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test-2001
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7890005
|
{'Case presentation': 'We report a 38-year old woman who presented with chronic diarrhea and progressive spastic paraparesis in her twenties. Brain magnetic resonance imaging (MRI) showed cerebral atrophy with diffuse periventricular white matter hyperintensities. Spinal MRI was normal. CYP27A1 gene sequencing confirmed the diagnosis of CTX. Chenodeoxycholic acid (CDCA) treatment was introduced with remission of diarrhea. Unfortunately, the treatment had to be discontinued several times and the patient developed psychosis and an severe ataxospastic gait. Spinal MRI revealed new linear hyperintensities of the corticospinal and gracile tracts. Thirty-three spinal CTX patients were identified by searching in Pubmed, EMBASE™ and Web of Science databases. All patients presented pyramidal signs and 48% had dorsal column signs. Juvenile cataracts were described in 78% of patients, chronic diarrhea in 65%, and tendon xanthomas in 31%. Disease improvement or stabilization with chenodeoxycholic acid was observed in 69% of patients. A higher prevalence of the Arg395Cys allele was observed in patients with spinal CTX as compared to CTX in general (ᵡ 2 ; p < 0.00001). A 38-year-old woman presented with progressive muscle stiffness, calf cramps and urinary frequency appeared in her twenties ( Fig. 1 ). Her past medical history included chronic diarrhea, scoliosis and bilateral cataract surgery at age 25. She did not take any treatment and had normal schooling. Family history was not relevant. Neurological examination revealed spastic paraparesis with pyramidal signs more prominent on the left lower extremity and flat feet. A neurocognitive study demonstrated severe anterograde verbal memory difficulties and minor executive dysfunction. Electroneuromyography (ENMG) was normal. Brain MRI showed subtle symmetric, bilateral hyperintense T2 ground-glass appearance of the deep white matter, possible symmetric T2 hyperintensity of the cerebellar dentate nuclei and two small ischemic infarct sequelae of the right cerebellar hemisphere ( Fig. 2 ). Spinal MRI was normal. 7 years later, due to progression of spastic paraparesis, CTX was considered. Cholestanol was increased to 64 μmol/L (3.3–12.5 μmol/L). A careful assessment did not found any tendinous xanthomas. Genetic analysis found two monoallelic mutations in the gene CYP27A1 : a missense mutation (c.1183C > T; p. Arg395Cys) in exon 6 and a splicing mutation (c.1184 + 1G > A) in intron 6 and confirmed CTX diagnosis. A treatment with 750 mg/d chenodeoxycholic acid (CDCA) and 20 mg/d simvastatine was introduced ( Fig. 1 ). Three months later, diarrhea was disappeared and no adverse effect was observed. One-year follow-up showed stabilization of neurologic and radiologic signs. Fig. 1 Patient timeline of clinical symptoms and biochemical values. Abbreviations: SP: spastic paraparesia; m: month; CDCA: chenodeoxycholic acid. Normal values for cholestanol (N: 0–15.45 μmol/L); bile acid (N: 0–10.02 μmol/L) Fig. 1 Fig. 2 Brain and spinal cord magnetic resonance imaging (MRI) of the patient. Brain and spinal cord MRI performed in 2008 (a,b,e) and 2019 (c,d,f,g). Axial plane T2 weighted images (a-d) at the level of the dentate nuclei and periventricular white matter showing stable minimal increased signal in the dentate nuclei (arrowheads) and questionable slightly abnormal periventricular white matter T2 hyperintensity (“ground-glass appearance”). The rest of brain MRI was unremarkable except for two small old infarcts in the right cerebellar hemisphere (one lesion shown in a and b*). Spinal cord MRI from 2008 (e) was unremarkable, though no axial plane images were performed. Spinal cord MRI in 2019 revealed subtle longitudinal high signal (white arrow-heads) of the posterior columns at the cervico-dorsal junction and middle dorsal region on sagittal T2-weighted images (f). Axial T2-weighted images confirmed bilateral, symmetric signal abnormalities corresponding to the gracilis tracts (g, black arrowhead) and the lateral cortico-spinal tracts (g, white arrows) at different cervical and dorsal levels, without spinal cord atrophy or contrast material (gadolinium) uptake. Fig. 2 CDCA treatment was stopped for 16 months due to product withdrawal. Over this period, diarrhea recurred and walking worsened. She had increased stiffness with muscle pain, new apallesthesia of the lower limbs and onset of cerebellar ataxia. When CDCA treatment was reintroduced (500 mg/d) walking, pain and diarrhea improved. Due to renewed product shortage and patient non-compliance, CDCA treatment was repeatedly discontinued, following which the patient developed an acute psychosis and, short after, a rapid worsening of her gait becaming rollator dependent. Neurologic evaluation showed a severe ataxospastic gait with knee recurvatum (additional files: video). ENMG was normal. Brain MRI was unchanged. Spinal MRI revealed extensive linear T2 weighted hyperintensities appearing bilaterally in lateral corticospinal and gracile tracts ( Fig. 2 ). Despite normal cholestanol levels (6.18 μmol/L; normal range 3.3–12.5 μmol/L), CDCA posology was increased to 750 mg/d. Six months later, the patient had resolution of diarrhea and psychiatric symptoms but no improvement of gait.'}
|
{'Case presentation': 'We report a 38-year old woman who presented with chronic diarrhea and progressive spastic paraparesis in her twenties. Brain magnetic resonance imaging (MRI) showed cerebral atrophy with diffuse periventricular white matter hyperintensities. Spinal MRI was normal. CYP27A1 gene sequencing confirmed the diagnosis of CTX. Chenodeoxycholic acid (CDCA) treatment was introduced with remission of diarrhea. Unfortunately, the treatment had to be discontinued several times and the patient developed psychosis and an severe ataxospastic gait. Spinal MRI revealed new linear hyperintensities of the corticospinal and gracile tracts. Thirty-three spinal CTX patients were identified by searching in Pubmed, EMBASE™ and Web of Science databases. All patients presented pyramidal signs and 48% had dorsal column signs. Juvenile cataracts were described in 78% of patients, chronic diarrhea in 65%, and tendon xanthomas in 31%. Disease improvement or stabilization with chenodeoxycholic acid was observed in 69% of patients. A higher prevalence of the Arg395Cys allele was observed in patients with spinal CTX as compared to CTX in general (ᵡ 2 ; p < 0.00001). A 38-year-old woman presented with progressive muscle stiffness, calf cramps and urinary frequency appeared in her twenties ( Fig. 1 ). Her past medical history included chronic diarrhea, scoliosis and bilateral cataract surgery at age 25. She did not take any treatment and had normal schooling. Family history was not relevant. Neurological examination revealed spastic paraparesis with pyramidal signs more prominent on the left lower extremity and flat feet. A neurocognitive study demonstrated severe anterograde verbal memory difficulties and minor executive dysfunction. Electroneuromyography (ENMG) was normal. Brain MRI showed subtle symmetric, bilateral hyperintense T2 ground-glass appearance of the deep white matter, possible symmetric T2 hyperintensity of the cerebellar dentate nuclei and two small ischemic infarct sequelae of the right cerebellar hemisphere ( Fig. 2 ). Spinal MRI was normal. 7 years later, due to progression of spastic paraparesis, CTX was considered. Cholestanol was increased to 64 μmol/L (3.3–12.5 μmol/L). A careful assessment did not found any tendinous xanthomas. Genetic analysis found two monoallelic mutations in the gene CYP27A1 : a missense mutation (c.1183C > T; p. Arg395Cys) in exon 6 and a splicing mutation (c.1184 + 1G > A) in intron 6 and confirmed CTX diagnosis. A treatment with 750 mg/d chenodeoxycholic acid (CDCA) and 20 mg/d simvastatine was introduced ( Fig. 1 ). Three months later, diarrhea was disappeared and no adverse effect was observed. One-year follow-up showed stabilization of neurologic and radiologic signs. Fig. 1 Patient timeline of clinical symptoms and biochemical values. Abbreviations: SP: spastic paraparesia; m: month; CDCA: chenodeoxycholic acid. Normal values for cholestanol (N: 0–15.45 μmol/L); bile acid (N: 0–10.02 μmol/L) Fig. 1 Fig. 2 Brain and spinal cord magnetic resonance imaging (MRI) of the patient. Brain and spinal cord MRI performed in 2008 (a,b,e) and 2019 (c,d,f,g). Axial plane T2 weighted images (a-d) at the level of the dentate nuclei and periventricular white matter showing stable minimal increased signal in the dentate nuclei (arrowheads) and questionable slightly abnormal periventricular white matter T2 hyperintensity (“ground-glass appearance”). The rest of brain MRI was unremarkable except for two small old infarcts in the right cerebellar hemisphere (one lesion shown in a and b*). Spinal cord MRI from 2008 (e) was unremarkable, though no axial plane images were performed. Spinal cord MRI in 2019 revealed subtle longitudinal high signal (white arrow-heads) of the posterior columns at the cervico-dorsal junction and middle dorsal region on sagittal T2-weighted images (f). Axial T2-weighted images confirmed bilateral, symmetric signal abnormalities corresponding to the gracilis tracts (g, black arrowhead) and the lateral cortico-spinal tracts (g, white arrows) at different cervical and dorsal levels, without spinal cord atrophy or contrast material (gadolinium) uptake. Fig. 2 CDCA treatment was stopped for 16 months due to product withdrawal. Over this period, diarrhea recurred and walking worsened. She had increased stiffness with muscle pain, new apallesthesia of the lower limbs and onset of cerebellar ataxia. When CDCA treatment was reintroduced (500 mg/d) walking, pain and diarrhea improved. Due to renewed product shortage and patient non-compliance, CDCA treatment was repeatedly discontinued, following which the patient developed an acute psychosis and, short after, a rapid worsening of her gait becaming rollator dependent. Neurologic evaluation showed a severe ataxospastic gait with knee recurvatum (additional files: video). ENMG was normal. Brain MRI was unchanged. Spinal MRI revealed extensive linear T2 weighted hyperintensities appearing bilaterally in lateral corticospinal and gracile tracts ( Fig. 2 ). Despite normal cholestanol levels (6.18 μmol/L; normal range 3.3–12.5 μmol/L), CDCA posology was increased to 750 mg/d. Six months later, the patient had resolution of diarrhea and psychiatric symptoms but no improvement of gait.'}
|
Patient-History
|
History
|
[
"We report a 38 - year old woman who presented with chronic diarrhea and progressive spastic paraparesis in her twenties",
"chronic diarrhea, scoliosis and bilateral cataract surgery at age 25"
] |
test-2002
|
7890005
|
{'Case presentation': 'We report a 38-year old woman who presented with chronic diarrhea and progressive spastic paraparesis in her twenties. Brain magnetic resonance imaging (MRI) showed cerebral atrophy with diffuse periventricular white matter hyperintensities. Spinal MRI was normal. CYP27A1 gene sequencing confirmed the diagnosis of CTX. Chenodeoxycholic acid (CDCA) treatment was introduced with remission of diarrhea. Unfortunately, the treatment had to be discontinued several times and the patient developed psychosis and an severe ataxospastic gait. Spinal MRI revealed new linear hyperintensities of the corticospinal and gracile tracts. Thirty-three spinal CTX patients were identified by searching in Pubmed, EMBASE™ and Web of Science databases. All patients presented pyramidal signs and 48% had dorsal column signs. Juvenile cataracts were described in 78% of patients, chronic diarrhea in 65%, and tendon xanthomas in 31%. Disease improvement or stabilization with chenodeoxycholic acid was observed in 69% of patients. A higher prevalence of the Arg395Cys allele was observed in patients with spinal CTX as compared to CTX in general (ᵡ 2 ; p < 0.00001). A 38-year-old woman presented with progressive muscle stiffness, calf cramps and urinary frequency appeared in her twenties ( Fig. 1 ). Her past medical history included chronic diarrhea, scoliosis and bilateral cataract surgery at age 25. She did not take any treatment and had normal schooling. Family history was not relevant. Neurological examination revealed spastic paraparesis with pyramidal signs more prominent on the left lower extremity and flat feet. A neurocognitive study demonstrated severe anterograde verbal memory difficulties and minor executive dysfunction. Electroneuromyography (ENMG) was normal. Brain MRI showed subtle symmetric, bilateral hyperintense T2 ground-glass appearance of the deep white matter, possible symmetric T2 hyperintensity of the cerebellar dentate nuclei and two small ischemic infarct sequelae of the right cerebellar hemisphere ( Fig. 2 ). Spinal MRI was normal. 7 years later, due to progression of spastic paraparesis, CTX was considered. Cholestanol was increased to 64 μmol/L (3.3–12.5 μmol/L). A careful assessment did not found any tendinous xanthomas. Genetic analysis found two monoallelic mutations in the gene CYP27A1 : a missense mutation (c.1183C > T; p. Arg395Cys) in exon 6 and a splicing mutation (c.1184 + 1G > A) in intron 6 and confirmed CTX diagnosis. A treatment with 750 mg/d chenodeoxycholic acid (CDCA) and 20 mg/d simvastatine was introduced ( Fig. 1 ). Three months later, diarrhea was disappeared and no adverse effect was observed. One-year follow-up showed stabilization of neurologic and radiologic signs. Fig. 1 Patient timeline of clinical symptoms and biochemical values. Abbreviations: SP: spastic paraparesia; m: month; CDCA: chenodeoxycholic acid. Normal values for cholestanol (N: 0–15.45 μmol/L); bile acid (N: 0–10.02 μmol/L) Fig. 1 Fig. 2 Brain and spinal cord magnetic resonance imaging (MRI) of the patient. Brain and spinal cord MRI performed in 2008 (a,b,e) and 2019 (c,d,f,g). Axial plane T2 weighted images (a-d) at the level of the dentate nuclei and periventricular white matter showing stable minimal increased signal in the dentate nuclei (arrowheads) and questionable slightly abnormal periventricular white matter T2 hyperintensity (“ground-glass appearance”). The rest of brain MRI was unremarkable except for two small old infarcts in the right cerebellar hemisphere (one lesion shown in a and b*). Spinal cord MRI from 2008 (e) was unremarkable, though no axial plane images were performed. Spinal cord MRI in 2019 revealed subtle longitudinal high signal (white arrow-heads) of the posterior columns at the cervico-dorsal junction and middle dorsal region on sagittal T2-weighted images (f). Axial T2-weighted images confirmed bilateral, symmetric signal abnormalities corresponding to the gracilis tracts (g, black arrowhead) and the lateral cortico-spinal tracts (g, white arrows) at different cervical and dorsal levels, without spinal cord atrophy or contrast material (gadolinium) uptake. Fig. 2 CDCA treatment was stopped for 16 months due to product withdrawal. Over this period, diarrhea recurred and walking worsened. She had increased stiffness with muscle pain, new apallesthesia of the lower limbs and onset of cerebellar ataxia. When CDCA treatment was reintroduced (500 mg/d) walking, pain and diarrhea improved. Due to renewed product shortage and patient non-compliance, CDCA treatment was repeatedly discontinued, following which the patient developed an acute psychosis and, short after, a rapid worsening of her gait becaming rollator dependent. Neurologic evaluation showed a severe ataxospastic gait with knee recurvatum (additional files: video). ENMG was normal. Brain MRI was unchanged. Spinal MRI revealed extensive linear T2 weighted hyperintensities appearing bilaterally in lateral corticospinal and gracile tracts ( Fig. 2 ). Despite normal cholestanol levels (6.18 μmol/L; normal range 3.3–12.5 μmol/L), CDCA posology was increased to 750 mg/d. Six months later, the patient had resolution of diarrhea and psychiatric symptoms but no improvement of gait.'}
|
{'Case presentation': 'We report a 38-year old woman who presented with chronic diarrhea and progressive spastic paraparesis in her twenties. Brain magnetic resonance imaging (MRI) showed cerebral atrophy with diffuse periventricular white matter hyperintensities. Spinal MRI was normal. CYP27A1 gene sequencing confirmed the diagnosis of CTX. Chenodeoxycholic acid (CDCA) treatment was introduced with remission of diarrhea. Unfortunately, the treatment had to be discontinued several times and the patient developed psychosis and an severe ataxospastic gait. Spinal MRI revealed new linear hyperintensities of the corticospinal and gracile tracts. Thirty-three spinal CTX patients were identified by searching in Pubmed, EMBASE™ and Web of Science databases. All patients presented pyramidal signs and 48% had dorsal column signs. Juvenile cataracts were described in 78% of patients, chronic diarrhea in 65%, and tendon xanthomas in 31%. Disease improvement or stabilization with chenodeoxycholic acid was observed in 69% of patients. A higher prevalence of the Arg395Cys allele was observed in patients with spinal CTX as compared to CTX in general (ᵡ 2 ; p < 0.00001). A 38-year-old woman presented with progressive muscle stiffness, calf cramps and urinary frequency appeared in her twenties ( Fig. 1 ). Her past medical history included chronic diarrhea, scoliosis and bilateral cataract surgery at age 25. She did not take any treatment and had normal schooling. Family history was not relevant. Neurological examination revealed spastic paraparesis with pyramidal signs more prominent on the left lower extremity and flat feet. A neurocognitive study demonstrated severe anterograde verbal memory difficulties and minor executive dysfunction. Electroneuromyography (ENMG) was normal. Brain MRI showed subtle symmetric, bilateral hyperintense T2 ground-glass appearance of the deep white matter, possible symmetric T2 hyperintensity of the cerebellar dentate nuclei and two small ischemic infarct sequelae of the right cerebellar hemisphere ( Fig. 2 ). Spinal MRI was normal. 7 years later, due to progression of spastic paraparesis, CTX was considered. Cholestanol was increased to 64 μmol/L (3.3–12.5 μmol/L). A careful assessment did not found any tendinous xanthomas. Genetic analysis found two monoallelic mutations in the gene CYP27A1 : a missense mutation (c.1183C > T; p. Arg395Cys) in exon 6 and a splicing mutation (c.1184 + 1G > A) in intron 6 and confirmed CTX diagnosis. A treatment with 750 mg/d chenodeoxycholic acid (CDCA) and 20 mg/d simvastatine was introduced ( Fig. 1 ). Three months later, diarrhea was disappeared and no adverse effect was observed. One-year follow-up showed stabilization of neurologic and radiologic signs. Fig. 1 Patient timeline of clinical symptoms and biochemical values. Abbreviations: SP: spastic paraparesia; m: month; CDCA: chenodeoxycholic acid. Normal values for cholestanol (N: 0–15.45 μmol/L); bile acid (N: 0–10.02 μmol/L) Fig. 1 Fig. 2 Brain and spinal cord magnetic resonance imaging (MRI) of the patient. Brain and spinal cord MRI performed in 2008 (a,b,e) and 2019 (c,d,f,g). Axial plane T2 weighted images (a-d) at the level of the dentate nuclei and periventricular white matter showing stable minimal increased signal in the dentate nuclei (arrowheads) and questionable slightly abnormal periventricular white matter T2 hyperintensity (“ground-glass appearance”). The rest of brain MRI was unremarkable except for two small old infarcts in the right cerebellar hemisphere (one lesion shown in a and b*). Spinal cord MRI from 2008 (e) was unremarkable, though no axial plane images were performed. Spinal cord MRI in 2019 revealed subtle longitudinal high signal (white arrow-heads) of the posterior columns at the cervico-dorsal junction and middle dorsal region on sagittal T2-weighted images (f). Axial T2-weighted images confirmed bilateral, symmetric signal abnormalities corresponding to the gracilis tracts (g, black arrowhead) and the lateral cortico-spinal tracts (g, white arrows) at different cervical and dorsal levels, without spinal cord atrophy or contrast material (gadolinium) uptake. Fig. 2 CDCA treatment was stopped for 16 months due to product withdrawal. Over this period, diarrhea recurred and walking worsened. She had increased stiffness with muscle pain, new apallesthesia of the lower limbs and onset of cerebellar ataxia. When CDCA treatment was reintroduced (500 mg/d) walking, pain and diarrhea improved. Due to renewed product shortage and patient non-compliance, CDCA treatment was repeatedly discontinued, following which the patient developed an acute psychosis and, short after, a rapid worsening of her gait becaming rollator dependent. Neurologic evaluation showed a severe ataxospastic gait with knee recurvatum (additional files: video). ENMG was normal. Brain MRI was unchanged. Spinal MRI revealed extensive linear T2 weighted hyperintensities appearing bilaterally in lateral corticospinal and gracile tracts ( Fig. 2 ). Despite normal cholestanol levels (6.18 μmol/L; normal range 3.3–12.5 μmol/L), CDCA posology was increased to 750 mg/d. Six months later, the patient had resolution of diarrhea and psychiatric symptoms but no improvement of gait.'}
|
Neurology
|
Neuro
|
[
"progressive spastic paraparesis in her twenties.",
"the patient developed psychosis and an severe ataxospastic gait.",
"All patients presented pyramidal signs and 48 % had dorsal column signs",
"A 38 - year - old woman presented with progressive muscle stiffness, calf cramps and urinary frequency appeared in her twenties",
"Neurological examination revealed spastic paraparesis with pyramidal signs more prominent on the left lower extremity and flat feet. A neurocognitive study demonstrated severe anterograde verbal memory difficulties and minor executive dysfunction. Electroneuromyography ( ENMG ) was normal.",
"Neurologic evaluation showed a severe ataxospastic gait with knee recurvatum ( additional files : video ). ENMG was normal."
