spontaneous vaginal delivery following an uncomplicated gestation. On the day of delivery, he was found to have persistent hypoglycemia with blood glucoses of 20 to 30s mg/dL. Initial physical examination was notable for bilateral descended testes and a fused scrotum with a small phallus (1.5 cm × 0.08 cm). Laboratory evaluation showed low cortisol at <0.2 µg/dL (both at time of hypoglycemia and following 1 µg adrenocorticotropic hormone stimulation test, with normal for these being ≥18 µg/dL), and he was started on hydrocortisone for adrenal insufficiency. At 10 days of life, he developed hyponatremia (sodium 130 mmol/L) and hyperkalemia (potassium 7.2 mmol/L). Fludrocortisone was added with resultant normalization of electrolytes. Additional neonatal evaluation included normal newborn screen (although undetectable 17-hydroxyprogesterone), normal pituitary on brain magnetic resonance imaging, normal chromosomal microarray, and 46,XY karyotype. He had an elevated ACTH >1250 pg/mL (normal 0-46), elevated plasma renin activity 193 ng/mL/h (normal 2-37), and low aldosterone 3 ng/dL (normal 6-179) indicative of primary adrenal insufficiency. Serum 17-hydroxyprogesterone was also undetectable at <10 ng/dL. At 2 months of age, during the minipuberty of infancy, he had an elevated luteinizing hormone 17.5 mIU/mL (normal 0.02-7.0) and follicle-stimulating hormone 7.9 mIU/mL (normal 0.16-4.1), and low total testosterone 5.6 ng/dL (normal 60-400) consistent with hypergonadotropic hypogonadism. He received testosterone 25 mg intramuscularly every 28 days for 4 doses, to replace the absent testosterone surge during the minipuberty of infancy.', 'Genetic Analysis': 'The patient underwent genetic testing at a commercial laboratory. The testing included sequencing of exonic regions and at least 10 bases of flanking intronic regions for 69 genes associated with differences in sex development. Initial sequencing and copy number variant detection was done using standard methods for next-generation (short read) sequencing. Read depth was at least 20× for all regions included on the panel. Potential pathogenic variants were confirmed using Sanger sequencing, also using standard methods. Results revealed a heterozygous novel variant in STAR at c.65-2A>C, confirming a diagnosis of LCAH. Targeted variant testing was negative for the variant in both parents, confirming a de novo pathogenic variant in the proband. No other potential pathogenic variants were detected in genes associated with a difference of sex development.'}
|
{'History, Clinical Examination, and Hormonal Laboratory Findings': 'The proband was born full-term to nonconsanguineous parents by spontaneous vaginal delivery following an uncomplicated gestation. On the day of delivery, he was found to have persistent hypoglycemia with blood glucoses of 20 to 30s mg/dL. Initial physical examination was notable for bilateral descended testes and a fused scrotum with a small phallus (1.5 cm × 0.08 cm). Laboratory evaluation showed low cortisol at <0.2 µg/dL (both at time of hypoglycemia and following 1 µg adrenocorticotropic hormone stimulation test, with normal for these being ≥18 µg/dL), and he was started on hydrocortisone for adrenal insufficiency. At 10 days of life, he developed hyponatremia (sodium 130 mmol/L) and hyperkalemia (potassium 7.2 mmol/L). Fludrocortisone was added with resultant normalization of electrolytes. Additional neonatal evaluation included normal newborn screen (although undetectable 17-hydroxyprogesterone), normal pituitary on brain magnetic resonance imaging, normal chromosomal microarray, and 46,XY karyotype. He had an elevated ACTH >1250 pg/mL (normal 0-46), elevated plasma renin activity 193 ng/mL/h (normal 2-37), and low aldosterone 3 ng/dL (normal 6-179) indicative of primary adrenal insufficiency. Serum 17-hydroxyprogesterone was also undetectable at <10 ng/dL. At 2 months of age, during the minipuberty of infancy, he had an elevated luteinizing hormone 17.5 mIU/mL (normal 0.02-7.0) and follicle-stimulating hormone 7.9 mIU/mL (normal 0.16-4.1), and low total testosterone 5.6 ng/dL (normal 60-400) consistent with hypergonadotropic hypogonadism. He received testosterone 25 mg intramuscularly every 28 days for 4 doses, to replace the absent testosterone surge during the minipuberty of infancy.', 'Genetic Analysis': 'The patient underwent genetic testing at a commercial laboratory. The testing included sequencing of exonic regions and at least 10 bases of flanking intronic regions for 69 genes associated with differences in sex development. Initial sequencing and copy number variant detection was done using standard methods for next-generation (short read) sequencing. Read depth was at least 20× for all regions included on the panel. Potential pathogenic variants were confirmed using Sanger sequencing, also using standard methods. Results revealed a heterozygous novel variant in STAR at c.65-2A>C, confirming a diagnosis of LCAH. Targeted variant testing was negative for the variant in both parents, confirming a de novo pathogenic variant in the proband. No other potential pathogenic variants were detected in genes associated with a difference of sex development.'}
|
IEM-Treatment
|
IEM_Treatment
|
[
"hydrocortisone",
"Fludrocortisone"
] |
test-2179
|
8760527
|
{'Case report': "An 18-year-old woman came in with swelling in her ankles and a cognitive decline. The patient was well until she was 7 years old, when she experienced bilateral increasing ankle edema. From the age of ten years old, her parents noted frequent stumbles and difficulty walking, followed by ataxia. The patient's knees swelled a few years later, when he was 12 years old. In addition, she had previously experienced sight issues. Over all Achilles, quadriceps, and patellar tendons, the osteo-myo-articular examination revealed bilateral painless and non-fistulized masses. Spastic paraparesis, rapid deep reflexes, and extensor plantar responses were discovered during a neurological examination. The Romberg test resulted in a positive result with 1 eye closed. A bilateral thick cataract with impaired vision was discovered during the ophthalmic examination. Total cholesterol, LDL, HDL, and triglyceride levels were all within normal limits. Otherwise, the amounts of cholestanol and bile alcohol in the bile and urine were high. An ultrasound of the ankles and knees revealed well-defined, homogeneous, hyperechoic masses that had nearly completely replaced the tendons (Achilles, quadriceps and patellar tendons ( Fig. 1 ). Fig. 1 US of ankle and knee swelling revealing a well-defined, homogenous, hyperechoic mass completely replacing the Achille (arrow) and patellar tendons (star) Fig 1 The Achilles tendons had a fusiform expansion with a convex anterior border and were isointense to muscle on MRI of the ankles. The axial image revealed low signal intensity patches strewn over the muscle, giving it the distinctive speckled look ( Fig. 2 ) Fig. 2 Sagittal proton density image (A), T1-weighted image (B), fat suppression on short tau inversion recovery (STIR) (C), T1-fat-saturated-weighted image following contrast agent injection (D), T1-weighted image with fat saturation (E)demonstrating a fusiform enlargement of the Achilles tendon, which has a convex anterior border and is isointense to muscle (arrows), with widely spaced tendon fibers interposed with fat (speckled appearance) (star) Fig 2 On T2 weighted and FLAIR sequences, MRI of the brain revealed hyperintensity of the dentate nuclei (with a hypo intensity on susceptibility weighted imaging corresponding to calcification deposits) ( Fig. 3 ). Fig. 3 Axial and coronal FLAIR images showing hyperintensities of dendate nuclei (arrows) and periventricular white matter (stars) Fig 3 A biopsy at the level of Achilles tumefaction showed an aspect of tendinous xanthoma made of fibroblastic tissue remodelled by a dense inflammatory granuloma rich in cholesterol crystals. In contact with these crystals, numerous multinucleated giant cells were observed, associated with numerous foamy histiocytes. All of these clinical, biological, radiological, and histological data supported the CTX diagnosis.", 'Patient consent': 'Written informed consent for publication was obtained from patient.'}
|
{'Case report': "An 18-year-old woman came in with swelling in her ankles and a cognitive decline. The patient was well until she was 7 years old, when she experienced bilateral increasing ankle edema. From the age of ten years old, her parents noted frequent stumbles and difficulty walking, followed by ataxia. The patient's knees swelled a few years later, when he was 12 years old. In addition, she had previously experienced sight issues. Over all Achilles, quadriceps, and patellar tendons, the osteo-myo-articular examination revealed bilateral painless and non-fistulized masses. Spastic paraparesis, rapid deep reflexes, and extensor plantar responses were discovered during a neurological examination. The Romberg test resulted in a positive result with 1 eye closed. A bilateral thick cataract with impaired vision was discovered during the ophthalmic examination. Total cholesterol, LDL, HDL, and triglyceride levels were all within normal limits. Otherwise, the amounts of cholestanol and bile alcohol in the bile and urine were high. An ultrasound of the ankles and knees revealed well-defined, homogeneous, hyperechoic masses that had nearly completely replaced the tendons (Achilles, quadriceps and patellar tendons ( Fig. 1 ). Fig. 1 US of ankle and knee swelling revealing a well-defined, homogenous, hyperechoic mass completely replacing the Achille (arrow) and patellar tendons (star) Fig 1 The Achilles tendons had a fusiform expansion with a convex anterior border and were isointense to muscle on MRI of the ankles. The axial image revealed low signal intensity patches strewn over the muscle, giving it the distinctive speckled look ( Fig. 2 ) Fig. 2 Sagittal proton density image (A), T1-weighted image (B), fat suppression on short tau inversion recovery (STIR) (C), T1-fat-saturated-weighted image following contrast agent injection (D), T1-weighted image with fat saturation (E)demonstrating a fusiform enlargement of the Achilles tendon, which has a convex anterior border and is isointense to muscle (arrows), with widely spaced tendon fibers interposed with fat (speckled appearance) (star) Fig 2 On T2 weighted and FLAIR sequences, MRI of the brain revealed hyperintensity of the dentate nuclei (with a hypo intensity on susceptibility weighted imaging corresponding to calcification deposits) ( Fig. 3 ). Fig. 3 Axial and coronal FLAIR images showing hyperintensities of dendate nuclei (arrows) and periventricular white matter (stars) Fig 3 A biopsy at the level of Achilles tumefaction showed an aspect of tendinous xanthoma made of fibroblastic tissue remodelled by a dense inflammatory granuloma rich in cholesterol crystals. In contact with these crystals, numerous multinucleated giant cells were observed, associated with numerous foamy histiocytes. All of these clinical, biological, radiological, and histological data supported the CTX diagnosis.", 'Patient consent': 'Written informed consent for publication was obtained from patient.'}
|
Vitals-and-Hematology
|
Vitals_Hema
|
[] |
test-2180
|
8760527
|
{'Case report': "An 18-year-old woman came in with swelling in her ankles and a cognitive decline. The patient was well until she was 7 years old, when she experienced bilateral increasing ankle edema. From the age of ten years old, her parents noted frequent stumbles and difficulty walking, followed by ataxia. The patient's knees swelled a few years later, when he was 12 years old. In addition, she had previously experienced sight issues. Over all Achilles, quadriceps, and patellar tendons, the osteo-myo-articular examination revealed bilateral painless and non-fistulized masses. Spastic paraparesis, rapid deep reflexes, and extensor plantar responses were discovered during a neurological examination. The Romberg test resulted in a positive result with 1 eye closed. A bilateral thick cataract with impaired vision was discovered during the ophthalmic examination. Total cholesterol, LDL, HDL, and triglyceride levels were all within normal limits. Otherwise, the amounts of cholestanol and bile alcohol in the bile and urine were high. An ultrasound of the ankles and knees revealed well-defined, homogeneous, hyperechoic masses that had nearly completely replaced the tendons (Achilles, quadriceps and patellar tendons ( Fig. 1 ). Fig. 1 US of ankle and knee swelling revealing a well-defined, homogenous, hyperechoic mass completely replacing the Achille (arrow) and patellar tendons (star) Fig 1 The Achilles tendons had a fusiform expansion with a convex anterior border and were isointense to muscle on MRI of the ankles. The axial image revealed low signal intensity patches strewn over the muscle, giving it the distinctive speckled look ( Fig. 2 ) Fig. 2 Sagittal proton density image (A), T1-weighted image (B), fat suppression on short tau inversion recovery (STIR) (C), T1-fat-saturated-weighted image following contrast agent injection (D), T1-weighted image with fat saturation (E)demonstrating a fusiform enlargement of the Achilles tendon, which has a convex anterior border and is isointense to muscle (arrows), with widely spaced tendon fibers interposed with fat (speckled appearance) (star) Fig 2 On T2 weighted and FLAIR sequences, MRI of the brain revealed hyperintensity of the dentate nuclei (with a hypo intensity on susceptibility weighted imaging corresponding to calcification deposits) ( Fig. 3 ). Fig. 3 Axial and coronal FLAIR images showing hyperintensities of dendate nuclei (arrows) and periventricular white matter (stars) Fig 3 A biopsy at the level of Achilles tumefaction showed an aspect of tendinous xanthoma made of fibroblastic tissue remodelled by a dense inflammatory granuloma rich in cholesterol crystals. In contact with these crystals, numerous multinucleated giant cells were observed, associated with numerous foamy histiocytes. All of these clinical, biological, radiological, and histological data supported the CTX diagnosis.", 'Patient consent': 'Written informed consent for publication was obtained from patient.'}
|
{'Case report': "An 18-year-old woman came in with swelling in her ankles and a cognitive decline. The patient was well until she was 7 years old, when she experienced bilateral increasing ankle edema. From the age of ten years old, her parents noted frequent stumbles and difficulty walking, followed by ataxia. The patient's knees swelled a few years later, when he was 12 years old. In addition, she had previously experienced sight issues. Over all Achilles, quadriceps, and patellar tendons, the osteo-myo-articular examination revealed bilateral painless and non-fistulized masses. Spastic paraparesis, rapid deep reflexes, and extensor plantar responses were discovered during a neurological examination. The Romberg test resulted in a positive result with 1 eye closed. A bilateral thick cataract with impaired vision was discovered during the ophthalmic examination. Total cholesterol, LDL, HDL, and triglyceride levels were all within normal limits. Otherwise, the amounts of cholestanol and bile alcohol in the bile and urine were high. An ultrasound of the ankles and knees revealed well-defined, homogeneous, hyperechoic masses that had nearly completely replaced the tendons (Achilles, quadriceps and patellar tendons ( Fig. 1 ). Fig. 1 US of ankle and knee swelling revealing a well-defined, homogenous, hyperechoic mass completely replacing the Achille (arrow) and patellar tendons (star) Fig 1 The Achilles tendons had a fusiform expansion with a convex anterior border and were isointense to muscle on MRI of the ankles. The axial image revealed low signal intensity patches strewn over the muscle, giving it the distinctive speckled look ( Fig. 2 ) Fig. 2 Sagittal proton density image (A), T1-weighted image (B), fat suppression on short tau inversion recovery (STIR) (C), T1-fat-saturated-weighted image following contrast agent injection (D), T1-weighted image with fat saturation (E)demonstrating a fusiform enlargement of the Achilles tendon, which has a convex anterior border and is isointense to muscle (arrows), with widely spaced tendon fibers interposed with fat (speckled appearance) (star) Fig 2 On T2 weighted and FLAIR sequences, MRI of the brain revealed hyperintensity of the dentate nuclei (with a hypo intensity on susceptibility weighted imaging corresponding to calcification deposits) ( Fig. 3 ). Fig. 3 Axial and coronal FLAIR images showing hyperintensities of dendate nuclei (arrows) and periventricular white matter (stars) Fig 3 A biopsy at the level of Achilles tumefaction showed an aspect of tendinous xanthoma made of fibroblastic tissue remodelled by a dense inflammatory granuloma rich in cholesterol crystals. In contact with these crystals, numerous multinucleated giant cells were observed, associated with numerous foamy histiocytes. All of these clinical, biological, radiological, and histological data supported the CTX diagnosis.", 'Patient consent': 'Written informed consent for publication was obtained from patient.'}
|
Gastrointestinal-System