] |
test-2003
|
7890005
|
{'Case presentation': 'We report a 38-year old woman who presented with chronic diarrhea and progressive spastic paraparesis in her twenties. Brain magnetic resonance imaging (MRI) showed cerebral atrophy with diffuse periventricular white matter hyperintensities. Spinal MRI was normal. CYP27A1 gene sequencing confirmed the diagnosis of CTX. Chenodeoxycholic acid (CDCA) treatment was introduced with remission of diarrhea. Unfortunately, the treatment had to be discontinued several times and the patient developed psychosis and an severe ataxospastic gait. Spinal MRI revealed new linear hyperintensities of the corticospinal and gracile tracts. Thirty-three spinal CTX patients were identified by searching in Pubmed, EMBASE™ and Web of Science databases. All patients presented pyramidal signs and 48% had dorsal column signs. Juvenile cataracts were described in 78% of patients, chronic diarrhea in 65%, and tendon xanthomas in 31%. Disease improvement or stabilization with chenodeoxycholic acid was observed in 69% of patients. A higher prevalence of the Arg395Cys allele was observed in patients with spinal CTX as compared to CTX in general (ᵡ 2 ; p < 0.00001). A 38-year-old woman presented with progressive muscle stiffness, calf cramps and urinary frequency appeared in her twenties ( Fig. 1 ). Her past medical history included chronic diarrhea, scoliosis and bilateral cataract surgery at age 25. She did not take any treatment and had normal schooling. Family history was not relevant. Neurological examination revealed spastic paraparesis with pyramidal signs more prominent on the left lower extremity and flat feet. A neurocognitive study demonstrated severe anterograde verbal memory difficulties and minor executive dysfunction. Electroneuromyography (ENMG) was normal. Brain MRI showed subtle symmetric, bilateral hyperintense T2 ground-glass appearance of the deep white matter, possible symmetric T2 hyperintensity of the cerebellar dentate nuclei and two small ischemic infarct sequelae of the right cerebellar hemisphere ( Fig. 2 ). Spinal MRI was normal. 7 years later, due to progression of spastic paraparesis, CTX was considered. Cholestanol was increased to 64 μmol/L (3.3–12.5 μmol/L). A careful assessment did not found any tendinous xanthomas. Genetic analysis found two monoallelic mutations in the gene CYP27A1 : a missense mutation (c.1183C > T; p. Arg395Cys) in exon 6 and a splicing mutation (c.1184 + 1G > A) in intron 6 and confirmed CTX diagnosis. A treatment with 750 mg/d chenodeoxycholic acid (CDCA) and 20 mg/d simvastatine was introduced ( Fig. 1 ). Three months later, diarrhea was disappeared and no adverse effect was observed. One-year follow-up showed stabilization of neurologic and radiologic signs. Fig. 1 Patient timeline of clinical symptoms and biochemical values. Abbreviations: SP: spastic paraparesia; m: month; CDCA: chenodeoxycholic acid. Normal values for cholestanol (N: 0–15.45 μmol/L); bile acid (N: 0–10.02 μmol/L) Fig. 1 Fig. 2 Brain and spinal cord magnetic resonance imaging (MRI) of the patient. Brain and spinal cord MRI performed in 2008 (a,b,e) and 2019 (c,d,f,g). Axial plane T2 weighted images (a-d) at the level of the dentate nuclei and periventricular white matter showing stable minimal increased signal in the dentate nuclei (arrowheads) and questionable slightly abnormal periventricular white matter T2 hyperintensity (“ground-glass appearance”). The rest of brain MRI was unremarkable except for two small old infarcts in the right cerebellar hemisphere (one lesion shown in a and b*). Spinal cord MRI from 2008 (e) was unremarkable, though no axial plane images were performed. Spinal cord MRI in 2019 revealed subtle longitudinal high signal (white arrow-heads) of the posterior columns at the cervico-dorsal junction and middle dorsal region on sagittal T2-weighted images (f). Axial T2-weighted images confirmed bilateral, symmetric signal abnormalities corresponding to the gracilis tracts (g, black arrowhead) and the lateral cortico-spinal tracts (g, white arrows) at different cervical and dorsal levels, without spinal cord atrophy or contrast material (gadolinium) uptake. Fig. 2 CDCA treatment was stopped for 16 months due to product withdrawal. Over this period, diarrhea recurred and walking worsened. She had increased stiffness with muscle pain, new apallesthesia of the lower limbs and onset of cerebellar ataxia. When CDCA treatment was reintroduced (500 mg/d) walking, pain and diarrhea improved. Due to renewed product shortage and patient non-compliance, CDCA treatment was repeatedly discontinued, following which the patient developed an acute psychosis and, short after, a rapid worsening of her gait becaming rollator dependent. Neurologic evaluation showed a severe ataxospastic gait with knee recurvatum (additional files: video). ENMG was normal. Brain MRI was unchanged. Spinal MRI revealed extensive linear T2 weighted hyperintensities appearing bilaterally in lateral corticospinal and gracile tracts ( Fig. 2 ). Despite normal cholestanol levels (6.18 μmol/L; normal range 3.3–12.5 μmol/L), CDCA posology was increased to 750 mg/d. Six months later, the patient had resolution of diarrhea and psychiatric symptoms but no improvement of gait.'}
|
{'Case presentation': 'We report a 38-year old woman who presented with chronic diarrhea and progressive spastic paraparesis in her twenties. Brain magnetic resonance imaging (MRI) showed cerebral atrophy with diffuse periventricular white matter hyperintensities. Spinal MRI was normal. CYP27A1 gene sequencing confirmed the diagnosis of CTX. Chenodeoxycholic acid (CDCA) treatment was introduced with remission of diarrhea. Unfortunately, the treatment had to be discontinued several times and the patient developed psychosis and an severe ataxospastic gait. Spinal MRI revealed new linear hyperintensities of the corticospinal and gracile tracts. Thirty-three spinal CTX patients were identified by searching in Pubmed, EMBASE™ and Web of Science databases. All patients presented pyramidal signs and 48% had dorsal column signs. Juvenile cataracts were described in 78% of patients, chronic diarrhea in 65%, and tendon xanthomas in 31%. Disease improvement or stabilization with chenodeoxycholic acid was observed in 69% of patients. A higher prevalence of the Arg395Cys allele was observed in patients with spinal CTX as compared to CTX in general (ᵡ 2 ; p < 0.00001). A 38-year-old woman presented with progressive muscle stiffness, calf cramps and urinary frequency appeared in her twenties ( Fig. 1 ). Her past medical history included chronic diarrhea, scoliosis and bilateral cataract surgery at age 25. She did not take any treatment and had normal schooling. Family history was not relevant. Neurological examination revealed spastic paraparesis with pyramidal signs more prominent on the left lower extremity and flat feet. A neurocognitive study demonstrated severe anterograde verbal memory difficulties and minor executive dysfunction. Electroneuromyography (ENMG) was normal. Brain MRI showed subtle symmetric, bilateral hyperintense T2 ground-glass appearance of the deep white matter, possible symmetric T2 hyperintensity of the cerebellar dentate nuclei and two small ischemic infarct sequelae of the right cerebellar hemisphere ( Fig. 2 ). Spinal MRI was normal. 7 years later, due to progression of spastic paraparesis, CTX was considered. Cholestanol was increased to 64 μmol/L (3.3–12.5 μmol/L). A careful assessment did not found any tendinous xanthomas. Genetic analysis found two monoallelic mutations in the gene CYP27A1 : a missense mutation (c.1183C > T; p. Arg395Cys) in exon 6 and a splicing mutation (c.1184 + 1G > A) in intron 6 and confirmed CTX diagnosis. A treatment with 750 mg/d chenodeoxycholic acid (CDCA) and 20 mg/d simvastatine was introduced ( Fig. 1 ). Three months later, diarrhea was disappeared and no adverse effect was observed. One-year follow-up showed stabilization of neurologic and radiologic signs. Fig. 1 Patient timeline of clinical symptoms and biochemical values. Abbreviations: SP: spastic paraparesia; m: month; CDCA: chenodeoxycholic acid. Normal values for cholestanol (N: 0–15.45 μmol/L); bile acid (N: 0–10.02 μmol/L) Fig. 1 Fig. 2 Brain and spinal cord magnetic resonance imaging (MRI) of the patient. Brain and spinal cord MRI performed in 2008 (a,b,e) and 2019 (c,d,f,g). Axial plane T2 weighted images (a-d) at the level of the dentate nuclei and periventricular white matter showing stable minimal increased signal in the dentate nuclei (arrowheads) and questionable slightly abnormal periventricular white matter T2 hyperintensity (“ground-glass appearance”). The rest of brain MRI was unremarkable except for two small old infarcts in the right cerebellar hemisphere (one lesion shown in a and b*). Spinal cord MRI from 2008 (e) was unremarkable, though no axial plane images were performed. Spinal cord MRI in 2019 revealed subtle longitudinal high signal (white arrow-heads) of the posterior columns at the cervico-dorsal junction and middle dorsal region on sagittal T2-weighted images (f). Axial T2-weighted images confirmed bilateral, symmetric signal abnormalities corresponding to the gracilis tracts (g, black arrowhead) and the lateral cortico-spinal tracts (g, white arrows) at different cervical and dorsal levels, without spinal cord atrophy or contrast material (gadolinium) uptake. Fig. 2 CDCA treatment was stopped for 16 months due to product withdrawal. Over this period, diarrhea recurred and walking worsened. She had increased stiffness with muscle pain, new apallesthesia of the lower limbs and onset of cerebellar ataxia. When CDCA treatment was reintroduced (500 mg/d) walking, pain and diarrhea improved. Due to renewed product shortage and patient non-compliance, CDCA treatment was repeatedly discontinued, following which the patient developed an acute psychosis and, short after, a rapid worsening of her gait becaming rollator dependent. Neurologic evaluation showed a severe ataxospastic gait with knee recurvatum (additional files: video). ENMG was normal. Brain MRI was unchanged. Spinal MRI revealed extensive linear T2 weighted hyperintensities appearing bilaterally in lateral corticospinal and gracile tracts ( Fig. 2 ). Despite normal cholestanol levels (6.18 μmol/L; normal range 3.3–12.5 μmol/L), CDCA posology was increased to 750 mg/d. Six months later, the patient had resolution of diarrhea and psychiatric symptoms but no improvement of gait.'}
|
Laboratory-and-Imaging
|
Lab_Image
|
[
"Brain magnetic resonance imaging ( MRI ) showed cerebral atrophy with diffuse periventricular white matter hyperintensities. Spinal MRI was normal. CYP27A1 gene sequencing confirmed the diagnosis of CTX.",
"Spinal MRI revealed new linear hyperintensities of the corticospinal and gracile tracts.",
"Brain MRI showed subtle symmetric, bilateral hyperintense T2 ground - glass appearance of the deep white matter, possible symmetric T2 hyperintensity of the cerebellar dentate nuclei and two small ischemic infarct sequelae of the right cerebellar hemisphere ( Fig. 2 ). Spinal MRI was normal.",
"Cholestanol was increased to 64 μmol / L ( 3.3–12.5 μmol / L )",
"Genetic analysis found two monoallelic mutations in the gene CYP27A1 : a missense mutation ( c.1183C > T; p. Arg395Cys ) in exon 6 and a splicing mutation ( c.1184 + 1 G > A ) in intron 6",
"Brain and spinal cord MRI performed in 2008 ( a, b, e ) and 2019 ( c, d, f, g ). Axial plane T2 weighted images ( a - d ) at the level of the dentate nuclei and periventricular white matter showing stable minimal increased signal in the dentate nuclei ( arrowheads ) and questionable slightly abnormal periventricular white matter T2 hyperintensity ( “ ground - glass appearance †). The rest of brain MRI was unremarkable except for two small old infarcts in the right cerebellar hemisphere ( one lesion shown in a and b * ). Spinal cord MRI from 2008 ( e ) was unremarkable, though no axial plane images were performed. Spinal cord MRI in 2019 revealed subtle longitudinal high signal ( white arrow - heads ) of the posterior columns at the cervico - dorsal junction and middle dorsal region on sagittal T2 - weighted images ( f ). Axial T2 - weighted images confirmed bilateral, symmetric signal abnormalities corresponding to the gracilis tracts ( g, black arrowhead ) and the lateral cortico - spinal tracts ( g, white arrows ) at different cervical and dorsal levels, without spinal cord atrophy or contrast material ( gadolinium ) uptake.",
"Brain MRI was unchanged. Spinal MRI revealed extensive linear T2 weighted hyperintensities appearing bilaterally in lateral corticospinal and gracile tracts",
"normal cholestanol levels ( 6.18 μmol / L; normal range 3.3–12.5 μmol / L"
] |
test-2004
|
7890005
|
{'Case presentation': 'We report a 38-year old woman who presented with chronic diarrhea and progressive spastic paraparesis in her twenties. Brain magnetic resonance imaging (MRI) showed cerebral atrophy with diffuse periventricular white matter hyperintensities. Spinal MRI was normal. CYP27A1 gene sequencing confirmed the diagnosis of CTX. Chenodeoxycholic acid (CDCA) treatment was introduced with remission of diarrhea. Unfortunately, the treatment had to be discontinued several times and the patient developed psychosis and an severe ataxospastic gait. Spinal MRI revealed new linear hyperintensities of the corticospinal and gracile tracts. Thirty-three spinal CTX patients were identified by searching in Pubmed, EMBASE™ and Web of Science databases. All patients presented pyramidal signs and 48% had dorsal column signs. Juvenile cataracts were described in 78% of patients, chronic diarrhea in 65%, and tendon xanthomas in 31%. Disease improvement or stabilization with chenodeoxycholic acid was observed in 69% of patients. A higher prevalence of the Arg395Cys allele was observed in patients with spinal CTX as compared to CTX in general (ᵡ 2 ; p < 0.00001). A 38-year-old woman presented with progressive muscle stiffness, calf cramps and urinary frequency appeared in her twenties ( Fig. 1 ). Her past medical history included chronic diarrhea, scoliosis and bilateral cataract surgery at age 25. She did not take any treatment and had normal schooling. Family history was not relevant. Neurological examination revealed spastic paraparesis with pyramidal signs more prominent on the left lower extremity and flat feet. A neurocognitive study demonstrated severe anterograde verbal memory difficulties and minor executive dysfunction. Electroneuromyography (ENMG) was normal. Brain MRI showed subtle symmetric, bilateral hyperintense T2 ground-glass appearance of the deep white matter, possible symmetric T2 hyperintensity of the cerebellar dentate nuclei and two small ischemic infarct sequelae of the right cerebellar hemisphere ( Fig. 2 ). Spinal MRI was normal. 7 years later, due to progression of spastic paraparesis, CTX was considered. Cholestanol was increased to 64 μmol/L (3.3–12.5 μmol/L). A careful assessment did not found any tendinous xanthomas. Genetic analysis found two monoallelic mutations in the gene CYP27A1 : a missense mutation (c.1183C > T; p. Arg395Cys) in exon 6 and a splicing mutation (c.1184 + 1G > A) in intron 6 and confirmed CTX diagnosis. A treatment with 750 mg/d chenodeoxycholic acid (CDCA) and 20 mg/d simvastatine was introduced ( Fig. 1 ). Three months later, diarrhea was disappeared and no adverse effect was observed. One-year follow-up showed stabilization of neurologic and radiologic signs. Fig. 1 Patient timeline of clinical symptoms and biochemical values. Abbreviations: SP: spastic paraparesia; m: month; CDCA: chenodeoxycholic acid. Normal values for cholestanol (N: 0–15.45 μmol/L); bile acid (N: 0–10.02 μmol/L) Fig. 1 Fig. 2 Brain and spinal cord magnetic resonance imaging (MRI) of the patient. Brain and spinal cord MRI performed in 2008 (a,b,e) and 2019 (c,d,f,g). Axial plane T2 weighted images (a-d) at the level of the dentate nuclei and periventricular white matter showing stable minimal increased signal in the dentate nuclei (arrowheads) and questionable slightly abnormal periventricular white matter T2 hyperintensity (“ground-glass appearance”). The rest of brain MRI was unremarkable except for two small old infarcts in the right cerebellar hemisphere (one lesion shown in a and b*). Spinal cord MRI from 2008 (e) was unremarkable, though no axial plane images were performed. Spinal cord MRI in 2019 revealed subtle longitudinal high signal (white arrow-heads) of the posterior columns at the cervico-dorsal junction and middle dorsal region on sagittal T2-weighted images (f). Axial T2-weighted images confirmed bilateral, symmetric signal abnormalities corresponding to the gracilis tracts (g, black arrowhead) and the lateral cortico-spinal tracts (g, white arrows) at different cervical and dorsal levels, without spinal cord atrophy or contrast material (gadolinium) uptake. Fig. 2 CDCA treatment was stopped for 16 months due to product withdrawal. Over this period, diarrhea recurred and walking worsened. She had increased stiffness with muscle pain, new apallesthesia of the lower limbs and onset of cerebellar ataxia. When CDCA treatment was reintroduced (500 mg/d) walking, pain and diarrhea improved. Due to renewed product shortage and patient non-compliance, CDCA treatment was repeatedly discontinued, following which the patient developed an acute psychosis and, short after, a rapid worsening of her gait becaming rollator dependent. Neurologic evaluation showed a severe ataxospastic gait with knee recurvatum (additional files: video). ENMG was normal. Brain MRI was unchanged. Spinal MRI revealed extensive linear T2 weighted hyperintensities appearing bilaterally in lateral corticospinal and gracile tracts ( Fig. 2 ). Despite normal cholestanol levels (6.18 μmol/L; normal range 3.3–12.5 μmol/L), CDCA posology was increased to 750 mg/d. Six months later, the patient had resolution of diarrhea and psychiatric symptoms but no improvement of gait.'}
|
{'Case presentation': 'We report a 38-year old woman who presented with chronic diarrhea and progressive spastic paraparesis in her twenties. Brain magnetic resonance imaging (MRI) showed cerebral atrophy with diffuse periventricular white matter hyperintensities. Spinal MRI was normal. CYP27A1 gene sequencing confirmed the diagnosis of CTX. Chenodeoxycholic acid (CDCA) treatment was introduced with remission of diarrhea. Unfortunately, the treatment had to be discontinued several times and the patient developed psychosis and an severe ataxospastic gait. Spinal MRI revealed new linear hyperintensities of the corticospinal and gracile tracts. Thirty-three spinal CTX patients were identified by searching in Pubmed, EMBASE™ and Web of Science databases. All patients presented pyramidal signs and 48% had dorsal column signs. Juvenile cataracts were described in 78% of patients, chronic diarrhea in 65%, and tendon xanthomas in 31%. Disease improvement or stabilization with chenodeoxycholic acid was observed in 69% of patients. A higher prevalence of the Arg395Cys allele was observed in patients with spinal CTX as compared to CTX in general (ᵡ 2 ; p < 0.00001). A 38-year-old woman presented with progressive muscle stiffness, calf cramps and urinary frequency appeared in her twenties ( Fig. 1 ). Her past medical history included chronic diarrhea, scoliosis and bilateral cataract surgery at age 25. She did not take any treatment and had normal schooling. Family history was not relevant. Neurological examination revealed spastic paraparesis with pyramidal signs more prominent on the left lower extremity and flat feet. A neurocognitive study demonstrated severe anterograde verbal memory difficulties and minor executive dysfunction. Electroneuromyography (ENMG) was normal. Brain MRI showed subtle symmetric, bilateral hyperintense T2 ground-glass appearance of the deep white matter, possible symmetric T2 hyperintensity of the cerebellar dentate nuclei and two small ischemic infarct sequelae of the right cerebellar hemisphere ( Fig. 2 ). Spinal MRI was normal. 7 years later, due to progression of spastic paraparesis, CTX was considered. Cholestanol was increased to 64 μmol/L (3.3–12.5 μmol/L). A careful assessment did not found any tendinous xanthomas. Genetic analysis found two monoallelic mutations in the gene CYP27A1 : a missense mutation (c.1183C > T; p. Arg395Cys) in exon 6 and a splicing mutation (c.1184 + 1G > A) in intron 6 and confirmed CTX diagnosis. A treatment with 750 mg/d chenodeoxycholic acid (CDCA) and 20 mg/d simvastatine was introduced ( Fig. 1 ). Three months later, diarrhea was disappeared and no adverse effect was observed. One-year follow-up showed stabilization of neurologic and radiologic signs. Fig. 1 Patient timeline of clinical symptoms and biochemical values. Abbreviations: SP: spastic paraparesia; m: month; CDCA: chenodeoxycholic acid. Normal values for cholestanol (N: 0–15.45 μmol/L); bile acid (N: 0–10.02 μmol/L) Fig. 1 Fig. 2 Brain and spinal cord magnetic resonance imaging (MRI) of the patient. Brain and spinal cord MRI performed in 2008 (a,b,e) and 2019 (c,d,f,g). Axial plane T2 weighted images (a-d) at the level of the dentate nuclei and periventricular white matter showing stable minimal increased signal in the dentate nuclei (arrowheads) and questionable slightly abnormal periventricular white matter T2 hyperintensity (“ground-glass appearance”). The rest of brain MRI was unremarkable except for two small old infarcts in the right cerebellar hemisphere (one lesion shown in a and b*). Spinal cord MRI from 2008 (e) was unremarkable, though no axial plane images were performed. Spinal cord MRI in 2019 revealed subtle longitudinal high signal (white arrow-heads) of the posterior columns at the cervico-dorsal junction and middle dorsal region on sagittal T2-weighted images (f). Axial T2-weighted images confirmed bilateral, symmetric signal abnormalities corresponding to the gracilis tracts (g, black arrowhead) and the lateral cortico-spinal tracts (g, white arrows) at different cervical and dorsal levels, without spinal cord atrophy or contrast material (gadolinium) uptake. Fig. 2 CDCA treatment was stopped for 16 months due to product withdrawal. Over this period, diarrhea recurred and walking worsened. She had increased stiffness with muscle pain, new apallesthesia of the lower limbs and onset of cerebellar ataxia. When CDCA treatment was reintroduced (500 mg/d) walking, pain and diarrhea improved. Due to renewed product shortage and patient non-compliance, CDCA treatment was repeatedly discontinued, following which the patient developed an acute psychosis and, short after, a rapid worsening of her gait becaming rollator dependent. Neurologic evaluation showed a severe ataxospastic gait with knee recurvatum (additional files: video). ENMG was normal. Brain MRI was unchanged. Spinal MRI revealed extensive linear T2 weighted hyperintensities appearing bilaterally in lateral corticospinal and gracile tracts ( Fig. 2 ). Despite normal cholestanol levels (6.18 μmol/L; normal range 3.3–12.5 μmol/L), CDCA posology was increased to 750 mg/d. Six months later, the patient had resolution of diarrhea and psychiatric symptoms but no improvement of gait.'}
|
Cardiovascular-System
|
CVS
|
[] |
test-2005
|
7890005
|
{'Case presentation': 'We report a 38-year old woman who presented with chronic diarrhea and progressive spastic paraparesis in her twenties. Brain magnetic resonance imaging (MRI) showed cerebral atrophy with diffuse periventricular white matter hyperintensities. Spinal MRI was normal. CYP27A1 gene sequencing confirmed the diagnosis of CTX. Chenodeoxycholic acid (CDCA) treatment was introduced with remission of diarrhea. Unfortunately, the treatment had to be discontinued several times and the patient developed psychosis and an severe ataxospastic gait. Spinal MRI revealed new linear hyperintensities of the corticospinal and gracile tracts. Thirty-three spinal CTX patients were identified by searching in Pubmed, EMBASE™ and Web of Science databases. All patients presented pyramidal signs and 48% had dorsal column signs. Juvenile cataracts were described in 78% of patients, chronic diarrhea in 65%, and tendon xanthomas in 31%. Disease improvement or stabilization with chenodeoxycholic acid was observed in 69% of patients. A higher prevalence of the Arg395Cys allele was observed in patients with spinal CTX as compared to CTX in general (ᵡ 2 ; p < 0.00001). A 38-year-old woman presented with progressive muscle stiffness, calf cramps and urinary frequency appeared in her twenties ( Fig. 1 ). Her past medical history included chronic diarrhea, scoliosis and bilateral cataract surgery at age 25. She did not take any treatment and had normal schooling. Family history was not relevant. Neurological examination revealed spastic paraparesis with pyramidal signs more prominent on the left lower extremity and flat feet. A neurocognitive study demonstrated severe anterograde verbal memory difficulties and minor executive dysfunction. Electroneuromyography (ENMG) was normal. Brain MRI showed subtle symmetric, bilateral hyperintense T2 ground-glass appearance of the deep white matter, possible symmetric T2 hyperintensity of the cerebellar dentate nuclei and two small ischemic infarct sequelae of the right cerebellar hemisphere ( Fig. 2 ). Spinal MRI was normal. 7 years later, due to progression of spastic paraparesis, CTX was considered. Cholestanol was increased to 64 μmol/L (3.3–12.5 μmol/L). A careful assessment did not found any tendinous xanthomas. Genetic analysis found two monoallelic mutations in the gene CYP27A1 : a missense mutation (c.1183C > T; p. Arg395Cys) in exon 6 and a splicing mutation (c.1184 + 1G > A) in intron 6 and confirmed CTX diagnosis. A treatment with 750 mg/d chenodeoxycholic acid (CDCA) and 20 mg/d simvastatine was introduced ( Fig. 1 ). Three months later, diarrhea was disappeared and no adverse effect was observed. One-year follow-up showed stabilization of neurologic and radiologic signs. Fig. 1 Patient timeline of clinical symptoms and biochemical values. Abbreviations: SP: spastic paraparesia; m: month; CDCA: chenodeoxycholic acid. Normal values for cholestanol (N: 0–15.45 μmol/L); bile acid (N: 0–10.02 μmol/L) Fig. 1 Fig. 2 Brain and spinal cord magnetic resonance imaging (MRI) of the patient. Brain and spinal cord MRI performed in 2008 (a,b,e) and 2019 (c,d,f,g). Axial plane T2 weighted images (a-d) at the level of the dentate nuclei and periventricular white matter showing stable minimal increased signal in the dentate nuclei (arrowheads) and questionable slightly abnormal periventricular white matter T2 hyperintensity (“ground-glass appearance”). The rest of brain MRI was unremarkable except for two small old infarcts in the right cerebellar hemisphere (one lesion shown in a and b*). Spinal cord MRI from 2008 (e) was unremarkable, though no axial plane images were performed. Spinal cord MRI in 2019 revealed subtle longitudinal high signal (white arrow-heads) of the posterior columns at the cervico-dorsal junction and middle dorsal region on sagittal T2-weighted images (f). Axial T2-weighted images confirmed bilateral, symmetric signal abnormalities corresponding to the gracilis tracts (g, black arrowhead) and the lateral cortico-spinal tracts (g, white arrows) at different cervical and dorsal levels, without spinal cord atrophy or contrast material (gadolinium) uptake. Fig. 2 CDCA treatment was stopped for 16 months due to product withdrawal. Over this period, diarrhea recurred and walking worsened. She had increased stiffness with muscle pain, new apallesthesia of the lower limbs and onset of cerebellar ataxia. When CDCA treatment was reintroduced (500 mg/d) walking, pain and diarrhea improved. Due to renewed product shortage and patient non-compliance, CDCA treatment was repeatedly discontinued, following which the patient developed an acute psychosis and, short after, a rapid worsening of her gait becaming rollator dependent. Neurologic evaluation showed a severe ataxospastic gait with knee recurvatum (additional files: video). ENMG was normal. Brain MRI was unchanged. Spinal MRI revealed extensive linear T2 weighted hyperintensities appearing bilaterally in lateral corticospinal and gracile tracts ( Fig. 2 ). Despite normal cholestanol levels (6.18 μmol/L; normal range 3.3–12.5 μmol/L), CDCA posology was increased to 750 mg/d. Six months later, the patient had resolution of diarrhea and psychiatric symptoms but no improvement of gait.'}
|
{'Case presentation': 'We report a 38-year old woman who presented with chronic diarrhea and progressive spastic paraparesis in her twenties. Brain magnetic resonance imaging (MRI) showed cerebral atrophy with diffuse periventricular white matter hyperintensities. Spinal MRI was normal. CYP27A1 gene sequencing confirmed the diagnosis of CTX. Chenodeoxycholic acid (CDCA) treatment was introduced with remission of diarrhea. Unfortunately, the treatment had to be discontinued several times and the patient developed psychosis and an severe ataxospastic gait. Spinal MRI revealed new linear hyperintensities of the corticospinal and gracile tracts. Thirty-three spinal CTX patients were identified by searching in Pubmed, EMBASE™ and Web of Science databases. All patients presented pyramidal signs and 48% had dorsal column signs. Juvenile cataracts were described in 78% of patients, chronic diarrhea in 65%, and tendon xanthomas in 31%. Disease improvement or stabilization with chenodeoxycholic acid was observed in 69% of patients. A higher prevalence of the Arg395Cys allele was observed in patients with spinal CTX as compared to CTX in general (ᵡ 2 ; p < 0.00001). A 38-year-old woman presented with progressive muscle stiffness, calf cramps and urinary frequency appeared in her twenties ( Fig. 1 ). Her past medical history included chronic diarrhea, scoliosis and bilateral cataract surgery at age 25. She did not take any treatment and had normal schooling. Family history was not relevant. Neurological examination revealed spastic paraparesis with pyramidal signs more prominent on the left lower extremity and flat feet. A neurocognitive study demonstrated severe anterograde verbal memory difficulties and minor executive dysfunction. Electroneuromyography (ENMG) was normal. Brain MRI showed subtle symmetric, bilateral hyperintense T2 ground-glass appearance of the deep white matter, possible symmetric T2 hyperintensity of the cerebellar dentate nuclei and two small ischemic infarct sequelae of the right cerebellar hemisphere ( Fig. 2 ). Spinal MRI was normal. 7 years later, due to progression of spastic paraparesis, CTX was considered. Cholestanol was increased to 64 μmol/L (3.3–12.5 μmol/L). A careful assessment did not found any tendinous xanthomas. Genetic analysis found two monoallelic mutations in the gene CYP27A1 : a missense mutation (c.1183C > T; p. Arg395Cys) in exon 6 and a splicing mutation (c.1184 + 1G > A) in intron 6 and confirmed CTX diagnosis. A treatment with 750 mg/d chenodeoxycholic acid (CDCA) and 20 mg/d simvastatine was introduced ( Fig. 1 ). Three months later, diarrhea was disappeared and no adverse effect was observed. One-year follow-up showed stabilization of neurologic and radiologic signs. Fig. 1 Patient timeline of clinical symptoms and biochemical values. Abbreviations: SP: spastic paraparesia; m: month; CDCA: chenodeoxycholic acid. Normal values for cholestanol (N: 0–15.45 μmol/L); bile acid (N: 0–10.02 μmol/L) Fig. 1 Fig. 2 Brain and spinal cord magnetic resonance imaging (MRI) of the patient. Brain and spinal cord MRI performed in 2008 (a,b,e) and 2019 (c,d,f,g). Axial plane T2 weighted images (a-d) at the level of the dentate nuclei and periventricular white matter showing stable minimal increased signal in the dentate nuclei (arrowheads) and questionable slightly abnormal periventricular white matter T2 hyperintensity (“ground-glass appearance”). The rest of brain MRI was unremarkable except for two small old infarcts in the right cerebellar hemisphere (one lesion shown in a and b*). Spinal cord MRI from 2008 (e) was unremarkable, though no axial plane images were performed. Spinal cord MRI in 2019 revealed subtle longitudinal high signal (white arrow-heads) of the posterior columns at the cervico-dorsal junction and middle dorsal region on sagittal T2-weighted images (f). Axial T2-weighted images confirmed bilateral, symmetric signal abnormalities corresponding to the gracilis tracts (g, black arrowhead) and the lateral cortico-spinal tracts (g, white arrows) at different cervical and dorsal levels, without spinal cord atrophy or contrast material (gadolinium) uptake. Fig. 2 CDCA treatment was stopped for 16 months due to product withdrawal. Over this period, diarrhea recurred and walking worsened. She had increased stiffness with muscle pain, new apallesthesia of the lower limbs and onset of cerebellar ataxia. When CDCA treatment was reintroduced (500 mg/d) walking, pain and diarrhea improved. Due to renewed product shortage and patient non-compliance, CDCA treatment was repeatedly discontinued, following which the patient developed an acute psychosis and, short after, a rapid worsening of her gait becaming rollator dependent. Neurologic evaluation showed a severe ataxospastic gait with knee recurvatum (additional files: video). ENMG was normal. Brain MRI was unchanged. Spinal MRI revealed extensive linear T2 weighted hyperintensities appearing bilaterally in lateral corticospinal and gracile tracts ( Fig. 2 ). Despite normal cholestanol levels (6.18 μmol/L; normal range 3.3–12.5 μmol/L), CDCA posology was increased to 750 mg/d. Six months later, the patient had resolution of diarrhea and psychiatric symptoms but no improvement of gait.'}