|
GI
|
[] |
test-2181
|
8760527
|
{'Case report': "An 18-year-old woman came in with swelling in her ankles and a cognitive decline. The patient was well until she was 7 years old, when she experienced bilateral increasing ankle edema. From the age of ten years old, her parents noted frequent stumbles and difficulty walking, followed by ataxia. The patient's knees swelled a few years later, when he was 12 years old. In addition, she had previously experienced sight issues. Over all Achilles, quadriceps, and patellar tendons, the osteo-myo-articular examination revealed bilateral painless and non-fistulized masses. Spastic paraparesis, rapid deep reflexes, and extensor plantar responses were discovered during a neurological examination. The Romberg test resulted in a positive result with 1 eye closed. A bilateral thick cataract with impaired vision was discovered during the ophthalmic examination. Total cholesterol, LDL, HDL, and triglyceride levels were all within normal limits. Otherwise, the amounts of cholestanol and bile alcohol in the bile and urine were high. An ultrasound of the ankles and knees revealed well-defined, homogeneous, hyperechoic masses that had nearly completely replaced the tendons (Achilles, quadriceps and patellar tendons ( Fig. 1 ). Fig. 1 US of ankle and knee swelling revealing a well-defined, homogenous, hyperechoic mass completely replacing the Achille (arrow) and patellar tendons (star) Fig 1 The Achilles tendons had a fusiform expansion with a convex anterior border and were isointense to muscle on MRI of the ankles. The axial image revealed low signal intensity patches strewn over the muscle, giving it the distinctive speckled look ( Fig. 2 ) Fig. 2 Sagittal proton density image (A), T1-weighted image (B), fat suppression on short tau inversion recovery (STIR) (C), T1-fat-saturated-weighted image following contrast agent injection (D), T1-weighted image with fat saturation (E)demonstrating a fusiform enlargement of the Achilles tendon, which has a convex anterior border and is isointense to muscle (arrows), with widely spaced tendon fibers interposed with fat (speckled appearance) (star) Fig 2 On T2 weighted and FLAIR sequences, MRI of the brain revealed hyperintensity of the dentate nuclei (with a hypo intensity on susceptibility weighted imaging corresponding to calcification deposits) ( Fig. 3 ). Fig. 3 Axial and coronal FLAIR images showing hyperintensities of dendate nuclei (arrows) and periventricular white matter (stars) Fig 3 A biopsy at the level of Achilles tumefaction showed an aspect of tendinous xanthoma made of fibroblastic tissue remodelled by a dense inflammatory granuloma rich in cholesterol crystals. In contact with these crystals, numerous multinucleated giant cells were observed, associated with numerous foamy histiocytes. All of these clinical, biological, radiological, and histological data supported the CTX diagnosis.", 'Patient consent': 'Written informed consent for publication was obtained from patient.'}
|
{'Case report': "An 18-year-old woman came in with swelling in her ankles and a cognitive decline. The patient was well until she was 7 years old, when she experienced bilateral increasing ankle edema. From the age of ten years old, her parents noted frequent stumbles and difficulty walking, followed by ataxia. The patient's knees swelled a few years later, when he was 12 years old. In addition, she had previously experienced sight issues. Over all Achilles, quadriceps, and patellar tendons, the osteo-myo-articular examination revealed bilateral painless and non-fistulized masses. Spastic paraparesis, rapid deep reflexes, and extensor plantar responses were discovered during a neurological examination. The Romberg test resulted in a positive result with 1 eye closed. A bilateral thick cataract with impaired vision was discovered during the ophthalmic examination. Total cholesterol, LDL, HDL, and triglyceride levels were all within normal limits. Otherwise, the amounts of cholestanol and bile alcohol in the bile and urine were high. An ultrasound of the ankles and knees revealed well-defined, homogeneous, hyperechoic masses that had nearly completely replaced the tendons (Achilles, quadriceps and patellar tendons ( Fig. 1 ). Fig. 1 US of ankle and knee swelling revealing a well-defined, homogenous, hyperechoic mass completely replacing the Achille (arrow) and patellar tendons (star) Fig 1 The Achilles tendons had a fusiform expansion with a convex anterior border and were isointense to muscle on MRI of the ankles. The axial image revealed low signal intensity patches strewn over the muscle, giving it the distinctive speckled look ( Fig. 2 ) Fig. 2 Sagittal proton density image (A), T1-weighted image (B), fat suppression on short tau inversion recovery (STIR) (C), T1-fat-saturated-weighted image following contrast agent injection (D), T1-weighted image with fat saturation (E)demonstrating a fusiform enlargement of the Achilles tendon, which has a convex anterior border and is isointense to muscle (arrows), with widely spaced tendon fibers interposed with fat (speckled appearance) (star) Fig 2 On T2 weighted and FLAIR sequences, MRI of the brain revealed hyperintensity of the dentate nuclei (with a hypo intensity on susceptibility weighted imaging corresponding to calcification deposits) ( Fig. 3 ). Fig. 3 Axial and coronal FLAIR images showing hyperintensities of dendate nuclei (arrows) and periventricular white matter (stars) Fig 3 A biopsy at the level of Achilles tumefaction showed an aspect of tendinous xanthoma made of fibroblastic tissue remodelled by a dense inflammatory granuloma rich in cholesterol crystals. In contact with these crystals, numerous multinucleated giant cells were observed, associated with numerous foamy histiocytes. All of these clinical, biological, radiological, and histological data supported the CTX diagnosis.", 'Patient consent': 'Written informed consent for publication was obtained from patient.'}
|
Patient-History
|
History
|
[
"An 18 - year - old woman came in with swelling in her ankles and a cognitive decline"
] |
test-2182
|
8760527
|
{'Case report': "An 18-year-old woman came in with swelling in her ankles and a cognitive decline. The patient was well until she was 7 years old, when she experienced bilateral increasing ankle edema. From the age of ten years old, her parents noted frequent stumbles and difficulty walking, followed by ataxia. The patient's knees swelled a few years later, when he was 12 years old. In addition, she had previously experienced sight issues. Over all Achilles, quadriceps, and patellar tendons, the osteo-myo-articular examination revealed bilateral painless and non-fistulized masses. Spastic paraparesis, rapid deep reflexes, and extensor plantar responses were discovered during a neurological examination. The Romberg test resulted in a positive result with 1 eye closed. A bilateral thick cataract with impaired vision was discovered during the ophthalmic examination. Total cholesterol, LDL, HDL, and triglyceride levels were all within normal limits. Otherwise, the amounts of cholestanol and bile alcohol in the bile and urine were high. An ultrasound of the ankles and knees revealed well-defined, homogeneous, hyperechoic masses that had nearly completely replaced the tendons (Achilles, quadriceps and patellar tendons ( Fig. 1 ). Fig. 1 US of ankle and knee swelling revealing a well-defined, homogenous, hyperechoic mass completely replacing the Achille (arrow) and patellar tendons (star) Fig 1 The Achilles tendons had a fusiform expansion with a convex anterior border and were isointense to muscle on MRI of the ankles. The axial image revealed low signal intensity patches strewn over the muscle, giving it the distinctive speckled look ( Fig. 2 ) Fig. 2 Sagittal proton density image (A), T1-weighted image (B), fat suppression on short tau inversion recovery (STIR) (C), T1-fat-saturated-weighted image following contrast agent injection (D), T1-weighted image with fat saturation (E)demonstrating a fusiform enlargement of the Achilles tendon, which has a convex anterior border and is isointense to muscle (arrows), with widely spaced tendon fibers interposed with fat (speckled appearance) (star) Fig 2 On T2 weighted and FLAIR sequences, MRI of the brain revealed hyperintensity of the dentate nuclei (with a hypo intensity on susceptibility weighted imaging corresponding to calcification deposits) ( Fig. 3 ). Fig. 3 Axial and coronal FLAIR images showing hyperintensities of dendate nuclei (arrows) and periventricular white matter (stars) Fig 3 A biopsy at the level of Achilles tumefaction showed an aspect of tendinous xanthoma made of fibroblastic tissue remodelled by a dense inflammatory granuloma rich in cholesterol crystals. In contact with these crystals, numerous multinucleated giant cells were observed, associated with numerous foamy histiocytes. All of these clinical, biological, radiological, and histological data supported the CTX diagnosis.", 'Patient consent': 'Written informed consent for publication was obtained from patient.'}
|
{'Case report': "An 18-year-old woman came in with swelling in her ankles and a cognitive decline. The patient was well until she was 7 years old, when she experienced bilateral increasing ankle edema. From the age of ten years old, her parents noted frequent stumbles and difficulty walking, followed by ataxia. The patient's knees swelled a few years later, when he was 12 years old. In addition, she had previously experienced sight issues. Over all Achilles, quadriceps, and patellar tendons, the osteo-myo-articular examination revealed bilateral painless and non-fistulized masses. Spastic paraparesis, rapid deep reflexes, and extensor plantar responses were discovered during a neurological examination. The Romberg test resulted in a positive result with 1 eye closed. A bilateral thick cataract with impaired vision was discovered during the ophthalmic examination. Total cholesterol, LDL, HDL, and triglyceride levels were all within normal limits. Otherwise, the amounts of cholestanol and bile alcohol in the bile and urine were high. An ultrasound of the ankles and knees revealed well-defined, homogeneous, hyperechoic masses that had nearly completely replaced the tendons (Achilles, quadriceps and patellar tendons ( Fig. 1 ). Fig. 1 US of ankle and knee swelling revealing a well-defined, homogenous, hyperechoic mass completely replacing the Achille (arrow) and patellar tendons (star) Fig 1 The Achilles tendons had a fusiform expansion with a convex anterior border and were isointense to muscle on MRI of the ankles. The axial image revealed low signal intensity patches strewn over the muscle, giving it the distinctive speckled look ( Fig. 2 ) Fig. 2 Sagittal proton density image (A), T1-weighted image (B), fat suppression on short tau inversion recovery (STIR) (C), T1-fat-saturated-weighted image following contrast agent injection (D), T1-weighted image with fat saturation (E)demonstrating a fusiform enlargement of the Achilles tendon, which has a convex anterior border and is isointense to muscle (arrows), with widely spaced tendon fibers interposed with fat (speckled appearance) (star) Fig 2 On T2 weighted and FLAIR sequences, MRI of the brain revealed hyperintensity of the dentate nuclei (with a hypo intensity on susceptibility weighted imaging corresponding to calcification deposits) ( Fig. 3 ). Fig. 3 Axial and coronal FLAIR images showing hyperintensities of dendate nuclei (arrows) and periventricular white matter (stars) Fig 3 A biopsy at the level of Achilles tumefaction showed an aspect of tendinous xanthoma made of fibroblastic tissue remodelled by a dense inflammatory granuloma rich in cholesterol crystals. In contact with these crystals, numerous multinucleated giant cells were observed, associated with numerous foamy histiocytes. All of these clinical, biological, radiological, and histological data supported the CTX diagnosis.", 'Patient consent': 'Written informed consent for publication was obtained from patient.'}
|
Neurology
|
Neuro
|
[
"cognitive decline",
"frequent stumbles and difficulty walking, followed by ataxia",
"Spastic paraparesis, rapid deep reflexes, and extensor plantar responses were discovered during a neurological examination. The Romberg test resulted in a positive result with 1 eye closed.",
"On T2 weighted and FLAIR sequences, MRI of the brain revealed hyperintensity of the dentate nuclei ( with a hypo intensity on susceptibility weighted imaging corresponding to calcification deposits )",
"Axial and coronal FLAIR images showing hyperintensities of dendate nuclei ( arrows ) and periventricular white matter"
] |
test-2183
|
8760527
|
{'Case report': "An 18-year-old woman came in with swelling in her ankles and a cognitive decline. The patient was well until she was 7 years old, when she experienced bilateral increasing ankle edema. From the age of ten years old, her parents noted frequent stumbles and difficulty walking, followed by ataxia. The patient's knees swelled a few years later, when he was 12 years old. In addition, she had previously experienced sight issues. Over all Achilles, quadriceps, and patellar tendons, the osteo-myo-articular examination revealed bilateral painless and non-fistulized masses. Spastic paraparesis, rapid deep reflexes, and extensor plantar responses were discovered during a neurological examination. The Romberg test resulted in a positive result with 1 eye closed. A bilateral thick cataract with impaired vision was discovered during the ophthalmic examination. Total cholesterol, LDL, HDL, and triglyceride levels were all within normal limits. Otherwise, the amounts of cholestanol and bile alcohol in the bile and urine were high. An ultrasound of the ankles and knees revealed well-defined, homogeneous, hyperechoic masses that had nearly completely replaced the tendons (Achilles, quadriceps and patellar tendons ( Fig. 1 ). Fig. 1 US of ankle and knee swelling revealing a well-defined, homogenous, hyperechoic mass completely replacing the Achille (arrow) and patellar tendons (star) Fig 1 The Achilles tendons had a fusiform expansion with a convex anterior border and were isointense to muscle on MRI of the ankles. The axial image revealed low signal intensity patches strewn over the muscle, giving it the distinctive speckled look ( Fig. 2 ) Fig. 2 Sagittal proton density image (A), T1-weighted image (B), fat suppression on short tau inversion recovery (STIR) (C), T1-fat-saturated-weighted image following contrast agent injection (D), T1-weighted image with fat saturation (E)demonstrating a fusiform enlargement of the Achilles tendon, which has a convex anterior border and is isointense to muscle (arrows), with widely spaced tendon fibers interposed with fat (speckled appearance) (star) Fig 2 On T2 weighted and FLAIR sequences, MRI of the brain revealed hyperintensity of the dentate nuclei (with a hypo intensity on susceptibility weighted imaging corresponding to calcification deposits) ( Fig. 3 ). Fig. 3 Axial and coronal FLAIR images showing hyperintensities of dendate nuclei (arrows) and periventricular white matter (stars) Fig 3 A biopsy at the level of Achilles tumefaction showed an aspect of tendinous xanthoma made of fibroblastic tissue remodelled by a dense inflammatory granuloma rich in cholesterol crystals. In contact with these crystals, numerous multinucleated giant cells were observed, associated with numerous foamy histiocytes. All of these clinical, biological, radiological, and histological data supported the CTX diagnosis.", 'Patient consent': 'Written informed consent for publication was obtained from patient.'}
|
{'Case report': "An 18-year-old woman came in with swelling in her ankles and a cognitive decline. The patient was well until she was 7 years old, when she experienced bilateral increasing ankle edema. From the age of ten years old, her parents noted frequent stumbles and difficulty walking, followed by ataxia. The patient's knees swelled a few years later, when he was 12 years old. In addition, she had previously experienced sight issues. Over all Achilles, quadriceps, and patellar tendons, the osteo-myo-articular examination revealed bilateral painless and non-fistulized masses. Spastic paraparesis, rapid deep reflexes, and extensor plantar responses were discovered during a neurological examination. The Romberg test resulted in a positive result with 1 eye closed. A bilateral thick cataract with impaired vision was discovered during the ophthalmic examination. Total cholesterol, LDL, HDL, and triglyceride levels were all within normal limits. Otherwise, the amounts of cholestanol and bile alcohol in the bile and urine were high. An ultrasound of the ankles and knees revealed well-defined, homogeneous, hyperechoic masses that had nearly completely replaced the tendons (Achilles, quadriceps and patellar tendons ( Fig. 1 ). Fig. 1 US of ankle and knee swelling revealing a well-defined, homogenous, hyperechoic mass completely replacing the Achille (arrow) and patellar tendons (star) Fig 1 The Achilles tendons had a fusiform expansion with a convex anterior border and were isointense to muscle on MRI of the ankles. The axial image revealed low signal intensity patches strewn over the muscle, giving it the distinctive speckled look ( Fig. 2 ) Fig. 2 Sagittal proton density image (A), T1-weighted image (B), fat suppression on short tau inversion recovery (STIR) (C), T1-fat-saturated-weighted image following contrast agent injection (D), T1-weighted image with fat saturation (E)demonstrating a fusiform enlargement of the Achilles tendon, which has a convex anterior border and is isointense to muscle (arrows), with widely spaced tendon fibers interposed with fat (speckled appearance) (star) Fig 2 On T2 weighted and FLAIR sequences, MRI of the brain revealed hyperintensity of the dentate nuclei (with a hypo intensity on susceptibility weighted imaging corresponding to calcification deposits) ( Fig. 3 ). Fig. 3 Axial and coronal FLAIR images showing hyperintensities of dendate nuclei (arrows) and periventricular white matter (stars) Fig 3 A biopsy at the level of Achilles tumefaction showed an aspect of tendinous xanthoma made of fibroblastic tissue remodelled by a dense inflammatory granuloma rich in cholesterol crystals. In contact with these crystals, numerous multinucleated giant cells were observed, associated with numerous foamy histiocytes. All of these clinical, biological, radiological, and histological data supported the CTX diagnosis.", 'Patient consent': 'Written informed consent for publication was obtained from patient.'}