|
Endocrinology
|
ENDO
|
[] |
test-2006
|
7890005
|
{'Case presentation': 'We report a 38-year old woman who presented with chronic diarrhea and progressive spastic paraparesis in her twenties. Brain magnetic resonance imaging (MRI) showed cerebral atrophy with diffuse periventricular white matter hyperintensities. Spinal MRI was normal. CYP27A1 gene sequencing confirmed the diagnosis of CTX. Chenodeoxycholic acid (CDCA) treatment was introduced with remission of diarrhea. Unfortunately, the treatment had to be discontinued several times and the patient developed psychosis and an severe ataxospastic gait. Spinal MRI revealed new linear hyperintensities of the corticospinal and gracile tracts. Thirty-three spinal CTX patients were identified by searching in Pubmed, EMBASE™ and Web of Science databases. All patients presented pyramidal signs and 48% had dorsal column signs. Juvenile cataracts were described in 78% of patients, chronic diarrhea in 65%, and tendon xanthomas in 31%. Disease improvement or stabilization with chenodeoxycholic acid was observed in 69% of patients. A higher prevalence of the Arg395Cys allele was observed in patients with spinal CTX as compared to CTX in general (ᵡ 2 ; p < 0.00001). A 38-year-old woman presented with progressive muscle stiffness, calf cramps and urinary frequency appeared in her twenties ( Fig. 1 ). Her past medical history included chronic diarrhea, scoliosis and bilateral cataract surgery at age 25. She did not take any treatment and had normal schooling. Family history was not relevant. Neurological examination revealed spastic paraparesis with pyramidal signs more prominent on the left lower extremity and flat feet. A neurocognitive study demonstrated severe anterograde verbal memory difficulties and minor executive dysfunction. Electroneuromyography (ENMG) was normal. Brain MRI showed subtle symmetric, bilateral hyperintense T2 ground-glass appearance of the deep white matter, possible symmetric T2 hyperintensity of the cerebellar dentate nuclei and two small ischemic infarct sequelae of the right cerebellar hemisphere ( Fig. 2 ). Spinal MRI was normal. 7 years later, due to progression of spastic paraparesis, CTX was considered. Cholestanol was increased to 64 μmol/L (3.3–12.5 μmol/L). A careful assessment did not found any tendinous xanthomas. Genetic analysis found two monoallelic mutations in the gene CYP27A1 : a missense mutation (c.1183C > T; p. Arg395Cys) in exon 6 and a splicing mutation (c.1184 + 1G > A) in intron 6 and confirmed CTX diagnosis. A treatment with 750 mg/d chenodeoxycholic acid (CDCA) and 20 mg/d simvastatine was introduced ( Fig. 1 ). Three months later, diarrhea was disappeared and no adverse effect was observed. One-year follow-up showed stabilization of neurologic and radiologic signs. Fig. 1 Patient timeline of clinical symptoms and biochemical values. Abbreviations: SP: spastic paraparesia; m: month; CDCA: chenodeoxycholic acid. Normal values for cholestanol (N: 0–15.45 μmol/L); bile acid (N: 0–10.02 μmol/L) Fig. 1 Fig. 2 Brain and spinal cord magnetic resonance imaging (MRI) of the patient. Brain and spinal cord MRI performed in 2008 (a,b,e) and 2019 (c,d,f,g). Axial plane T2 weighted images (a-d) at the level of the dentate nuclei and periventricular white matter showing stable minimal increased signal in the dentate nuclei (arrowheads) and questionable slightly abnormal periventricular white matter T2 hyperintensity (“ground-glass appearance”). The rest of brain MRI was unremarkable except for two small old infarcts in the right cerebellar hemisphere (one lesion shown in a and b*). Spinal cord MRI from 2008 (e) was unremarkable, though no axial plane images were performed. Spinal cord MRI in 2019 revealed subtle longitudinal high signal (white arrow-heads) of the posterior columns at the cervico-dorsal junction and middle dorsal region on sagittal T2-weighted images (f). Axial T2-weighted images confirmed bilateral, symmetric signal abnormalities corresponding to the gracilis tracts (g, black arrowhead) and the lateral cortico-spinal tracts (g, white arrows) at different cervical and dorsal levels, without spinal cord atrophy or contrast material (gadolinium) uptake. Fig. 2 CDCA treatment was stopped for 16 months due to product withdrawal. Over this period, diarrhea recurred and walking worsened. She had increased stiffness with muscle pain, new apallesthesia of the lower limbs and onset of cerebellar ataxia. When CDCA treatment was reintroduced (500 mg/d) walking, pain and diarrhea improved. Due to renewed product shortage and patient non-compliance, CDCA treatment was repeatedly discontinued, following which the patient developed an acute psychosis and, short after, a rapid worsening of her gait becaming rollator dependent. Neurologic evaluation showed a severe ataxospastic gait with knee recurvatum (additional files: video). ENMG was normal. Brain MRI was unchanged. Spinal MRI revealed extensive linear T2 weighted hyperintensities appearing bilaterally in lateral corticospinal and gracile tracts ( Fig. 2 ). Despite normal cholestanol levels (6.18 μmol/L; normal range 3.3–12.5 μmol/L), CDCA posology was increased to 750 mg/d. Six months later, the patient had resolution of diarrhea and psychiatric symptoms but no improvement of gait.'}
|
{'Case presentation': 'We report a 38-year old woman who presented with chronic diarrhea and progressive spastic paraparesis in her twenties. Brain magnetic resonance imaging (MRI) showed cerebral atrophy with diffuse periventricular white matter hyperintensities. Spinal MRI was normal. CYP27A1 gene sequencing confirmed the diagnosis of CTX. Chenodeoxycholic acid (CDCA) treatment was introduced with remission of diarrhea. Unfortunately, the treatment had to be discontinued several times and the patient developed psychosis and an severe ataxospastic gait. Spinal MRI revealed new linear hyperintensities of the corticospinal and gracile tracts. Thirty-three spinal CTX patients were identified by searching in Pubmed, EMBASE™ and Web of Science databases. All patients presented pyramidal signs and 48% had dorsal column signs. Juvenile cataracts were described in 78% of patients, chronic diarrhea in 65%, and tendon xanthomas in 31%. Disease improvement or stabilization with chenodeoxycholic acid was observed in 69% of patients. A higher prevalence of the Arg395Cys allele was observed in patients with spinal CTX as compared to CTX in general (ᵡ 2 ; p < 0.00001). A 38-year-old woman presented with progressive muscle stiffness, calf cramps and urinary frequency appeared in her twenties ( Fig. 1 ). Her past medical history included chronic diarrhea, scoliosis and bilateral cataract surgery at age 25. She did not take any treatment and had normal schooling. Family history was not relevant. Neurological examination revealed spastic paraparesis with pyramidal signs more prominent on the left lower extremity and flat feet. A neurocognitive study demonstrated severe anterograde verbal memory difficulties and minor executive dysfunction. Electroneuromyography (ENMG) was normal. Brain MRI showed subtle symmetric, bilateral hyperintense T2 ground-glass appearance of the deep white matter, possible symmetric T2 hyperintensity of the cerebellar dentate nuclei and two small ischemic infarct sequelae of the right cerebellar hemisphere ( Fig. 2 ). Spinal MRI was normal. 7 years later, due to progression of spastic paraparesis, CTX was considered. Cholestanol was increased to 64 μmol/L (3.3–12.5 μmol/L). A careful assessment did not found any tendinous xanthomas. Genetic analysis found two monoallelic mutations in the gene CYP27A1 : a missense mutation (c.1183C > T; p. Arg395Cys) in exon 6 and a splicing mutation (c.1184 + 1G > A) in intron 6 and confirmed CTX diagnosis. A treatment with 750 mg/d chenodeoxycholic acid (CDCA) and 20 mg/d simvastatine was introduced ( Fig. 1 ). Three months later, diarrhea was disappeared and no adverse effect was observed. One-year follow-up showed stabilization of neurologic and radiologic signs. Fig. 1 Patient timeline of clinical symptoms and biochemical values. Abbreviations: SP: spastic paraparesia; m: month; CDCA: chenodeoxycholic acid. Normal values for cholestanol (N: 0–15.45 μmol/L); bile acid (N: 0–10.02 μmol/L) Fig. 1 Fig. 2 Brain and spinal cord magnetic resonance imaging (MRI) of the patient. Brain and spinal cord MRI performed in 2008 (a,b,e) and 2019 (c,d,f,g). Axial plane T2 weighted images (a-d) at the level of the dentate nuclei and periventricular white matter showing stable minimal increased signal in the dentate nuclei (arrowheads) and questionable slightly abnormal periventricular white matter T2 hyperintensity (“ground-glass appearance”). The rest of brain MRI was unremarkable except for two small old infarcts in the right cerebellar hemisphere (one lesion shown in a and b*). Spinal cord MRI from 2008 (e) was unremarkable, though no axial plane images were performed. Spinal cord MRI in 2019 revealed subtle longitudinal high signal (white arrow-heads) of the posterior columns at the cervico-dorsal junction and middle dorsal region on sagittal T2-weighted images (f). Axial T2-weighted images confirmed bilateral, symmetric signal abnormalities corresponding to the gracilis tracts (g, black arrowhead) and the lateral cortico-spinal tracts (g, white arrows) at different cervical and dorsal levels, without spinal cord atrophy or contrast material (gadolinium) uptake. Fig. 2 CDCA treatment was stopped for 16 months due to product withdrawal. Over this period, diarrhea recurred and walking worsened. She had increased stiffness with muscle pain, new apallesthesia of the lower limbs and onset of cerebellar ataxia. When CDCA treatment was reintroduced (500 mg/d) walking, pain and diarrhea improved. Due to renewed product shortage and patient non-compliance, CDCA treatment was repeatedly discontinued, following which the patient developed an acute psychosis and, short after, a rapid worsening of her gait becaming rollator dependent. Neurologic evaluation showed a severe ataxospastic gait with knee recurvatum (additional files: video). ENMG was normal. Brain MRI was unchanged. Spinal MRI revealed extensive linear T2 weighted hyperintensities appearing bilaterally in lateral corticospinal and gracile tracts ( Fig. 2 ). Despite normal cholestanol levels (6.18 μmol/L; normal range 3.3–12.5 μmol/L), CDCA posology was increased to 750 mg/d. Six months later, the patient had resolution of diarrhea and psychiatric symptoms but no improvement of gait.'}
|
Genitourinary-System
|
GU
|
[
"urinary frequency"
] |
test-2007
|
7890005
|
{'Case presentation': 'We report a 38-year old woman who presented with chronic diarrhea and progressive spastic paraparesis in her twenties. Brain magnetic resonance imaging (MRI) showed cerebral atrophy with diffuse periventricular white matter hyperintensities. Spinal MRI was normal. CYP27A1 gene sequencing confirmed the diagnosis of CTX. Chenodeoxycholic acid (CDCA) treatment was introduced with remission of diarrhea. Unfortunately, the treatment had to be discontinued several times and the patient developed psychosis and an severe ataxospastic gait. Spinal MRI revealed new linear hyperintensities of the corticospinal and gracile tracts. Thirty-three spinal CTX patients were identified by searching in Pubmed, EMBASE™ and Web of Science databases. All patients presented pyramidal signs and 48% had dorsal column signs. Juvenile cataracts were described in 78% of patients, chronic diarrhea in 65%, and tendon xanthomas in 31%. Disease improvement or stabilization with chenodeoxycholic acid was observed in 69% of patients. A higher prevalence of the Arg395Cys allele was observed in patients with spinal CTX as compared to CTX in general (ᵡ 2 ; p < 0.00001). A 38-year-old woman presented with progressive muscle stiffness, calf cramps and urinary frequency appeared in her twenties ( Fig. 1 ). Her past medical history included chronic diarrhea, scoliosis and bilateral cataract surgery at age 25. She did not take any treatment and had normal schooling. Family history was not relevant. Neurological examination revealed spastic paraparesis with pyramidal signs more prominent on the left lower extremity and flat feet. A neurocognitive study demonstrated severe anterograde verbal memory difficulties and minor executive dysfunction. Electroneuromyography (ENMG) was normal. Brain MRI showed subtle symmetric, bilateral hyperintense T2 ground-glass appearance of the deep white matter, possible symmetric T2 hyperintensity of the cerebellar dentate nuclei and two small ischemic infarct sequelae of the right cerebellar hemisphere ( Fig. 2 ). Spinal MRI was normal. 7 years later, due to progression of spastic paraparesis, CTX was considered. Cholestanol was increased to 64 μmol/L (3.3–12.5 μmol/L). A careful assessment did not found any tendinous xanthomas. Genetic analysis found two monoallelic mutations in the gene CYP27A1 : a missense mutation (c.1183C > T; p. Arg395Cys) in exon 6 and a splicing mutation (c.1184 + 1G > A) in intron 6 and confirmed CTX diagnosis. A treatment with 750 mg/d chenodeoxycholic acid (CDCA) and 20 mg/d simvastatine was introduced ( Fig. 1 ). Three months later, diarrhea was disappeared and no adverse effect was observed. One-year follow-up showed stabilization of neurologic and radiologic signs. Fig. 1 Patient timeline of clinical symptoms and biochemical values. Abbreviations: SP: spastic paraparesia; m: month; CDCA: chenodeoxycholic acid. Normal values for cholestanol (N: 0–15.45 μmol/L); bile acid (N: 0–10.02 μmol/L) Fig. 1 Fig. 2 Brain and spinal cord magnetic resonance imaging (MRI) of the patient. Brain and spinal cord MRI performed in 2008 (a,b,e) and 2019 (c,d,f,g). Axial plane T2 weighted images (a-d) at the level of the dentate nuclei and periventricular white matter showing stable minimal increased signal in the dentate nuclei (arrowheads) and questionable slightly abnormal periventricular white matter T2 hyperintensity (“ground-glass appearance”). The rest of brain MRI was unremarkable except for two small old infarcts in the right cerebellar hemisphere (one lesion shown in a and b*). Spinal cord MRI from 2008 (e) was unremarkable, though no axial plane images were performed. Spinal cord MRI in 2019 revealed subtle longitudinal high signal (white arrow-heads) of the posterior columns at the cervico-dorsal junction and middle dorsal region on sagittal T2-weighted images (f). Axial T2-weighted images confirmed bilateral, symmetric signal abnormalities corresponding to the gracilis tracts (g, black arrowhead) and the lateral cortico-spinal tracts (g, white arrows) at different cervical and dorsal levels, without spinal cord atrophy or contrast material (gadolinium) uptake. Fig. 2 CDCA treatment was stopped for 16 months due to product withdrawal. Over this period, diarrhea recurred and walking worsened. She had increased stiffness with muscle pain, new apallesthesia of the lower limbs and onset of cerebellar ataxia. When CDCA treatment was reintroduced (500 mg/d) walking, pain and diarrhea improved. Due to renewed product shortage and patient non-compliance, CDCA treatment was repeatedly discontinued, following which the patient developed an acute psychosis and, short after, a rapid worsening of her gait becaming rollator dependent. Neurologic evaluation showed a severe ataxospastic gait with knee recurvatum (additional files: video). ENMG was normal. Brain MRI was unchanged. Spinal MRI revealed extensive linear T2 weighted hyperintensities appearing bilaterally in lateral corticospinal and gracile tracts ( Fig. 2 ). Despite normal cholestanol levels (6.18 μmol/L; normal range 3.3–12.5 μmol/L), CDCA posology was increased to 750 mg/d. Six months later, the patient had resolution of diarrhea and psychiatric symptoms but no improvement of gait.'}
|
{'Case presentation': 'We report a 38-year old woman who presented with chronic diarrhea and progressive spastic paraparesis in her twenties. Brain magnetic resonance imaging (MRI) showed cerebral atrophy with diffuse periventricular white matter hyperintensities. Spinal MRI was normal. CYP27A1 gene sequencing confirmed the diagnosis of CTX. Chenodeoxycholic acid (CDCA) treatment was introduced with remission of diarrhea. Unfortunately, the treatment had to be discontinued several times and the patient developed psychosis and an severe ataxospastic gait. Spinal MRI revealed new linear hyperintensities of the corticospinal and gracile tracts. Thirty-three spinal CTX patients were identified by searching in Pubmed, EMBASE™ and Web of Science databases. All patients presented pyramidal signs and 48% had dorsal column signs. Juvenile cataracts were described in 78% of patients, chronic diarrhea in 65%, and tendon xanthomas in 31%. Disease improvement or stabilization with chenodeoxycholic acid was observed in 69% of patients. A higher prevalence of the Arg395Cys allele was observed in patients with spinal CTX as compared to CTX in general (ᵡ 2 ; p < 0.00001). A 38-year-old woman presented with progressive muscle stiffness, calf cramps and urinary frequency appeared in her twenties ( Fig. 1 ). Her past medical history included chronic diarrhea, scoliosis and bilateral cataract surgery at age 25. She did not take any treatment and had normal schooling. Family history was not relevant. Neurological examination revealed spastic paraparesis with pyramidal signs more prominent on the left lower extremity and flat feet. A neurocognitive study demonstrated severe anterograde verbal memory difficulties and minor executive dysfunction. Electroneuromyography (ENMG) was normal. Brain MRI showed subtle symmetric, bilateral hyperintense T2 ground-glass appearance of the deep white matter, possible symmetric T2 hyperintensity of the cerebellar dentate nuclei and two small ischemic infarct sequelae of the right cerebellar hemisphere ( Fig. 2 ). Spinal MRI was normal. 7 years later, due to progression of spastic paraparesis, CTX was considered. Cholestanol was increased to 64 μmol/L (3.3–12.5 μmol/L). A careful assessment did not found any tendinous xanthomas. Genetic analysis found two monoallelic mutations in the gene CYP27A1 : a missense mutation (c.1183C > T; p. Arg395Cys) in exon 6 and a splicing mutation (c.1184 + 1G > A) in intron 6 and confirmed CTX diagnosis. A treatment with 750 mg/d chenodeoxycholic acid (CDCA) and 20 mg/d simvastatine was introduced ( Fig. 1 ). Three months later, diarrhea was disappeared and no adverse effect was observed. One-year follow-up showed stabilization of neurologic and radiologic signs. Fig. 1 Patient timeline of clinical symptoms and biochemical values. Abbreviations: SP: spastic paraparesia; m: month; CDCA: chenodeoxycholic acid. Normal values for cholestanol (N: 0–15.45 μmol/L); bile acid (N: 0–10.02 μmol/L) Fig. 1 Fig. 2 Brain and spinal cord magnetic resonance imaging (MRI) of the patient. Brain and spinal cord MRI performed in 2008 (a,b,e) and 2019 (c,d,f,g). Axial plane T2 weighted images (a-d) at the level of the dentate nuclei and periventricular white matter showing stable minimal increased signal in the dentate nuclei (arrowheads) and questionable slightly abnormal periventricular white matter T2 hyperintensity (“ground-glass appearance”). The rest of brain MRI was unremarkable except for two small old infarcts in the right cerebellar hemisphere (one lesion shown in a and b*). Spinal cord MRI from 2008 (e) was unremarkable, though no axial plane images were performed. Spinal cord MRI in 2019 revealed subtle longitudinal high signal (white arrow-heads) of the posterior columns at the cervico-dorsal junction and middle dorsal region on sagittal T2-weighted images (f). Axial T2-weighted images confirmed bilateral, symmetric signal abnormalities corresponding to the gracilis tracts (g, black arrowhead) and the lateral cortico-spinal tracts (g, white arrows) at different cervical and dorsal levels, without spinal cord atrophy or contrast material (gadolinium) uptake. Fig. 2 CDCA treatment was stopped for 16 months due to product withdrawal. Over this period, diarrhea recurred and walking worsened. She had increased stiffness with muscle pain, new apallesthesia of the lower limbs and onset of cerebellar ataxia. When CDCA treatment was reintroduced (500 mg/d) walking, pain and diarrhea improved. Due to renewed product shortage and patient non-compliance, CDCA treatment was repeatedly discontinued, following which the patient developed an acute psychosis and, short after, a rapid worsening of her gait becaming rollator dependent. Neurologic evaluation showed a severe ataxospastic gait with knee recurvatum (additional files: video). ENMG was normal. Brain MRI was unchanged. Spinal MRI revealed extensive linear T2 weighted hyperintensities appearing bilaterally in lateral corticospinal and gracile tracts ( Fig. 2 ). Despite normal cholestanol levels (6.18 μmol/L; normal range 3.3–12.5 μmol/L), CDCA posology was increased to 750 mg/d. Six months later, the patient had resolution of diarrhea and psychiatric symptoms but no improvement of gait.'}
|
Respiratory-System
|
RESP
|
[] |
test-2008
|
7890005
|
{'Case presentation': 'We report a 38-year old woman who presented with chronic diarrhea and progressive spastic paraparesis in her twenties. Brain magnetic resonance imaging (MRI) showed cerebral atrophy with diffuse periventricular white matter hyperintensities. Spinal MRI was normal. CYP27A1 gene sequencing confirmed the diagnosis of CTX. Chenodeoxycholic acid (CDCA) treatment was introduced with remission of diarrhea. Unfortunately, the treatment had to be discontinued several times and the patient developed psychosis and an severe ataxospastic gait. Spinal MRI revealed new linear hyperintensities of the corticospinal and gracile tracts. Thirty-three spinal CTX patients were identified by searching in Pubmed, EMBASE™ and Web of Science databases. All patients presented pyramidal signs and 48% had dorsal column signs. Juvenile cataracts were described in 78% of patients, chronic diarrhea in 65%, and tendon xanthomas in 31%. Disease improvement or stabilization with chenodeoxycholic acid was observed in 69% of patients. A higher prevalence of the Arg395Cys allele was observed in patients with spinal CTX as compared to CTX in general (ᵡ 2 ; p < 0.00001). A 38-year-old woman presented with progressive muscle stiffness, calf cramps and urinary frequency appeared in her twenties ( Fig. 1 ). Her past medical history included chronic diarrhea, scoliosis and bilateral cataract surgery at age 25. She did not take any treatment and had normal schooling. Family history was not relevant. Neurological examination revealed spastic paraparesis with pyramidal signs more prominent on the left lower extremity and flat feet. A neurocognitive study demonstrated severe anterograde verbal memory difficulties and minor executive dysfunction. Electroneuromyography (ENMG) was normal. Brain MRI showed subtle symmetric, bilateral hyperintense T2 ground-glass appearance of the deep white matter, possible symmetric T2 hyperintensity of the cerebellar dentate nuclei and two small ischemic infarct sequelae of the right cerebellar hemisphere ( Fig. 2 ). Spinal MRI was normal. 7 years later, due to progression of spastic paraparesis, CTX was considered. Cholestanol was increased to 64 μmol/L (3.3–12.5 μmol/L). A careful assessment did not found any tendinous xanthomas. Genetic analysis found two monoallelic mutations in the gene CYP27A1 : a missense mutation (c.1183C > T; p. Arg395Cys) in exon 6 and a splicing mutation (c.1184 + 1G > A) in intron 6 and confirmed CTX diagnosis. A treatment with 750 mg/d chenodeoxycholic acid (CDCA) and 20 mg/d simvastatine was introduced ( Fig. 1 ). Three months later, diarrhea was disappeared and no adverse effect was observed. One-year follow-up showed stabilization of neurologic and radiologic signs. Fig. 1 Patient timeline of clinical symptoms and biochemical values. Abbreviations: SP: spastic paraparesia; m: month; CDCA: chenodeoxycholic acid. Normal values for cholestanol (N: 0–15.45 μmol/L); bile acid (N: 0–10.02 μmol/L) Fig. 1 Fig. 2 Brain and spinal cord magnetic resonance imaging (MRI) of the patient. Brain and spinal cord MRI performed in 2008 (a,b,e) and 2019 (c,d,f,g). Axial plane T2 weighted images (a-d) at the level of the dentate nuclei and periventricular white matter showing stable minimal increased signal in the dentate nuclei (arrowheads) and questionable slightly abnormal periventricular white matter T2 hyperintensity (“ground-glass appearance”). The rest of brain MRI was unremarkable except for two small old infarcts in the right cerebellar hemisphere (one lesion shown in a and b*). Spinal cord MRI from 2008 (e) was unremarkable, though no axial plane images were performed. Spinal cord MRI in 2019 revealed subtle longitudinal high signal (white arrow-heads) of the posterior columns at the cervico-dorsal junction and middle dorsal region on sagittal T2-weighted images (f). Axial T2-weighted images confirmed bilateral, symmetric signal abnormalities corresponding to the gracilis tracts (g, black arrowhead) and the lateral cortico-spinal tracts (g, white arrows) at different cervical and dorsal levels, without spinal cord atrophy or contrast material (gadolinium) uptake. Fig. 2 CDCA treatment was stopped for 16 months due to product withdrawal. Over this period, diarrhea recurred and walking worsened. She had increased stiffness with muscle pain, new apallesthesia of the lower limbs and onset of cerebellar ataxia. When CDCA treatment was reintroduced (500 mg/d) walking, pain and diarrhea improved. Due to renewed product shortage and patient non-compliance, CDCA treatment was repeatedly discontinued, following which the patient developed an acute psychosis and, short after, a rapid worsening of her gait becaming rollator dependent. Neurologic evaluation showed a severe ataxospastic gait with knee recurvatum (additional files: video). ENMG was normal. Brain MRI was unchanged. Spinal MRI revealed extensive linear T2 weighted hyperintensities appearing bilaterally in lateral corticospinal and gracile tracts ( Fig. 2 ). Despite normal cholestanol levels (6.18 μmol/L; normal range 3.3–12.5 μmol/L), CDCA posology was increased to 750 mg/d. Six months later, the patient had resolution of diarrhea and psychiatric symptoms but no improvement of gait.'}
|
{'Case presentation': 'We report a 38-year old woman who presented with chronic diarrhea and progressive spastic paraparesis in her twenties. Brain magnetic resonance imaging (MRI) showed cerebral atrophy with diffuse periventricular white matter hyperintensities. Spinal MRI was normal. CYP27A1 gene sequencing confirmed the diagnosis of CTX. Chenodeoxycholic acid (CDCA) treatment was introduced with remission of diarrhea. Unfortunately, the treatment had to be discontinued several times and the patient developed psychosis and an severe ataxospastic gait. Spinal MRI revealed new linear hyperintensities of the corticospinal and gracile tracts. Thirty-three spinal CTX patients were identified by searching in Pubmed, EMBASE™ and Web of Science databases. All patients presented pyramidal signs and 48% had dorsal column signs. Juvenile cataracts were described in 78% of patients, chronic diarrhea in 65%, and tendon xanthomas in 31%. Disease improvement or stabilization with chenodeoxycholic acid was observed in 69% of patients. A higher prevalence of the Arg395Cys allele was observed in patients with spinal CTX as compared to CTX in general (ᵡ 2 ; p < 0.00001). A 38-year-old woman presented with progressive muscle stiffness, calf cramps and urinary frequency appeared in her twenties ( Fig. 1 ). Her past medical history included chronic diarrhea, scoliosis and bilateral cataract surgery at age 25. She did not take any treatment and had normal schooling. Family history was not relevant. Neurological examination revealed spastic paraparesis with pyramidal signs more prominent on the left lower extremity and flat feet. A neurocognitive study demonstrated severe anterograde verbal memory difficulties and minor executive dysfunction. Electroneuromyography (ENMG) was normal. Brain MRI showed subtle symmetric, bilateral hyperintense T2 ground-glass appearance of the deep white matter, possible symmetric T2 hyperintensity of the cerebellar dentate nuclei and two small ischemic infarct sequelae of the right cerebellar hemisphere ( Fig. 2 ). Spinal MRI was normal. 7 years later, due to progression of spastic paraparesis, CTX was considered. Cholestanol was increased to 64 μmol/L (3.3–12.5 μmol/L). A careful assessment did not found any tendinous xanthomas. Genetic analysis found two monoallelic mutations in the gene CYP27A1 : a missense mutation (c.1183C > T; p. Arg395Cys) in exon 6 and a splicing mutation (c.1184 + 1G > A) in intron 6 and confirmed CTX diagnosis. A treatment with 750 mg/d chenodeoxycholic acid (CDCA) and 20 mg/d simvastatine was introduced ( Fig. 1 ). Three months later, diarrhea was disappeared and no adverse effect was observed. One-year follow-up showed stabilization of neurologic and radiologic signs. Fig. 1 Patient timeline of clinical symptoms and biochemical values. Abbreviations: SP: spastic paraparesia; m: month; CDCA: chenodeoxycholic acid. Normal values for cholestanol (N: 0–15.45 μmol/L); bile acid (N: 0–10.02 μmol/L) Fig. 1 Fig. 2 Brain and spinal cord magnetic resonance imaging (MRI) of the patient. Brain and spinal cord MRI performed in 2008 (a,b,e) and 2019 (c,d,f,g). Axial plane T2 weighted images (a-d) at the level of the dentate nuclei and periventricular white matter showing stable minimal increased signal in the dentate nuclei (arrowheads) and questionable slightly abnormal periventricular white matter T2 hyperintensity (“ground-glass appearance”). The rest of brain MRI was unremarkable except for two small old infarcts in the right cerebellar hemisphere (one lesion shown in a and b*). Spinal cord MRI from 2008 (e) was unremarkable, though no axial plane images were performed. Spinal cord MRI in 2019 revealed subtle longitudinal high signal (white arrow-heads) of the posterior columns at the cervico-dorsal junction and middle dorsal region on sagittal T2-weighted images (f). Axial T2-weighted images confirmed bilateral, symmetric signal abnormalities corresponding to the gracilis tracts (g, black arrowhead) and the lateral cortico-spinal tracts (g, white arrows) at different cervical and dorsal levels, without spinal cord atrophy or contrast material (gadolinium) uptake. Fig. 2 CDCA treatment was stopped for 16 months due to product withdrawal. Over this period, diarrhea recurred and walking worsened. She had increased stiffness with muscle pain, new apallesthesia of the lower limbs and onset of cerebellar ataxia. When CDCA treatment was reintroduced (500 mg/d) walking, pain and diarrhea improved. Due to renewed product shortage and patient non-compliance, CDCA treatment was repeatedly discontinued, following which the patient developed an acute psychosis and, short after, a rapid worsening of her gait becaming rollator dependent. Neurologic evaluation showed a severe ataxospastic gait with knee recurvatum (additional files: video). ENMG was normal. Brain MRI was unchanged. Spinal MRI revealed extensive linear T2 weighted hyperintensities appearing bilaterally in lateral corticospinal and gracile tracts ( Fig. 2 ). Despite normal cholestanol levels (6.18 μmol/L; normal range 3.3–12.5 μmol/L), CDCA posology was increased to 750 mg/d. Six months later, the patient had resolution of diarrhea and psychiatric symptoms but no improvement of gait.'}
|
Musculoskeletal-System
|
MSK
|
[
"progressive muscle stiffness, calf cramps",
"scoliosis",
"did not found any tendinous xanthomas"
] |
test-2009
|
7890005
|
{'Case presentation': 'We report a 38-year old woman who presented with chronic diarrhea and progressive spastic paraparesis in her twenties. Brain magnetic resonance imaging (MRI) showed cerebral atrophy with diffuse periventricular white matter hyperintensities. Spinal MRI was normal. CYP27A1 gene sequencing confirmed the diagnosis of CTX. Chenodeoxycholic acid (CDCA) treatment was introduced with remission of diarrhea. Unfortunately, the treatment had to be discontinued several times and the patient developed psychosis and an severe ataxospastic gait. Spinal MRI revealed new linear hyperintensities of the corticospinal and gracile tracts. Thirty-three spinal CTX patients were identified by searching in Pubmed, EMBASE™ and Web of Science databases. All patients presented pyramidal signs and 48% had dorsal column signs. Juvenile cataracts were described in 78% of patients, chronic diarrhea in 65%, and tendon xanthomas in 31%. Disease improvement or stabilization with chenodeoxycholic acid was observed in 69% of patients. A higher prevalence of the Arg395Cys allele was observed in patients with spinal CTX as compared to CTX in general (ᵡ 2 ; p < 0.00001). A 38-year-old woman presented with progressive muscle stiffness, calf cramps and urinary frequency appeared in her twenties ( Fig. 1 ). Her past medical history included chronic diarrhea, scoliosis and bilateral cataract surgery at age 25. She did not take any treatment and had normal schooling. Family history was not relevant. Neurological examination revealed spastic paraparesis with pyramidal signs more prominent on the left lower extremity and flat feet. A neurocognitive study demonstrated severe anterograde verbal memory difficulties and minor executive dysfunction. Electroneuromyography (ENMG) was normal. Brain MRI showed subtle symmetric, bilateral hyperintense T2 ground-glass appearance of the deep white matter, possible symmetric T2 hyperintensity of the cerebellar dentate nuclei and two small ischemic infarct sequelae of the right cerebellar hemisphere ( Fig. 2 ). Spinal MRI was normal. 7 years later, due to progression of spastic paraparesis, CTX was considered. Cholestanol was increased to 64 μmol/L (3.3–12.5 μmol/L). A careful assessment did not found any tendinous xanthomas. Genetic analysis found two monoallelic mutations in the gene CYP27A1 : a missense mutation (c.1183C > T; p. Arg395Cys) in exon 6 and a splicing mutation (c.1184 + 1G > A) in intron 6 and confirmed CTX diagnosis. A treatment with 750 mg/d chenodeoxycholic acid (CDCA) and 20 mg/d simvastatine was introduced ( Fig. 1 ). Three months later, diarrhea was disappeared and no adverse effect was observed. One-year follow-up showed stabilization of neurologic and radiologic signs. Fig. 1 Patient timeline of clinical symptoms and biochemical values. Abbreviations: SP: spastic paraparesia; m: month; CDCA: chenodeoxycholic acid. Normal values for cholestanol (N: 0–15.45 μmol/L); bile acid (N: 0–10.02 μmol/L) Fig. 1 Fig. 2 Brain and spinal cord magnetic resonance imaging (MRI) of the patient. Brain and spinal cord MRI performed in 2008 (a,b,e) and 2019 (c,d,f,g). Axial plane T2 weighted images (a-d) at the level of the dentate nuclei and periventricular white matter showing stable minimal increased signal in the dentate nuclei (arrowheads) and questionable slightly abnormal periventricular white matter T2 hyperintensity (“ground-glass appearance”). The rest of brain MRI was unremarkable except for two small old infarcts in the right cerebellar hemisphere (one lesion shown in a and b*). Spinal cord MRI from 2008 (e) was unremarkable, though no axial plane images were performed. Spinal cord MRI in 2019 revealed subtle longitudinal high signal (white arrow-heads) of the posterior columns at the cervico-dorsal junction and middle dorsal region on sagittal T2-weighted images (f). Axial T2-weighted images confirmed bilateral, symmetric signal abnormalities corresponding to the gracilis tracts (g, black arrowhead) and the lateral cortico-spinal tracts (g, white arrows) at different cervical and dorsal levels, without spinal cord atrophy or contrast material (gadolinium) uptake. Fig. 2 CDCA treatment was stopped for 16 months due to product withdrawal. Over this period, diarrhea recurred and walking worsened. She had increased stiffness with muscle pain, new apallesthesia of the lower limbs and onset of cerebellar ataxia. When CDCA treatment was reintroduced (500 mg/d) walking, pain and diarrhea improved. Due to renewed product shortage and patient non-compliance, CDCA treatment was repeatedly discontinued, following which the patient developed an acute psychosis and, short after, a rapid worsening of her gait becaming rollator dependent. Neurologic evaluation showed a severe ataxospastic gait with knee recurvatum (additional files: video). ENMG was normal. Brain MRI was unchanged. Spinal MRI revealed extensive linear T2 weighted hyperintensities appearing bilaterally in lateral corticospinal and gracile tracts ( Fig. 2 ). Despite normal cholestanol levels (6.18 μmol/L; normal range 3.3–12.5 μmol/L), CDCA posology was increased to 750 mg/d. Six months later, the patient had resolution of diarrhea and psychiatric symptoms but no improvement of gait.'}
|
{'Case presentation': 'We report a 38-year old woman who presented with chronic diarrhea and progressive spastic paraparesis in her twenties. Brain magnetic resonance imaging (MRI) showed cerebral atrophy with diffuse periventricular white matter hyperintensities. Spinal MRI was normal. CYP27A1 gene sequencing confirmed the diagnosis of CTX. Chenodeoxycholic acid (CDCA) treatment was introduced with remission of diarrhea. Unfortunately, the treatment had to be discontinued several times and the patient developed psychosis and an severe ataxospastic gait. Spinal MRI revealed new linear hyperintensities of the corticospinal and gracile tracts. Thirty-three spinal CTX patients were identified by searching in Pubmed, EMBASE™ and Web of Science databases. All patients presented pyramidal signs and 48% had dorsal column signs. Juvenile cataracts were described in 78% of patients, chronic diarrhea in 65%, and tendon xanthomas in 31%. Disease improvement or stabilization with chenodeoxycholic acid was observed in 69% of patients. A higher prevalence of the Arg395Cys allele was observed in patients with spinal CTX as compared to CTX in general (ᵡ 2 ; p < 0.00001). A 38-year-old woman presented with progressive muscle stiffness, calf cramps and urinary frequency appeared in her twenties ( Fig. 1 ). Her past medical history included chronic diarrhea, scoliosis and bilateral cataract surgery at age 25. She did not take any treatment and had normal schooling. Family history was not relevant. Neurological examination revealed spastic paraparesis with pyramidal signs more prominent on the left lower extremity and flat feet. A neurocognitive study demonstrated severe anterograde verbal memory difficulties and minor executive dysfunction. Electroneuromyography (ENMG) was normal. Brain MRI showed subtle symmetric, bilateral hyperintense T2 ground-glass appearance of the deep white matter, possible symmetric T2 hyperintensity of the cerebellar dentate nuclei and two small ischemic infarct sequelae of the right cerebellar hemisphere ( Fig. 2 ). Spinal MRI was normal. 7 years later, due to progression of spastic paraparesis, CTX was considered. Cholestanol was increased to 64 μmol/L (3.3–12.5 μmol/L). A careful assessment did not found any tendinous xanthomas. Genetic analysis found two monoallelic mutations in the gene CYP27A1 : a missense mutation (c.1183C > T; p. Arg395Cys) in exon 6 and a splicing mutation (c.1184 + 1G > A) in intron 6 and confirmed CTX diagnosis. A treatment with 750 mg/d chenodeoxycholic acid (CDCA) and 20 mg/d simvastatine was introduced ( Fig. 1 ). Three months later, diarrhea was disappeared and no adverse effect was observed. One-year follow-up showed stabilization of neurologic and radiologic signs. Fig. 1 Patient timeline of clinical symptoms and biochemical values. Abbreviations: SP: spastic paraparesia; m: month; CDCA: chenodeoxycholic acid. Normal values for cholestanol (N: 0–15.45 μmol/L); bile acid (N: 0–10.02 μmol/L) Fig. 1 Fig. 2 Brain and spinal cord magnetic resonance imaging (MRI) of the patient. Brain and spinal cord MRI performed in 2008 (a,b,e) and 2019 (c,d,f,g). Axial plane T2 weighted images (a-d) at the level of the dentate nuclei and periventricular white matter showing stable minimal increased signal in the dentate nuclei (arrowheads) and questionable slightly abnormal periventricular white matter T2 hyperintensity (“ground-glass appearance”). The rest of brain MRI was unremarkable except for two small old infarcts in the right cerebellar hemisphere (one lesion shown in a and b*). Spinal cord MRI from 2008 (e) was unremarkable, though no axial plane images were performed. Spinal cord MRI in 2019 revealed subtle longitudinal high signal (white arrow-heads) of the posterior columns at the cervico-dorsal junction and middle dorsal region on sagittal T2-weighted images (f). Axial T2-weighted images confirmed bilateral, symmetric signal abnormalities corresponding to the gracilis tracts (g, black arrowhead) and the lateral cortico-spinal tracts (g, white arrows) at different cervical and dorsal levels, without spinal cord atrophy or contrast material (gadolinium) uptake. Fig. 2 CDCA treatment was stopped for 16 months due to product withdrawal. Over this period, diarrhea recurred and walking worsened. She had increased stiffness with muscle pain, new apallesthesia of the lower limbs and onset of cerebellar ataxia. When CDCA treatment was reintroduced (500 mg/d) walking, pain and diarrhea improved. Due to renewed product shortage and patient non-compliance, CDCA treatment was repeatedly discontinued, following which the patient developed an acute psychosis and, short after, a rapid worsening of her gait becaming rollator dependent. Neurologic evaluation showed a severe ataxospastic gait with knee recurvatum (additional files: video). ENMG was normal. Brain MRI was unchanged. Spinal MRI revealed extensive linear T2 weighted hyperintensities appearing bilaterally in lateral corticospinal and gracile tracts ( Fig. 2 ). Despite normal cholestanol levels (6.18 μmol/L; normal range 3.3–12.5 μmol/L), CDCA posology was increased to 750 mg/d. Six months later, the patient had resolution of diarrhea and psychiatric symptoms but no improvement of gait.'}
|
Eyes-Ears-Nose-Throat
|
EENT
|
[
"bilateral cataract"
] |
test-2010
|
7890005
|
{'Case presentation': 'We report a 38-year old woman who presented with chronic diarrhea and progressive spastic paraparesis in her twenties. Brain magnetic resonance imaging (MRI) showed cerebral atrophy with diffuse periventricular white matter hyperintensities. Spinal MRI was normal. CYP27A1 gene sequencing confirmed the diagnosis of CTX. Chenodeoxycholic acid (CDCA) treatment was introduced with remission of diarrhea. Unfortunately, the treatment had to be discontinued several times and the patient developed psychosis and an severe ataxospastic gait. Spinal MRI revealed new linear hyperintensities of the corticospinal and gracile tracts. Thirty-three spinal CTX patients were identified by searching in Pubmed, EMBASE™ and Web of Science databases. All patients presented pyramidal signs and 48% had dorsal column signs. Juvenile cataracts were described in 78% of patients, chronic diarrhea in 65%, and tendon xanthomas in 31%. Disease improvement or stabilization with chenodeoxycholic acid was observed in 69% of patients. A higher prevalence of the Arg395Cys allele was observed in patients with spinal CTX as compared to CTX in general (ᵡ 2 ; p < 0.00001). A 38-year-old woman presented with progressive muscle stiffness, calf cramps and urinary frequency appeared in her twenties ( Fig. 1 ). Her past medical history included chronic diarrhea, scoliosis and bilateral cataract surgery at age 25. She did not take any treatment and had normal schooling. Family history was not relevant. Neurological examination revealed spastic paraparesis with pyramidal signs more prominent on the left lower extremity and flat feet. A neurocognitive study demonstrated severe anterograde verbal memory difficulties and minor executive dysfunction. Electroneuromyography (ENMG) was normal. Brain MRI showed subtle symmetric, bilateral hyperintense T2 ground-glass appearance of the deep white matter, possible symmetric T2 hyperintensity of the cerebellar dentate nuclei and two small ischemic infarct sequelae of the right cerebellar hemisphere ( Fig. 2 ). Spinal MRI was normal. 7 years later, due to progression of spastic paraparesis, CTX was considered. Cholestanol was increased to 64 μmol/L (3.3–12.5 μmol/L). A careful assessment did not found any tendinous xanthomas. Genetic analysis found two monoallelic mutations in the gene CYP27A1 : a missense mutation (c.1183C > T; p. Arg395Cys) in exon 6 and a splicing mutation (c.1184 + 1G > A) in intron 6 and confirmed CTX diagnosis. A treatment with 750 mg/d chenodeoxycholic acid (CDCA) and 20 mg/d simvastatine was introduced ( Fig. 1 ). Three months later, diarrhea was disappeared and no adverse effect was observed. One-year follow-up showed stabilization of neurologic and radiologic signs. Fig. 1 Patient timeline of clinical symptoms and biochemical values. Abbreviations: SP: spastic paraparesia; m: month; CDCA: chenodeoxycholic acid. Normal values for cholestanol (N: 0–15.45 μmol/L); bile acid (N: 0–10.02 μmol/L) Fig. 1 Fig. 2 Brain and spinal cord magnetic resonance imaging (MRI) of the patient. Brain and spinal cord MRI performed in 2008 (a,b,e) and 2019 (c,d,f,g). Axial plane T2 weighted images (a-d) at the level of the dentate nuclei and periventricular white matter showing stable minimal increased signal in the dentate nuclei (arrowheads) and questionable slightly abnormal periventricular white matter T2 hyperintensity (“ground-glass appearance”). The rest of brain MRI was unremarkable except for two small old infarcts in the right cerebellar hemisphere (one lesion shown in a and b*). Spinal cord MRI from 2008 (e) was unremarkable, though no axial plane images were performed. Spinal cord MRI in 2019 revealed subtle longitudinal high signal (white arrow-heads) of the posterior columns at the cervico-dorsal junction and middle dorsal region on sagittal T2-weighted images (f). Axial T2-weighted images confirmed bilateral, symmetric signal abnormalities corresponding to the gracilis tracts (g, black arrowhead) and the lateral cortico-spinal tracts (g, white arrows) at different cervical and dorsal levels, without spinal cord atrophy or contrast material (gadolinium) uptake. Fig. 2 CDCA treatment was stopped for 16 months due to product withdrawal. Over this period, diarrhea recurred and walking worsened. She had increased stiffness with muscle pain, new apallesthesia of the lower limbs and onset of cerebellar ataxia. When CDCA treatment was reintroduced (500 mg/d) walking, pain and diarrhea improved. Due to renewed product shortage and patient non-compliance, CDCA treatment was repeatedly discontinued, following which the patient developed an acute psychosis and, short after, a rapid worsening of her gait becaming rollator dependent. Neurologic evaluation showed a severe ataxospastic gait with knee recurvatum (additional files: video). ENMG was normal. Brain MRI was unchanged. Spinal MRI revealed extensive linear T2 weighted hyperintensities appearing bilaterally in lateral corticospinal and gracile tracts ( Fig. 2 ). Despite normal cholestanol levels (6.18 μmol/L; normal range 3.3–12.5 μmol/L), CDCA posology was increased to 750 mg/d. Six months later, the patient had resolution of diarrhea and psychiatric symptoms but no improvement of gait.'}
|
{'Case presentation': 'We report a 38-year old woman who presented with chronic diarrhea and progressive spastic paraparesis in her twenties. Brain magnetic resonance imaging (MRI) showed cerebral atrophy with diffuse periventricular white matter hyperintensities. Spinal MRI was normal. CYP27A1 gene sequencing confirmed the diagnosis of CTX. Chenodeoxycholic acid (CDCA) treatment was introduced with remission of diarrhea. Unfortunately, the treatment had to be discontinued several times and the patient developed psychosis and an severe ataxospastic gait. Spinal MRI revealed new linear hyperintensities of the corticospinal and gracile tracts. Thirty-three spinal CTX patients were identified by searching in Pubmed, EMBASE™ and Web of Science databases. All patients presented pyramidal signs and 48% had dorsal column signs. Juvenile cataracts were described in 78% of patients, chronic diarrhea in 65%, and tendon xanthomas in 31%. Disease improvement or stabilization with chenodeoxycholic acid was observed in 69% of patients. A higher prevalence of the Arg395Cys allele was observed in patients with spinal CTX as compared to CTX in general (ᵡ 2 ; p < 0.00001). A 38-year-old woman presented with progressive muscle stiffness, calf cramps and urinary frequency appeared in her twenties ( Fig. 1 ). Her past medical history included chronic diarrhea, scoliosis and bilateral cataract surgery at age 25. She did not take any treatment and had normal schooling. Family history was not relevant. Neurological examination revealed spastic paraparesis with pyramidal signs more prominent on the left lower extremity and flat feet. A neurocognitive study demonstrated severe anterograde verbal memory difficulties and minor executive dysfunction. Electroneuromyography (ENMG) was normal. Brain MRI showed subtle symmetric, bilateral hyperintense T2 ground-glass appearance of the deep white matter, possible symmetric T2 hyperintensity of the cerebellar dentate nuclei and two small ischemic infarct sequelae of the right cerebellar hemisphere ( Fig. 2 ). Spinal MRI was normal. 7 years later, due to progression of spastic paraparesis, CTX was considered. Cholestanol was increased to 64 μmol/L (3.3–12.5 μmol/L). A careful assessment did not found any tendinous xanthomas. Genetic analysis found two monoallelic mutations in the gene CYP27A1 : a missense mutation (c.1183C > T; p. Arg395Cys) in exon 6 and a splicing mutation (c.1184 + 1G > A) in intron 6 and confirmed CTX diagnosis. A treatment with 750 mg/d chenodeoxycholic acid (CDCA) and 20 mg/d simvastatine was introduced ( Fig. 1 ). Three months later, diarrhea was disappeared and no adverse effect was observed. One-year follow-up showed stabilization of neurologic and radiologic signs. Fig. 1 Patient timeline of clinical symptoms and biochemical values. Abbreviations: SP: spastic paraparesia; m: month; CDCA: chenodeoxycholic acid. Normal values for cholestanol (N: 0–15.45 μmol/L); bile acid (N: 0–10.02 μmol/L) Fig. 1 Fig. 2 Brain and spinal cord magnetic resonance imaging (MRI) of the patient. Brain and spinal cord MRI performed in 2008 (a,b,e) and 2019 (c,d,f,g). Axial plane T2 weighted images (a-d) at the level of the dentate nuclei and periventricular white matter showing stable minimal increased signal in the dentate nuclei (arrowheads) and questionable slightly abnormal periventricular white matter T2 hyperintensity (“ground-glass appearance”). The rest of brain MRI was unremarkable except for two small old infarcts in the right cerebellar hemisphere (one lesion shown in a and b*). Spinal cord MRI from 2008 (e) was unremarkable, though no axial plane images were performed. Spinal cord MRI in 2019 revealed subtle longitudinal high signal (white arrow-heads) of the posterior columns at the cervico-dorsal junction and middle dorsal region on sagittal T2-weighted images (f). Axial T2-weighted images confirmed bilateral, symmetric signal abnormalities corresponding to the gracilis tracts (g, black arrowhead) and the lateral cortico-spinal tracts (g, white arrows) at different cervical and dorsal levels, without spinal cord atrophy or contrast material (gadolinium) uptake. Fig. 2 CDCA treatment was stopped for 16 months due to product withdrawal. Over this period, diarrhea recurred and walking worsened. She had increased stiffness with muscle pain, new apallesthesia of the lower limbs and onset of cerebellar ataxia. When CDCA treatment was reintroduced (500 mg/d) walking, pain and diarrhea improved. Due to renewed product shortage and patient non-compliance, CDCA treatment was repeatedly discontinued, following which the patient developed an acute psychosis and, short after, a rapid worsening of her gait becaming rollator dependent. Neurologic evaluation showed a severe ataxospastic gait with knee recurvatum (additional files: video). ENMG was normal. Brain MRI was unchanged. Spinal MRI revealed extensive linear T2 weighted hyperintensities appearing bilaterally in lateral corticospinal and gracile tracts ( Fig. 2 ). Despite normal cholestanol levels (6.18 μmol/L; normal range 3.3–12.5 μmol/L), CDCA posology was increased to 750 mg/d. Six months later, the patient had resolution of diarrhea and psychiatric symptoms but no improvement of gait.'}
|
Dermatology
|
DERM
|
[] |
test-2011
|
7890005
|
{'Case presentation': 'We report a 38-year old woman who presented with chronic diarrhea and progressive spastic paraparesis in her twenties. Brain magnetic resonance imaging (MRI) showed cerebral atrophy with diffuse periventricular white matter hyperintensities. Spinal MRI was normal. CYP27A1 gene sequencing confirmed the diagnosis of CTX. Chenodeoxycholic acid (CDCA) treatment was introduced with remission of diarrhea. Unfortunately, the treatment had to be discontinued several times and the patient developed psychosis and an severe ataxospastic gait. Spinal MRI revealed new linear hyperintensities of the corticospinal and gracile tracts. Thirty-three spinal CTX patients were identified by searching in Pubmed, EMBASE™ and Web of Science databases. All patients presented pyramidal signs and 48% had dorsal column signs. Juvenile cataracts were described in 78% of patients, chronic diarrhea in 65%, and tendon xanthomas in 31%. Disease improvement or stabilization with chenodeoxycholic acid was observed in 69% of patients. A higher prevalence of the Arg395Cys allele was observed in patients with spinal CTX as compared to CTX in general (ᵡ 2 ; p < 0.00001). A 38-year-old woman presented with progressive muscle stiffness, calf cramps and urinary frequency appeared in her twenties ( Fig. 1 ). Her past medical history included chronic diarrhea, scoliosis and bilateral cataract surgery at age 25. She did not take any treatment and had normal schooling. Family history was not relevant. Neurological examination revealed spastic paraparesis with pyramidal signs more prominent on the left lower extremity and flat feet. A neurocognitive study demonstrated severe anterograde verbal memory difficulties and minor executive dysfunction. Electroneuromyography (ENMG) was normal. Brain MRI showed subtle symmetric, bilateral hyperintense T2 ground-glass appearance of the deep white matter, possible symmetric T2 hyperintensity of the cerebellar dentate nuclei and two small ischemic infarct sequelae of the right cerebellar hemisphere ( Fig. 2 ). Spinal MRI was normal. 7 years later, due to progression of spastic paraparesis, CTX was considered. Cholestanol was increased to 64 μmol/L (3.3–12.5 μmol/L). A careful assessment did not found any tendinous xanthomas. Genetic analysis found two monoallelic mutations in the gene CYP27A1 : a missense mutation (c.1183C > T; p. Arg395Cys) in exon 6 and a splicing mutation (c.1184 + 1G > A) in intron 6 and confirmed CTX diagnosis. A treatment with 750 mg/d chenodeoxycholic acid (CDCA) and 20 mg/d simvastatine was introduced ( Fig. 1 ). Three months later, diarrhea was disappeared and no adverse effect was observed. One-year follow-up showed stabilization of neurologic and radiologic signs. Fig. 1 Patient timeline of clinical symptoms and biochemical values. Abbreviations: SP: spastic paraparesia; m: month; CDCA: chenodeoxycholic acid. Normal values for cholestanol (N: 0–15.45 μmol/L); bile acid (N: 0–10.02 μmol/L) Fig. 1 Fig. 2 Brain and spinal cord magnetic resonance imaging (MRI) of the patient. Brain and spinal cord MRI performed in 2008 (a,b,e) and 2019 (c,d,f,g). Axial plane T2 weighted images (a-d) at the level of the dentate nuclei and periventricular white matter showing stable minimal increased signal in the dentate nuclei (arrowheads) and questionable slightly abnormal periventricular white matter T2 hyperintensity (“ground-glass appearance”). The rest of brain MRI was unremarkable except for two small old infarcts in the right cerebellar hemisphere (one lesion shown in a and b*). Spinal cord MRI from 2008 (e) was unremarkable, though no axial plane images were performed. Spinal cord MRI in 2019 revealed subtle longitudinal high signal (white arrow-heads) of the posterior columns at the cervico-dorsal junction and middle dorsal region on sagittal T2-weighted images (f). Axial T2-weighted images confirmed bilateral, symmetric signal abnormalities corresponding to the gracilis tracts (g, black arrowhead) and the lateral cortico-spinal tracts (g, white arrows) at different cervical and dorsal levels, without spinal cord atrophy or contrast material (gadolinium) uptake. Fig. 2 CDCA treatment was stopped for 16 months due to product withdrawal. Over this period, diarrhea recurred and walking worsened. She had increased stiffness with muscle pain, new apallesthesia of the lower limbs and onset of cerebellar ataxia. When CDCA treatment was reintroduced (500 mg/d) walking, pain and diarrhea improved. Due to renewed product shortage and patient non-compliance, CDCA treatment was repeatedly discontinued, following which the patient developed an acute psychosis and, short after, a rapid worsening of her gait becaming rollator dependent. Neurologic evaluation showed a severe ataxospastic gait with knee recurvatum (additional files: video). ENMG was normal. Brain MRI was unchanged. Spinal MRI revealed extensive linear T2 weighted hyperintensities appearing bilaterally in lateral corticospinal and gracile tracts ( Fig. 2 ). Despite normal cholestanol levels (6.18 μmol/L; normal range 3.3–12.5 μmol/L), CDCA posology was increased to 750 mg/d. Six months later, the patient had resolution of diarrhea and psychiatric symptoms but no improvement of gait.'}
|
{'Case presentation': 'We report a 38-year old woman who presented with chronic diarrhea and progressive spastic paraparesis in her twenties. Brain magnetic resonance imaging (MRI) showed cerebral atrophy with diffuse periventricular white matter hyperintensities. Spinal MRI was normal. CYP27A1 gene sequencing confirmed the diagnosis of CTX. Chenodeoxycholic acid (CDCA) treatment was introduced with remission of diarrhea. Unfortunately, the treatment had to be discontinued several times and the patient developed psychosis and an severe ataxospastic gait. Spinal MRI revealed new linear hyperintensities of the corticospinal and gracile tracts. Thirty-three spinal CTX patients were identified by searching in Pubmed, EMBASE™ and Web of Science databases. All patients presented pyramidal signs and 48% had dorsal column signs. Juvenile cataracts were described in 78% of patients, chronic diarrhea in 65%, and tendon xanthomas in 31%. Disease improvement or stabilization with chenodeoxycholic acid was observed in 69% of patients. A higher prevalence of the Arg395Cys allele was observed in patients with spinal CTX as compared to CTX in general (ᵡ 2 ; p < 0.00001). A 38-year-old woman presented with progressive muscle stiffness, calf cramps and urinary frequency appeared in her twenties ( Fig. 1 ). Her past medical history included chronic diarrhea, scoliosis and bilateral cataract surgery at age 25. She did not take any treatment and had normal schooling. Family history was not relevant. Neurological examination revealed spastic paraparesis with pyramidal signs more prominent on the left lower extremity and flat feet. A neurocognitive study demonstrated severe anterograde verbal memory difficulties and minor executive dysfunction. Electroneuromyography (ENMG) was normal. Brain MRI showed subtle symmetric, bilateral hyperintense T2 ground-glass appearance of the deep white matter, possible symmetric T2 hyperintensity of the cerebellar dentate nuclei and two small ischemic infarct sequelae of the right cerebellar hemisphere ( Fig. 2 ). Spinal MRI was normal. 7 years later, due to progression of spastic paraparesis, CTX was considered. Cholestanol was increased to 64 μmol/L (3.3–12.5 μmol/L). A careful assessment did not found any tendinous xanthomas. Genetic analysis found two monoallelic mutations in the gene CYP27A1 : a missense mutation (c.1183C > T; p. Arg395Cys) in exon 6 and a splicing mutation (c.1184 + 1G > A) in intron 6 and confirmed CTX diagnosis. A treatment with 750 mg/d chenodeoxycholic acid (CDCA) and 20 mg/d simvastatine was introduced ( Fig. 1 ). Three months later, diarrhea was disappeared and no adverse effect was observed. One-year follow-up showed stabilization of neurologic and radiologic signs. Fig. 1 Patient timeline of clinical symptoms and biochemical values. Abbreviations: SP: spastic paraparesia; m: month; CDCA: chenodeoxycholic acid. Normal values for cholestanol (N: 0–15.45 μmol/L); bile acid (N: 0–10.02 μmol/L) Fig. 1 Fig. 2 Brain and spinal cord magnetic resonance imaging (MRI) of the patient. Brain and spinal cord MRI performed in 2008 (a,b,e) and 2019 (c,d,f,g). Axial plane T2 weighted images (a-d) at the level of the dentate nuclei and periventricular white matter showing stable minimal increased signal in the dentate nuclei (arrowheads) and questionable slightly abnormal periventricular white matter T2 hyperintensity (“ground-glass appearance”). The rest of brain MRI was unremarkable except for two small old infarcts in the right cerebellar hemisphere (one lesion shown in a and b*). Spinal cord MRI from 2008 (e) was unremarkable, though no axial plane images were performed. Spinal cord MRI in 2019 revealed subtle longitudinal high signal (white arrow-heads) of the posterior columns at the cervico-dorsal junction and middle dorsal region on sagittal T2-weighted images (f). Axial T2-weighted images confirmed bilateral, symmetric signal abnormalities corresponding to the gracilis tracts (g, black arrowhead) and the lateral cortico-spinal tracts (g, white arrows) at different cervical and dorsal levels, without spinal cord atrophy or contrast material (gadolinium) uptake. Fig. 2 CDCA treatment was stopped for 16 months due to product withdrawal. Over this period, diarrhea recurred and walking worsened. She had increased stiffness with muscle pain, new apallesthesia of the lower limbs and onset of cerebellar ataxia. When CDCA treatment was reintroduced (500 mg/d) walking, pain and diarrhea improved. Due to renewed product shortage and patient non-compliance, CDCA treatment was repeatedly discontinued, following which the patient developed an acute psychosis and, short after, a rapid worsening of her gait becaming rollator dependent. Neurologic evaluation showed a severe ataxospastic gait with knee recurvatum (additional files: video). ENMG was normal. Brain MRI was unchanged. Spinal MRI revealed extensive linear T2 weighted hyperintensities appearing bilaterally in lateral corticospinal and gracile tracts ( Fig. 2 ). Despite normal cholestanol levels (6.18 μmol/L; normal range 3.3–12.5 μmol/L), CDCA posology was increased to 750 mg/d. Six months later, the patient had resolution of diarrhea and psychiatric symptoms but no improvement of gait.'}