|
Laboratory-and-Imaging
|
Lab_Image
|
[
"Total cholesterol, LDL, HDL, and triglyceride levels were all within normal limits. Otherwise, the amounts of cholestanol and bile alcohol in the bile and urine were high. An ultrasound of the ankles and knees revealed well - defined, homogeneous, hyperechoic masses that had nearly completely replaced the tendons ( Achilles, quadriceps and patellar tendons ( Fig. 1 ). Fig. 1 US of ankle and knee swelling revealing a well - defined, homogenous, hyperechoic mass completely replacing the Achille ( arrow ) and patellar tendons ( star ) Fig 1 The Achilles tendons had a fusiform expansion with a convex anterior border and were isointense to muscle on MRI of the ankles. The axial image revealed low signal intensity patches strewn over the muscle, giving it the distinctive speckled look ( Fig. 2 ) Fig. 2 Sagittal proton density image ( A ), T1 - weighted image ( B ), fat suppression on short tau inversion recovery ( STIR ) ( C ), T1 - fat - saturated - weighted image following contrast agent injection ( D ), T1 - weighted image with fat saturation ( E)demonstrating a fusiform enlargement of the Achilles tendon, which has a convex anterior border and is isointense to muscle ( arrows ), with widely spaced tendon fibers interposed with fat ( speckled appearance ) ( star ) Fig 2 On T2 weighted and FLAIR sequences, MRI of the brain revealed hyperintensity of the dentate nuclei ( with a hypo intensity on susceptibility weighted imaging corresponding to calcification deposits ) ( Fig. 3 ). Fig. 3 Axial and coronal FLAIR images showing hyperintensities of dendate nuclei ( arrows ) and periventricular white matter ( stars ) Fig 3 A biopsy at the level of Achilles tumefaction showed an aspect of tendinous xanthoma made of fibroblastic tissue remodelled by a dense inflammatory granuloma rich in cholesterol crystals. In contact with these crystals, numerous multinucleated giant cells were observed, associated with numerous foamy histiocytes"
] |
test-2184
|
8760527
|
{'Case report': "An 18-year-old woman came in with swelling in her ankles and a cognitive decline. The patient was well until she was 7 years old, when she experienced bilateral increasing ankle edema. From the age of ten years old, her parents noted frequent stumbles and difficulty walking, followed by ataxia. The patient's knees swelled a few years later, when he was 12 years old. In addition, she had previously experienced sight issues. Over all Achilles, quadriceps, and patellar tendons, the osteo-myo-articular examination revealed bilateral painless and non-fistulized masses. Spastic paraparesis, rapid deep reflexes, and extensor plantar responses were discovered during a neurological examination. The Romberg test resulted in a positive result with 1 eye closed. A bilateral thick cataract with impaired vision was discovered during the ophthalmic examination. Total cholesterol, LDL, HDL, and triglyceride levels were all within normal limits. Otherwise, the amounts of cholestanol and bile alcohol in the bile and urine were high. An ultrasound of the ankles and knees revealed well-defined, homogeneous, hyperechoic masses that had nearly completely replaced the tendons (Achilles, quadriceps and patellar tendons ( Fig. 1 ). Fig. 1 US of ankle and knee swelling revealing a well-defined, homogenous, hyperechoic mass completely replacing the Achille (arrow) and patellar tendons (star) Fig 1 The Achilles tendons had a fusiform expansion with a convex anterior border and were isointense to muscle on MRI of the ankles. The axial image revealed low signal intensity patches strewn over the muscle, giving it the distinctive speckled look ( Fig. 2 ) Fig. 2 Sagittal proton density image (A), T1-weighted image (B), fat suppression on short tau inversion recovery (STIR) (C), T1-fat-saturated-weighted image following contrast agent injection (D), T1-weighted image with fat saturation (E)demonstrating a fusiform enlargement of the Achilles tendon, which has a convex anterior border and is isointense to muscle (arrows), with widely spaced tendon fibers interposed with fat (speckled appearance) (star) Fig 2 On T2 weighted and FLAIR sequences, MRI of the brain revealed hyperintensity of the dentate nuclei (with a hypo intensity on susceptibility weighted imaging corresponding to calcification deposits) ( Fig. 3 ). Fig. 3 Axial and coronal FLAIR images showing hyperintensities of dendate nuclei (arrows) and periventricular white matter (stars) Fig 3 A biopsy at the level of Achilles tumefaction showed an aspect of tendinous xanthoma made of fibroblastic tissue remodelled by a dense inflammatory granuloma rich in cholesterol crystals. In contact with these crystals, numerous multinucleated giant cells were observed, associated with numerous foamy histiocytes. All of these clinical, biological, radiological, and histological data supported the CTX diagnosis.", 'Patient consent': 'Written informed consent for publication was obtained from patient.'}
|
{'Case report': "An 18-year-old woman came in with swelling in her ankles and a cognitive decline. The patient was well until she was 7 years old, when she experienced bilateral increasing ankle edema. From the age of ten years old, her parents noted frequent stumbles and difficulty walking, followed by ataxia. The patient's knees swelled a few years later, when he was 12 years old. In addition, she had previously experienced sight issues. Over all Achilles, quadriceps, and patellar tendons, the osteo-myo-articular examination revealed bilateral painless and non-fistulized masses. Spastic paraparesis, rapid deep reflexes, and extensor plantar responses were discovered during a neurological examination. The Romberg test resulted in a positive result with 1 eye closed. A bilateral thick cataract with impaired vision was discovered during the ophthalmic examination. Total cholesterol, LDL, HDL, and triglyceride levels were all within normal limits. Otherwise, the amounts of cholestanol and bile alcohol in the bile and urine were high. An ultrasound of the ankles and knees revealed well-defined, homogeneous, hyperechoic masses that had nearly completely replaced the tendons (Achilles, quadriceps and patellar tendons ( Fig. 1 ). Fig. 1 US of ankle and knee swelling revealing a well-defined, homogenous, hyperechoic mass completely replacing the Achille (arrow) and patellar tendons (star) Fig 1 The Achilles tendons had a fusiform expansion with a convex anterior border and were isointense to muscle on MRI of the ankles. The axial image revealed low signal intensity patches strewn over the muscle, giving it the distinctive speckled look ( Fig. 2 ) Fig. 2 Sagittal proton density image (A), T1-weighted image (B), fat suppression on short tau inversion recovery (STIR) (C), T1-fat-saturated-weighted image following contrast agent injection (D), T1-weighted image with fat saturation (E)demonstrating a fusiform enlargement of the Achilles tendon, which has a convex anterior border and is isointense to muscle (arrows), with widely spaced tendon fibers interposed with fat (speckled appearance) (star) Fig 2 On T2 weighted and FLAIR sequences, MRI of the brain revealed hyperintensity of the dentate nuclei (with a hypo intensity on susceptibility weighted imaging corresponding to calcification deposits) ( Fig. 3 ). Fig. 3 Axial and coronal FLAIR images showing hyperintensities of dendate nuclei (arrows) and periventricular white matter (stars) Fig 3 A biopsy at the level of Achilles tumefaction showed an aspect of tendinous xanthoma made of fibroblastic tissue remodelled by a dense inflammatory granuloma rich in cholesterol crystals. In contact with these crystals, numerous multinucleated giant cells were observed, associated with numerous foamy histiocytes. All of these clinical, biological, radiological, and histological data supported the CTX diagnosis.", 'Patient consent': 'Written informed consent for publication was obtained from patient.'}
|
Cardiovascular-System
|
CVS
|
[] |
test-2185
|
8760527
|
{'Case report': "An 18-year-old woman came in with swelling in her ankles and a cognitive decline. The patient was well until she was 7 years old, when she experienced bilateral increasing ankle edema. From the age of ten years old, her parents noted frequent stumbles and difficulty walking, followed by ataxia. The patient's knees swelled a few years later, when he was 12 years old. In addition, she had previously experienced sight issues. Over all Achilles, quadriceps, and patellar tendons, the osteo-myo-articular examination revealed bilateral painless and non-fistulized masses. Spastic paraparesis, rapid deep reflexes, and extensor plantar responses were discovered during a neurological examination. The Romberg test resulted in a positive result with 1 eye closed. A bilateral thick cataract with impaired vision was discovered during the ophthalmic examination. Total cholesterol, LDL, HDL, and triglyceride levels were all within normal limits. Otherwise, the amounts of cholestanol and bile alcohol in the bile and urine were high. An ultrasound of the ankles and knees revealed well-defined, homogeneous, hyperechoic masses that had nearly completely replaced the tendons (Achilles, quadriceps and patellar tendons ( Fig. 1 ). Fig. 1 US of ankle and knee swelling revealing a well-defined, homogenous, hyperechoic mass completely replacing the Achille (arrow) and patellar tendons (star) Fig 1 The Achilles tendons had a fusiform expansion with a convex anterior border and were isointense to muscle on MRI of the ankles. The axial image revealed low signal intensity patches strewn over the muscle, giving it the distinctive speckled look ( Fig. 2 ) Fig. 2 Sagittal proton density image (A), T1-weighted image (B), fat suppression on short tau inversion recovery (STIR) (C), T1-fat-saturated-weighted image following contrast agent injection (D), T1-weighted image with fat saturation (E)demonstrating a fusiform enlargement of the Achilles tendon, which has a convex anterior border and is isointense to muscle (arrows), with widely spaced tendon fibers interposed with fat (speckled appearance) (star) Fig 2 On T2 weighted and FLAIR sequences, MRI of the brain revealed hyperintensity of the dentate nuclei (with a hypo intensity on susceptibility weighted imaging corresponding to calcification deposits) ( Fig. 3 ). Fig. 3 Axial and coronal FLAIR images showing hyperintensities of dendate nuclei (arrows) and periventricular white matter (stars) Fig 3 A biopsy at the level of Achilles tumefaction showed an aspect of tendinous xanthoma made of fibroblastic tissue remodelled by a dense inflammatory granuloma rich in cholesterol crystals. In contact with these crystals, numerous multinucleated giant cells were observed, associated with numerous foamy histiocytes. All of these clinical, biological, radiological, and histological data supported the CTX diagnosis.", 'Patient consent': 'Written informed consent for publication was obtained from patient.'}
|
{'Case report': "An 18-year-old woman came in with swelling in her ankles and a cognitive decline. The patient was well until she was 7 years old, when she experienced bilateral increasing ankle edema. From the age of ten years old, her parents noted frequent stumbles and difficulty walking, followed by ataxia. The patient's knees swelled a few years later, when he was 12 years old. In addition, she had previously experienced sight issues. Over all Achilles, quadriceps, and patellar tendons, the osteo-myo-articular examination revealed bilateral painless and non-fistulized masses. Spastic paraparesis, rapid deep reflexes, and extensor plantar responses were discovered during a neurological examination. The Romberg test resulted in a positive result with 1 eye closed. A bilateral thick cataract with impaired vision was discovered during the ophthalmic examination. Total cholesterol, LDL, HDL, and triglyceride levels were all within normal limits. Otherwise, the amounts of cholestanol and bile alcohol in the bile and urine were high. An ultrasound of the ankles and knees revealed well-defined, homogeneous, hyperechoic masses that had nearly completely replaced the tendons (Achilles, quadriceps and patellar tendons ( Fig. 1 ). Fig. 1 US of ankle and knee swelling revealing a well-defined, homogenous, hyperechoic mass completely replacing the Achille (arrow) and patellar tendons (star) Fig 1 The Achilles tendons had a fusiform expansion with a convex anterior border and were isointense to muscle on MRI of the ankles. The axial image revealed low signal intensity patches strewn over the muscle, giving it the distinctive speckled look ( Fig. 2 ) Fig. 2 Sagittal proton density image (A), T1-weighted image (B), fat suppression on short tau inversion recovery (STIR) (C), T1-fat-saturated-weighted image following contrast agent injection (D), T1-weighted image with fat saturation (E)demonstrating a fusiform enlargement of the Achilles tendon, which has a convex anterior border and is isointense to muscle (arrows), with widely spaced tendon fibers interposed with fat (speckled appearance) (star) Fig 2 On T2 weighted and FLAIR sequences, MRI of the brain revealed hyperintensity of the dentate nuclei (with a hypo intensity on susceptibility weighted imaging corresponding to calcification deposits) ( Fig. 3 ). Fig. 3 Axial and coronal FLAIR images showing hyperintensities of dendate nuclei (arrows) and periventricular white matter (stars) Fig 3 A biopsy at the level of Achilles tumefaction showed an aspect of tendinous xanthoma made of fibroblastic tissue remodelled by a dense inflammatory granuloma rich in cholesterol crystals. In contact with these crystals, numerous multinucleated giant cells were observed, associated with numerous foamy histiocytes. All of these clinical, biological, radiological, and histological data supported the CTX diagnosis.", 'Patient consent': 'Written informed consent for publication was obtained from patient.'}
|
Endocrinology
|
ENDO
|
[] |
test-2186
|
8760527
|
{'Case report': "An 18-year-old woman came in with swelling in her ankles and a cognitive decline. The patient was well until she was 7 years old, when she experienced bilateral increasing ankle edema. From the age of ten years old, her parents noted frequent stumbles and difficulty walking, followed by ataxia. The patient's knees swelled a few years later, when he was 12 years old. In addition, she had previously experienced sight issues. Over all Achilles, quadriceps, and patellar tendons, the osteo-myo-articular examination revealed bilateral painless and non-fistulized masses. Spastic paraparesis, rapid deep reflexes, and extensor plantar responses were discovered during a neurological examination. The Romberg test resulted in a positive result with 1 eye closed. A bilateral thick cataract with impaired vision was discovered during the ophthalmic examination. Total cholesterol, LDL, HDL, and triglyceride levels were all within normal limits. Otherwise, the amounts of cholestanol and bile alcohol in the bile and urine were high. An ultrasound of the ankles and knees revealed well-defined, homogeneous, hyperechoic masses that had nearly completely replaced the tendons (Achilles, quadriceps and patellar tendons ( Fig. 1 ). Fig. 1 US of ankle and knee swelling revealing a well-defined, homogenous, hyperechoic mass completely replacing the Achille (arrow) and patellar tendons (star) Fig 1 The Achilles tendons had a fusiform expansion with a convex anterior border and were isointense to muscle on MRI of the ankles. The axial image revealed low signal intensity patches strewn over the muscle, giving it the distinctive speckled look ( Fig. 2 ) Fig. 2 Sagittal proton density image (A), T1-weighted image (B), fat suppression on short tau inversion recovery (STIR) (C), T1-fat-saturated-weighted image following contrast agent injection (D), T1-weighted image with fat saturation (E)demonstrating a fusiform enlargement of the Achilles tendon, which has a convex anterior border and is isointense to muscle (arrows), with widely spaced tendon fibers interposed with fat (speckled appearance) (star) Fig 2 On T2 weighted and FLAIR sequences, MRI of the brain revealed hyperintensity of the dentate nuclei (with a hypo intensity on susceptibility weighted imaging corresponding to calcification deposits) ( Fig. 3 ). Fig. 3 Axial and coronal FLAIR images showing hyperintensities of dendate nuclei (arrows) and periventricular white matter (stars) Fig 3 A biopsy at the level of Achilles tumefaction showed an aspect of tendinous xanthoma made of fibroblastic tissue remodelled by a dense inflammatory granuloma rich in cholesterol crystals. In contact with these crystals, numerous multinucleated giant cells were observed, associated with numerous foamy histiocytes. All of these clinical, biological, radiological, and histological data supported the CTX diagnosis.", 'Patient consent': 'Written informed consent for publication was obtained from patient.'}
|
{'Case report': "An 18-year-old woman came in with swelling in her ankles and a cognitive decline. The patient was well until she was 7 years old, when she experienced bilateral increasing ankle edema. From the age of ten years old, her parents noted frequent stumbles and difficulty walking, followed by ataxia. The patient's knees swelled a few years later, when he was 12 years old. In addition, she had previously experienced sight issues. Over all Achilles, quadriceps, and patellar tendons, the osteo-myo-articular examination revealed bilateral painless and non-fistulized masses. Spastic paraparesis, rapid deep reflexes, and extensor plantar responses were discovered during a neurological examination. The Romberg test resulted in a positive result with 1 eye closed. A bilateral thick cataract with impaired vision was discovered during the ophthalmic examination. Total cholesterol, LDL, HDL, and triglyceride levels were all within normal limits. Otherwise, the amounts of cholestanol and bile alcohol in the bile and urine were high. An ultrasound of the ankles and knees revealed well-defined, homogeneous, hyperechoic masses that had nearly completely replaced the tendons (Achilles, quadriceps and patellar tendons ( Fig. 1 ). Fig. 1 US of ankle and knee swelling revealing a well-defined, homogenous, hyperechoic mass completely replacing the Achille (arrow) and patellar tendons (star) Fig 1 The Achilles tendons had a fusiform expansion with a convex anterior border and were isointense to muscle on MRI of the ankles. The axial image revealed low signal intensity patches strewn over the muscle, giving it the distinctive speckled look ( Fig. 2 ) Fig. 2 Sagittal proton density image (A), T1-weighted image (B), fat suppression on short tau inversion recovery (STIR) (C), T1-fat-saturated-weighted image following contrast agent injection (D), T1-weighted image with fat saturation (E)demonstrating a fusiform enlargement of the Achilles tendon, which has a convex anterior border and is isointense to muscle (arrows), with widely spaced tendon fibers interposed with fat (speckled appearance) (star) Fig 2 On T2 weighted and FLAIR sequences, MRI of the brain revealed hyperintensity of the dentate nuclei (with a hypo intensity on susceptibility weighted imaging corresponding to calcification deposits) ( Fig. 3 ). Fig. 3 Axial and coronal FLAIR images showing hyperintensities of dendate nuclei (arrows) and periventricular white matter (stars) Fig 3 A biopsy at the level of Achilles tumefaction showed an aspect of tendinous xanthoma made of fibroblastic tissue remodelled by a dense inflammatory granuloma rich in cholesterol crystals. In contact with these crystals, numerous multinucleated giant cells were observed, associated with numerous foamy histiocytes. All of these clinical, biological, radiological, and histological data supported the CTX diagnosis.", 'Patient consent': 'Written informed consent for publication was obtained from patient.'}
|
Genitourinary-System
|
GU
|
[] |
test-2187
|
8760527
|
{'Case report': "An 18-year-old woman came in with swelling in her ankles and a cognitive decline. The patient was well until she was 7 years old, when she experienced bilateral increasing ankle edema. From the age of ten years old, her parents noted frequent stumbles and difficulty walking, followed by ataxia. The patient's knees swelled a few years later, when he was 12 years old. In addition, she had previously experienced sight issues. Over all Achilles, quadriceps, and patellar tendons, the osteo-myo-articular examination revealed bilateral painless and non-fistulized masses. Spastic paraparesis, rapid deep reflexes, and extensor plantar responses were discovered during a neurological examination. The Romberg test resulted in a positive result with 1 eye closed. A bilateral thick cataract with impaired vision was discovered during the ophthalmic examination. Total cholesterol, LDL, HDL, and triglyceride levels were all within normal limits. Otherwise, the amounts of cholestanol and bile alcohol in the bile and urine were high. An ultrasound of the ankles and knees revealed well-defined, homogeneous, hyperechoic masses that had nearly completely replaced the tendons (Achilles, quadriceps and patellar tendons ( Fig. 1 ). Fig. 1 US of ankle and knee swelling revealing a well-defined, homogenous, hyperechoic mass completely replacing the Achille (arrow) and patellar tendons (star) Fig 1 The Achilles tendons had a fusiform expansion with a convex anterior border and were isointense to muscle on MRI of the ankles. The axial image revealed low signal intensity patches strewn over the muscle, giving it the distinctive speckled look ( Fig. 2 ) Fig. 2 Sagittal proton density image (A), T1-weighted image (B), fat suppression on short tau inversion recovery (STIR) (C), T1-fat-saturated-weighted image following contrast agent injection (D), T1-weighted image with fat saturation (E)demonstrating a fusiform enlargement of the Achilles tendon, which has a convex anterior border and is isointense to muscle (arrows), with widely spaced tendon fibers interposed with fat (speckled appearance) (star) Fig 2 On T2 weighted and FLAIR sequences, MRI of the brain revealed hyperintensity of the dentate nuclei (with a hypo intensity on susceptibility weighted imaging corresponding to calcification deposits) ( Fig. 3 ). Fig. 3 Axial and coronal FLAIR images showing hyperintensities of dendate nuclei (arrows) and periventricular white matter (stars) Fig 3 A biopsy at the level of Achilles tumefaction showed an aspect of tendinous xanthoma made of fibroblastic tissue remodelled by a dense inflammatory granuloma rich in cholesterol crystals. In contact with these crystals, numerous multinucleated giant cells were observed, associated with numerous foamy histiocytes. All of these clinical, biological, radiological, and histological data supported the CTX diagnosis.", 'Patient consent': 'Written informed consent for publication was obtained from patient.'}
|
{'Case report': "An 18-year-old woman came in with swelling in her ankles and a cognitive decline. The patient was well until she was 7 years old, when she experienced bilateral increasing ankle edema. From the age of ten years old, her parents noted frequent stumbles and difficulty walking, followed by ataxia. The patient's knees swelled a few years later, when he was 12 years old. In addition, she had previously experienced sight issues. Over all Achilles, quadriceps, and patellar tendons, the osteo-myo-articular examination revealed bilateral painless and non-fistulized masses. Spastic paraparesis, rapid deep reflexes, and extensor plantar responses were discovered during a neurological examination. The Romberg test resulted in a positive result with 1 eye closed. A bilateral thick cataract with impaired vision was discovered during the ophthalmic examination. Total cholesterol, LDL, HDL, and triglyceride levels were all within normal limits. Otherwise, the amounts of cholestanol and bile alcohol in the bile and urine were high. An ultrasound of the ankles and knees revealed well-defined, homogeneous, hyperechoic masses that had nearly completely replaced the tendons (Achilles, quadriceps and patellar tendons ( Fig. 1 ). Fig. 1 US of ankle and knee swelling revealing a well-defined, homogenous, hyperechoic mass completely replacing the Achille (arrow) and patellar tendons (star) Fig 1 The Achilles tendons had a fusiform expansion with a convex anterior border and were isointense to muscle on MRI of the ankles. The axial image revealed low signal intensity patches strewn over the muscle, giving it the distinctive speckled look ( Fig. 2 ) Fig. 2 Sagittal proton density image (A), T1-weighted image (B), fat suppression on short tau inversion recovery (STIR) (C), T1-fat-saturated-weighted image following contrast agent injection (D), T1-weighted image with fat saturation (E)demonstrating a fusiform enlargement of the Achilles tendon, which has a convex anterior border and is isointense to muscle (arrows), with widely spaced tendon fibers interposed with fat (speckled appearance) (star) Fig 2 On T2 weighted and FLAIR sequences, MRI of the brain revealed hyperintensity of the dentate nuclei (with a hypo intensity on susceptibility weighted imaging corresponding to calcification deposits) ( Fig. 3 ). Fig. 3 Axial and coronal FLAIR images showing hyperintensities of dendate nuclei (arrows) and periventricular white matter (stars) Fig 3 A biopsy at the level of Achilles tumefaction showed an aspect of tendinous xanthoma made of fibroblastic tissue remodelled by a dense inflammatory granuloma rich in cholesterol crystals. In contact with these crystals, numerous multinucleated giant cells were observed, associated with numerous foamy histiocytes. All of these clinical, biological, radiological, and histological data supported the CTX diagnosis.", 'Patient consent': 'Written informed consent for publication was obtained from patient.'}
|
Respiratory-System
|
RESP
|
[] |
test-2188
|
8760527
|
{'Case report': "An 18-year-old woman came in with swelling in her ankles and a cognitive decline. The patient was well until she was 7 years old, when she experienced bilateral increasing ankle edema. From the age of ten years old, her parents noted frequent stumbles and difficulty walking, followed by ataxia. The patient's knees swelled a few years later, when he was 12 years old. In addition, she had previously experienced sight issues. Over all Achilles, quadriceps, and patellar tendons, the osteo-myo-articular examination revealed bilateral painless and non-fistulized masses. Spastic paraparesis, rapid deep reflexes, and extensor plantar responses were discovered during a neurological examination. The Romberg test resulted in a positive result with 1 eye closed. A bilateral thick cataract with impaired vision was discovered during the ophthalmic examination. Total cholesterol, LDL, HDL, and triglyceride levels were all within normal limits. Otherwise, the amounts of cholestanol and bile alcohol in the bile and urine were high. An ultrasound of the ankles and knees revealed well-defined, homogeneous, hyperechoic masses that had nearly completely replaced the tendons (Achilles, quadriceps and patellar tendons ( Fig. 1 ). Fig. 1 US of ankle and knee swelling revealing a well-defined, homogenous, hyperechoic mass completely replacing the Achille (arrow) and patellar tendons (star) Fig 1 The Achilles tendons had a fusiform expansion with a convex anterior border and were isointense to muscle on MRI of the ankles. The axial image revealed low signal intensity patches strewn over the muscle, giving it the distinctive speckled look ( Fig. 2 ) Fig. 2 Sagittal proton density image (A), T1-weighted image (B), fat suppression on short tau inversion recovery (STIR) (C), T1-fat-saturated-weighted image following contrast agent injection (D), T1-weighted image with fat saturation (E)demonstrating a fusiform enlargement of the Achilles tendon, which has a convex anterior border and is isointense to muscle (arrows), with widely spaced tendon fibers interposed with fat (speckled appearance) (star) Fig 2 On T2 weighted and FLAIR sequences, MRI of the brain revealed hyperintensity of the dentate nuclei (with a hypo intensity on susceptibility weighted imaging corresponding to calcification deposits) ( Fig. 3 ). Fig. 3 Axial and coronal FLAIR images showing hyperintensities of dendate nuclei (arrows) and periventricular white matter (stars) Fig 3 A biopsy at the level of Achilles tumefaction showed an aspect of tendinous xanthoma made of fibroblastic tissue remodelled by a dense inflammatory granuloma rich in cholesterol crystals. In contact with these crystals, numerous multinucleated giant cells were observed, associated with numerous foamy histiocytes. All of these clinical, biological, radiological, and histological data supported the CTX diagnosis.", 'Patient consent': 'Written informed consent for publication was obtained from patient.'}
|
{'Case report': "An 18-year-old woman came in with swelling in her ankles and a cognitive decline. The patient was well until she was 7 years old, when she experienced bilateral increasing ankle edema. From the age of ten years old, her parents noted frequent stumbles and difficulty walking, followed by ataxia. The patient's knees swelled a few years later, when he was 12 years old. In addition, she had previously experienced sight issues. Over all Achilles, quadriceps, and patellar tendons, the osteo-myo-articular examination revealed bilateral painless and non-fistulized masses. Spastic paraparesis, rapid deep reflexes, and extensor plantar responses were discovered during a neurological examination. The Romberg test resulted in a positive result with 1 eye closed. A bilateral thick cataract with impaired vision was discovered during the ophthalmic examination. Total cholesterol, LDL, HDL, and triglyceride levels were all within normal limits. Otherwise, the amounts of cholestanol and bile alcohol in the bile and urine were high. An ultrasound of the ankles and knees revealed well-defined, homogeneous, hyperechoic masses that had nearly completely replaced the tendons (Achilles, quadriceps and patellar tendons ( Fig. 1 ). Fig. 1 US of ankle and knee swelling revealing a well-defined, homogenous, hyperechoic mass completely replacing the Achille (arrow) and patellar tendons (star) Fig 1 The Achilles tendons had a fusiform expansion with a convex anterior border and were isointense to muscle on MRI of the ankles. The axial image revealed low signal intensity patches strewn over the muscle, giving it the distinctive speckled look ( Fig. 2 ) Fig. 2 Sagittal proton density image (A), T1-weighted image (B), fat suppression on short tau inversion recovery (STIR) (C), T1-fat-saturated-weighted image following contrast agent injection (D), T1-weighted image with fat saturation (E)demonstrating a fusiform enlargement of the Achilles tendon, which has a convex anterior border and is isointense to muscle (arrows), with widely spaced tendon fibers interposed with fat (speckled appearance) (star) Fig 2 On T2 weighted and FLAIR sequences, MRI of the brain revealed hyperintensity of the dentate nuclei (with a hypo intensity on susceptibility weighted imaging corresponding to calcification deposits) ( Fig. 3 ). Fig. 3 Axial and coronal FLAIR images showing hyperintensities of dendate nuclei (arrows) and periventricular white matter (stars) Fig 3 A biopsy at the level of Achilles tumefaction showed an aspect of tendinous xanthoma made of fibroblastic tissue remodelled by a dense inflammatory granuloma rich in cholesterol crystals. In contact with these crystals, numerous multinucleated giant cells were observed, associated with numerous foamy histiocytes. All of these clinical, biological, radiological, and histological data supported the CTX diagnosis.", 'Patient consent': 'Written informed consent for publication was obtained from patient.'}
|
Musculoskeletal-System
|
MSK
|
[
"swelling in her ankles",
"bilateral increasing ankle edema.",
"knees swelled",
"Over all Achilles, quadriceps, and patellar tendons, the osteo - myo - articular examination revealed bilateral painless and non - fistulized masses",
"An ultrasound of the ankles and knees revealed well - defined, homogeneous, hyperechoic masses that had nearly completely replaced the tendons ( Achilles, quadriceps and patellar tendons",
"well - defined, homogenous, hyperechoic mass completely replacing the Achille ( arrow ) and patellar tendons ( star )",
"The Achilles tendons had a fusiform expansion with a convex anterior border and were isointense to muscle on MRI of the ankles.",
"fusiform enlargement of the Achilles tendon, which has a convex anterior border and is isointense to muscle ( arrows ), with widely spaced tendon fibers interposed with fat ( speckled appearance ) (",
"A biopsy at the level of Achilles tumefaction showed an aspect of tendinous xanthoma made of fibroblastic tissue remodelled by a dense inflammatory granuloma rich in cholesterol crystals. In contact with these crystals, numerous multinucleated giant cells were observed, associated with numerous foamy histiocytes."