|
Pregnancy
|
Pregnancy
|
[] |
test-2012
|
7890005
|
{'Case presentation': 'We report a 38-year old woman who presented with chronic diarrhea and progressive spastic paraparesis in her twenties. Brain magnetic resonance imaging (MRI) showed cerebral atrophy with diffuse periventricular white matter hyperintensities. Spinal MRI was normal. CYP27A1 gene sequencing confirmed the diagnosis of CTX. Chenodeoxycholic acid (CDCA) treatment was introduced with remission of diarrhea. Unfortunately, the treatment had to be discontinued several times and the patient developed psychosis and an severe ataxospastic gait. Spinal MRI revealed new linear hyperintensities of the corticospinal and gracile tracts. Thirty-three spinal CTX patients were identified by searching in Pubmed, EMBASE™ and Web of Science databases. All patients presented pyramidal signs and 48% had dorsal column signs. Juvenile cataracts were described in 78% of patients, chronic diarrhea in 65%, and tendon xanthomas in 31%. Disease improvement or stabilization with chenodeoxycholic acid was observed in 69% of patients. A higher prevalence of the Arg395Cys allele was observed in patients with spinal CTX as compared to CTX in general (ᵡ 2 ; p < 0.00001). A 38-year-old woman presented with progressive muscle stiffness, calf cramps and urinary frequency appeared in her twenties ( Fig. 1 ). Her past medical history included chronic diarrhea, scoliosis and bilateral cataract surgery at age 25. She did not take any treatment and had normal schooling. Family history was not relevant. Neurological examination revealed spastic paraparesis with pyramidal signs more prominent on the left lower extremity and flat feet. A neurocognitive study demonstrated severe anterograde verbal memory difficulties and minor executive dysfunction. Electroneuromyography (ENMG) was normal. Brain MRI showed subtle symmetric, bilateral hyperintense T2 ground-glass appearance of the deep white matter, possible symmetric T2 hyperintensity of the cerebellar dentate nuclei and two small ischemic infarct sequelae of the right cerebellar hemisphere ( Fig. 2 ). Spinal MRI was normal. 7 years later, due to progression of spastic paraparesis, CTX was considered. Cholestanol was increased to 64 μmol/L (3.3–12.5 μmol/L). A careful assessment did not found any tendinous xanthomas. Genetic analysis found two monoallelic mutations in the gene CYP27A1 : a missense mutation (c.1183C > T; p. Arg395Cys) in exon 6 and a splicing mutation (c.1184 + 1G > A) in intron 6 and confirmed CTX diagnosis. A treatment with 750 mg/d chenodeoxycholic acid (CDCA) and 20 mg/d simvastatine was introduced ( Fig. 1 ). Three months later, diarrhea was disappeared and no adverse effect was observed. One-year follow-up showed stabilization of neurologic and radiologic signs. Fig. 1 Patient timeline of clinical symptoms and biochemical values. Abbreviations: SP: spastic paraparesia; m: month; CDCA: chenodeoxycholic acid. Normal values for cholestanol (N: 0–15.45 μmol/L); bile acid (N: 0–10.02 μmol/L) Fig. 1 Fig. 2 Brain and spinal cord magnetic resonance imaging (MRI) of the patient. Brain and spinal cord MRI performed in 2008 (a,b,e) and 2019 (c,d,f,g). Axial plane T2 weighted images (a-d) at the level of the dentate nuclei and periventricular white matter showing stable minimal increased signal in the dentate nuclei (arrowheads) and questionable slightly abnormal periventricular white matter T2 hyperintensity (“ground-glass appearance”). The rest of brain MRI was unremarkable except for two small old infarcts in the right cerebellar hemisphere (one lesion shown in a and b*). Spinal cord MRI from 2008 (e) was unremarkable, though no axial plane images were performed. Spinal cord MRI in 2019 revealed subtle longitudinal high signal (white arrow-heads) of the posterior columns at the cervico-dorsal junction and middle dorsal region on sagittal T2-weighted images (f). Axial T2-weighted images confirmed bilateral, symmetric signal abnormalities corresponding to the gracilis tracts (g, black arrowhead) and the lateral cortico-spinal tracts (g, white arrows) at different cervical and dorsal levels, without spinal cord atrophy or contrast material (gadolinium) uptake. Fig. 2 CDCA treatment was stopped for 16 months due to product withdrawal. Over this period, diarrhea recurred and walking worsened. She had increased stiffness with muscle pain, new apallesthesia of the lower limbs and onset of cerebellar ataxia. When CDCA treatment was reintroduced (500 mg/d) walking, pain and diarrhea improved. Due to renewed product shortage and patient non-compliance, CDCA treatment was repeatedly discontinued, following which the patient developed an acute psychosis and, short after, a rapid worsening of her gait becaming rollator dependent. Neurologic evaluation showed a severe ataxospastic gait with knee recurvatum (additional files: video). ENMG was normal. Brain MRI was unchanged. Spinal MRI revealed extensive linear T2 weighted hyperintensities appearing bilaterally in lateral corticospinal and gracile tracts ( Fig. 2 ). Despite normal cholestanol levels (6.18 μmol/L; normal range 3.3–12.5 μmol/L), CDCA posology was increased to 750 mg/d. Six months later, the patient had resolution of diarrhea and psychiatric symptoms but no improvement of gait.'}
|
{'Case presentation': 'We report a 38-year old woman who presented with chronic diarrhea and progressive spastic paraparesis in her twenties. Brain magnetic resonance imaging (MRI) showed cerebral atrophy with diffuse periventricular white matter hyperintensities. Spinal MRI was normal. CYP27A1 gene sequencing confirmed the diagnosis of CTX. Chenodeoxycholic acid (CDCA) treatment was introduced with remission of diarrhea. Unfortunately, the treatment had to be discontinued several times and the patient developed psychosis and an severe ataxospastic gait. Spinal MRI revealed new linear hyperintensities of the corticospinal and gracile tracts. Thirty-three spinal CTX patients were identified by searching in Pubmed, EMBASE™ and Web of Science databases. All patients presented pyramidal signs and 48% had dorsal column signs. Juvenile cataracts were described in 78% of patients, chronic diarrhea in 65%, and tendon xanthomas in 31%. Disease improvement or stabilization with chenodeoxycholic acid was observed in 69% of patients. A higher prevalence of the Arg395Cys allele was observed in patients with spinal CTX as compared to CTX in general (ᵡ 2 ; p < 0.00001). A 38-year-old woman presented with progressive muscle stiffness, calf cramps and urinary frequency appeared in her twenties ( Fig. 1 ). Her past medical history included chronic diarrhea, scoliosis and bilateral cataract surgery at age 25. She did not take any treatment and had normal schooling. Family history was not relevant. Neurological examination revealed spastic paraparesis with pyramidal signs more prominent on the left lower extremity and flat feet. A neurocognitive study demonstrated severe anterograde verbal memory difficulties and minor executive dysfunction. Electroneuromyography (ENMG) was normal. Brain MRI showed subtle symmetric, bilateral hyperintense T2 ground-glass appearance of the deep white matter, possible symmetric T2 hyperintensity of the cerebellar dentate nuclei and two small ischemic infarct sequelae of the right cerebellar hemisphere ( Fig. 2 ). Spinal MRI was normal. 7 years later, due to progression of spastic paraparesis, CTX was considered. Cholestanol was increased to 64 μmol/L (3.3–12.5 μmol/L). A careful assessment did not found any tendinous xanthomas. Genetic analysis found two monoallelic mutations in the gene CYP27A1 : a missense mutation (c.1183C > T; p. Arg395Cys) in exon 6 and a splicing mutation (c.1184 + 1G > A) in intron 6 and confirmed CTX diagnosis. A treatment with 750 mg/d chenodeoxycholic acid (CDCA) and 20 mg/d simvastatine was introduced ( Fig. 1 ). Three months later, diarrhea was disappeared and no adverse effect was observed. One-year follow-up showed stabilization of neurologic and radiologic signs. Fig. 1 Patient timeline of clinical symptoms and biochemical values. Abbreviations: SP: spastic paraparesia; m: month; CDCA: chenodeoxycholic acid. Normal values for cholestanol (N: 0–15.45 μmol/L); bile acid (N: 0–10.02 μmol/L) Fig. 1 Fig. 2 Brain and spinal cord magnetic resonance imaging (MRI) of the patient. Brain and spinal cord MRI performed in 2008 (a,b,e) and 2019 (c,d,f,g). Axial plane T2 weighted images (a-d) at the level of the dentate nuclei and periventricular white matter showing stable minimal increased signal in the dentate nuclei (arrowheads) and questionable slightly abnormal periventricular white matter T2 hyperintensity (“ground-glass appearance”). The rest of brain MRI was unremarkable except for two small old infarcts in the right cerebellar hemisphere (one lesion shown in a and b*). Spinal cord MRI from 2008 (e) was unremarkable, though no axial plane images were performed. Spinal cord MRI in 2019 revealed subtle longitudinal high signal (white arrow-heads) of the posterior columns at the cervico-dorsal junction and middle dorsal region on sagittal T2-weighted images (f). Axial T2-weighted images confirmed bilateral, symmetric signal abnormalities corresponding to the gracilis tracts (g, black arrowhead) and the lateral cortico-spinal tracts (g, white arrows) at different cervical and dorsal levels, without spinal cord atrophy or contrast material (gadolinium) uptake. Fig. 2 CDCA treatment was stopped for 16 months due to product withdrawal. Over this period, diarrhea recurred and walking worsened. She had increased stiffness with muscle pain, new apallesthesia of the lower limbs and onset of cerebellar ataxia. When CDCA treatment was reintroduced (500 mg/d) walking, pain and diarrhea improved. Due to renewed product shortage and patient non-compliance, CDCA treatment was repeatedly discontinued, following which the patient developed an acute psychosis and, short after, a rapid worsening of her gait becaming rollator dependent. Neurologic evaluation showed a severe ataxospastic gait with knee recurvatum (additional files: video). ENMG was normal. Brain MRI was unchanged. Spinal MRI revealed extensive linear T2 weighted hyperintensities appearing bilaterally in lateral corticospinal and gracile tracts ( Fig. 2 ). Despite normal cholestanol levels (6.18 μmol/L; normal range 3.3–12.5 μmol/L), CDCA posology was increased to 750 mg/d. Six months later, the patient had resolution of diarrhea and psychiatric symptoms but no improvement of gait.'}
|
Lymphatic-System
|
LYMPH
|
[] |
test-2013
|
7890005
|
{'Case presentation': 'We report a 38-year old woman who presented with chronic diarrhea and progressive spastic paraparesis in her twenties. Brain magnetic resonance imaging (MRI) showed cerebral atrophy with diffuse periventricular white matter hyperintensities. Spinal MRI was normal. CYP27A1 gene sequencing confirmed the diagnosis of CTX. Chenodeoxycholic acid (CDCA) treatment was introduced with remission of diarrhea. Unfortunately, the treatment had to be discontinued several times and the patient developed psychosis and an severe ataxospastic gait. Spinal MRI revealed new linear hyperintensities of the corticospinal and gracile tracts. Thirty-three spinal CTX patients were identified by searching in Pubmed, EMBASE™ and Web of Science databases. All patients presented pyramidal signs and 48% had dorsal column signs. Juvenile cataracts were described in 78% of patients, chronic diarrhea in 65%, and tendon xanthomas in 31%. Disease improvement or stabilization with chenodeoxycholic acid was observed in 69% of patients. A higher prevalence of the Arg395Cys allele was observed in patients with spinal CTX as compared to CTX in general (ᵡ 2 ; p < 0.00001). A 38-year-old woman presented with progressive muscle stiffness, calf cramps and urinary frequency appeared in her twenties ( Fig. 1 ). Her past medical history included chronic diarrhea, scoliosis and bilateral cataract surgery at age 25. She did not take any treatment and had normal schooling. Family history was not relevant. Neurological examination revealed spastic paraparesis with pyramidal signs more prominent on the left lower extremity and flat feet. A neurocognitive study demonstrated severe anterograde verbal memory difficulties and minor executive dysfunction. Electroneuromyography (ENMG) was normal. Brain MRI showed subtle symmetric, bilateral hyperintense T2 ground-glass appearance of the deep white matter, possible symmetric T2 hyperintensity of the cerebellar dentate nuclei and two small ischemic infarct sequelae of the right cerebellar hemisphere ( Fig. 2 ). Spinal MRI was normal. 7 years later, due to progression of spastic paraparesis, CTX was considered. Cholestanol was increased to 64 μmol/L (3.3–12.5 μmol/L). A careful assessment did not found any tendinous xanthomas. Genetic analysis found two monoallelic mutations in the gene CYP27A1 : a missense mutation (c.1183C > T; p. Arg395Cys) in exon 6 and a splicing mutation (c.1184 + 1G > A) in intron 6 and confirmed CTX diagnosis. A treatment with 750 mg/d chenodeoxycholic acid (CDCA) and 20 mg/d simvastatine was introduced ( Fig. 1 ). Three months later, diarrhea was disappeared and no adverse effect was observed. One-year follow-up showed stabilization of neurologic and radiologic signs. Fig. 1 Patient timeline of clinical symptoms and biochemical values. Abbreviations: SP: spastic paraparesia; m: month; CDCA: chenodeoxycholic acid. Normal values for cholestanol (N: 0–15.45 μmol/L); bile acid (N: 0–10.02 μmol/L) Fig. 1 Fig. 2 Brain and spinal cord magnetic resonance imaging (MRI) of the patient. Brain and spinal cord MRI performed in 2008 (a,b,e) and 2019 (c,d,f,g). Axial plane T2 weighted images (a-d) at the level of the dentate nuclei and periventricular white matter showing stable minimal increased signal in the dentate nuclei (arrowheads) and questionable slightly abnormal periventricular white matter T2 hyperintensity (“ground-glass appearance”). The rest of brain MRI was unremarkable except for two small old infarcts in the right cerebellar hemisphere (one lesion shown in a and b*). Spinal cord MRI from 2008 (e) was unremarkable, though no axial plane images were performed. Spinal cord MRI in 2019 revealed subtle longitudinal high signal (white arrow-heads) of the posterior columns at the cervico-dorsal junction and middle dorsal region on sagittal T2-weighted images (f). Axial T2-weighted images confirmed bilateral, symmetric signal abnormalities corresponding to the gracilis tracts (g, black arrowhead) and the lateral cortico-spinal tracts (g, white arrows) at different cervical and dorsal levels, without spinal cord atrophy or contrast material (gadolinium) uptake. Fig. 2 CDCA treatment was stopped for 16 months due to product withdrawal. Over this period, diarrhea recurred and walking worsened. She had increased stiffness with muscle pain, new apallesthesia of the lower limbs and onset of cerebellar ataxia. When CDCA treatment was reintroduced (500 mg/d) walking, pain and diarrhea improved. Due to renewed product shortage and patient non-compliance, CDCA treatment was repeatedly discontinued, following which the patient developed an acute psychosis and, short after, a rapid worsening of her gait becaming rollator dependent. Neurologic evaluation showed a severe ataxospastic gait with knee recurvatum (additional files: video). ENMG was normal. Brain MRI was unchanged. Spinal MRI revealed extensive linear T2 weighted hyperintensities appearing bilaterally in lateral corticospinal and gracile tracts ( Fig. 2 ). Despite normal cholestanol levels (6.18 μmol/L; normal range 3.3–12.5 μmol/L), CDCA posology was increased to 750 mg/d. Six months later, the patient had resolution of diarrhea and psychiatric symptoms but no improvement of gait.'}
|
{'Case presentation': 'We report a 38-year old woman who presented with chronic diarrhea and progressive spastic paraparesis in her twenties. Brain magnetic resonance imaging (MRI) showed cerebral atrophy with diffuse periventricular white matter hyperintensities. Spinal MRI was normal. CYP27A1 gene sequencing confirmed the diagnosis of CTX. Chenodeoxycholic acid (CDCA) treatment was introduced with remission of diarrhea. Unfortunately, the treatment had to be discontinued several times and the patient developed psychosis and an severe ataxospastic gait. Spinal MRI revealed new linear hyperintensities of the corticospinal and gracile tracts. Thirty-three spinal CTX patients were identified by searching in Pubmed, EMBASE™ and Web of Science databases. All patients presented pyramidal signs and 48% had dorsal column signs. Juvenile cataracts were described in 78% of patients, chronic diarrhea in 65%, and tendon xanthomas in 31%. Disease improvement or stabilization with chenodeoxycholic acid was observed in 69% of patients. A higher prevalence of the Arg395Cys allele was observed in patients with spinal CTX as compared to CTX in general (ᵡ 2 ; p < 0.00001). A 38-year-old woman presented with progressive muscle stiffness, calf cramps and urinary frequency appeared in her twenties ( Fig. 1 ). Her past medical history included chronic diarrhea, scoliosis and bilateral cataract surgery at age 25. She did not take any treatment and had normal schooling. Family history was not relevant. Neurological examination revealed spastic paraparesis with pyramidal signs more prominent on the left lower extremity and flat feet. A neurocognitive study demonstrated severe anterograde verbal memory difficulties and minor executive dysfunction. Electroneuromyography (ENMG) was normal. Brain MRI showed subtle symmetric, bilateral hyperintense T2 ground-glass appearance of the deep white matter, possible symmetric T2 hyperintensity of the cerebellar dentate nuclei and two small ischemic infarct sequelae of the right cerebellar hemisphere ( Fig. 2 ). Spinal MRI was normal. 7 years later, due to progression of spastic paraparesis, CTX was considered. Cholestanol was increased to 64 μmol/L (3.3–12.5 μmol/L). A careful assessment did not found any tendinous xanthomas. Genetic analysis found two monoallelic mutations in the gene CYP27A1 : a missense mutation (c.1183C > T; p. Arg395Cys) in exon 6 and a splicing mutation (c.1184 + 1G > A) in intron 6 and confirmed CTX diagnosis. A treatment with 750 mg/d chenodeoxycholic acid (CDCA) and 20 mg/d simvastatine was introduced ( Fig. 1 ). Three months later, diarrhea was disappeared and no adverse effect was observed. One-year follow-up showed stabilization of neurologic and radiologic signs. Fig. 1 Patient timeline of clinical symptoms and biochemical values. Abbreviations: SP: spastic paraparesia; m: month; CDCA: chenodeoxycholic acid. Normal values for cholestanol (N: 0–15.45 μmol/L); bile acid (N: 0–10.02 μmol/L) Fig. 1 Fig. 2 Brain and spinal cord magnetic resonance imaging (MRI) of the patient. Brain and spinal cord MRI performed in 2008 (a,b,e) and 2019 (c,d,f,g). Axial plane T2 weighted images (a-d) at the level of the dentate nuclei and periventricular white matter showing stable minimal increased signal in the dentate nuclei (arrowheads) and questionable slightly abnormal periventricular white matter T2 hyperintensity (“ground-glass appearance”). The rest of brain MRI was unremarkable except for two small old infarcts in the right cerebellar hemisphere (one lesion shown in a and b*). Spinal cord MRI from 2008 (e) was unremarkable, though no axial plane images were performed. Spinal cord MRI in 2019 revealed subtle longitudinal high signal (white arrow-heads) of the posterior columns at the cervico-dorsal junction and middle dorsal region on sagittal T2-weighted images (f). Axial T2-weighted images confirmed bilateral, symmetric signal abnormalities corresponding to the gracilis tracts (g, black arrowhead) and the lateral cortico-spinal tracts (g, white arrows) at different cervical and dorsal levels, without spinal cord atrophy or contrast material (gadolinium) uptake. Fig. 2 CDCA treatment was stopped for 16 months due to product withdrawal. Over this period, diarrhea recurred and walking worsened. She had increased stiffness with muscle pain, new apallesthesia of the lower limbs and onset of cerebellar ataxia. When CDCA treatment was reintroduced (500 mg/d) walking, pain and diarrhea improved. Due to renewed product shortage and patient non-compliance, CDCA treatment was repeatedly discontinued, following which the patient developed an acute psychosis and, short after, a rapid worsening of her gait becaming rollator dependent. Neurologic evaluation showed a severe ataxospastic gait with knee recurvatum (additional files: video). ENMG was normal. Brain MRI was unchanged. Spinal MRI revealed extensive linear T2 weighted hyperintensities appearing bilaterally in lateral corticospinal and gracile tracts ( Fig. 2 ). Despite normal cholestanol levels (6.18 μmol/L; normal range 3.3–12.5 μmol/L), CDCA posology was increased to 750 mg/d. Six months later, the patient had resolution of diarrhea and psychiatric symptoms but no improvement of gait.'}
|
Age-at-Presentation
|
Age (at case presentation)
|
[
"38 - year old"
] |
test-2014
|
7890005
|
{'Case presentation': 'We report a 38-year old woman who presented with chronic diarrhea and progressive spastic paraparesis in her twenties. Brain magnetic resonance imaging (MRI) showed cerebral atrophy with diffuse periventricular white matter hyperintensities. Spinal MRI was normal. CYP27A1 gene sequencing confirmed the diagnosis of CTX. Chenodeoxycholic acid (CDCA) treatment was introduced with remission of diarrhea. Unfortunately, the treatment had to be discontinued several times and the patient developed psychosis and an severe ataxospastic gait. Spinal MRI revealed new linear hyperintensities of the corticospinal and gracile tracts. Thirty-three spinal CTX patients were identified by searching in Pubmed, EMBASE™ and Web of Science databases. All patients presented pyramidal signs and 48% had dorsal column signs. Juvenile cataracts were described in 78% of patients, chronic diarrhea in 65%, and tendon xanthomas in 31%. Disease improvement or stabilization with chenodeoxycholic acid was observed in 69% of patients. A higher prevalence of the Arg395Cys allele was observed in patients with spinal CTX as compared to CTX in general (ᵡ 2 ; p < 0.00001). A 38-year-old woman presented with progressive muscle stiffness, calf cramps and urinary frequency appeared in her twenties ( Fig. 1 ). Her past medical history included chronic diarrhea, scoliosis and bilateral cataract surgery at age 25. She did not take any treatment and had normal schooling. Family history was not relevant. Neurological examination revealed spastic paraparesis with pyramidal signs more prominent on the left lower extremity and flat feet. A neurocognitive study demonstrated severe anterograde verbal memory difficulties and minor executive dysfunction. Electroneuromyography (ENMG) was normal. Brain MRI showed subtle symmetric, bilateral hyperintense T2 ground-glass appearance of the deep white matter, possible symmetric T2 hyperintensity of the cerebellar dentate nuclei and two small ischemic infarct sequelae of the right cerebellar hemisphere ( Fig. 2 ). Spinal MRI was normal. 7 years later, due to progression of spastic paraparesis, CTX was considered. Cholestanol was increased to 64 μmol/L (3.3–12.5 μmol/L). A careful assessment did not found any tendinous xanthomas. Genetic analysis found two monoallelic mutations in the gene CYP27A1 : a missense mutation (c.1183C > T; p. Arg395Cys) in exon 6 and a splicing mutation (c.1184 + 1G > A) in intron 6 and confirmed CTX diagnosis. A treatment with 750 mg/d chenodeoxycholic acid (CDCA) and 20 mg/d simvastatine was introduced ( Fig. 1 ). Three months later, diarrhea was disappeared and no adverse effect was observed. One-year follow-up showed stabilization of neurologic and radiologic signs. Fig. 1 Patient timeline of clinical symptoms and biochemical values. Abbreviations: SP: spastic paraparesia; m: month; CDCA: chenodeoxycholic acid. Normal values for cholestanol (N: 0–15.45 μmol/L); bile acid (N: 0–10.02 μmol/L) Fig. 1 Fig. 2 Brain and spinal cord magnetic resonance imaging (MRI) of the patient. Brain and spinal cord MRI performed in 2008 (a,b,e) and 2019 (c,d,f,g). Axial plane T2 weighted images (a-d) at the level of the dentate nuclei and periventricular white matter showing stable minimal increased signal in the dentate nuclei (arrowheads) and questionable slightly abnormal periventricular white matter T2 hyperintensity (“ground-glass appearance”). The rest of brain MRI was unremarkable except for two small old infarcts in the right cerebellar hemisphere (one lesion shown in a and b*). Spinal cord MRI from 2008 (e) was unremarkable, though no axial plane images were performed. Spinal cord MRI in 2019 revealed subtle longitudinal high signal (white arrow-heads) of the posterior columns at the cervico-dorsal junction and middle dorsal region on sagittal T2-weighted images (f). Axial T2-weighted images confirmed bilateral, symmetric signal abnormalities corresponding to the gracilis tracts (g, black arrowhead) and the lateral cortico-spinal tracts (g, white arrows) at different cervical and dorsal levels, without spinal cord atrophy or contrast material (gadolinium) uptake. Fig. 2 CDCA treatment was stopped for 16 months due to product withdrawal. Over this period, diarrhea recurred and walking worsened. She had increased stiffness with muscle pain, new apallesthesia of the lower limbs and onset of cerebellar ataxia. When CDCA treatment was reintroduced (500 mg/d) walking, pain and diarrhea improved. Due to renewed product shortage and patient non-compliance, CDCA treatment was repeatedly discontinued, following which the patient developed an acute psychosis and, short after, a rapid worsening of her gait becaming rollator dependent. Neurologic evaluation showed a severe ataxospastic gait with knee recurvatum (additional files: video). ENMG was normal. Brain MRI was unchanged. Spinal MRI revealed extensive linear T2 weighted hyperintensities appearing bilaterally in lateral corticospinal and gracile tracts ( Fig. 2 ). Despite normal cholestanol levels (6.18 μmol/L; normal range 3.3–12.5 μmol/L), CDCA posology was increased to 750 mg/d. Six months later, the patient had resolution of diarrhea and psychiatric symptoms but no improvement of gait.'}
|
{'Case presentation': 'We report a 38-year old woman who presented with chronic diarrhea and progressive spastic paraparesis in her twenties. Brain magnetic resonance imaging (MRI) showed cerebral atrophy with diffuse periventricular white matter hyperintensities. Spinal MRI was normal. CYP27A1 gene sequencing confirmed the diagnosis of CTX. Chenodeoxycholic acid (CDCA) treatment was introduced with remission of diarrhea. Unfortunately, the treatment had to be discontinued several times and the patient developed psychosis and an severe ataxospastic gait. Spinal MRI revealed new linear hyperintensities of the corticospinal and gracile tracts. Thirty-three spinal CTX patients were identified by searching in Pubmed, EMBASE™ and Web of Science databases. All patients presented pyramidal signs and 48% had dorsal column signs. Juvenile cataracts were described in 78% of patients, chronic diarrhea in 65%, and tendon xanthomas in 31%. Disease improvement or stabilization with chenodeoxycholic acid was observed in 69% of patients. A higher prevalence of the Arg395Cys allele was observed in patients with spinal CTX as compared to CTX in general (ᵡ 2 ; p < 0.00001). A 38-year-old woman presented with progressive muscle stiffness, calf cramps and urinary frequency appeared in her twenties ( Fig. 1 ). Her past medical history included chronic diarrhea, scoliosis and bilateral cataract surgery at age 25. She did not take any treatment and had normal schooling. Family history was not relevant. Neurological examination revealed spastic paraparesis with pyramidal signs more prominent on the left lower extremity and flat feet. A neurocognitive study demonstrated severe anterograde verbal memory difficulties and minor executive dysfunction. Electroneuromyography (ENMG) was normal. Brain MRI showed subtle symmetric, bilateral hyperintense T2 ground-glass appearance of the deep white matter, possible symmetric T2 hyperintensity of the cerebellar dentate nuclei and two small ischemic infarct sequelae of the right cerebellar hemisphere ( Fig. 2 ). Spinal MRI was normal. 7 years later, due to progression of spastic paraparesis, CTX was considered. Cholestanol was increased to 64 μmol/L (3.3–12.5 μmol/L). A careful assessment did not found any tendinous xanthomas. Genetic analysis found two monoallelic mutations in the gene CYP27A1 : a missense mutation (c.1183C > T; p. Arg395Cys) in exon 6 and a splicing mutation (c.1184 + 1G > A) in intron 6 and confirmed CTX diagnosis. A treatment with 750 mg/d chenodeoxycholic acid (CDCA) and 20 mg/d simvastatine was introduced ( Fig. 1 ). Three months later, diarrhea was disappeared and no adverse effect was observed. One-year follow-up showed stabilization of neurologic and radiologic signs. Fig. 1 Patient timeline of clinical symptoms and biochemical values. Abbreviations: SP: spastic paraparesia; m: month; CDCA: chenodeoxycholic acid. Normal values for cholestanol (N: 0–15.45 μmol/L); bile acid (N: 0–10.02 μmol/L) Fig. 1 Fig. 2 Brain and spinal cord magnetic resonance imaging (MRI) of the patient. Brain and spinal cord MRI performed in 2008 (a,b,e) and 2019 (c,d,f,g). Axial plane T2 weighted images (a-d) at the level of the dentate nuclei and periventricular white matter showing stable minimal increased signal in the dentate nuclei (arrowheads) and questionable slightly abnormal periventricular white matter T2 hyperintensity (“ground-glass appearance”). The rest of brain MRI was unremarkable except for two small old infarcts in the right cerebellar hemisphere (one lesion shown in a and b*). Spinal cord MRI from 2008 (e) was unremarkable, though no axial plane images were performed. Spinal cord MRI in 2019 revealed subtle longitudinal high signal (white arrow-heads) of the posterior columns at the cervico-dorsal junction and middle dorsal region on sagittal T2-weighted images (f). Axial T2-weighted images confirmed bilateral, symmetric signal abnormalities corresponding to the gracilis tracts (g, black arrowhead) and the lateral cortico-spinal tracts (g, white arrows) at different cervical and dorsal levels, without spinal cord atrophy or contrast material (gadolinium) uptake. Fig. 2 CDCA treatment was stopped for 16 months due to product withdrawal. Over this period, diarrhea recurred and walking worsened. She had increased stiffness with muscle pain, new apallesthesia of the lower limbs and onset of cerebellar ataxia. When CDCA treatment was reintroduced (500 mg/d) walking, pain and diarrhea improved. Due to renewed product shortage and patient non-compliance, CDCA treatment was repeatedly discontinued, following which the patient developed an acute psychosis and, short after, a rapid worsening of her gait becaming rollator dependent. Neurologic evaluation showed a severe ataxospastic gait with knee recurvatum (additional files: video). ENMG was normal. Brain MRI was unchanged. Spinal MRI revealed extensive linear T2 weighted hyperintensities appearing bilaterally in lateral corticospinal and gracile tracts ( Fig. 2 ). Despite normal cholestanol levels (6.18 μmol/L; normal range 3.3–12.5 μmol/L), CDCA posology was increased to 750 mg/d. Six months later, the patient had resolution of diarrhea and psychiatric symptoms but no improvement of gait.'}