] |
test-2189
|
8760527
|
{'Case report': "An 18-year-old woman came in with swelling in her ankles and a cognitive decline. The patient was well until she was 7 years old, when she experienced bilateral increasing ankle edema. From the age of ten years old, her parents noted frequent stumbles and difficulty walking, followed by ataxia. The patient's knees swelled a few years later, when he was 12 years old. In addition, she had previously experienced sight issues. Over all Achilles, quadriceps, and patellar tendons, the osteo-myo-articular examination revealed bilateral painless and non-fistulized masses. Spastic paraparesis, rapid deep reflexes, and extensor plantar responses were discovered during a neurological examination. The Romberg test resulted in a positive result with 1 eye closed. A bilateral thick cataract with impaired vision was discovered during the ophthalmic examination. Total cholesterol, LDL, HDL, and triglyceride levels were all within normal limits. Otherwise, the amounts of cholestanol and bile alcohol in the bile and urine were high. An ultrasound of the ankles and knees revealed well-defined, homogeneous, hyperechoic masses that had nearly completely replaced the tendons (Achilles, quadriceps and patellar tendons ( Fig. 1 ). Fig. 1 US of ankle and knee swelling revealing a well-defined, homogenous, hyperechoic mass completely replacing the Achille (arrow) and patellar tendons (star) Fig 1 The Achilles tendons had a fusiform expansion with a convex anterior border and were isointense to muscle on MRI of the ankles. The axial image revealed low signal intensity patches strewn over the muscle, giving it the distinctive speckled look ( Fig. 2 ) Fig. 2 Sagittal proton density image (A), T1-weighted image (B), fat suppression on short tau inversion recovery (STIR) (C), T1-fat-saturated-weighted image following contrast agent injection (D), T1-weighted image with fat saturation (E)demonstrating a fusiform enlargement of the Achilles tendon, which has a convex anterior border and is isointense to muscle (arrows), with widely spaced tendon fibers interposed with fat (speckled appearance) (star) Fig 2 On T2 weighted and FLAIR sequences, MRI of the brain revealed hyperintensity of the dentate nuclei (with a hypo intensity on susceptibility weighted imaging corresponding to calcification deposits) ( Fig. 3 ). Fig. 3 Axial and coronal FLAIR images showing hyperintensities of dendate nuclei (arrows) and periventricular white matter (stars) Fig 3 A biopsy at the level of Achilles tumefaction showed an aspect of tendinous xanthoma made of fibroblastic tissue remodelled by a dense inflammatory granuloma rich in cholesterol crystals. In contact with these crystals, numerous multinucleated giant cells were observed, associated with numerous foamy histiocytes. All of these clinical, biological, radiological, and histological data supported the CTX diagnosis.", 'Patient consent': 'Written informed consent for publication was obtained from patient.'}
|
{'Case report': "An 18-year-old woman came in with swelling in her ankles and a cognitive decline. The patient was well until she was 7 years old, when she experienced bilateral increasing ankle edema. From the age of ten years old, her parents noted frequent stumbles and difficulty walking, followed by ataxia. The patient's knees swelled a few years later, when he was 12 years old. In addition, she had previously experienced sight issues. Over all Achilles, quadriceps, and patellar tendons, the osteo-myo-articular examination revealed bilateral painless and non-fistulized masses. Spastic paraparesis, rapid deep reflexes, and extensor plantar responses were discovered during a neurological examination. The Romberg test resulted in a positive result with 1 eye closed. A bilateral thick cataract with impaired vision was discovered during the ophthalmic examination. Total cholesterol, LDL, HDL, and triglyceride levels were all within normal limits. Otherwise, the amounts of cholestanol and bile alcohol in the bile and urine were high. An ultrasound of the ankles and knees revealed well-defined, homogeneous, hyperechoic masses that had nearly completely replaced the tendons (Achilles, quadriceps and patellar tendons ( Fig. 1 ). Fig. 1 US of ankle and knee swelling revealing a well-defined, homogenous, hyperechoic mass completely replacing the Achille (arrow) and patellar tendons (star) Fig 1 The Achilles tendons had a fusiform expansion with a convex anterior border and were isointense to muscle on MRI of the ankles. The axial image revealed low signal intensity patches strewn over the muscle, giving it the distinctive speckled look ( Fig. 2 ) Fig. 2 Sagittal proton density image (A), T1-weighted image (B), fat suppression on short tau inversion recovery (STIR) (C), T1-fat-saturated-weighted image following contrast agent injection (D), T1-weighted image with fat saturation (E)demonstrating a fusiform enlargement of the Achilles tendon, which has a convex anterior border and is isointense to muscle (arrows), with widely spaced tendon fibers interposed with fat (speckled appearance) (star) Fig 2 On T2 weighted and FLAIR sequences, MRI of the brain revealed hyperintensity of the dentate nuclei (with a hypo intensity on susceptibility weighted imaging corresponding to calcification deposits) ( Fig. 3 ). Fig. 3 Axial and coronal FLAIR images showing hyperintensities of dendate nuclei (arrows) and periventricular white matter (stars) Fig 3 A biopsy at the level of Achilles tumefaction showed an aspect of tendinous xanthoma made of fibroblastic tissue remodelled by a dense inflammatory granuloma rich in cholesterol crystals. In contact with these crystals, numerous multinucleated giant cells were observed, associated with numerous foamy histiocytes. All of these clinical, biological, radiological, and histological data supported the CTX diagnosis.", 'Patient consent': 'Written informed consent for publication was obtained from patient.'}
|
Eyes-Ears-Nose-Throat
|
EENT
|
[
"sight issues.",
"A bilateral thick cataract with impaired vision"
] |
test-2190
|
8760527
|
{'Case report': "An 18-year-old woman came in with swelling in her ankles and a cognitive decline. The patient was well until she was 7 years old, when she experienced bilateral increasing ankle edema. From the age of ten years old, her parents noted frequent stumbles and difficulty walking, followed by ataxia. The patient's knees swelled a few years later, when he was 12 years old. In addition, she had previously experienced sight issues. Over all Achilles, quadriceps, and patellar tendons, the osteo-myo-articular examination revealed bilateral painless and non-fistulized masses. Spastic paraparesis, rapid deep reflexes, and extensor plantar responses were discovered during a neurological examination. The Romberg test resulted in a positive result with 1 eye closed. A bilateral thick cataract with impaired vision was discovered during the ophthalmic examination. Total cholesterol, LDL, HDL, and triglyceride levels were all within normal limits. Otherwise, the amounts of cholestanol and bile alcohol in the bile and urine were high. An ultrasound of the ankles and knees revealed well-defined, homogeneous, hyperechoic masses that had nearly completely replaced the tendons (Achilles, quadriceps and patellar tendons ( Fig. 1 ). Fig. 1 US of ankle and knee swelling revealing a well-defined, homogenous, hyperechoic mass completely replacing the Achille (arrow) and patellar tendons (star) Fig 1 The Achilles tendons had a fusiform expansion with a convex anterior border and were isointense to muscle on MRI of the ankles. The axial image revealed low signal intensity patches strewn over the muscle, giving it the distinctive speckled look ( Fig. 2 ) Fig. 2 Sagittal proton density image (A), T1-weighted image (B), fat suppression on short tau inversion recovery (STIR) (C), T1-fat-saturated-weighted image following contrast agent injection (D), T1-weighted image with fat saturation (E)demonstrating a fusiform enlargement of the Achilles tendon, which has a convex anterior border and is isointense to muscle (arrows), with widely spaced tendon fibers interposed with fat (speckled appearance) (star) Fig 2 On T2 weighted and FLAIR sequences, MRI of the brain revealed hyperintensity of the dentate nuclei (with a hypo intensity on susceptibility weighted imaging corresponding to calcification deposits) ( Fig. 3 ). Fig. 3 Axial and coronal FLAIR images showing hyperintensities of dendate nuclei (arrows) and periventricular white matter (stars) Fig 3 A biopsy at the level of Achilles tumefaction showed an aspect of tendinous xanthoma made of fibroblastic tissue remodelled by a dense inflammatory granuloma rich in cholesterol crystals. In contact with these crystals, numerous multinucleated giant cells were observed, associated with numerous foamy histiocytes. All of these clinical, biological, radiological, and histological data supported the CTX diagnosis.", 'Patient consent': 'Written informed consent for publication was obtained from patient.'}
|
{'Case report': "An 18-year-old woman came in with swelling in her ankles and a cognitive decline. The patient was well until she was 7 years old, when she experienced bilateral increasing ankle edema. From the age of ten years old, her parents noted frequent stumbles and difficulty walking, followed by ataxia. The patient's knees swelled a few years later, when he was 12 years old. In addition, she had previously experienced sight issues. Over all Achilles, quadriceps, and patellar tendons, the osteo-myo-articular examination revealed bilateral painless and non-fistulized masses. Spastic paraparesis, rapid deep reflexes, and extensor plantar responses were discovered during a neurological examination. The Romberg test resulted in a positive result with 1 eye closed. A bilateral thick cataract with impaired vision was discovered during the ophthalmic examination. Total cholesterol, LDL, HDL, and triglyceride levels were all within normal limits. Otherwise, the amounts of cholestanol and bile alcohol in the bile and urine were high. An ultrasound of the ankles and knees revealed well-defined, homogeneous, hyperechoic masses that had nearly completely replaced the tendons (Achilles, quadriceps and patellar tendons ( Fig. 1 ). Fig. 1 US of ankle and knee swelling revealing a well-defined, homogenous, hyperechoic mass completely replacing the Achille (arrow) and patellar tendons (star) Fig 1 The Achilles tendons had a fusiform expansion with a convex anterior border and were isointense to muscle on MRI of the ankles. The axial image revealed low signal intensity patches strewn over the muscle, giving it the distinctive speckled look ( Fig. 2 ) Fig. 2 Sagittal proton density image (A), T1-weighted image (B), fat suppression on short tau inversion recovery (STIR) (C), T1-fat-saturated-weighted image following contrast agent injection (D), T1-weighted image with fat saturation (E)demonstrating a fusiform enlargement of the Achilles tendon, which has a convex anterior border and is isointense to muscle (arrows), with widely spaced tendon fibers interposed with fat (speckled appearance) (star) Fig 2 On T2 weighted and FLAIR sequences, MRI of the brain revealed hyperintensity of the dentate nuclei (with a hypo intensity on susceptibility weighted imaging corresponding to calcification deposits) ( Fig. 3 ). Fig. 3 Axial and coronal FLAIR images showing hyperintensities of dendate nuclei (arrows) and periventricular white matter (stars) Fig 3 A biopsy at the level of Achilles tumefaction showed an aspect of tendinous xanthoma made of fibroblastic tissue remodelled by a dense inflammatory granuloma rich in cholesterol crystals. In contact with these crystals, numerous multinucleated giant cells were observed, associated with numerous foamy histiocytes. All of these clinical, biological, radiological, and histological data supported the CTX diagnosis.", 'Patient consent': 'Written informed consent for publication was obtained from patient.'}
|
Dermatology
|
DERM
|
[] |
test-2191
|
8760527
|
{'Case report': "An 18-year-old woman came in with swelling in her ankles and a cognitive decline. The patient was well until she was 7 years old, when she experienced bilateral increasing ankle edema. From the age of ten years old, her parents noted frequent stumbles and difficulty walking, followed by ataxia. The patient's knees swelled a few years later, when he was 12 years old. In addition, she had previously experienced sight issues. Over all Achilles, quadriceps, and patellar tendons, the osteo-myo-articular examination revealed bilateral painless and non-fistulized masses. Spastic paraparesis, rapid deep reflexes, and extensor plantar responses were discovered during a neurological examination. The Romberg test resulted in a positive result with 1 eye closed. A bilateral thick cataract with impaired vision was discovered during the ophthalmic examination. Total cholesterol, LDL, HDL, and triglyceride levels were all within normal limits. Otherwise, the amounts of cholestanol and bile alcohol in the bile and urine were high. An ultrasound of the ankles and knees revealed well-defined, homogeneous, hyperechoic masses that had nearly completely replaced the tendons (Achilles, quadriceps and patellar tendons ( Fig. 1 ). Fig. 1 US of ankle and knee swelling revealing a well-defined, homogenous, hyperechoic mass completely replacing the Achille (arrow) and patellar tendons (star) Fig 1 The Achilles tendons had a fusiform expansion with a convex anterior border and were isointense to muscle on MRI of the ankles. The axial image revealed low signal intensity patches strewn over the muscle, giving it the distinctive speckled look ( Fig. 2 ) Fig. 2 Sagittal proton density image (A), T1-weighted image (B), fat suppression on short tau inversion recovery (STIR) (C), T1-fat-saturated-weighted image following contrast agent injection (D), T1-weighted image with fat saturation (E)demonstrating a fusiform enlargement of the Achilles tendon, which has a convex anterior border and is isointense to muscle (arrows), with widely spaced tendon fibers interposed with fat (speckled appearance) (star) Fig 2 On T2 weighted and FLAIR sequences, MRI of the brain revealed hyperintensity of the dentate nuclei (with a hypo intensity on susceptibility weighted imaging corresponding to calcification deposits) ( Fig. 3 ). Fig. 3 Axial and coronal FLAIR images showing hyperintensities of dendate nuclei (arrows) and periventricular white matter (stars) Fig 3 A biopsy at the level of Achilles tumefaction showed an aspect of tendinous xanthoma made of fibroblastic tissue remodelled by a dense inflammatory granuloma rich in cholesterol crystals. In contact with these crystals, numerous multinucleated giant cells were observed, associated with numerous foamy histiocytes. All of these clinical, biological, radiological, and histological data supported the CTX diagnosis.", 'Patient consent': 'Written informed consent for publication was obtained from patient.'}
|
{'Case report': "An 18-year-old woman came in with swelling in her ankles and a cognitive decline. The patient was well until she was 7 years old, when she experienced bilateral increasing ankle edema. From the age of ten years old, her parents noted frequent stumbles and difficulty walking, followed by ataxia. The patient's knees swelled a few years later, when he was 12 years old. In addition, she had previously experienced sight issues. Over all Achilles, quadriceps, and patellar tendons, the osteo-myo-articular examination revealed bilateral painless and non-fistulized masses. Spastic paraparesis, rapid deep reflexes, and extensor plantar responses were discovered during a neurological examination. The Romberg test resulted in a positive result with 1 eye closed. A bilateral thick cataract with impaired vision was discovered during the ophthalmic examination. Total cholesterol, LDL, HDL, and triglyceride levels were all within normal limits. Otherwise, the amounts of cholestanol and bile alcohol in the bile and urine were high. An ultrasound of the ankles and knees revealed well-defined, homogeneous, hyperechoic masses that had nearly completely replaced the tendons (Achilles, quadriceps and patellar tendons ( Fig. 1 ). Fig. 1 US of ankle and knee swelling revealing a well-defined, homogenous, hyperechoic mass completely replacing the Achille (arrow) and patellar tendons (star) Fig 1 The Achilles tendons had a fusiform expansion with a convex anterior border and were isointense to muscle on MRI of the ankles. The axial image revealed low signal intensity patches strewn over the muscle, giving it the distinctive speckled look ( Fig. 2 ) Fig. 2 Sagittal proton density image (A), T1-weighted image (B), fat suppression on short tau inversion recovery (STIR) (C), T1-fat-saturated-weighted image following contrast agent injection (D), T1-weighted image with fat saturation (E)demonstrating a fusiform enlargement of the Achilles tendon, which has a convex anterior border and is isointense to muscle (arrows), with widely spaced tendon fibers interposed with fat (speckled appearance) (star) Fig 2 On T2 weighted and FLAIR sequences, MRI of the brain revealed hyperintensity of the dentate nuclei (with a hypo intensity on susceptibility weighted imaging corresponding to calcification deposits) ( Fig. 3 ). Fig. 3 Axial and coronal FLAIR images showing hyperintensities of dendate nuclei (arrows) and periventricular white matter (stars) Fig 3 A biopsy at the level of Achilles tumefaction showed an aspect of tendinous xanthoma made of fibroblastic tissue remodelled by a dense inflammatory granuloma rich in cholesterol crystals. In contact with these crystals, numerous multinucleated giant cells were observed, associated with numerous foamy histiocytes. All of these clinical, biological, radiological, and histological data supported the CTX diagnosis.", 'Patient consent': 'Written informed consent for publication was obtained from patient.'}
|
Pregnancy
|
Pregnancy
|
[] |
test-2192
|
8760527
|
{'Case report': "An 18-year-old woman came in with swelling in her ankles and a cognitive decline. The patient was well until she was 7 years old, when she experienced bilateral increasing ankle edema. From the age of ten years old, her parents noted frequent stumbles and difficulty walking, followed by ataxia. The patient's knees swelled a few years later, when he was 12 years old. In addition, she had previously experienced sight issues. Over all Achilles, quadriceps, and patellar tendons, the osteo-myo-articular examination revealed bilateral painless and non-fistulized masses. Spastic paraparesis, rapid deep reflexes, and extensor plantar responses were discovered during a neurological examination. The Romberg test resulted in a positive result with 1 eye closed. A bilateral thick cataract with impaired vision was discovered during the ophthalmic examination. Total cholesterol, LDL, HDL, and triglyceride levels were all within normal limits. Otherwise, the amounts of cholestanol and bile alcohol in the bile and urine were high. An ultrasound of the ankles and knees revealed well-defined, homogeneous, hyperechoic masses that had nearly completely replaced the tendons (Achilles, quadriceps and patellar tendons ( Fig. 1 ). Fig. 1 US of ankle and knee swelling revealing a well-defined, homogenous, hyperechoic mass completely replacing the Achille (arrow) and patellar tendons (star) Fig 1 The Achilles tendons had a fusiform expansion with a convex anterior border and were isointense to muscle on MRI of the ankles. The axial image revealed low signal intensity patches strewn over the muscle, giving it the distinctive speckled look ( Fig. 2 ) Fig. 2 Sagittal proton density image (A), T1-weighted image (B), fat suppression on short tau inversion recovery (STIR) (C), T1-fat-saturated-weighted image following contrast agent injection (D), T1-weighted image with fat saturation (E)demonstrating a fusiform enlargement of the Achilles tendon, which has a convex anterior border and is isointense to muscle (arrows), with widely spaced tendon fibers interposed with fat (speckled appearance) (star) Fig 2 On T2 weighted and FLAIR sequences, MRI of the brain revealed hyperintensity of the dentate nuclei (with a hypo intensity on susceptibility weighted imaging corresponding to calcification deposits) ( Fig. 3 ). Fig. 3 Axial and coronal FLAIR images showing hyperintensities of dendate nuclei (arrows) and periventricular white matter (stars) Fig 3 A biopsy at the level of Achilles tumefaction showed an aspect of tendinous xanthoma made of fibroblastic tissue remodelled by a dense inflammatory granuloma rich in cholesterol crystals. In contact with these crystals, numerous multinucleated giant cells were observed, associated with numerous foamy histiocytes. All of these clinical, biological, radiological, and histological data supported the CTX diagnosis.", 'Patient consent': 'Written informed consent for publication was obtained from patient.'}
|
{'Case report': "An 18-year-old woman came in with swelling in her ankles and a cognitive decline. The patient was well until she was 7 years old, when she experienced bilateral increasing ankle edema. From the age of ten years old, her parents noted frequent stumbles and difficulty walking, followed by ataxia. The patient's knees swelled a few years later, when he was 12 years old. In addition, she had previously experienced sight issues. Over all Achilles, quadriceps, and patellar tendons, the osteo-myo-articular examination revealed bilateral painless and non-fistulized masses. Spastic paraparesis, rapid deep reflexes, and extensor plantar responses were discovered during a neurological examination. The Romberg test resulted in a positive result with 1 eye closed. A bilateral thick cataract with impaired vision was discovered during the ophthalmic examination. Total cholesterol, LDL, HDL, and triglyceride levels were all within normal limits. Otherwise, the amounts of cholestanol and bile alcohol in the bile and urine were high. An ultrasound of the ankles and knees revealed well-defined, homogeneous, hyperechoic masses that had nearly completely replaced the tendons (Achilles, quadriceps and patellar tendons ( Fig. 1 ). Fig. 1 US of ankle and knee swelling revealing a well-defined, homogenous, hyperechoic mass completely replacing the Achille (arrow) and patellar tendons (star) Fig 1 The Achilles tendons had a fusiform expansion with a convex anterior border and were isointense to muscle on MRI of the ankles. The axial image revealed low signal intensity patches strewn over the muscle, giving it the distinctive speckled look ( Fig. 2 ) Fig. 2 Sagittal proton density image (A), T1-weighted image (B), fat suppression on short tau inversion recovery (STIR) (C), T1-fat-saturated-weighted image following contrast agent injection (D), T1-weighted image with fat saturation (E)demonstrating a fusiform enlargement of the Achilles tendon, which has a convex anterior border and is isointense to muscle (arrows), with widely spaced tendon fibers interposed with fat (speckled appearance) (star) Fig 2 On T2 weighted and FLAIR sequences, MRI of the brain revealed hyperintensity of the dentate nuclei (with a hypo intensity on susceptibility weighted imaging corresponding to calcification deposits) ( Fig. 3 ). Fig. 3 Axial and coronal FLAIR images showing hyperintensities of dendate nuclei (arrows) and periventricular white matter (stars) Fig 3 A biopsy at the level of Achilles tumefaction showed an aspect of tendinous xanthoma made of fibroblastic tissue remodelled by a dense inflammatory granuloma rich in cholesterol crystals. In contact with these crystals, numerous multinucleated giant cells were observed, associated with numerous foamy histiocytes. All of these clinical, biological, radiological, and histological data supported the CTX diagnosis.", 'Patient consent': 'Written informed consent for publication was obtained from patient.'}
|
Lymphatic-System
|
LYMPH
|
[] |
test-2193
|
8760527
|
{'Case report': "An 18-year-old woman came in with swelling in her ankles and a cognitive decline. The patient was well until she was 7 years old, when she experienced bilateral increasing ankle edema. From the age of ten years old, her parents noted frequent stumbles and difficulty walking, followed by ataxia. The patient's knees swelled a few years later, when he was 12 years old. In addition, she had previously experienced sight issues. Over all Achilles, quadriceps, and patellar tendons, the osteo-myo-articular examination revealed bilateral painless and non-fistulized masses. Spastic paraparesis, rapid deep reflexes, and extensor plantar responses were discovered during a neurological examination. The Romberg test resulted in a positive result with 1 eye closed. A bilateral thick cataract with impaired vision was discovered during the ophthalmic examination. Total cholesterol, LDL, HDL, and triglyceride levels were all within normal limits. Otherwise, the amounts of cholestanol and bile alcohol in the bile and urine were high. An ultrasound of the ankles and knees revealed well-defined, homogeneous, hyperechoic masses that had nearly completely replaced the tendons (Achilles, quadriceps and patellar tendons ( Fig. 1 ). Fig. 1 US of ankle and knee swelling revealing a well-defined, homogenous, hyperechoic mass completely replacing the Achille (arrow) and patellar tendons (star) Fig 1 The Achilles tendons had a fusiform expansion with a convex anterior border and were isointense to muscle on MRI of the ankles. The axial image revealed low signal intensity patches strewn over the muscle, giving it the distinctive speckled look ( Fig. 2 ) Fig. 2 Sagittal proton density image (A), T1-weighted image (B), fat suppression on short tau inversion recovery (STIR) (C), T1-fat-saturated-weighted image following contrast agent injection (D), T1-weighted image with fat saturation (E)demonstrating a fusiform enlargement of the Achilles tendon, which has a convex anterior border and is isointense to muscle (arrows), with widely spaced tendon fibers interposed with fat (speckled appearance) (star) Fig 2 On T2 weighted and FLAIR sequences, MRI of the brain revealed hyperintensity of the dentate nuclei (with a hypo intensity on susceptibility weighted imaging corresponding to calcification deposits) ( Fig. 3 ). Fig. 3 Axial and coronal FLAIR images showing hyperintensities of dendate nuclei (arrows) and periventricular white matter (stars) Fig 3 A biopsy at the level of Achilles tumefaction showed an aspect of tendinous xanthoma made of fibroblastic tissue remodelled by a dense inflammatory granuloma rich in cholesterol crystals. In contact with these crystals, numerous multinucleated giant cells were observed, associated with numerous foamy histiocytes. All of these clinical, biological, radiological, and histological data supported the CTX diagnosis.", 'Patient consent': 'Written informed consent for publication was obtained from patient.'}
|
{'Case report': "An 18-year-old woman came in with swelling in her ankles and a cognitive decline. The patient was well until she was 7 years old, when she experienced bilateral increasing ankle edema. From the age of ten years old, her parents noted frequent stumbles and difficulty walking, followed by ataxia. The patient's knees swelled a few years later, when he was 12 years old. In addition, she had previously experienced sight issues. Over all Achilles, quadriceps, and patellar tendons, the osteo-myo-articular examination revealed bilateral painless and non-fistulized masses. Spastic paraparesis, rapid deep reflexes, and extensor plantar responses were discovered during a neurological examination. The Romberg test resulted in a positive result with 1 eye closed. A bilateral thick cataract with impaired vision was discovered during the ophthalmic examination. Total cholesterol, LDL, HDL, and triglyceride levels were all within normal limits. Otherwise, the amounts of cholestanol and bile alcohol in the bile and urine were high. An ultrasound of the ankles and knees revealed well-defined, homogeneous, hyperechoic masses that had nearly completely replaced the tendons (Achilles, quadriceps and patellar tendons ( Fig. 1 ). Fig. 1 US of ankle and knee swelling revealing a well-defined, homogenous, hyperechoic mass completely replacing the Achille (arrow) and patellar tendons (star) Fig 1 The Achilles tendons had a fusiform expansion with a convex anterior border and were isointense to muscle on MRI of the ankles. The axial image revealed low signal intensity patches strewn over the muscle, giving it the distinctive speckled look ( Fig. 2 ) Fig. 2 Sagittal proton density image (A), T1-weighted image (B), fat suppression on short tau inversion recovery (STIR) (C), T1-fat-saturated-weighted image following contrast agent injection (D), T1-weighted image with fat saturation (E)demonstrating a fusiform enlargement of the Achilles tendon, which has a convex anterior border and is isointense to muscle (arrows), with widely spaced tendon fibers interposed with fat (speckled appearance) (star) Fig 2 On T2 weighted and FLAIR sequences, MRI of the brain revealed hyperintensity of the dentate nuclei (with a hypo intensity on susceptibility weighted imaging corresponding to calcification deposits) ( Fig. 3 ). Fig. 3 Axial and coronal FLAIR images showing hyperintensities of dendate nuclei (arrows) and periventricular white matter (stars) Fig 3 A biopsy at the level of Achilles tumefaction showed an aspect of tendinous xanthoma made of fibroblastic tissue remodelled by a dense inflammatory granuloma rich in cholesterol crystals. In contact with these crystals, numerous multinucleated giant cells were observed, associated with numerous foamy histiocytes. All of these clinical, biological, radiological, and histological data supported the CTX diagnosis.", 'Patient consent': 'Written informed consent for publication was obtained from patient.'}
|
Age-at-Presentation
|
Age (at case presentation)
|
[
"18 - year - old"
] |
test-2194
|
8760527
|
{'Case report': "An 18-year-old woman came in with swelling in her ankles and a cognitive decline. The patient was well until she was 7 years old, when she experienced bilateral increasing ankle edema. From the age of ten years old, her parents noted frequent stumbles and difficulty walking, followed by ataxia. The patient's knees swelled a few years later, when he was 12 years old. In addition, she had previously experienced sight issues. Over all Achilles, quadriceps, and patellar tendons, the osteo-myo-articular examination revealed bilateral painless and non-fistulized masses. Spastic paraparesis, rapid deep reflexes, and extensor plantar responses were discovered during a neurological examination. The Romberg test resulted in a positive result with 1 eye closed. A bilateral thick cataract with impaired vision was discovered during the ophthalmic examination. Total cholesterol, LDL, HDL, and triglyceride levels were all within normal limits. Otherwise, the amounts of cholestanol and bile alcohol in the bile and urine were high. An ultrasound of the ankles and knees revealed well-defined, homogeneous, hyperechoic masses that had nearly completely replaced the tendons (Achilles, quadriceps and patellar tendons ( Fig. 1 ). Fig. 1 US of ankle and knee swelling revealing a well-defined, homogenous, hyperechoic mass completely replacing the Achille (arrow) and patellar tendons (star) Fig 1 The Achilles tendons had a fusiform expansion with a convex anterior border and were isointense to muscle on MRI of the ankles. The axial image revealed low signal intensity patches strewn over the muscle, giving it the distinctive speckled look ( Fig. 2 ) Fig. 2 Sagittal proton density image (A), T1-weighted image (B), fat suppression on short tau inversion recovery (STIR) (C), T1-fat-saturated-weighted image following contrast agent injection (D), T1-weighted image with fat saturation (E)demonstrating a fusiform enlargement of the Achilles tendon, which has a convex anterior border and is isointense to muscle (arrows), with widely spaced tendon fibers interposed with fat (speckled appearance) (star) Fig 2 On T2 weighted and FLAIR sequences, MRI of the brain revealed hyperintensity of the dentate nuclei (with a hypo intensity on susceptibility weighted imaging corresponding to calcification deposits) ( Fig. 3 ). Fig. 3 Axial and coronal FLAIR images showing hyperintensities of dendate nuclei (arrows) and periventricular white matter (stars) Fig 3 A biopsy at the level of Achilles tumefaction showed an aspect of tendinous xanthoma made of fibroblastic tissue remodelled by a dense inflammatory granuloma rich in cholesterol crystals. In contact with these crystals, numerous multinucleated giant cells were observed, associated with numerous foamy histiocytes. All of these clinical, biological, radiological, and histological data supported the CTX diagnosis.", 'Patient consent': 'Written informed consent for publication was obtained from patient.'}
|
{'Case report': "An 18-year-old woman came in with swelling in her ankles and a cognitive decline. The patient was well until she was 7 years old, when she experienced bilateral increasing ankle edema. From the age of ten years old, her parents noted frequent stumbles and difficulty walking, followed by ataxia. The patient's knees swelled a few years later, when he was 12 years old. In addition, she had previously experienced sight issues. Over all Achilles, quadriceps, and patellar tendons, the osteo-myo-articular examination revealed bilateral painless and non-fistulized masses. Spastic paraparesis, rapid deep reflexes, and extensor plantar responses were discovered during a neurological examination. The Romberg test resulted in a positive result with 1 eye closed. A bilateral thick cataract with impaired vision was discovered during the ophthalmic examination. Total cholesterol, LDL, HDL, and triglyceride levels were all within normal limits. Otherwise, the amounts of cholestanol and bile alcohol in the bile and urine were high. An ultrasound of the ankles and knees revealed well-defined, homogeneous, hyperechoic masses that had nearly completely replaced the tendons (Achilles, quadriceps and patellar tendons ( Fig. 1 ). Fig. 1 US of ankle and knee swelling revealing a well-defined, homogenous, hyperechoic mass completely replacing the Achille (arrow) and patellar tendons (star) Fig 1 The Achilles tendons had a fusiform expansion with a convex anterior border and were isointense to muscle on MRI of the ankles. The axial image revealed low signal intensity patches strewn over the muscle, giving it the distinctive speckled look ( Fig. 2 ) Fig. 2 Sagittal proton density image (A), T1-weighted image (B), fat suppression on short tau inversion recovery (STIR) (C), T1-fat-saturated-weighted image following contrast agent injection (D), T1-weighted image with fat saturation (E)demonstrating a fusiform enlargement of the Achilles tendon, which has a convex anterior border and is isointense to muscle (arrows), with widely spaced tendon fibers interposed with fat (speckled appearance) (star) Fig 2 On T2 weighted and FLAIR sequences, MRI of the brain revealed hyperintensity of the dentate nuclei (with a hypo intensity on susceptibility weighted imaging corresponding to calcification deposits) ( Fig. 3 ). Fig. 3 Axial and coronal FLAIR images showing hyperintensities of dendate nuclei (arrows) and periventricular white matter (stars) Fig 3 A biopsy at the level of Achilles tumefaction showed an aspect of tendinous xanthoma made of fibroblastic tissue remodelled by a dense inflammatory granuloma rich in cholesterol crystals. In contact with these crystals, numerous multinucleated giant cells were observed, associated with numerous foamy histiocytes. All of these clinical, biological, radiological, and histological data supported the CTX diagnosis.", 'Patient consent': 'Written informed consent for publication was obtained from patient.'}
|
Age-of-Onset
|
Age (of onset)
|
[
"7 years old"
] |
test-2195
|
8760527
|
{'Case report': "An 18-year-old woman came in with swelling in her ankles and a cognitive decline. The patient was well until she was 7 years old, when she experienced bilateral increasing ankle edema. From the age of ten years old, her parents noted frequent stumbles and difficulty walking, followed by ataxia. The patient's knees swelled a few years later, when he was 12 years old. In addition, she had previously experienced sight issues. Over all Achilles, quadriceps, and patellar tendons, the osteo-myo-articular examination revealed bilateral painless and non-fistulized masses. Spastic paraparesis, rapid deep reflexes, and extensor plantar responses were discovered during a neurological examination. The Romberg test resulted in a positive result with 1 eye closed. A bilateral thick cataract with impaired vision was discovered during the ophthalmic examination. Total cholesterol, LDL, HDL, and triglyceride levels were all within normal limits. Otherwise, the amounts of cholestanol and bile alcohol in the bile and urine were high. An ultrasound of the ankles and knees revealed well-defined, homogeneous, hyperechoic masses that had nearly completely replaced the tendons (Achilles, quadriceps and patellar tendons ( Fig. 1 ). Fig. 1 US of ankle and knee swelling revealing a well-defined, homogenous, hyperechoic mass completely replacing the Achille (arrow) and patellar tendons (star) Fig 1 The Achilles tendons had a fusiform expansion with a convex anterior border and were isointense to muscle on MRI of the ankles. The axial image revealed low signal intensity patches strewn over the muscle, giving it the distinctive speckled look ( Fig. 2 ) Fig. 2 Sagittal proton density image (A), T1-weighted image (B), fat suppression on short tau inversion recovery (STIR) (C), T1-fat-saturated-weighted image following contrast agent injection (D), T1-weighted image with fat saturation (E)demonstrating a fusiform enlargement of the Achilles tendon, which has a convex anterior border and is isointense to muscle (arrows), with widely spaced tendon fibers interposed with fat (speckled appearance) (star) Fig 2 On T2 weighted and FLAIR sequences, MRI of the brain revealed hyperintensity of the dentate nuclei (with a hypo intensity on susceptibility weighted imaging corresponding to calcification deposits) ( Fig. 3 ). Fig. 3 Axial and coronal FLAIR images showing hyperintensities of dendate nuclei (arrows) and periventricular white matter (stars) Fig 3 A biopsy at the level of Achilles tumefaction showed an aspect of tendinous xanthoma made of fibroblastic tissue remodelled by a dense inflammatory granuloma rich in cholesterol crystals. In contact with these crystals, numerous multinucleated giant cells were observed, associated with numerous foamy histiocytes. All of these clinical, biological, radiological, and histological data supported the CTX diagnosis.", 'Patient consent': 'Written informed consent for publication was obtained from patient.'}