|
Age-of-Onset
|
Age (of onset)
|
[
"her twenties",
"her twenties"
] |
test-2015
|
7890005
|
{'Case presentation': 'We report a 38-year old woman who presented with chronic diarrhea and progressive spastic paraparesis in her twenties. Brain magnetic resonance imaging (MRI) showed cerebral atrophy with diffuse periventricular white matter hyperintensities. Spinal MRI was normal. CYP27A1 gene sequencing confirmed the diagnosis of CTX. Chenodeoxycholic acid (CDCA) treatment was introduced with remission of diarrhea. Unfortunately, the treatment had to be discontinued several times and the patient developed psychosis and an severe ataxospastic gait. Spinal MRI revealed new linear hyperintensities of the corticospinal and gracile tracts. Thirty-three spinal CTX patients were identified by searching in Pubmed, EMBASE™ and Web of Science databases. All patients presented pyramidal signs and 48% had dorsal column signs. Juvenile cataracts were described in 78% of patients, chronic diarrhea in 65%, and tendon xanthomas in 31%. Disease improvement or stabilization with chenodeoxycholic acid was observed in 69% of patients. A higher prevalence of the Arg395Cys allele was observed in patients with spinal CTX as compared to CTX in general (ᵡ 2 ; p < 0.00001). A 38-year-old woman presented with progressive muscle stiffness, calf cramps and urinary frequency appeared in her twenties ( Fig. 1 ). Her past medical history included chronic diarrhea, scoliosis and bilateral cataract surgery at age 25. She did not take any treatment and had normal schooling. Family history was not relevant. Neurological examination revealed spastic paraparesis with pyramidal signs more prominent on the left lower extremity and flat feet. A neurocognitive study demonstrated severe anterograde verbal memory difficulties and minor executive dysfunction. Electroneuromyography (ENMG) was normal. Brain MRI showed subtle symmetric, bilateral hyperintense T2 ground-glass appearance of the deep white matter, possible symmetric T2 hyperintensity of the cerebellar dentate nuclei and two small ischemic infarct sequelae of the right cerebellar hemisphere ( Fig. 2 ). Spinal MRI was normal. 7 years later, due to progression of spastic paraparesis, CTX was considered. Cholestanol was increased to 64 μmol/L (3.3–12.5 μmol/L). A careful assessment did not found any tendinous xanthomas. Genetic analysis found two monoallelic mutations in the gene CYP27A1 : a missense mutation (c.1183C > T; p. Arg395Cys) in exon 6 and a splicing mutation (c.1184 + 1G > A) in intron 6 and confirmed CTX diagnosis. A treatment with 750 mg/d chenodeoxycholic acid (CDCA) and 20 mg/d simvastatine was introduced ( Fig. 1 ). Three months later, diarrhea was disappeared and no adverse effect was observed. One-year follow-up showed stabilization of neurologic and radiologic signs. Fig. 1 Patient timeline of clinical symptoms and biochemical values. Abbreviations: SP: spastic paraparesia; m: month; CDCA: chenodeoxycholic acid. Normal values for cholestanol (N: 0–15.45 μmol/L); bile acid (N: 0–10.02 μmol/L) Fig. 1 Fig. 2 Brain and spinal cord magnetic resonance imaging (MRI) of the patient. Brain and spinal cord MRI performed in 2008 (a,b,e) and 2019 (c,d,f,g). Axial plane T2 weighted images (a-d) at the level of the dentate nuclei and periventricular white matter showing stable minimal increased signal in the dentate nuclei (arrowheads) and questionable slightly abnormal periventricular white matter T2 hyperintensity (“ground-glass appearance”). The rest of brain MRI was unremarkable except for two small old infarcts in the right cerebellar hemisphere (one lesion shown in a and b*). Spinal cord MRI from 2008 (e) was unremarkable, though no axial plane images were performed. Spinal cord MRI in 2019 revealed subtle longitudinal high signal (white arrow-heads) of the posterior columns at the cervico-dorsal junction and middle dorsal region on sagittal T2-weighted images (f). Axial T2-weighted images confirmed bilateral, symmetric signal abnormalities corresponding to the gracilis tracts (g, black arrowhead) and the lateral cortico-spinal tracts (g, white arrows) at different cervical and dorsal levels, without spinal cord atrophy or contrast material (gadolinium) uptake. Fig. 2 CDCA treatment was stopped for 16 months due to product withdrawal. Over this period, diarrhea recurred and walking worsened. She had increased stiffness with muscle pain, new apallesthesia of the lower limbs and onset of cerebellar ataxia. When CDCA treatment was reintroduced (500 mg/d) walking, pain and diarrhea improved. Due to renewed product shortage and patient non-compliance, CDCA treatment was repeatedly discontinued, following which the patient developed an acute psychosis and, short after, a rapid worsening of her gait becaming rollator dependent. Neurologic evaluation showed a severe ataxospastic gait with knee recurvatum (additional files: video). ENMG was normal. Brain MRI was unchanged. Spinal MRI revealed extensive linear T2 weighted hyperintensities appearing bilaterally in lateral corticospinal and gracile tracts ( Fig. 2 ). Despite normal cholestanol levels (6.18 μmol/L; normal range 3.3–12.5 μmol/L), CDCA posology was increased to 750 mg/d. Six months later, the patient had resolution of diarrhea and psychiatric symptoms but no improvement of gait.'}
|
{'Case presentation': 'We report a 38-year old woman who presented with chronic diarrhea and progressive spastic paraparesis in her twenties. Brain magnetic resonance imaging (MRI) showed cerebral atrophy with diffuse periventricular white matter hyperintensities. Spinal MRI was normal. CYP27A1 gene sequencing confirmed the diagnosis of CTX. Chenodeoxycholic acid (CDCA) treatment was introduced with remission of diarrhea. Unfortunately, the treatment had to be discontinued several times and the patient developed psychosis and an severe ataxospastic gait. Spinal MRI revealed new linear hyperintensities of the corticospinal and gracile tracts. Thirty-three spinal CTX patients were identified by searching in Pubmed, EMBASE™ and Web of Science databases. All patients presented pyramidal signs and 48% had dorsal column signs. Juvenile cataracts were described in 78% of patients, chronic diarrhea in 65%, and tendon xanthomas in 31%. Disease improvement or stabilization with chenodeoxycholic acid was observed in 69% of patients. A higher prevalence of the Arg395Cys allele was observed in patients with spinal CTX as compared to CTX in general (ᵡ 2 ; p < 0.00001). A 38-year-old woman presented with progressive muscle stiffness, calf cramps and urinary frequency appeared in her twenties ( Fig. 1 ). Her past medical history included chronic diarrhea, scoliosis and bilateral cataract surgery at age 25. She did not take any treatment and had normal schooling. Family history was not relevant. Neurological examination revealed spastic paraparesis with pyramidal signs more prominent on the left lower extremity and flat feet. A neurocognitive study demonstrated severe anterograde verbal memory difficulties and minor executive dysfunction. Electroneuromyography (ENMG) was normal. Brain MRI showed subtle symmetric, bilateral hyperintense T2 ground-glass appearance of the deep white matter, possible symmetric T2 hyperintensity of the cerebellar dentate nuclei and two small ischemic infarct sequelae of the right cerebellar hemisphere ( Fig. 2 ). Spinal MRI was normal. 7 years later, due to progression of spastic paraparesis, CTX was considered. Cholestanol was increased to 64 μmol/L (3.3–12.5 μmol/L). A careful assessment did not found any tendinous xanthomas. Genetic analysis found two monoallelic mutations in the gene CYP27A1 : a missense mutation (c.1183C > T; p. Arg395Cys) in exon 6 and a splicing mutation (c.1184 + 1G > A) in intron 6 and confirmed CTX diagnosis. A treatment with 750 mg/d chenodeoxycholic acid (CDCA) and 20 mg/d simvastatine was introduced ( Fig. 1 ). Three months later, diarrhea was disappeared and no adverse effect was observed. One-year follow-up showed stabilization of neurologic and radiologic signs. Fig. 1 Patient timeline of clinical symptoms and biochemical values. Abbreviations: SP: spastic paraparesia; m: month; CDCA: chenodeoxycholic acid. Normal values for cholestanol (N: 0–15.45 μmol/L); bile acid (N: 0–10.02 μmol/L) Fig. 1 Fig. 2 Brain and spinal cord magnetic resonance imaging (MRI) of the patient. Brain and spinal cord MRI performed in 2008 (a,b,e) and 2019 (c,d,f,g). Axial plane T2 weighted images (a-d) at the level of the dentate nuclei and periventricular white matter showing stable minimal increased signal in the dentate nuclei (arrowheads) and questionable slightly abnormal periventricular white matter T2 hyperintensity (“ground-glass appearance”). The rest of brain MRI was unremarkable except for two small old infarcts in the right cerebellar hemisphere (one lesion shown in a and b*). Spinal cord MRI from 2008 (e) was unremarkable, though no axial plane images were performed. Spinal cord MRI in 2019 revealed subtle longitudinal high signal (white arrow-heads) of the posterior columns at the cervico-dorsal junction and middle dorsal region on sagittal T2-weighted images (f). Axial T2-weighted images confirmed bilateral, symmetric signal abnormalities corresponding to the gracilis tracts (g, black arrowhead) and the lateral cortico-spinal tracts (g, white arrows) at different cervical and dorsal levels, without spinal cord atrophy or contrast material (gadolinium) uptake. Fig. 2 CDCA treatment was stopped for 16 months due to product withdrawal. Over this period, diarrhea recurred and walking worsened. She had increased stiffness with muscle pain, new apallesthesia of the lower limbs and onset of cerebellar ataxia. When CDCA treatment was reintroduced (500 mg/d) walking, pain and diarrhea improved. Due to renewed product shortage and patient non-compliance, CDCA treatment was repeatedly discontinued, following which the patient developed an acute psychosis and, short after, a rapid worsening of her gait becaming rollator dependent. Neurologic evaluation showed a severe ataxospastic gait with knee recurvatum (additional files: video). ENMG was normal. Brain MRI was unchanged. Spinal MRI revealed extensive linear T2 weighted hyperintensities appearing bilaterally in lateral corticospinal and gracile tracts ( Fig. 2 ). Despite normal cholestanol levels (6.18 μmol/L; normal range 3.3–12.5 μmol/L), CDCA posology was increased to 750 mg/d. Six months later, the patient had resolution of diarrhea and psychiatric symptoms but no improvement of gait.'}
|
Confirmed-Diagnosis-IEM
|
Confirmed_Diagnosis(IEM)
|
[
"CYP27A1 gene sequencing confirmed the diagnosis of CTX .",
"confirmed CTX diagnosis ."
] |
test-2016
|
7890005
|
{'Case presentation': 'We report a 38-year old woman who presented with chronic diarrhea and progressive spastic paraparesis in her twenties. Brain magnetic resonance imaging (MRI) showed cerebral atrophy with diffuse periventricular white matter hyperintensities. Spinal MRI was normal. CYP27A1 gene sequencing confirmed the diagnosis of CTX. Chenodeoxycholic acid (CDCA) treatment was introduced with remission of diarrhea. Unfortunately, the treatment had to be discontinued several times and the patient developed psychosis and an severe ataxospastic gait. Spinal MRI revealed new linear hyperintensities of the corticospinal and gracile tracts. Thirty-three spinal CTX patients were identified by searching in Pubmed, EMBASE™ and Web of Science databases. All patients presented pyramidal signs and 48% had dorsal column signs. Juvenile cataracts were described in 78% of patients, chronic diarrhea in 65%, and tendon xanthomas in 31%. Disease improvement or stabilization with chenodeoxycholic acid was observed in 69% of patients. A higher prevalence of the Arg395Cys allele was observed in patients with spinal CTX as compared to CTX in general (ᵡ 2 ; p < 0.00001). A 38-year-old woman presented with progressive muscle stiffness, calf cramps and urinary frequency appeared in her twenties ( Fig. 1 ). Her past medical history included chronic diarrhea, scoliosis and bilateral cataract surgery at age 25. She did not take any treatment and had normal schooling. Family history was not relevant. Neurological examination revealed spastic paraparesis with pyramidal signs more prominent on the left lower extremity and flat feet. A neurocognitive study demonstrated severe anterograde verbal memory difficulties and minor executive dysfunction. Electroneuromyography (ENMG) was normal. Brain MRI showed subtle symmetric, bilateral hyperintense T2 ground-glass appearance of the deep white matter, possible symmetric T2 hyperintensity of the cerebellar dentate nuclei and two small ischemic infarct sequelae of the right cerebellar hemisphere ( Fig. 2 ). Spinal MRI was normal. 7 years later, due to progression of spastic paraparesis, CTX was considered. Cholestanol was increased to 64 μmol/L (3.3–12.5 μmol/L). A careful assessment did not found any tendinous xanthomas. Genetic analysis found two monoallelic mutations in the gene CYP27A1 : a missense mutation (c.1183C > T; p. Arg395Cys) in exon 6 and a splicing mutation (c.1184 + 1G > A) in intron 6 and confirmed CTX diagnosis. A treatment with 750 mg/d chenodeoxycholic acid (CDCA) and 20 mg/d simvastatine was introduced ( Fig. 1 ). Three months later, diarrhea was disappeared and no adverse effect was observed. One-year follow-up showed stabilization of neurologic and radiologic signs. Fig. 1 Patient timeline of clinical symptoms and biochemical values. Abbreviations: SP: spastic paraparesia; m: month; CDCA: chenodeoxycholic acid. Normal values for cholestanol (N: 0–15.45 μmol/L); bile acid (N: 0–10.02 μmol/L) Fig. 1 Fig. 2 Brain and spinal cord magnetic resonance imaging (MRI) of the patient. Brain and spinal cord MRI performed in 2008 (a,b,e) and 2019 (c,d,f,g). Axial plane T2 weighted images (a-d) at the level of the dentate nuclei and periventricular white matter showing stable minimal increased signal in the dentate nuclei (arrowheads) and questionable slightly abnormal periventricular white matter T2 hyperintensity (“ground-glass appearance”). The rest of brain MRI was unremarkable except for two small old infarcts in the right cerebellar hemisphere (one lesion shown in a and b*). Spinal cord MRI from 2008 (e) was unremarkable, though no axial plane images were performed. Spinal cord MRI in 2019 revealed subtle longitudinal high signal (white arrow-heads) of the posterior columns at the cervico-dorsal junction and middle dorsal region on sagittal T2-weighted images (f). Axial T2-weighted images confirmed bilateral, symmetric signal abnormalities corresponding to the gracilis tracts (g, black arrowhead) and the lateral cortico-spinal tracts (g, white arrows) at different cervical and dorsal levels, without spinal cord atrophy or contrast material (gadolinium) uptake. Fig. 2 CDCA treatment was stopped for 16 months due to product withdrawal. Over this period, diarrhea recurred and walking worsened. She had increased stiffness with muscle pain, new apallesthesia of the lower limbs and onset of cerebellar ataxia. When CDCA treatment was reintroduced (500 mg/d) walking, pain and diarrhea improved. Due to renewed product shortage and patient non-compliance, CDCA treatment was repeatedly discontinued, following which the patient developed an acute psychosis and, short after, a rapid worsening of her gait becaming rollator dependent. Neurologic evaluation showed a severe ataxospastic gait with knee recurvatum (additional files: video). ENMG was normal. Brain MRI was unchanged. Spinal MRI revealed extensive linear T2 weighted hyperintensities appearing bilaterally in lateral corticospinal and gracile tracts ( Fig. 2 ). Despite normal cholestanol levels (6.18 μmol/L; normal range 3.3–12.5 μmol/L), CDCA posology was increased to 750 mg/d. Six months later, the patient had resolution of diarrhea and psychiatric symptoms but no improvement of gait.'}
|
{'Case presentation': 'We report a 38-year old woman who presented with chronic diarrhea and progressive spastic paraparesis in her twenties. Brain magnetic resonance imaging (MRI) showed cerebral atrophy with diffuse periventricular white matter hyperintensities. Spinal MRI was normal. CYP27A1 gene sequencing confirmed the diagnosis of CTX. Chenodeoxycholic acid (CDCA) treatment was introduced with remission of diarrhea. Unfortunately, the treatment had to be discontinued several times and the patient developed psychosis and an severe ataxospastic gait. Spinal MRI revealed new linear hyperintensities of the corticospinal and gracile tracts. Thirty-three spinal CTX patients were identified by searching in Pubmed, EMBASE™ and Web of Science databases. All patients presented pyramidal signs and 48% had dorsal column signs. Juvenile cataracts were described in 78% of patients, chronic diarrhea in 65%, and tendon xanthomas in 31%. Disease improvement or stabilization with chenodeoxycholic acid was observed in 69% of patients. A higher prevalence of the Arg395Cys allele was observed in patients with spinal CTX as compared to CTX in general (ᵡ 2 ; p < 0.00001). A 38-year-old woman presented with progressive muscle stiffness, calf cramps and urinary frequency appeared in her twenties ( Fig. 1 ). Her past medical history included chronic diarrhea, scoliosis and bilateral cataract surgery at age 25. She did not take any treatment and had normal schooling. Family history was not relevant. Neurological examination revealed spastic paraparesis with pyramidal signs more prominent on the left lower extremity and flat feet. A neurocognitive study demonstrated severe anterograde verbal memory difficulties and minor executive dysfunction. Electroneuromyography (ENMG) was normal. Brain MRI showed subtle symmetric, bilateral hyperintense T2 ground-glass appearance of the deep white matter, possible symmetric T2 hyperintensity of the cerebellar dentate nuclei and two small ischemic infarct sequelae of the right cerebellar hemisphere ( Fig. 2 ). Spinal MRI was normal. 7 years later, due to progression of spastic paraparesis, CTX was considered. Cholestanol was increased to 64 μmol/L (3.3–12.5 μmol/L). A careful assessment did not found any tendinous xanthomas. Genetic analysis found two monoallelic mutations in the gene CYP27A1 : a missense mutation (c.1183C > T; p. Arg395Cys) in exon 6 and a splicing mutation (c.1184 + 1G > A) in intron 6 and confirmed CTX diagnosis. A treatment with 750 mg/d chenodeoxycholic acid (CDCA) and 20 mg/d simvastatine was introduced ( Fig. 1 ). Three months later, diarrhea was disappeared and no adverse effect was observed. One-year follow-up showed stabilization of neurologic and radiologic signs. Fig. 1 Patient timeline of clinical symptoms and biochemical values. Abbreviations: SP: spastic paraparesia; m: month; CDCA: chenodeoxycholic acid. Normal values for cholestanol (N: 0–15.45 μmol/L); bile acid (N: 0–10.02 μmol/L) Fig. 1 Fig. 2 Brain and spinal cord magnetic resonance imaging (MRI) of the patient. Brain and spinal cord MRI performed in 2008 (a,b,e) and 2019 (c,d,f,g). Axial plane T2 weighted images (a-d) at the level of the dentate nuclei and periventricular white matter showing stable minimal increased signal in the dentate nuclei (arrowheads) and questionable slightly abnormal periventricular white matter T2 hyperintensity (“ground-glass appearance”). The rest of brain MRI was unremarkable except for two small old infarcts in the right cerebellar hemisphere (one lesion shown in a and b*). Spinal cord MRI from 2008 (e) was unremarkable, though no axial plane images were performed. Spinal cord MRI in 2019 revealed subtle longitudinal high signal (white arrow-heads) of the posterior columns at the cervico-dorsal junction and middle dorsal region on sagittal T2-weighted images (f). Axial T2-weighted images confirmed bilateral, symmetric signal abnormalities corresponding to the gracilis tracts (g, black arrowhead) and the lateral cortico-spinal tracts (g, white arrows) at different cervical and dorsal levels, without spinal cord atrophy or contrast material (gadolinium) uptake. Fig. 2 CDCA treatment was stopped for 16 months due to product withdrawal. Over this period, diarrhea recurred and walking worsened. She had increased stiffness with muscle pain, new apallesthesia of the lower limbs and onset of cerebellar ataxia. When CDCA treatment was reintroduced (500 mg/d) walking, pain and diarrhea improved. Due to renewed product shortage and patient non-compliance, CDCA treatment was repeatedly discontinued, following which the patient developed an acute psychosis and, short after, a rapid worsening of her gait becaming rollator dependent. Neurologic evaluation showed a severe ataxospastic gait with knee recurvatum (additional files: video). ENMG was normal. Brain MRI was unchanged. Spinal MRI revealed extensive linear T2 weighted hyperintensities appearing bilaterally in lateral corticospinal and gracile tracts ( Fig. 2 ). Despite normal cholestanol levels (6.18 μmol/L; normal range 3.3–12.5 μmol/L), CDCA posology was increased to 750 mg/d. Six months later, the patient had resolution of diarrhea and psychiatric symptoms but no improvement of gait.'}
|
IEM-Treatment
|
IEM_Treatment
|
[
"Chenodeoxycholic acid ( CDCA ) treatment was introduced with remission of diarrhea",
"Disease improvement or stabilization with chenodeoxycholic acid was observed in 69 % of patients",
"A treatment with 750 mg / d chenodeoxycholic acid ( CDCA ) and 20 mg / d simvastatine was introduced"
] |
test-2017
|
7882281
|
{'Case presentation': 'All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient’s parents. An 8-year-old girl of non-consanguineous parents from southern China with history of recurrent abdominal pain and vomiting since 4 years of age presented to the gastroenterology department. Colonoscopy was unremarkable, while multiple ulcers were identified in the small intestine on video capsule endoscopy. She was diagnosed with Crohn’s disease, and initially treated with exclusive enteral nutrition, mesalamine and azathioprine in a local hospital. She still complained of abdominal pain and had multiple episodes of vomiting and was referred to our unit. Apart from gastrointestinal symptoms, she also reported muscle weakness during attacks. On presentation, her physical examination was unremarkable. There was no sign of perianal diseases. Inflammatory markers, including C-reactive protein and erythrocyte sedimentation rate were within normal limits. Other laboratory investigations showed a lactate of 2.9 mmol/L, pH of 7.311, serum free fatty acid of 2.161 mmol/L. Considering the onset of age and recurrent vomiting, serum tandem mass spectrometry was performed, and showed C10 of 1.29 µM, C8 of 0.57 µM, C5/C3 of 0.362 µM. Upper endoscopy and colonoscopy were unremarkable. A repeat video capsule endoscopy revealed diffuse whitish velvet-like changes in several segments without apparent mucosal ulcerations ( Figure 1 ). Abdominal computed tomography without contrast showed hepatic lipomatosis ( Figure 2 ). As a result, diagnosis of Crohn’s disease cannot be supported in our patient. Hepatic lipomatosis might not be a usual cause of recurrent abdominal pain and vomiting in children. However, when associated with elevated free fatty acid, lactate and abnormal results of serum tandem mass spectrometry, metabolic disorders are of high suspicion. Endocrinology was consulted. Genomic DNA was extracted from the peripheral whole blood of the patient and parent using the Agilent SureSelectXT Human All Exon 50-Mb kit. Exome sequencing resulted in an average 100× coverage using the Illumina HiSeq2000/2500 sequencer (Illumina, San Diego, CA, USA). Sequence read alignments were completed using Novoalign (V2.07.18) against the human reference genome GRCh37.p10 ( http://www.novocraft.com ). The bioinformatics pipeline has been previously described ( 3 ). In brief, after quality control, variants were filtered by means of public databases, including Human Gene Mutation Database (HGMD) Professional, the Exome Aggregation Consortium (ExAC), and an in-house database. Sanger sequencing was performed with a Biosystems 3500 DNA Analyzer and analyzed by Mutation Surveyor V4.0.9. Trios exome sequencing showed that compound heterozygous mutations of c. + were identified in ETFDH, which was confirmed by Sanger sequencing ( Figure 3 ). This patient was diagnosed with late-onset MADD and treated with riboflavin with a dosage of 100 mg/day instead of mesalamine and azathioprine. She was symptom-free soon after initiation of treatment. In addition, she did not complain about any adverse effects of the treatment. We followed the patient for 2 years, and she did not report any attack of vomiting and abdominal pain. The parent refused endoscopy since the patient did not show any symptoms after treatment. The timeline of this case was shown in Figure 4 .'}
|
{'Case presentation': 'All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient’s parents. An 8-year-old girl of non-consanguineous parents from southern China with history of recurrent abdominal pain and vomiting since 4 years of age presented to the gastroenterology department. Colonoscopy was unremarkable, while multiple ulcers were identified in the small intestine on video capsule endoscopy. She was diagnosed with Crohn’s disease, and initially treated with exclusive enteral nutrition, mesalamine and azathioprine in a local hospital. She still complained of abdominal pain and had multiple episodes of vomiting and was referred to our unit. Apart from gastrointestinal symptoms, she also reported muscle weakness during attacks. On presentation, her physical examination was unremarkable. There was no sign of perianal diseases. Inflammatory markers, including C-reactive protein and erythrocyte sedimentation rate were within normal limits. Other laboratory investigations showed a lactate of 2.9 mmol/L, pH of 7.311, serum free fatty acid of 2.161 mmol/L. Considering the onset of age and recurrent vomiting, serum tandem mass spectrometry was performed, and showed C10 of 1.29 µM, C8 of 0.57 µM, C5/C3 of 0.362 µM. Upper endoscopy and colonoscopy were unremarkable. A repeat video capsule endoscopy revealed diffuse whitish velvet-like changes in several segments without apparent mucosal ulcerations ( Figure 1 ). Abdominal computed tomography without contrast showed hepatic lipomatosis ( Figure 2 ). As a result, diagnosis of Crohn’s disease cannot be supported in our patient. Hepatic lipomatosis might not be a usual cause of recurrent abdominal pain and vomiting in children. However, when associated with elevated free fatty acid, lactate and abnormal results of serum tandem mass spectrometry, metabolic disorders are of high suspicion. Endocrinology was consulted. Genomic DNA was extracted from the peripheral whole blood of the patient and parent using the Agilent SureSelectXT Human All Exon 50-Mb kit. Exome sequencing resulted in an average 100× coverage using the Illumina HiSeq2000/2500 sequencer (Illumina, San Diego, CA, USA). Sequence read alignments were completed using Novoalign (V2.07.18) against the human reference genome GRCh37.p10 ( http://www.novocraft.com ). The bioinformatics pipeline has been previously described ( 3 ). In brief, after quality control, variants were filtered by means of public databases, including Human Gene Mutation Database (HGMD) Professional, the Exome Aggregation Consortium (ExAC), and an in-house database. Sanger sequencing was performed with a Biosystems 3500 DNA Analyzer and analyzed by Mutation Surveyor V4.0.9. Trios exome sequencing showed that compound heterozygous mutations of c. + were identified in ETFDH, which was confirmed by Sanger sequencing ( Figure 3 ). This patient was diagnosed with late-onset MADD and treated with riboflavin with a dosage of 100 mg/day instead of mesalamine and azathioprine. She was symptom-free soon after initiation of treatment. In addition, she did not complain about any adverse effects of the treatment. We followed the patient for 2 years, and she did not report any attack of vomiting and abdominal pain. The parent refused endoscopy since the patient did not show any symptoms after treatment. The timeline of this case was shown in Figure 4 .'}
|
Vitals-and-Hematology
|
Vitals_Hema
|
[] |
test-2018
|
7882281
|
{'Case presentation': 'All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient’s parents. An 8-year-old girl of non-consanguineous parents from southern China with history of recurrent abdominal pain and vomiting since 4 years of age presented to the gastroenterology department. Colonoscopy was unremarkable, while multiple ulcers were identified in the small intestine on video capsule endoscopy. She was diagnosed with Crohn’s disease, and initially treated with exclusive enteral nutrition, mesalamine and azathioprine in a local hospital. She still complained of abdominal pain and had multiple episodes of vomiting and was referred to our unit. Apart from gastrointestinal symptoms, she also reported muscle weakness during attacks. On presentation, her physical examination was unremarkable. There was no sign of perianal diseases. Inflammatory markers, including C-reactive protein and erythrocyte sedimentation rate were within normal limits. Other laboratory investigations showed a lactate of 2.9 mmol/L, pH of 7.311, serum free fatty acid of 2.161 mmol/L. Considering the onset of age and recurrent vomiting, serum tandem mass spectrometry was performed, and showed C10 of 1.29 µM, C8 of 0.57 µM, C5/C3 of 0.362 µM. Upper endoscopy and colonoscopy were unremarkable. A repeat video capsule endoscopy revealed diffuse whitish velvet-like changes in several segments without apparent mucosal ulcerations ( Figure 1 ). Abdominal computed tomography without contrast showed hepatic lipomatosis ( Figure 2 ). As a result, diagnosis of Crohn’s disease cannot be supported in our patient. Hepatic lipomatosis might not be a usual cause of recurrent abdominal pain and vomiting in children. However, when associated with elevated free fatty acid, lactate and abnormal results of serum tandem mass spectrometry, metabolic disorders are of high suspicion. Endocrinology was consulted. Genomic DNA was extracted from the peripheral whole blood of the patient and parent using the Agilent SureSelectXT Human All Exon 50-Mb kit. Exome sequencing resulted in an average 100× coverage using the Illumina HiSeq2000/2500 sequencer (Illumina, San Diego, CA, USA). Sequence read alignments were completed using Novoalign (V2.07.18) against the human reference genome GRCh37.p10 ( http://www.novocraft.com ). The bioinformatics pipeline has been previously described ( 3 ). In brief, after quality control, variants were filtered by means of public databases, including Human Gene Mutation Database (HGMD) Professional, the Exome Aggregation Consortium (ExAC), and an in-house database. Sanger sequencing was performed with a Biosystems 3500 DNA Analyzer and analyzed by Mutation Surveyor V4.0.9. Trios exome sequencing showed that compound heterozygous mutations of c. + were identified in ETFDH, which was confirmed by Sanger sequencing ( Figure 3 ). This patient was diagnosed with late-onset MADD and treated with riboflavin with a dosage of 100 mg/day instead of mesalamine and azathioprine. She was symptom-free soon after initiation of treatment. In addition, she did not complain about any adverse effects of the treatment. We followed the patient for 2 years, and she did not report any attack of vomiting and abdominal pain. The parent refused endoscopy since the patient did not show any symptoms after treatment. The timeline of this case was shown in Figure 4 .'}