|
{'Case report': "An 18-year-old woman came in with swelling in her ankles and a cognitive decline. The patient was well until she was 7 years old, when she experienced bilateral increasing ankle edema. From the age of ten years old, her parents noted frequent stumbles and difficulty walking, followed by ataxia. The patient's knees swelled a few years later, when he was 12 years old. In addition, she had previously experienced sight issues. Over all Achilles, quadriceps, and patellar tendons, the osteo-myo-articular examination revealed bilateral painless and non-fistulized masses. Spastic paraparesis, rapid deep reflexes, and extensor plantar responses were discovered during a neurological examination. The Romberg test resulted in a positive result with 1 eye closed. A bilateral thick cataract with impaired vision was discovered during the ophthalmic examination. Total cholesterol, LDL, HDL, and triglyceride levels were all within normal limits. Otherwise, the amounts of cholestanol and bile alcohol in the bile and urine were high. An ultrasound of the ankles and knees revealed well-defined, homogeneous, hyperechoic masses that had nearly completely replaced the tendons (Achilles, quadriceps and patellar tendons ( Fig. 1 ). Fig. 1 US of ankle and knee swelling revealing a well-defined, homogenous, hyperechoic mass completely replacing the Achille (arrow) and patellar tendons (star) Fig 1 The Achilles tendons had a fusiform expansion with a convex anterior border and were isointense to muscle on MRI of the ankles. The axial image revealed low signal intensity patches strewn over the muscle, giving it the distinctive speckled look ( Fig. 2 ) Fig. 2 Sagittal proton density image (A), T1-weighted image (B), fat suppression on short tau inversion recovery (STIR) (C), T1-fat-saturated-weighted image following contrast agent injection (D), T1-weighted image with fat saturation (E)demonstrating a fusiform enlargement of the Achilles tendon, which has a convex anterior border and is isointense to muscle (arrows), with widely spaced tendon fibers interposed with fat (speckled appearance) (star) Fig 2 On T2 weighted and FLAIR sequences, MRI of the brain revealed hyperintensity of the dentate nuclei (with a hypo intensity on susceptibility weighted imaging corresponding to calcification deposits) ( Fig. 3 ). Fig. 3 Axial and coronal FLAIR images showing hyperintensities of dendate nuclei (arrows) and periventricular white matter (stars) Fig 3 A biopsy at the level of Achilles tumefaction showed an aspect of tendinous xanthoma made of fibroblastic tissue remodelled by a dense inflammatory granuloma rich in cholesterol crystals. In contact with these crystals, numerous multinucleated giant cells were observed, associated with numerous foamy histiocytes. All of these clinical, biological, radiological, and histological data supported the CTX diagnosis.", 'Patient consent': 'Written informed consent for publication was obtained from patient.'}
|
Confirmed-Diagnosis-IEM
|
Confirmed_Diagnosis(IEM)
|
[
"CTX"
] |
test-2196
|
8760527
|
{'Case report': "An 18-year-old woman came in with swelling in her ankles and a cognitive decline. The patient was well until she was 7 years old, when she experienced bilateral increasing ankle edema. From the age of ten years old, her parents noted frequent stumbles and difficulty walking, followed by ataxia. The patient's knees swelled a few years later, when he was 12 years old. In addition, she had previously experienced sight issues. Over all Achilles, quadriceps, and patellar tendons, the osteo-myo-articular examination revealed bilateral painless and non-fistulized masses. Spastic paraparesis, rapid deep reflexes, and extensor plantar responses were discovered during a neurological examination. The Romberg test resulted in a positive result with 1 eye closed. A bilateral thick cataract with impaired vision was discovered during the ophthalmic examination. Total cholesterol, LDL, HDL, and triglyceride levels were all within normal limits. Otherwise, the amounts of cholestanol and bile alcohol in the bile and urine were high. An ultrasound of the ankles and knees revealed well-defined, homogeneous, hyperechoic masses that had nearly completely replaced the tendons (Achilles, quadriceps and patellar tendons ( Fig. 1 ). Fig. 1 US of ankle and knee swelling revealing a well-defined, homogenous, hyperechoic mass completely replacing the Achille (arrow) and patellar tendons (star) Fig 1 The Achilles tendons had a fusiform expansion with a convex anterior border and were isointense to muscle on MRI of the ankles. The axial image revealed low signal intensity patches strewn over the muscle, giving it the distinctive speckled look ( Fig. 2 ) Fig. 2 Sagittal proton density image (A), T1-weighted image (B), fat suppression on short tau inversion recovery (STIR) (C), T1-fat-saturated-weighted image following contrast agent injection (D), T1-weighted image with fat saturation (E)demonstrating a fusiform enlargement of the Achilles tendon, which has a convex anterior border and is isointense to muscle (arrows), with widely spaced tendon fibers interposed with fat (speckled appearance) (star) Fig 2 On T2 weighted and FLAIR sequences, MRI of the brain revealed hyperintensity of the dentate nuclei (with a hypo intensity on susceptibility weighted imaging corresponding to calcification deposits) ( Fig. 3 ). Fig. 3 Axial and coronal FLAIR images showing hyperintensities of dendate nuclei (arrows) and periventricular white matter (stars) Fig 3 A biopsy at the level of Achilles tumefaction showed an aspect of tendinous xanthoma made of fibroblastic tissue remodelled by a dense inflammatory granuloma rich in cholesterol crystals. In contact with these crystals, numerous multinucleated giant cells were observed, associated with numerous foamy histiocytes. All of these clinical, biological, radiological, and histological data supported the CTX diagnosis.", 'Patient consent': 'Written informed consent for publication was obtained from patient.'}
|
{'Case report': "An 18-year-old woman came in with swelling in her ankles and a cognitive decline. The patient was well until she was 7 years old, when she experienced bilateral increasing ankle edema. From the age of ten years old, her parents noted frequent stumbles and difficulty walking, followed by ataxia. The patient's knees swelled a few years later, when he was 12 years old. In addition, she had previously experienced sight issues. Over all Achilles, quadriceps, and patellar tendons, the osteo-myo-articular examination revealed bilateral painless and non-fistulized masses. Spastic paraparesis, rapid deep reflexes, and extensor plantar responses were discovered during a neurological examination. The Romberg test resulted in a positive result with 1 eye closed. A bilateral thick cataract with impaired vision was discovered during the ophthalmic examination. Total cholesterol, LDL, HDL, and triglyceride levels were all within normal limits. Otherwise, the amounts of cholestanol and bile alcohol in the bile and urine were high. An ultrasound of the ankles and knees revealed well-defined, homogeneous, hyperechoic masses that had nearly completely replaced the tendons (Achilles, quadriceps and patellar tendons ( Fig. 1 ). Fig. 1 US of ankle and knee swelling revealing a well-defined, homogenous, hyperechoic mass completely replacing the Achille (arrow) and patellar tendons (star) Fig 1 The Achilles tendons had a fusiform expansion with a convex anterior border and were isointense to muscle on MRI of the ankles. The axial image revealed low signal intensity patches strewn over the muscle, giving it the distinctive speckled look ( Fig. 2 ) Fig. 2 Sagittal proton density image (A), T1-weighted image (B), fat suppression on short tau inversion recovery (STIR) (C), T1-fat-saturated-weighted image following contrast agent injection (D), T1-weighted image with fat saturation (E)demonstrating a fusiform enlargement of the Achilles tendon, which has a convex anterior border and is isointense to muscle (arrows), with widely spaced tendon fibers interposed with fat (speckled appearance) (star) Fig 2 On T2 weighted and FLAIR sequences, MRI of the brain revealed hyperintensity of the dentate nuclei (with a hypo intensity on susceptibility weighted imaging corresponding to calcification deposits) ( Fig. 3 ). Fig. 3 Axial and coronal FLAIR images showing hyperintensities of dendate nuclei (arrows) and periventricular white matter (stars) Fig 3 A biopsy at the level of Achilles tumefaction showed an aspect of tendinous xanthoma made of fibroblastic tissue remodelled by a dense inflammatory granuloma rich in cholesterol crystals. In contact with these crystals, numerous multinucleated giant cells were observed, associated with numerous foamy histiocytes. All of these clinical, biological, radiological, and histological data supported the CTX diagnosis.", 'Patient consent': 'Written informed consent for publication was obtained from patient.'}
|
IEM-Treatment
|
IEM_Treatment
|
[] |
test-2197
|
8138145
|
{'Case Number One': 'A female patient of 36 years, resident and original of the city of Tula, Hidalgo, Mexico, without pathological antecedents of importance, attended a medical appointment due to presenting dermatosis in the neck with a 3-month evolution. During physical examination, it was described to be characterized by confluent papules, of 2 to 3 mm approximately, discretely hyperpigmented and asymptomatic (Fig. 1a ). An incisional biopsy was taken by punching, with diagnosis of PXE versus mucinous papulosis. The biopsy showed anfractuous epidermis, with stratum corneum in basket weave, the stratum spinosum thinned with flattening of the interpapillary projections and hyperpigmentation of the cells of the lower third. A perivascular inflammatory infiltrate formed by lymphocytes was observed in the papillary dermis and the superficial reticular dermis. In the middle reticular dermis, short, basophilic, granular, and irregularly shaped fibers were observed (Fig. 1b ). With staining for elastic fibers, they were shown to be fragmented, and Von Kossa staining evidenced their calcification (Fig. 1c ). These clinical and histopathological findings confirmed the diagnosis of pseudoxanthoma.', 'Case Number Two': 'A female patient of 59 years, resident and originally from the city of Zacatecas, Zacatecas, Mexico, was referred by the ophthalmological service due to severe visual acuity diminution and angioid striae of the retina, with no other important data. During physical examination, bilateral symmetrical dermatosis was observed, predominantly in folds, characterized by loose skin, soft texture, and plaques consisting of skin-colored papules 3–4 mm in diameter (Fig. 2a ). An incisional biopsy was taken by punching, with a clinical diagnosis of PXE. In the sections, thin and anfractuous epidermis was observed, with the stratum corneum in basket weave and the stratum spinosum with flattening of the interpapillary projections. In the middle reticular dermis, irregularly arranged short basophilic fibers were observed (Fig. 2b ). The staining of elastic fibers (Fig. 2c ) showed that the fragmented debris corresponded to these fibers and Von Kosa staining showed the presence of calcium inside. Fundus examination in both eyes revealed classic-appearing angioid streaks with crystalline spots, retinal pigment with epithelial atrophy (peripapillary), and choroidal neovascularization (Fig. 3a, b ). With the histopathological study and fundus examination findings, the diagnosis of PXE was confirmed this case. The diagnosis criteria used were in the first case skin findings like characteristic pseudoxanthomatous papules and plaques on the neck or flexural creases, and histopathological changes in lesional skin: calcified elastic fibers in the mid and lower dermis, confirmed by positive calcium stain. For the second case, the diagnosis criteria included ocular findings. The difficulty in diagnosing PXE often relates to the observation of PXE-like cutaneous lesions. In both cases, we performed differential diagnosis with Marfan syndrome, papillary dermal elastolysis, papular elastorrhexis body skin hyperlaxity due to vitamin K dependent coagulation factor deficiency, severe actinic damage to the lateral part of the neck, and cutis laxa. However, histopathology of these lesions did not reveal tissue mineralization PXE-like cutaneous changes.'}
|
{'Case Number One': 'A female patient of 36 years, resident and original of the city of Tula, Hidalgo, Mexico, without pathological antecedents of importance, attended a medical appointment due to presenting dermatosis in the neck with a 3-month evolution. During physical examination, it was described to be characterized by confluent papules, of 2 to 3 mm approximately, discretely hyperpigmented and asymptomatic (Fig. 1a ). An incisional biopsy was taken by punching, with diagnosis of PXE versus mucinous papulosis. The biopsy showed anfractuous epidermis, with stratum corneum in basket weave, the stratum spinosum thinned with flattening of the interpapillary projections and hyperpigmentation of the cells of the lower third. A perivascular inflammatory infiltrate formed by lymphocytes was observed in the papillary dermis and the superficial reticular dermis. In the middle reticular dermis, short, basophilic, granular, and irregularly shaped fibers were observed (Fig. 1b ). With staining for elastic fibers, they were shown to be fragmented, and Von Kossa staining evidenced their calcification (Fig. 1c ). These clinical and histopathological findings confirmed the diagnosis of pseudoxanthoma.', 'Case Number Two': 'A female patient of 59 years, resident and originally from the city of Zacatecas, Zacatecas, Mexico, was referred by the ophthalmological service due to severe visual acuity diminution and angioid striae of the retina, with no other important data. During physical examination, bilateral symmetrical dermatosis was observed, predominantly in folds, characterized by loose skin, soft texture, and plaques consisting of skin-colored papules 3–4 mm in diameter (Fig. 2a ). An incisional biopsy was taken by punching, with a clinical diagnosis of PXE. In the sections, thin and anfractuous epidermis was observed, with the stratum corneum in basket weave and the stratum spinosum with flattening of the interpapillary projections. In the middle reticular dermis, irregularly arranged short basophilic fibers were observed (Fig. 2b ). The staining of elastic fibers (Fig. 2c ) showed that the fragmented debris corresponded to these fibers and Von Kosa staining showed the presence of calcium inside. Fundus examination in both eyes revealed classic-appearing angioid streaks with crystalline spots, retinal pigment with epithelial atrophy (peripapillary), and choroidal neovascularization (Fig. 3a, b ). With the histopathological study and fundus examination findings, the diagnosis of PXE was confirmed this case. The diagnosis criteria used were in the first case skin findings like characteristic pseudoxanthomatous papules and plaques on the neck or flexural creases, and histopathological changes in lesional skin: calcified elastic fibers in the mid and lower dermis, confirmed by positive calcium stain. For the second case, the diagnosis criteria included ocular findings. The difficulty in diagnosing PXE often relates to the observation of PXE-like cutaneous lesions. In both cases, we performed differential diagnosis with Marfan syndrome, papillary dermal elastolysis, papular elastorrhexis body skin hyperlaxity due to vitamin K dependent coagulation factor deficiency, severe actinic damage to the lateral part of the neck, and cutis laxa. However, histopathology of these lesions did not reveal tissue mineralization PXE-like cutaneous changes.'}
|
Vitals-and-Hematology
|
Vitals_Hema
|
[] |
test-2198
|
8138145
|
{'Case Number One': 'A female patient of 36 years, resident and original of the city of Tula, Hidalgo, Mexico, without pathological antecedents of importance, attended a medical appointment due to presenting dermatosis in the neck with a 3-month evolution. During physical examination, it was described to be characterized by confluent papules, of 2 to 3 mm approximately, discretely hyperpigmented and asymptomatic (Fig. 1a ). An incisional biopsy was taken by punching, with diagnosis of PXE versus mucinous papulosis. The biopsy showed anfractuous epidermis, with stratum corneum in basket weave, the stratum spinosum thinned with flattening of the interpapillary projections and hyperpigmentation of the cells of the lower third. A perivascular inflammatory infiltrate formed by lymphocytes was observed in the papillary dermis and the superficial reticular dermis. In the middle reticular dermis, short, basophilic, granular, and irregularly shaped fibers were observed (Fig. 1b ). With staining for elastic fibers, they were shown to be fragmented, and Von Kossa staining evidenced their calcification (Fig. 1c ). These clinical and histopathological findings confirmed the diagnosis of pseudoxanthoma.', 'Case Number Two': 'A female patient of 59 years, resident and originally from the city of Zacatecas, Zacatecas, Mexico, was referred by the ophthalmological service due to severe visual acuity diminution and angioid striae of the retina, with no other important data. During physical examination, bilateral symmetrical dermatosis was observed, predominantly in folds, characterized by loose skin, soft texture, and plaques consisting of skin-colored papules 3–4 mm in diameter (Fig. 2a ). An incisional biopsy was taken by punching, with a clinical diagnosis of PXE. In the sections, thin and anfractuous epidermis was observed, with the stratum corneum in basket weave and the stratum spinosum with flattening of the interpapillary projections. In the middle reticular dermis, irregularly arranged short basophilic fibers were observed (Fig. 2b ). The staining of elastic fibers (Fig. 2c ) showed that the fragmented debris corresponded to these fibers and Von Kosa staining showed the presence of calcium inside. Fundus examination in both eyes revealed classic-appearing angioid streaks with crystalline spots, retinal pigment with epithelial atrophy (peripapillary), and choroidal neovascularization (Fig. 3a, b ). With the histopathological study and fundus examination findings, the diagnosis of PXE was confirmed this case. The diagnosis criteria used were in the first case skin findings like characteristic pseudoxanthomatous papules and plaques on the neck or flexural creases, and histopathological changes in lesional skin: calcified elastic fibers in the mid and lower dermis, confirmed by positive calcium stain. For the second case, the diagnosis criteria included ocular findings. The difficulty in diagnosing PXE often relates to the observation of PXE-like cutaneous lesions. In both cases, we performed differential diagnosis with Marfan syndrome, papillary dermal elastolysis, papular elastorrhexis body skin hyperlaxity due to vitamin K dependent coagulation factor deficiency, severe actinic damage to the lateral part of the neck, and cutis laxa. However, histopathology of these lesions did not reveal tissue mineralization PXE-like cutaneous changes.'}