|
{'Case presentation': 'All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient’s parents. An 8-year-old girl of non-consanguineous parents from southern China with history of recurrent abdominal pain and vomiting since 4 years of age presented to the gastroenterology department. Colonoscopy was unremarkable, while multiple ulcers were identified in the small intestine on video capsule endoscopy. She was diagnosed with Crohn’s disease, and initially treated with exclusive enteral nutrition, mesalamine and azathioprine in a local hospital. She still complained of abdominal pain and had multiple episodes of vomiting and was referred to our unit. Apart from gastrointestinal symptoms, she also reported muscle weakness during attacks. On presentation, her physical examination was unremarkable. There was no sign of perianal diseases. Inflammatory markers, including C-reactive protein and erythrocyte sedimentation rate were within normal limits. Other laboratory investigations showed a lactate of 2.9 mmol/L, pH of 7.311, serum free fatty acid of 2.161 mmol/L. Considering the onset of age and recurrent vomiting, serum tandem mass spectrometry was performed, and showed C10 of 1.29 µM, C8 of 0.57 µM, C5/C3 of 0.362 µM. Upper endoscopy and colonoscopy were unremarkable. A repeat video capsule endoscopy revealed diffuse whitish velvet-like changes in several segments without apparent mucosal ulcerations ( Figure 1 ). Abdominal computed tomography without contrast showed hepatic lipomatosis ( Figure 2 ). As a result, diagnosis of Crohn’s disease cannot be supported in our patient. Hepatic lipomatosis might not be a usual cause of recurrent abdominal pain and vomiting in children. However, when associated with elevated free fatty acid, lactate and abnormal results of serum tandem mass spectrometry, metabolic disorders are of high suspicion. Endocrinology was consulted. Genomic DNA was extracted from the peripheral whole blood of the patient and parent using the Agilent SureSelectXT Human All Exon 50-Mb kit. Exome sequencing resulted in an average 100× coverage using the Illumina HiSeq2000/2500 sequencer (Illumina, San Diego, CA, USA). Sequence read alignments were completed using Novoalign (V2.07.18) against the human reference genome GRCh37.p10 ( http://www.novocraft.com ). The bioinformatics pipeline has been previously described ( 3 ). In brief, after quality control, variants were filtered by means of public databases, including Human Gene Mutation Database (HGMD) Professional, the Exome Aggregation Consortium (ExAC), and an in-house database. Sanger sequencing was performed with a Biosystems 3500 DNA Analyzer and analyzed by Mutation Surveyor V4.0.9. Trios exome sequencing showed that compound heterozygous mutations of c. + were identified in ETFDH, which was confirmed by Sanger sequencing ( Figure 3 ). This patient was diagnosed with late-onset MADD and treated with riboflavin with a dosage of 100 mg/day instead of mesalamine and azathioprine. She was symptom-free soon after initiation of treatment. In addition, she did not complain about any adverse effects of the treatment. We followed the patient for 2 years, and she did not report any attack of vomiting and abdominal pain. The parent refused endoscopy since the patient did not show any symptoms after treatment. The timeline of this case was shown in Figure 4 .'}
|
Gastrointestinal-System
|
GI
|
[
"recurrent abdominal pain and vomiting",
"abdominal pain",
"multiple episodes of vomiting",
"no sign of perianal diseases",
"recurrent vomiting"
] |
test-2019
|
7882281
|
{'Case presentation': 'All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient’s parents. An 8-year-old girl of non-consanguineous parents from southern China with history of recurrent abdominal pain and vomiting since 4 years of age presented to the gastroenterology department. Colonoscopy was unremarkable, while multiple ulcers were identified in the small intestine on video capsule endoscopy. She was diagnosed with Crohn’s disease, and initially treated with exclusive enteral nutrition, mesalamine and azathioprine in a local hospital. She still complained of abdominal pain and had multiple episodes of vomiting and was referred to our unit. Apart from gastrointestinal symptoms, she also reported muscle weakness during attacks. On presentation, her physical examination was unremarkable. There was no sign of perianal diseases. Inflammatory markers, including C-reactive protein and erythrocyte sedimentation rate were within normal limits. Other laboratory investigations showed a lactate of 2.9 mmol/L, pH of 7.311, serum free fatty acid of 2.161 mmol/L. Considering the onset of age and recurrent vomiting, serum tandem mass spectrometry was performed, and showed C10 of 1.29 µM, C8 of 0.57 µM, C5/C3 of 0.362 µM. Upper endoscopy and colonoscopy were unremarkable. A repeat video capsule endoscopy revealed diffuse whitish velvet-like changes in several segments without apparent mucosal ulcerations ( Figure 1 ). Abdominal computed tomography without contrast showed hepatic lipomatosis ( Figure 2 ). As a result, diagnosis of Crohn’s disease cannot be supported in our patient. Hepatic lipomatosis might not be a usual cause of recurrent abdominal pain and vomiting in children. However, when associated with elevated free fatty acid, lactate and abnormal results of serum tandem mass spectrometry, metabolic disorders are of high suspicion. Endocrinology was consulted. Genomic DNA was extracted from the peripheral whole blood of the patient and parent using the Agilent SureSelectXT Human All Exon 50-Mb kit. Exome sequencing resulted in an average 100× coverage using the Illumina HiSeq2000/2500 sequencer (Illumina, San Diego, CA, USA). Sequence read alignments were completed using Novoalign (V2.07.18) against the human reference genome GRCh37.p10 ( http://www.novocraft.com ). The bioinformatics pipeline has been previously described ( 3 ). In brief, after quality control, variants were filtered by means of public databases, including Human Gene Mutation Database (HGMD) Professional, the Exome Aggregation Consortium (ExAC), and an in-house database. Sanger sequencing was performed with a Biosystems 3500 DNA Analyzer and analyzed by Mutation Surveyor V4.0.9. Trios exome sequencing showed that compound heterozygous mutations of c. + were identified in ETFDH, which was confirmed by Sanger sequencing ( Figure 3 ). This patient was diagnosed with late-onset MADD and treated with riboflavin with a dosage of 100 mg/day instead of mesalamine and azathioprine. She was symptom-free soon after initiation of treatment. In addition, she did not complain about any adverse effects of the treatment. We followed the patient for 2 years, and she did not report any attack of vomiting and abdominal pain. The parent refused endoscopy since the patient did not show any symptoms after treatment. The timeline of this case was shown in Figure 4 .'}
|
{'Case presentation': 'All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient’s parents. An 8-year-old girl of non-consanguineous parents from southern China with history of recurrent abdominal pain and vomiting since 4 years of age presented to the gastroenterology department. Colonoscopy was unremarkable, while multiple ulcers were identified in the small intestine on video capsule endoscopy. She was diagnosed with Crohn’s disease, and initially treated with exclusive enteral nutrition, mesalamine and azathioprine in a local hospital. She still complained of abdominal pain and had multiple episodes of vomiting and was referred to our unit. Apart from gastrointestinal symptoms, she also reported muscle weakness during attacks. On presentation, her physical examination was unremarkable. There was no sign of perianal diseases. Inflammatory markers, including C-reactive protein and erythrocyte sedimentation rate were within normal limits. Other laboratory investigations showed a lactate of 2.9 mmol/L, pH of 7.311, serum free fatty acid of 2.161 mmol/L. Considering the onset of age and recurrent vomiting, serum tandem mass spectrometry was performed, and showed C10 of 1.29 µM, C8 of 0.57 µM, C5/C3 of 0.362 µM. Upper endoscopy and colonoscopy were unremarkable. A repeat video capsule endoscopy revealed diffuse whitish velvet-like changes in several segments without apparent mucosal ulcerations ( Figure 1 ). Abdominal computed tomography without contrast showed hepatic lipomatosis ( Figure 2 ). As a result, diagnosis of Crohn’s disease cannot be supported in our patient. Hepatic lipomatosis might not be a usual cause of recurrent abdominal pain and vomiting in children. However, when associated with elevated free fatty acid, lactate and abnormal results of serum tandem mass spectrometry, metabolic disorders are of high suspicion. Endocrinology was consulted. Genomic DNA was extracted from the peripheral whole blood of the patient and parent using the Agilent SureSelectXT Human All Exon 50-Mb kit. Exome sequencing resulted in an average 100× coverage using the Illumina HiSeq2000/2500 sequencer (Illumina, San Diego, CA, USA). Sequence read alignments were completed using Novoalign (V2.07.18) against the human reference genome GRCh37.p10 ( http://www.novocraft.com ). The bioinformatics pipeline has been previously described ( 3 ). In brief, after quality control, variants were filtered by means of public databases, including Human Gene Mutation Database (HGMD) Professional, the Exome Aggregation Consortium (ExAC), and an in-house database. Sanger sequencing was performed with a Biosystems 3500 DNA Analyzer and analyzed by Mutation Surveyor V4.0.9. Trios exome sequencing showed that compound heterozygous mutations of c. + were identified in ETFDH, which was confirmed by Sanger sequencing ( Figure 3 ). This patient was diagnosed with late-onset MADD and treated with riboflavin with a dosage of 100 mg/day instead of mesalamine and azathioprine. She was symptom-free soon after initiation of treatment. In addition, she did not complain about any adverse effects of the treatment. We followed the patient for 2 years, and she did not report any attack of vomiting and abdominal pain. The parent refused endoscopy since the patient did not show any symptoms after treatment. The timeline of this case was shown in Figure 4 .'}
|
Patient-History
|
History
|
[
"An 8 - year - old girl of non - consanguineous parents from southern China with history of recurrent abdominal pain and vomiting since 4 years of age presented to the gastroenterology department"
] |
test-2020
|
7882281
|
{'Case presentation': 'All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient’s parents. An 8-year-old girl of non-consanguineous parents from southern China with history of recurrent abdominal pain and vomiting since 4 years of age presented to the gastroenterology department. Colonoscopy was unremarkable, while multiple ulcers were identified in the small intestine on video capsule endoscopy. She was diagnosed with Crohn’s disease, and initially treated with exclusive enteral nutrition, mesalamine and azathioprine in a local hospital. She still complained of abdominal pain and had multiple episodes of vomiting and was referred to our unit. Apart from gastrointestinal symptoms, she also reported muscle weakness during attacks. On presentation, her physical examination was unremarkable. There was no sign of perianal diseases. Inflammatory markers, including C-reactive protein and erythrocyte sedimentation rate were within normal limits. Other laboratory investigations showed a lactate of 2.9 mmol/L, pH of 7.311, serum free fatty acid of 2.161 mmol/L. Considering the onset of age and recurrent vomiting, serum tandem mass spectrometry was performed, and showed C10 of 1.29 µM, C8 of 0.57 µM, C5/C3 of 0.362 µM. Upper endoscopy and colonoscopy were unremarkable. A repeat video capsule endoscopy revealed diffuse whitish velvet-like changes in several segments without apparent mucosal ulcerations ( Figure 1 ). Abdominal computed tomography without contrast showed hepatic lipomatosis ( Figure 2 ). As a result, diagnosis of Crohn’s disease cannot be supported in our patient. Hepatic lipomatosis might not be a usual cause of recurrent abdominal pain and vomiting in children. However, when associated with elevated free fatty acid, lactate and abnormal results of serum tandem mass spectrometry, metabolic disorders are of high suspicion. Endocrinology was consulted. Genomic DNA was extracted from the peripheral whole blood of the patient and parent using the Agilent SureSelectXT Human All Exon 50-Mb kit. Exome sequencing resulted in an average 100× coverage using the Illumina HiSeq2000/2500 sequencer (Illumina, San Diego, CA, USA). Sequence read alignments were completed using Novoalign (V2.07.18) against the human reference genome GRCh37.p10 ( http://www.novocraft.com ). The bioinformatics pipeline has been previously described ( 3 ). In brief, after quality control, variants were filtered by means of public databases, including Human Gene Mutation Database (HGMD) Professional, the Exome Aggregation Consortium (ExAC), and an in-house database. Sanger sequencing was performed with a Biosystems 3500 DNA Analyzer and analyzed by Mutation Surveyor V4.0.9. Trios exome sequencing showed that compound heterozygous mutations of c. + were identified in ETFDH, which was confirmed by Sanger sequencing ( Figure 3 ). This patient was diagnosed with late-onset MADD and treated with riboflavin with a dosage of 100 mg/day instead of mesalamine and azathioprine. She was symptom-free soon after initiation of treatment. In addition, she did not complain about any adverse effects of the treatment. We followed the patient for 2 years, and she did not report any attack of vomiting and abdominal pain. The parent refused endoscopy since the patient did not show any symptoms after treatment. The timeline of this case was shown in Figure 4 .'}
|
{'Case presentation': 'All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient’s parents. An 8-year-old girl of non-consanguineous parents from southern China with history of recurrent abdominal pain and vomiting since 4 years of age presented to the gastroenterology department. Colonoscopy was unremarkable, while multiple ulcers were identified in the small intestine on video capsule endoscopy. She was diagnosed with Crohn’s disease, and initially treated with exclusive enteral nutrition, mesalamine and azathioprine in a local hospital. She still complained of abdominal pain and had multiple episodes of vomiting and was referred to our unit. Apart from gastrointestinal symptoms, she also reported muscle weakness during attacks. On presentation, her physical examination was unremarkable. There was no sign of perianal diseases. Inflammatory markers, including C-reactive protein and erythrocyte sedimentation rate were within normal limits. Other laboratory investigations showed a lactate of 2.9 mmol/L, pH of 7.311, serum free fatty acid of 2.161 mmol/L. Considering the onset of age and recurrent vomiting, serum tandem mass spectrometry was performed, and showed C10 of 1.29 µM, C8 of 0.57 µM, C5/C3 of 0.362 µM. Upper endoscopy and colonoscopy were unremarkable. A repeat video capsule endoscopy revealed diffuse whitish velvet-like changes in several segments without apparent mucosal ulcerations ( Figure 1 ). Abdominal computed tomography without contrast showed hepatic lipomatosis ( Figure 2 ). As a result, diagnosis of Crohn’s disease cannot be supported in our patient. Hepatic lipomatosis might not be a usual cause of recurrent abdominal pain and vomiting in children. However, when associated with elevated free fatty acid, lactate and abnormal results of serum tandem mass spectrometry, metabolic disorders are of high suspicion. Endocrinology was consulted. Genomic DNA was extracted from the peripheral whole blood of the patient and parent using the Agilent SureSelectXT Human All Exon 50-Mb kit. Exome sequencing resulted in an average 100× coverage using the Illumina HiSeq2000/2500 sequencer (Illumina, San Diego, CA, USA). Sequence read alignments were completed using Novoalign (V2.07.18) against the human reference genome GRCh37.p10 ( http://www.novocraft.com ). The bioinformatics pipeline has been previously described ( 3 ). In brief, after quality control, variants were filtered by means of public databases, including Human Gene Mutation Database (HGMD) Professional, the Exome Aggregation Consortium (ExAC), and an in-house database. Sanger sequencing was performed with a Biosystems 3500 DNA Analyzer and analyzed by Mutation Surveyor V4.0.9. Trios exome sequencing showed that compound heterozygous mutations of c. + were identified in ETFDH, which was confirmed by Sanger sequencing ( Figure 3 ). This patient was diagnosed with late-onset MADD and treated with riboflavin with a dosage of 100 mg/day instead of mesalamine and azathioprine. She was symptom-free soon after initiation of treatment. In addition, she did not complain about any adverse effects of the treatment. We followed the patient for 2 years, and she did not report any attack of vomiting and abdominal pain. The parent refused endoscopy since the patient did not show any symptoms after treatment. The timeline of this case was shown in Figure 4 .'}
|
Neurology
|
Neuro
|
[
"muscle weakness during attacks."
] |
test-2021
|
7882281
|
{'Case presentation': 'All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient’s parents. An 8-year-old girl of non-consanguineous parents from southern China with history of recurrent abdominal pain and vomiting since 4 years of age presented to the gastroenterology department. Colonoscopy was unremarkable, while multiple ulcers were identified in the small intestine on video capsule endoscopy. She was diagnosed with Crohn’s disease, and initially treated with exclusive enteral nutrition, mesalamine and azathioprine in a local hospital. She still complained of abdominal pain and had multiple episodes of vomiting and was referred to our unit. Apart from gastrointestinal symptoms, she also reported muscle weakness during attacks. On presentation, her physical examination was unremarkable. There was no sign of perianal diseases. Inflammatory markers, including C-reactive protein and erythrocyte sedimentation rate were within normal limits. Other laboratory investigations showed a lactate of 2.9 mmol/L, pH of 7.311, serum free fatty acid of 2.161 mmol/L. Considering the onset of age and recurrent vomiting, serum tandem mass spectrometry was performed, and showed C10 of 1.29 µM, C8 of 0.57 µM, C5/C3 of 0.362 µM. Upper endoscopy and colonoscopy were unremarkable. A repeat video capsule endoscopy revealed diffuse whitish velvet-like changes in several segments without apparent mucosal ulcerations ( Figure 1 ). Abdominal computed tomography without contrast showed hepatic lipomatosis ( Figure 2 ). As a result, diagnosis of Crohn’s disease cannot be supported in our patient. Hepatic lipomatosis might not be a usual cause of recurrent abdominal pain and vomiting in children. However, when associated with elevated free fatty acid, lactate and abnormal results of serum tandem mass spectrometry, metabolic disorders are of high suspicion. Endocrinology was consulted. Genomic DNA was extracted from the peripheral whole blood of the patient and parent using the Agilent SureSelectXT Human All Exon 50-Mb kit. Exome sequencing resulted in an average 100× coverage using the Illumina HiSeq2000/2500 sequencer (Illumina, San Diego, CA, USA). Sequence read alignments were completed using Novoalign (V2.07.18) against the human reference genome GRCh37.p10 ( http://www.novocraft.com ). The bioinformatics pipeline has been previously described ( 3 ). In brief, after quality control, variants were filtered by means of public databases, including Human Gene Mutation Database (HGMD) Professional, the Exome Aggregation Consortium (ExAC), and an in-house database. Sanger sequencing was performed with a Biosystems 3500 DNA Analyzer and analyzed by Mutation Surveyor V4.0.9. Trios exome sequencing showed that compound heterozygous mutations of c. + were identified in ETFDH, which was confirmed by Sanger sequencing ( Figure 3 ). This patient was diagnosed with late-onset MADD and treated with riboflavin with a dosage of 100 mg/day instead of mesalamine and azathioprine. She was symptom-free soon after initiation of treatment. In addition, she did not complain about any adverse effects of the treatment. We followed the patient for 2 years, and she did not report any attack of vomiting and abdominal pain. The parent refused endoscopy since the patient did not show any symptoms after treatment. The timeline of this case was shown in Figure 4 .'}
|
{'Case presentation': 'All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient’s parents. An 8-year-old girl of non-consanguineous parents from southern China with history of recurrent abdominal pain and vomiting since 4 years of age presented to the gastroenterology department. Colonoscopy was unremarkable, while multiple ulcers were identified in the small intestine on video capsule endoscopy. She was diagnosed with Crohn’s disease, and initially treated with exclusive enteral nutrition, mesalamine and azathioprine in a local hospital. She still complained of abdominal pain and had multiple episodes of vomiting and was referred to our unit. Apart from gastrointestinal symptoms, she also reported muscle weakness during attacks. On presentation, her physical examination was unremarkable. There was no sign of perianal diseases. Inflammatory markers, including C-reactive protein and erythrocyte sedimentation rate were within normal limits. Other laboratory investigations showed a lactate of 2.9 mmol/L, pH of 7.311, serum free fatty acid of 2.161 mmol/L. Considering the onset of age and recurrent vomiting, serum tandem mass spectrometry was performed, and showed C10 of 1.29 µM, C8 of 0.57 µM, C5/C3 of 0.362 µM. Upper endoscopy and colonoscopy were unremarkable. A repeat video capsule endoscopy revealed diffuse whitish velvet-like changes in several segments without apparent mucosal ulcerations ( Figure 1 ). Abdominal computed tomography without contrast showed hepatic lipomatosis ( Figure 2 ). As a result, diagnosis of Crohn’s disease cannot be supported in our patient. Hepatic lipomatosis might not be a usual cause of recurrent abdominal pain and vomiting in children. However, when associated with elevated free fatty acid, lactate and abnormal results of serum tandem mass spectrometry, metabolic disorders are of high suspicion. Endocrinology was consulted. Genomic DNA was extracted from the peripheral whole blood of the patient and parent using the Agilent SureSelectXT Human All Exon 50-Mb kit. Exome sequencing resulted in an average 100× coverage using the Illumina HiSeq2000/2500 sequencer (Illumina, San Diego, CA, USA). Sequence read alignments were completed using Novoalign (V2.07.18) against the human reference genome GRCh37.p10 ( http://www.novocraft.com ). The bioinformatics pipeline has been previously described ( 3 ). In brief, after quality control, variants were filtered by means of public databases, including Human Gene Mutation Database (HGMD) Professional, the Exome Aggregation Consortium (ExAC), and an in-house database. Sanger sequencing was performed with a Biosystems 3500 DNA Analyzer and analyzed by Mutation Surveyor V4.0.9. Trios exome sequencing showed that compound heterozygous mutations of c. + were identified in ETFDH, which was confirmed by Sanger sequencing ( Figure 3 ). This patient was diagnosed with late-onset MADD and treated with riboflavin with a dosage of 100 mg/day instead of mesalamine and azathioprine. She was symptom-free soon after initiation of treatment. In addition, she did not complain about any adverse effects of the treatment. We followed the patient for 2 years, and she did not report any attack of vomiting and abdominal pain. The parent refused endoscopy since the patient did not show any symptoms after treatment. The timeline of this case was shown in Figure 4 .'}
|
Laboratory-and-Imaging
|
Lab_Image
|
[
"Inflammatory markers, including C - reactive protein and erythrocyte sedimentation rate were within normal limits. Other laboratory investigations showed a lactate of 2.9 mmol / L, pH of 7.311, serum free fatty acid of 2.161 mmol / L.",
"serum tandem mass spectrometry was performed, and showed C10 of 1.29 µM, C8 of 0.57 µM, C5 / C3 of 0.362 µM.",
"Abdominal computed tomography without contrast showed hepatic lipomatosis",
"Trios exome sequencing showed that compound heterozygous mutations of c. + were identified in ETFDH, which was confirmed by Sanger sequencing"
] |
test-2022
|
7882281
|
{'Case presentation': 'All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient’s parents. An 8-year-old girl of non-consanguineous parents from southern China with history of recurrent abdominal pain and vomiting since 4 years of age presented to the gastroenterology department. Colonoscopy was unremarkable, while multiple ulcers were identified in the small intestine on video capsule endoscopy. She was diagnosed with Crohn’s disease, and initially treated with exclusive enteral nutrition, mesalamine and azathioprine in a local hospital. She still complained of abdominal pain and had multiple episodes of vomiting and was referred to our unit. Apart from gastrointestinal symptoms, she also reported muscle weakness during attacks. On presentation, her physical examination was unremarkable. There was no sign of perianal diseases. Inflammatory markers, including C-reactive protein and erythrocyte sedimentation rate were within normal limits. Other laboratory investigations showed a lactate of 2.9 mmol/L, pH of 7.311, serum free fatty acid of 2.161 mmol/L. Considering the onset of age and recurrent vomiting, serum tandem mass spectrometry was performed, and showed C10 of 1.29 µM, C8 of 0.57 µM, C5/C3 of 0.362 µM. Upper endoscopy and colonoscopy were unremarkable. A repeat video capsule endoscopy revealed diffuse whitish velvet-like changes in several segments without apparent mucosal ulcerations ( Figure 1 ). Abdominal computed tomography without contrast showed hepatic lipomatosis ( Figure 2 ). As a result, diagnosis of Crohn’s disease cannot be supported in our patient. Hepatic lipomatosis might not be a usual cause of recurrent abdominal pain and vomiting in children. However, when associated with elevated free fatty acid, lactate and abnormal results of serum tandem mass spectrometry, metabolic disorders are of high suspicion. Endocrinology was consulted. Genomic DNA was extracted from the peripheral whole blood of the patient and parent using the Agilent SureSelectXT Human All Exon 50-Mb kit. Exome sequencing resulted in an average 100× coverage using the Illumina HiSeq2000/2500 sequencer (Illumina, San Diego, CA, USA). Sequence read alignments were completed using Novoalign (V2.07.18) against the human reference genome GRCh37.p10 ( http://www.novocraft.com ). The bioinformatics pipeline has been previously described ( 3 ). In brief, after quality control, variants were filtered by means of public databases, including Human Gene Mutation Database (HGMD) Professional, the Exome Aggregation Consortium (ExAC), and an in-house database. Sanger sequencing was performed with a Biosystems 3500 DNA Analyzer and analyzed by Mutation Surveyor V4.0.9. Trios exome sequencing showed that compound heterozygous mutations of c. + were identified in ETFDH, which was confirmed by Sanger sequencing ( Figure 3 ). This patient was diagnosed with late-onset MADD and treated with riboflavin with a dosage of 100 mg/day instead of mesalamine and azathioprine. She was symptom-free soon after initiation of treatment. In addition, she did not complain about any adverse effects of the treatment. We followed the patient for 2 years, and she did not report any attack of vomiting and abdominal pain. The parent refused endoscopy since the patient did not show any symptoms after treatment. The timeline of this case was shown in Figure 4 .'}
|
{'Case presentation': 'All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient’s parents. An 8-year-old girl of non-consanguineous parents from southern China with history of recurrent abdominal pain and vomiting since 4 years of age presented to the gastroenterology department. Colonoscopy was unremarkable, while multiple ulcers were identified in the small intestine on video capsule endoscopy. She was diagnosed with Crohn’s disease, and initially treated with exclusive enteral nutrition, mesalamine and azathioprine in a local hospital. She still complained of abdominal pain and had multiple episodes of vomiting and was referred to our unit. Apart from gastrointestinal symptoms, she also reported muscle weakness during attacks. On presentation, her physical examination was unremarkable. There was no sign of perianal diseases. Inflammatory markers, including C-reactive protein and erythrocyte sedimentation rate were within normal limits. Other laboratory investigations showed a lactate of 2.9 mmol/L, pH of 7.311, serum free fatty acid of 2.161 mmol/L. Considering the onset of age and recurrent vomiting, serum tandem mass spectrometry was performed, and showed C10 of 1.29 µM, C8 of 0.57 µM, C5/C3 of 0.362 µM. Upper endoscopy and colonoscopy were unremarkable. A repeat video capsule endoscopy revealed diffuse whitish velvet-like changes in several segments without apparent mucosal ulcerations ( Figure 1 ). Abdominal computed tomography without contrast showed hepatic lipomatosis ( Figure 2 ). As a result, diagnosis of Crohn’s disease cannot be supported in our patient. Hepatic lipomatosis might not be a usual cause of recurrent abdominal pain and vomiting in children. However, when associated with elevated free fatty acid, lactate and abnormal results of serum tandem mass spectrometry, metabolic disorders are of high suspicion. Endocrinology was consulted. Genomic DNA was extracted from the peripheral whole blood of the patient and parent using the Agilent SureSelectXT Human All Exon 50-Mb kit. Exome sequencing resulted in an average 100× coverage using the Illumina HiSeq2000/2500 sequencer (Illumina, San Diego, CA, USA). Sequence read alignments were completed using Novoalign (V2.07.18) against the human reference genome GRCh37.p10 ( http://www.novocraft.com ). The bioinformatics pipeline has been previously described ( 3 ). In brief, after quality control, variants were filtered by means of public databases, including Human Gene Mutation Database (HGMD) Professional, the Exome Aggregation Consortium (ExAC), and an in-house database. Sanger sequencing was performed with a Biosystems 3500 DNA Analyzer and analyzed by Mutation Surveyor V4.0.9. Trios exome sequencing showed that compound heterozygous mutations of c. + were identified in ETFDH, which was confirmed by Sanger sequencing ( Figure 3 ). This patient was diagnosed with late-onset MADD and treated with riboflavin with a dosage of 100 mg/day instead of mesalamine and azathioprine. She was symptom-free soon after initiation of treatment. In addition, she did not complain about any adverse effects of the treatment. We followed the patient for 2 years, and she did not report any attack of vomiting and abdominal pain. The parent refused endoscopy since the patient did not show any symptoms after treatment. The timeline of this case was shown in Figure 4 .'}