|
{'Case Number One': 'A female patient of 36 years, resident and original of the city of Tula, Hidalgo, Mexico, without pathological antecedents of importance, attended a medical appointment due to presenting dermatosis in the neck with a 3-month evolution. During physical examination, it was described to be characterized by confluent papules, of 2 to 3 mm approximately, discretely hyperpigmented and asymptomatic (Fig. 1a ). An incisional biopsy was taken by punching, with diagnosis of PXE versus mucinous papulosis. The biopsy showed anfractuous epidermis, with stratum corneum in basket weave, the stratum spinosum thinned with flattening of the interpapillary projections and hyperpigmentation of the cells of the lower third. A perivascular inflammatory infiltrate formed by lymphocytes was observed in the papillary dermis and the superficial reticular dermis. In the middle reticular dermis, short, basophilic, granular, and irregularly shaped fibers were observed (Fig. 1b ). With staining for elastic fibers, they were shown to be fragmented, and Von Kossa staining evidenced their calcification (Fig. 1c ). These clinical and histopathological findings confirmed the diagnosis of pseudoxanthoma.', 'Case Number Two': 'A female patient of 59 years, resident and originally from the city of Zacatecas, Zacatecas, Mexico, was referred by the ophthalmological service due to severe visual acuity diminution and angioid striae of the retina, with no other important data. During physical examination, bilateral symmetrical dermatosis was observed, predominantly in folds, characterized by loose skin, soft texture, and plaques consisting of skin-colored papules 3–4 mm in diameter (Fig. 2a ). An incisional biopsy was taken by punching, with a clinical diagnosis of PXE. In the sections, thin and anfractuous epidermis was observed, with the stratum corneum in basket weave and the stratum spinosum with flattening of the interpapillary projections. In the middle reticular dermis, irregularly arranged short basophilic fibers were observed (Fig. 2b ). The staining of elastic fibers (Fig. 2c ) showed that the fragmented debris corresponded to these fibers and Von Kosa staining showed the presence of calcium inside. Fundus examination in both eyes revealed classic-appearing angioid streaks with crystalline spots, retinal pigment with epithelial atrophy (peripapillary), and choroidal neovascularization (Fig. 3a, b ). With the histopathological study and fundus examination findings, the diagnosis of PXE was confirmed this case. The diagnosis criteria used were in the first case skin findings like characteristic pseudoxanthomatous papules and plaques on the neck or flexural creases, and histopathological changes in lesional skin: calcified elastic fibers in the mid and lower dermis, confirmed by positive calcium stain. For the second case, the diagnosis criteria included ocular findings. The difficulty in diagnosing PXE often relates to the observation of PXE-like cutaneous lesions. In both cases, we performed differential diagnosis with Marfan syndrome, papillary dermal elastolysis, papular elastorrhexis body skin hyperlaxity due to vitamin K dependent coagulation factor deficiency, severe actinic damage to the lateral part of the neck, and cutis laxa. However, histopathology of these lesions did not reveal tissue mineralization PXE-like cutaneous changes.'}
|
Gastrointestinal-System
|
GI
|
[] |
test-2199
|
8138145
|
{'Case Number One': 'A female patient of 36 years, resident and original of the city of Tula, Hidalgo, Mexico, without pathological antecedents of importance, attended a medical appointment due to presenting dermatosis in the neck with a 3-month evolution. During physical examination, it was described to be characterized by confluent papules, of 2 to 3 mm approximately, discretely hyperpigmented and asymptomatic (Fig. 1a ). An incisional biopsy was taken by punching, with diagnosis of PXE versus mucinous papulosis. The biopsy showed anfractuous epidermis, with stratum corneum in basket weave, the stratum spinosum thinned with flattening of the interpapillary projections and hyperpigmentation of the cells of the lower third. A perivascular inflammatory infiltrate formed by lymphocytes was observed in the papillary dermis and the superficial reticular dermis. In the middle reticular dermis, short, basophilic, granular, and irregularly shaped fibers were observed (Fig. 1b ). With staining for elastic fibers, they were shown to be fragmented, and Von Kossa staining evidenced their calcification (Fig. 1c ). These clinical and histopathological findings confirmed the diagnosis of pseudoxanthoma.', 'Case Number Two': 'A female patient of 59 years, resident and originally from the city of Zacatecas, Zacatecas, Mexico, was referred by the ophthalmological service due to severe visual acuity diminution and angioid striae of the retina, with no other important data. During physical examination, bilateral symmetrical dermatosis was observed, predominantly in folds, characterized by loose skin, soft texture, and plaques consisting of skin-colored papules 3–4 mm in diameter (Fig. 2a ). An incisional biopsy was taken by punching, with a clinical diagnosis of PXE. In the sections, thin and anfractuous epidermis was observed, with the stratum corneum in basket weave and the stratum spinosum with flattening of the interpapillary projections. In the middle reticular dermis, irregularly arranged short basophilic fibers were observed (Fig. 2b ). The staining of elastic fibers (Fig. 2c ) showed that the fragmented debris corresponded to these fibers and Von Kosa staining showed the presence of calcium inside. Fundus examination in both eyes revealed classic-appearing angioid streaks with crystalline spots, retinal pigment with epithelial atrophy (peripapillary), and choroidal neovascularization (Fig. 3a, b ). With the histopathological study and fundus examination findings, the diagnosis of PXE was confirmed this case. The diagnosis criteria used were in the first case skin findings like characteristic pseudoxanthomatous papules and plaques on the neck or flexural creases, and histopathological changes in lesional skin: calcified elastic fibers in the mid and lower dermis, confirmed by positive calcium stain. For the second case, the diagnosis criteria included ocular findings. The difficulty in diagnosing PXE often relates to the observation of PXE-like cutaneous lesions. In both cases, we performed differential diagnosis with Marfan syndrome, papillary dermal elastolysis, papular elastorrhexis body skin hyperlaxity due to vitamin K dependent coagulation factor deficiency, severe actinic damage to the lateral part of the neck, and cutis laxa. However, histopathology of these lesions did not reveal tissue mineralization PXE-like cutaneous changes.'}
|
{'Case Number One': 'A female patient of 36 years, resident and original of the city of Tula, Hidalgo, Mexico, without pathological antecedents of importance, attended a medical appointment due to presenting dermatosis in the neck with a 3-month evolution. During physical examination, it was described to be characterized by confluent papules, of 2 to 3 mm approximately, discretely hyperpigmented and asymptomatic (Fig. 1a ). An incisional biopsy was taken by punching, with diagnosis of PXE versus mucinous papulosis. The biopsy showed anfractuous epidermis, with stratum corneum in basket weave, the stratum spinosum thinned with flattening of the interpapillary projections and hyperpigmentation of the cells of the lower third. A perivascular inflammatory infiltrate formed by lymphocytes was observed in the papillary dermis and the superficial reticular dermis. In the middle reticular dermis, short, basophilic, granular, and irregularly shaped fibers were observed (Fig. 1b ). With staining for elastic fibers, they were shown to be fragmented, and Von Kossa staining evidenced their calcification (Fig. 1c ). These clinical and histopathological findings confirmed the diagnosis of pseudoxanthoma.', 'Case Number Two': 'A female patient of 59 years, resident and originally from the city of Zacatecas, Zacatecas, Mexico, was referred by the ophthalmological service due to severe visual acuity diminution and angioid striae of the retina, with no other important data. During physical examination, bilateral symmetrical dermatosis was observed, predominantly in folds, characterized by loose skin, soft texture, and plaques consisting of skin-colored papules 3–4 mm in diameter (Fig. 2a ). An incisional biopsy was taken by punching, with a clinical diagnosis of PXE. In the sections, thin and anfractuous epidermis was observed, with the stratum corneum in basket weave and the stratum spinosum with flattening of the interpapillary projections. In the middle reticular dermis, irregularly arranged short basophilic fibers were observed (Fig. 2b ). The staining of elastic fibers (Fig. 2c ) showed that the fragmented debris corresponded to these fibers and Von Kosa staining showed the presence of calcium inside. Fundus examination in both eyes revealed classic-appearing angioid streaks with crystalline spots, retinal pigment with epithelial atrophy (peripapillary), and choroidal neovascularization (Fig. 3a, b ). With the histopathological study and fundus examination findings, the diagnosis of PXE was confirmed this case. The diagnosis criteria used were in the first case skin findings like characteristic pseudoxanthomatous papules and plaques on the neck or flexural creases, and histopathological changes in lesional skin: calcified elastic fibers in the mid and lower dermis, confirmed by positive calcium stain. For the second case, the diagnosis criteria included ocular findings. The difficulty in diagnosing PXE often relates to the observation of PXE-like cutaneous lesions. In both cases, we performed differential diagnosis with Marfan syndrome, papillary dermal elastolysis, papular elastorrhexis body skin hyperlaxity due to vitamin K dependent coagulation factor deficiency, severe actinic damage to the lateral part of the neck, and cutis laxa. However, histopathology of these lesions did not reveal tissue mineralization PXE-like cutaneous changes.'}
|
Patient-History
|
History
|
[
"presenting dermatosis in the neck with a 3 - month evolution",
"severe visual acuity diminution and angioid striae of the retina"
] |
test-2200
|
8138145
|
{'Case Number One': 'A female patient of 36 years, resident and original of the city of Tula, Hidalgo, Mexico, without pathological antecedents of importance, attended a medical appointment due to presenting dermatosis in the neck with a 3-month evolution. During physical examination, it was described to be characterized by confluent papules, of 2 to 3 mm approximately, discretely hyperpigmented and asymptomatic (Fig. 1a ). An incisional biopsy was taken by punching, with diagnosis of PXE versus mucinous papulosis. The biopsy showed anfractuous epidermis, with stratum corneum in basket weave, the stratum spinosum thinned with flattening of the interpapillary projections and hyperpigmentation of the cells of the lower third. A perivascular inflammatory infiltrate formed by lymphocytes was observed in the papillary dermis and the superficial reticular dermis. In the middle reticular dermis, short, basophilic, granular, and irregularly shaped fibers were observed (Fig. 1b ). With staining for elastic fibers, they were shown to be fragmented, and Von Kossa staining evidenced their calcification (Fig. 1c ). These clinical and histopathological findings confirmed the diagnosis of pseudoxanthoma.', 'Case Number Two': 'A female patient of 59 years, resident and originally from the city of Zacatecas, Zacatecas, Mexico, was referred by the ophthalmological service due to severe visual acuity diminution and angioid striae of the retina, with no other important data. During physical examination, bilateral symmetrical dermatosis was observed, predominantly in folds, characterized by loose skin, soft texture, and plaques consisting of skin-colored papules 3–4 mm in diameter (Fig. 2a ). An incisional biopsy was taken by punching, with a clinical diagnosis of PXE. In the sections, thin and anfractuous epidermis was observed, with the stratum corneum in basket weave and the stratum spinosum with flattening of the interpapillary projections. In the middle reticular dermis, irregularly arranged short basophilic fibers were observed (Fig. 2b ). The staining of elastic fibers (Fig. 2c ) showed that the fragmented debris corresponded to these fibers and Von Kosa staining showed the presence of calcium inside. Fundus examination in both eyes revealed classic-appearing angioid streaks with crystalline spots, retinal pigment with epithelial atrophy (peripapillary), and choroidal neovascularization (Fig. 3a, b ). With the histopathological study and fundus examination findings, the diagnosis of PXE was confirmed this case. The diagnosis criteria used were in the first case skin findings like characteristic pseudoxanthomatous papules and plaques on the neck or flexural creases, and histopathological changes in lesional skin: calcified elastic fibers in the mid and lower dermis, confirmed by positive calcium stain. For the second case, the diagnosis criteria included ocular findings. The difficulty in diagnosing PXE often relates to the observation of PXE-like cutaneous lesions. In both cases, we performed differential diagnosis with Marfan syndrome, papillary dermal elastolysis, papular elastorrhexis body skin hyperlaxity due to vitamin K dependent coagulation factor deficiency, severe actinic damage to the lateral part of the neck, and cutis laxa. However, histopathology of these lesions did not reveal tissue mineralization PXE-like cutaneous changes.'}
|
{'Case Number One': 'A female patient of 36 years, resident and original of the city of Tula, Hidalgo, Mexico, without pathological antecedents of importance, attended a medical appointment due to presenting dermatosis in the neck with a 3-month evolution. During physical examination, it was described to be characterized by confluent papules, of 2 to 3 mm approximately, discretely hyperpigmented and asymptomatic (Fig. 1a ). An incisional biopsy was taken by punching, with diagnosis of PXE versus mucinous papulosis. The biopsy showed anfractuous epidermis, with stratum corneum in basket weave, the stratum spinosum thinned with flattening of the interpapillary projections and hyperpigmentation of the cells of the lower third. A perivascular inflammatory infiltrate formed by lymphocytes was observed in the papillary dermis and the superficial reticular dermis. In the middle reticular dermis, short, basophilic, granular, and irregularly shaped fibers were observed (Fig. 1b ). With staining for elastic fibers, they were shown to be fragmented, and Von Kossa staining evidenced their calcification (Fig. 1c ). These clinical and histopathological findings confirmed the diagnosis of pseudoxanthoma.', 'Case Number Two': 'A female patient of 59 years, resident and originally from the city of Zacatecas, Zacatecas, Mexico, was referred by the ophthalmological service due to severe visual acuity diminution and angioid striae of the retina, with no other important data. During physical examination, bilateral symmetrical dermatosis was observed, predominantly in folds, characterized by loose skin, soft texture, and plaques consisting of skin-colored papules 3–4 mm in diameter (Fig. 2a ). An incisional biopsy was taken by punching, with a clinical diagnosis of PXE. In the sections, thin and anfractuous epidermis was observed, with the stratum corneum in basket weave and the stratum spinosum with flattening of the interpapillary projections. In the middle reticular dermis, irregularly arranged short basophilic fibers were observed (Fig. 2b ). The staining of elastic fibers (Fig. 2c ) showed that the fragmented debris corresponded to these fibers and Von Kosa staining showed the presence of calcium inside. Fundus examination in both eyes revealed classic-appearing angioid streaks with crystalline spots, retinal pigment with epithelial atrophy (peripapillary), and choroidal neovascularization (Fig. 3a, b ). With the histopathological study and fundus examination findings, the diagnosis of PXE was confirmed this case. The diagnosis criteria used were in the first case skin findings like characteristic pseudoxanthomatous papules and plaques on the neck or flexural creases, and histopathological changes in lesional skin: calcified elastic fibers in the mid and lower dermis, confirmed by positive calcium stain. For the second case, the diagnosis criteria included ocular findings. The difficulty in diagnosing PXE often relates to the observation of PXE-like cutaneous lesions. In both cases, we performed differential diagnosis with Marfan syndrome, papillary dermal elastolysis, papular elastorrhexis body skin hyperlaxity due to vitamin K dependent coagulation factor deficiency, severe actinic damage to the lateral part of the neck, and cutis laxa. However, histopathology of these lesions did not reveal tissue mineralization PXE-like cutaneous changes.'}
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Neurology
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Neuro
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[] |
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