|
Cardiovascular-System
|
CVS
|
[] |
test-2023
|
7882281
|
{'Case presentation': 'All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient’s parents. An 8-year-old girl of non-consanguineous parents from southern China with history of recurrent abdominal pain and vomiting since 4 years of age presented to the gastroenterology department. Colonoscopy was unremarkable, while multiple ulcers were identified in the small intestine on video capsule endoscopy. She was diagnosed with Crohn’s disease, and initially treated with exclusive enteral nutrition, mesalamine and azathioprine in a local hospital. She still complained of abdominal pain and had multiple episodes of vomiting and was referred to our unit. Apart from gastrointestinal symptoms, she also reported muscle weakness during attacks. On presentation, her physical examination was unremarkable. There was no sign of perianal diseases. Inflammatory markers, including C-reactive protein and erythrocyte sedimentation rate were within normal limits. Other laboratory investigations showed a lactate of 2.9 mmol/L, pH of 7.311, serum free fatty acid of 2.161 mmol/L. Considering the onset of age and recurrent vomiting, serum tandem mass spectrometry was performed, and showed C10 of 1.29 µM, C8 of 0.57 µM, C5/C3 of 0.362 µM. Upper endoscopy and colonoscopy were unremarkable. A repeat video capsule endoscopy revealed diffuse whitish velvet-like changes in several segments without apparent mucosal ulcerations ( Figure 1 ). Abdominal computed tomography without contrast showed hepatic lipomatosis ( Figure 2 ). As a result, diagnosis of Crohn’s disease cannot be supported in our patient. Hepatic lipomatosis might not be a usual cause of recurrent abdominal pain and vomiting in children. However, when associated with elevated free fatty acid, lactate and abnormal results of serum tandem mass spectrometry, metabolic disorders are of high suspicion. Endocrinology was consulted. Genomic DNA was extracted from the peripheral whole blood of the patient and parent using the Agilent SureSelectXT Human All Exon 50-Mb kit. Exome sequencing resulted in an average 100× coverage using the Illumina HiSeq2000/2500 sequencer (Illumina, San Diego, CA, USA). Sequence read alignments were completed using Novoalign (V2.07.18) against the human reference genome GRCh37.p10 ( http://www.novocraft.com ). The bioinformatics pipeline has been previously described ( 3 ). In brief, after quality control, variants were filtered by means of public databases, including Human Gene Mutation Database (HGMD) Professional, the Exome Aggregation Consortium (ExAC), and an in-house database. Sanger sequencing was performed with a Biosystems 3500 DNA Analyzer and analyzed by Mutation Surveyor V4.0.9. Trios exome sequencing showed that compound heterozygous mutations of c. + were identified in ETFDH, which was confirmed by Sanger sequencing ( Figure 3 ). This patient was diagnosed with late-onset MADD and treated with riboflavin with a dosage of 100 mg/day instead of mesalamine and azathioprine. She was symptom-free soon after initiation of treatment. In addition, she did not complain about any adverse effects of the treatment. We followed the patient for 2 years, and she did not report any attack of vomiting and abdominal pain. The parent refused endoscopy since the patient did not show any symptoms after treatment. The timeline of this case was shown in Figure 4 .'}
|
{'Case presentation': 'All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient’s parents. An 8-year-old girl of non-consanguineous parents from southern China with history of recurrent abdominal pain and vomiting since 4 years of age presented to the gastroenterology department. Colonoscopy was unremarkable, while multiple ulcers were identified in the small intestine on video capsule endoscopy. She was diagnosed with Crohn’s disease, and initially treated with exclusive enteral nutrition, mesalamine and azathioprine in a local hospital. She still complained of abdominal pain and had multiple episodes of vomiting and was referred to our unit. Apart from gastrointestinal symptoms, she also reported muscle weakness during attacks. On presentation, her physical examination was unremarkable. There was no sign of perianal diseases. Inflammatory markers, including C-reactive protein and erythrocyte sedimentation rate were within normal limits. Other laboratory investigations showed a lactate of 2.9 mmol/L, pH of 7.311, serum free fatty acid of 2.161 mmol/L. Considering the onset of age and recurrent vomiting, serum tandem mass spectrometry was performed, and showed C10 of 1.29 µM, C8 of 0.57 µM, C5/C3 of 0.362 µM. Upper endoscopy and colonoscopy were unremarkable. A repeat video capsule endoscopy revealed diffuse whitish velvet-like changes in several segments without apparent mucosal ulcerations ( Figure 1 ). Abdominal computed tomography without contrast showed hepatic lipomatosis ( Figure 2 ). As a result, diagnosis of Crohn’s disease cannot be supported in our patient. Hepatic lipomatosis might not be a usual cause of recurrent abdominal pain and vomiting in children. However, when associated with elevated free fatty acid, lactate and abnormal results of serum tandem mass spectrometry, metabolic disorders are of high suspicion. Endocrinology was consulted. Genomic DNA was extracted from the peripheral whole blood of the patient and parent using the Agilent SureSelectXT Human All Exon 50-Mb kit. Exome sequencing resulted in an average 100× coverage using the Illumina HiSeq2000/2500 sequencer (Illumina, San Diego, CA, USA). Sequence read alignments were completed using Novoalign (V2.07.18) against the human reference genome GRCh37.p10 ( http://www.novocraft.com ). The bioinformatics pipeline has been previously described ( 3 ). In brief, after quality control, variants were filtered by means of public databases, including Human Gene Mutation Database (HGMD) Professional, the Exome Aggregation Consortium (ExAC), and an in-house database. Sanger sequencing was performed with a Biosystems 3500 DNA Analyzer and analyzed by Mutation Surveyor V4.0.9. Trios exome sequencing showed that compound heterozygous mutations of c. + were identified in ETFDH, which was confirmed by Sanger sequencing ( Figure 3 ). This patient was diagnosed with late-onset MADD and treated with riboflavin with a dosage of 100 mg/day instead of mesalamine and azathioprine. She was symptom-free soon after initiation of treatment. In addition, she did not complain about any adverse effects of the treatment. We followed the patient for 2 years, and she did not report any attack of vomiting and abdominal pain. The parent refused endoscopy since the patient did not show any symptoms after treatment. The timeline of this case was shown in Figure 4 .'}
|
Endocrinology
|
ENDO
|
[] |
test-2024
|
7882281
|
{'Case presentation': 'All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient’s parents. An 8-year-old girl of non-consanguineous parents from southern China with history of recurrent abdominal pain and vomiting since 4 years of age presented to the gastroenterology department. Colonoscopy was unremarkable, while multiple ulcers were identified in the small intestine on video capsule endoscopy. She was diagnosed with Crohn’s disease, and initially treated with exclusive enteral nutrition, mesalamine and azathioprine in a local hospital. She still complained of abdominal pain and had multiple episodes of vomiting and was referred to our unit. Apart from gastrointestinal symptoms, she also reported muscle weakness during attacks. On presentation, her physical examination was unremarkable. There was no sign of perianal diseases. Inflammatory markers, including C-reactive protein and erythrocyte sedimentation rate were within normal limits. Other laboratory investigations showed a lactate of 2.9 mmol/L, pH of 7.311, serum free fatty acid of 2.161 mmol/L. Considering the onset of age and recurrent vomiting, serum tandem mass spectrometry was performed, and showed C10 of 1.29 µM, C8 of 0.57 µM, C5/C3 of 0.362 µM. Upper endoscopy and colonoscopy were unremarkable. A repeat video capsule endoscopy revealed diffuse whitish velvet-like changes in several segments without apparent mucosal ulcerations ( Figure 1 ). Abdominal computed tomography without contrast showed hepatic lipomatosis ( Figure 2 ). As a result, diagnosis of Crohn’s disease cannot be supported in our patient. Hepatic lipomatosis might not be a usual cause of recurrent abdominal pain and vomiting in children. However, when associated with elevated free fatty acid, lactate and abnormal results of serum tandem mass spectrometry, metabolic disorders are of high suspicion. Endocrinology was consulted. Genomic DNA was extracted from the peripheral whole blood of the patient and parent using the Agilent SureSelectXT Human All Exon 50-Mb kit. Exome sequencing resulted in an average 100× coverage using the Illumina HiSeq2000/2500 sequencer (Illumina, San Diego, CA, USA). Sequence read alignments were completed using Novoalign (V2.07.18) against the human reference genome GRCh37.p10 ( http://www.novocraft.com ). The bioinformatics pipeline has been previously described ( 3 ). In brief, after quality control, variants were filtered by means of public databases, including Human Gene Mutation Database (HGMD) Professional, the Exome Aggregation Consortium (ExAC), and an in-house database. Sanger sequencing was performed with a Biosystems 3500 DNA Analyzer and analyzed by Mutation Surveyor V4.0.9. Trios exome sequencing showed that compound heterozygous mutations of c. + were identified in ETFDH, which was confirmed by Sanger sequencing ( Figure 3 ). This patient was diagnosed with late-onset MADD and treated with riboflavin with a dosage of 100 mg/day instead of mesalamine and azathioprine. She was symptom-free soon after initiation of treatment. In addition, she did not complain about any adverse effects of the treatment. We followed the patient for 2 years, and she did not report any attack of vomiting and abdominal pain. The parent refused endoscopy since the patient did not show any symptoms after treatment. The timeline of this case was shown in Figure 4 .'}
|
{'Case presentation': 'All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient’s parents. An 8-year-old girl of non-consanguineous parents from southern China with history of recurrent abdominal pain and vomiting since 4 years of age presented to the gastroenterology department. Colonoscopy was unremarkable, while multiple ulcers were identified in the small intestine on video capsule endoscopy. She was diagnosed with Crohn’s disease, and initially treated with exclusive enteral nutrition, mesalamine and azathioprine in a local hospital. She still complained of abdominal pain and had multiple episodes of vomiting and was referred to our unit. Apart from gastrointestinal symptoms, she also reported muscle weakness during attacks. On presentation, her physical examination was unremarkable. There was no sign of perianal diseases. Inflammatory markers, including C-reactive protein and erythrocyte sedimentation rate were within normal limits. Other laboratory investigations showed a lactate of 2.9 mmol/L, pH of 7.311, serum free fatty acid of 2.161 mmol/L. Considering the onset of age and recurrent vomiting, serum tandem mass spectrometry was performed, and showed C10 of 1.29 µM, C8 of 0.57 µM, C5/C3 of 0.362 µM. Upper endoscopy and colonoscopy were unremarkable. A repeat video capsule endoscopy revealed diffuse whitish velvet-like changes in several segments without apparent mucosal ulcerations ( Figure 1 ). Abdominal computed tomography without contrast showed hepatic lipomatosis ( Figure 2 ). As a result, diagnosis of Crohn’s disease cannot be supported in our patient. Hepatic lipomatosis might not be a usual cause of recurrent abdominal pain and vomiting in children. However, when associated with elevated free fatty acid, lactate and abnormal results of serum tandem mass spectrometry, metabolic disorders are of high suspicion. Endocrinology was consulted. Genomic DNA was extracted from the peripheral whole blood of the patient and parent using the Agilent SureSelectXT Human All Exon 50-Mb kit. Exome sequencing resulted in an average 100× coverage using the Illumina HiSeq2000/2500 sequencer (Illumina, San Diego, CA, USA). Sequence read alignments were completed using Novoalign (V2.07.18) against the human reference genome GRCh37.p10 ( http://www.novocraft.com ). The bioinformatics pipeline has been previously described ( 3 ). In brief, after quality control, variants were filtered by means of public databases, including Human Gene Mutation Database (HGMD) Professional, the Exome Aggregation Consortium (ExAC), and an in-house database. Sanger sequencing was performed with a Biosystems 3500 DNA Analyzer and analyzed by Mutation Surveyor V4.0.9. Trios exome sequencing showed that compound heterozygous mutations of c. + were identified in ETFDH, which was confirmed by Sanger sequencing ( Figure 3 ). This patient was diagnosed with late-onset MADD and treated with riboflavin with a dosage of 100 mg/day instead of mesalamine and azathioprine. She was symptom-free soon after initiation of treatment. In addition, she did not complain about any adverse effects of the treatment. We followed the patient for 2 years, and she did not report any attack of vomiting and abdominal pain. The parent refused endoscopy since the patient did not show any symptoms after treatment. The timeline of this case was shown in Figure 4 .'}
|
Genitourinary-System
|
GU
|
[] |
test-2025
|
7882281
|
{'Case presentation': 'All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient’s parents. An 8-year-old girl of non-consanguineous parents from southern China with history of recurrent abdominal pain and vomiting since 4 years of age presented to the gastroenterology department. Colonoscopy was unremarkable, while multiple ulcers were identified in the small intestine on video capsule endoscopy. She was diagnosed with Crohn’s disease, and initially treated with exclusive enteral nutrition, mesalamine and azathioprine in a local hospital. She still complained of abdominal pain and had multiple episodes of vomiting and was referred to our unit. Apart from gastrointestinal symptoms, she also reported muscle weakness during attacks. On presentation, her physical examination was unremarkable. There was no sign of perianal diseases. Inflammatory markers, including C-reactive protein and erythrocyte sedimentation rate were within normal limits. Other laboratory investigations showed a lactate of 2.9 mmol/L, pH of 7.311, serum free fatty acid of 2.161 mmol/L. Considering the onset of age and recurrent vomiting, serum tandem mass spectrometry was performed, and showed C10 of 1.29 µM, C8 of 0.57 µM, C5/C3 of 0.362 µM. Upper endoscopy and colonoscopy were unremarkable. A repeat video capsule endoscopy revealed diffuse whitish velvet-like changes in several segments without apparent mucosal ulcerations ( Figure 1 ). Abdominal computed tomography without contrast showed hepatic lipomatosis ( Figure 2 ). As a result, diagnosis of Crohn’s disease cannot be supported in our patient. Hepatic lipomatosis might not be a usual cause of recurrent abdominal pain and vomiting in children. However, when associated with elevated free fatty acid, lactate and abnormal results of serum tandem mass spectrometry, metabolic disorders are of high suspicion. Endocrinology was consulted. Genomic DNA was extracted from the peripheral whole blood of the patient and parent using the Agilent SureSelectXT Human All Exon 50-Mb kit. Exome sequencing resulted in an average 100× coverage using the Illumina HiSeq2000/2500 sequencer (Illumina, San Diego, CA, USA). Sequence read alignments were completed using Novoalign (V2.07.18) against the human reference genome GRCh37.p10 ( http://www.novocraft.com ). The bioinformatics pipeline has been previously described ( 3 ). In brief, after quality control, variants were filtered by means of public databases, including Human Gene Mutation Database (HGMD) Professional, the Exome Aggregation Consortium (ExAC), and an in-house database. Sanger sequencing was performed with a Biosystems 3500 DNA Analyzer and analyzed by Mutation Surveyor V4.0.9. Trios exome sequencing showed that compound heterozygous mutations of c. + were identified in ETFDH, which was confirmed by Sanger sequencing ( Figure 3 ). This patient was diagnosed with late-onset MADD and treated with riboflavin with a dosage of 100 mg/day instead of mesalamine and azathioprine. She was symptom-free soon after initiation of treatment. In addition, she did not complain about any adverse effects of the treatment. We followed the patient for 2 years, and she did not report any attack of vomiting and abdominal pain. The parent refused endoscopy since the patient did not show any symptoms after treatment. The timeline of this case was shown in Figure 4 .'}
|
{'Case presentation': 'All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient’s parents. An 8-year-old girl of non-consanguineous parents from southern China with history of recurrent abdominal pain and vomiting since 4 years of age presented to the gastroenterology department. Colonoscopy was unremarkable, while multiple ulcers were identified in the small intestine on video capsule endoscopy. She was diagnosed with Crohn’s disease, and initially treated with exclusive enteral nutrition, mesalamine and azathioprine in a local hospital. She still complained of abdominal pain and had multiple episodes of vomiting and was referred to our unit. Apart from gastrointestinal symptoms, she also reported muscle weakness during attacks. On presentation, her physical examination was unremarkable. There was no sign of perianal diseases. Inflammatory markers, including C-reactive protein and erythrocyte sedimentation rate were within normal limits. Other laboratory investigations showed a lactate of 2.9 mmol/L, pH of 7.311, serum free fatty acid of 2.161 mmol/L. Considering the onset of age and recurrent vomiting, serum tandem mass spectrometry was performed, and showed C10 of 1.29 µM, C8 of 0.57 µM, C5/C3 of 0.362 µM. Upper endoscopy and colonoscopy were unremarkable. A repeat video capsule endoscopy revealed diffuse whitish velvet-like changes in several segments without apparent mucosal ulcerations ( Figure 1 ). Abdominal computed tomography without contrast showed hepatic lipomatosis ( Figure 2 ). As a result, diagnosis of Crohn’s disease cannot be supported in our patient. Hepatic lipomatosis might not be a usual cause of recurrent abdominal pain and vomiting in children. However, when associated with elevated free fatty acid, lactate and abnormal results of serum tandem mass spectrometry, metabolic disorders are of high suspicion. Endocrinology was consulted. Genomic DNA was extracted from the peripheral whole blood of the patient and parent using the Agilent SureSelectXT Human All Exon 50-Mb kit. Exome sequencing resulted in an average 100× coverage using the Illumina HiSeq2000/2500 sequencer (Illumina, San Diego, CA, USA). Sequence read alignments were completed using Novoalign (V2.07.18) against the human reference genome GRCh37.p10 ( http://www.novocraft.com ). The bioinformatics pipeline has been previously described ( 3 ). In brief, after quality control, variants were filtered by means of public databases, including Human Gene Mutation Database (HGMD) Professional, the Exome Aggregation Consortium (ExAC), and an in-house database. Sanger sequencing was performed with a Biosystems 3500 DNA Analyzer and analyzed by Mutation Surveyor V4.0.9. Trios exome sequencing showed that compound heterozygous mutations of c. + were identified in ETFDH, which was confirmed by Sanger sequencing ( Figure 3 ). This patient was diagnosed with late-onset MADD and treated with riboflavin with a dosage of 100 mg/day instead of mesalamine and azathioprine. She was symptom-free soon after initiation of treatment. In addition, she did not complain about any adverse effects of the treatment. We followed the patient for 2 years, and she did not report any attack of vomiting and abdominal pain. The parent refused endoscopy since the patient did not show any symptoms after treatment. The timeline of this case was shown in Figure 4 .'}
|
Respiratory-System
|
RESP
|
[] |
test-2026
|
7882281
|
{'Case presentation': 'All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient’s parents. An 8-year-old girl of non-consanguineous parents from southern China with history of recurrent abdominal pain and vomiting since 4 years of age presented to the gastroenterology department. Colonoscopy was unremarkable, while multiple ulcers were identified in the small intestine on video capsule endoscopy. She was diagnosed with Crohn’s disease, and initially treated with exclusive enteral nutrition, mesalamine and azathioprine in a local hospital. She still complained of abdominal pain and had multiple episodes of vomiting and was referred to our unit. Apart from gastrointestinal symptoms, she also reported muscle weakness during attacks. On presentation, her physical examination was unremarkable. There was no sign of perianal diseases. Inflammatory markers, including C-reactive protein and erythrocyte sedimentation rate were within normal limits. Other laboratory investigations showed a lactate of 2.9 mmol/L, pH of 7.311, serum free fatty acid of 2.161 mmol/L. Considering the onset of age and recurrent vomiting, serum tandem mass spectrometry was performed, and showed C10 of 1.29 µM, C8 of 0.57 µM, C5/C3 of 0.362 µM. Upper endoscopy and colonoscopy were unremarkable. A repeat video capsule endoscopy revealed diffuse whitish velvet-like changes in several segments without apparent mucosal ulcerations ( Figure 1 ). Abdominal computed tomography without contrast showed hepatic lipomatosis ( Figure 2 ). As a result, diagnosis of Crohn’s disease cannot be supported in our patient. Hepatic lipomatosis might not be a usual cause of recurrent abdominal pain and vomiting in children. However, when associated with elevated free fatty acid, lactate and abnormal results of serum tandem mass spectrometry, metabolic disorders are of high suspicion. Endocrinology was consulted. Genomic DNA was extracted from the peripheral whole blood of the patient and parent using the Agilent SureSelectXT Human All Exon 50-Mb kit. Exome sequencing resulted in an average 100× coverage using the Illumina HiSeq2000/2500 sequencer (Illumina, San Diego, CA, USA). Sequence read alignments were completed using Novoalign (V2.07.18) against the human reference genome GRCh37.p10 ( http://www.novocraft.com ). The bioinformatics pipeline has been previously described ( 3 ). In brief, after quality control, variants were filtered by means of public databases, including Human Gene Mutation Database (HGMD) Professional, the Exome Aggregation Consortium (ExAC), and an in-house database. Sanger sequencing was performed with a Biosystems 3500 DNA Analyzer and analyzed by Mutation Surveyor V4.0.9. Trios exome sequencing showed that compound heterozygous mutations of c. + were identified in ETFDH, which was confirmed by Sanger sequencing ( Figure 3 ). This patient was diagnosed with late-onset MADD and treated with riboflavin with a dosage of 100 mg/day instead of mesalamine and azathioprine. She was symptom-free soon after initiation of treatment. In addition, she did not complain about any adverse effects of the treatment. We followed the patient for 2 years, and she did not report any attack of vomiting and abdominal pain. The parent refused endoscopy since the patient did not show any symptoms after treatment. The timeline of this case was shown in Figure 4 .'}
|
{'Case presentation': 'All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient’s parents. An 8-year-old girl of non-consanguineous parents from southern China with history of recurrent abdominal pain and vomiting since 4 years of age presented to the gastroenterology department. Colonoscopy was unremarkable, while multiple ulcers were identified in the small intestine on video capsule endoscopy. She was diagnosed with Crohn’s disease, and initially treated with exclusive enteral nutrition, mesalamine and azathioprine in a local hospital. She still complained of abdominal pain and had multiple episodes of vomiting and was referred to our unit. Apart from gastrointestinal symptoms, she also reported muscle weakness during attacks. On presentation, her physical examination was unremarkable. There was no sign of perianal diseases. Inflammatory markers, including C-reactive protein and erythrocyte sedimentation rate were within normal limits. Other laboratory investigations showed a lactate of 2.9 mmol/L, pH of 7.311, serum free fatty acid of 2.161 mmol/L. Considering the onset of age and recurrent vomiting, serum tandem mass spectrometry was performed, and showed C10 of 1.29 µM, C8 of 0.57 µM, C5/C3 of 0.362 µM. Upper endoscopy and colonoscopy were unremarkable. A repeat video capsule endoscopy revealed diffuse whitish velvet-like changes in several segments without apparent mucosal ulcerations ( Figure 1 ). Abdominal computed tomography without contrast showed hepatic lipomatosis ( Figure 2 ). As a result, diagnosis of Crohn’s disease cannot be supported in our patient. Hepatic lipomatosis might not be a usual cause of recurrent abdominal pain and vomiting in children. However, when associated with elevated free fatty acid, lactate and abnormal results of serum tandem mass spectrometry, metabolic disorders are of high suspicion. Endocrinology was consulted. Genomic DNA was extracted from the peripheral whole blood of the patient and parent using the Agilent SureSelectXT Human All Exon 50-Mb kit. Exome sequencing resulted in an average 100× coverage using the Illumina HiSeq2000/2500 sequencer (Illumina, San Diego, CA, USA). Sequence read alignments were completed using Novoalign (V2.07.18) against the human reference genome GRCh37.p10 ( http://www.novocraft.com ). The bioinformatics pipeline has been previously described ( 3 ). In brief, after quality control, variants were filtered by means of public databases, including Human Gene Mutation Database (HGMD) Professional, the Exome Aggregation Consortium (ExAC), and an in-house database. Sanger sequencing was performed with a Biosystems 3500 DNA Analyzer and analyzed by Mutation Surveyor V4.0.9. Trios exome sequencing showed that compound heterozygous mutations of c. + were identified in ETFDH, which was confirmed by Sanger sequencing ( Figure 3 ). This patient was diagnosed with late-onset MADD and treated with riboflavin with a dosage of 100 mg/day instead of mesalamine and azathioprine. She was symptom-free soon after initiation of treatment. In addition, she did not complain about any adverse effects of the treatment. We followed the patient for 2 years, and she did not report any attack of vomiting and abdominal pain. The parent refused endoscopy since the patient did not show any symptoms after treatment. The timeline of this case was shown in Figure 4 .'}
|
Musculoskeletal-System
|
MSK
|
[] |
test-2027
|
7882281
|
{'Case presentation': 'All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient’s parents. An 8-year-old girl of non-consanguineous parents from southern China with history of recurrent abdominal pain and vomiting since 4 years of age presented to the gastroenterology department. Colonoscopy was unremarkable, while multiple ulcers were identified in the small intestine on video capsule endoscopy. She was diagnosed with Crohn’s disease, and initially treated with exclusive enteral nutrition, mesalamine and azathioprine in a local hospital. She still complained of abdominal pain and had multiple episodes of vomiting and was referred to our unit. Apart from gastrointestinal symptoms, she also reported muscle weakness during attacks. On presentation, her physical examination was unremarkable. There was no sign of perianal diseases. Inflammatory markers, including C-reactive protein and erythrocyte sedimentation rate were within normal limits. Other laboratory investigations showed a lactate of 2.9 mmol/L, pH of 7.311, serum free fatty acid of 2.161 mmol/L. Considering the onset of age and recurrent vomiting, serum tandem mass spectrometry was performed, and showed C10 of 1.29 µM, C8 of 0.57 µM, C5/C3 of 0.362 µM. Upper endoscopy and colonoscopy were unremarkable. A repeat video capsule endoscopy revealed diffuse whitish velvet-like changes in several segments without apparent mucosal ulcerations ( Figure 1 ). Abdominal computed tomography without contrast showed hepatic lipomatosis ( Figure 2 ). As a result, diagnosis of Crohn’s disease cannot be supported in our patient. Hepatic lipomatosis might not be a usual cause of recurrent abdominal pain and vomiting in children. However, when associated with elevated free fatty acid, lactate and abnormal results of serum tandem mass spectrometry, metabolic disorders are of high suspicion. Endocrinology was consulted. Genomic DNA was extracted from the peripheral whole blood of the patient and parent using the Agilent SureSelectXT Human All Exon 50-Mb kit. Exome sequencing resulted in an average 100× coverage using the Illumina HiSeq2000/2500 sequencer (Illumina, San Diego, CA, USA). Sequence read alignments were completed using Novoalign (V2.07.18) against the human reference genome GRCh37.p10 ( http://www.novocraft.com ). The bioinformatics pipeline has been previously described ( 3 ). In brief, after quality control, variants were filtered by means of public databases, including Human Gene Mutation Database (HGMD) Professional, the Exome Aggregation Consortium (ExAC), and an in-house database. Sanger sequencing was performed with a Biosystems 3500 DNA Analyzer and analyzed by Mutation Surveyor V4.0.9. Trios exome sequencing showed that compound heterozygous mutations of c. + were identified in ETFDH, which was confirmed by Sanger sequencing ( Figure 3 ). This patient was diagnosed with late-onset MADD and treated with riboflavin with a dosage of 100 mg/day instead of mesalamine and azathioprine. She was symptom-free soon after initiation of treatment. In addition, she did not complain about any adverse effects of the treatment. We followed the patient for 2 years, and she did not report any attack of vomiting and abdominal pain. The parent refused endoscopy since the patient did not show any symptoms after treatment. The timeline of this case was shown in Figure 4 .'}
|
{'Case presentation': 'All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient’s parents. An 8-year-old girl of non-consanguineous parents from southern China with history of recurrent abdominal pain and vomiting since 4 years of age presented to the gastroenterology department. Colonoscopy was unremarkable, while multiple ulcers were identified in the small intestine on video capsule endoscopy. She was diagnosed with Crohn’s disease, and initially treated with exclusive enteral nutrition, mesalamine and azathioprine in a local hospital. She still complained of abdominal pain and had multiple episodes of vomiting and was referred to our unit. Apart from gastrointestinal symptoms, she also reported muscle weakness during attacks. On presentation, her physical examination was unremarkable. There was no sign of perianal diseases. Inflammatory markers, including C-reactive protein and erythrocyte sedimentation rate were within normal limits. Other laboratory investigations showed a lactate of 2.9 mmol/L, pH of 7.311, serum free fatty acid of 2.161 mmol/L. Considering the onset of age and recurrent vomiting, serum tandem mass spectrometry was performed, and showed C10 of 1.29 µM, C8 of 0.57 µM, C5/C3 of 0.362 µM. Upper endoscopy and colonoscopy were unremarkable. A repeat video capsule endoscopy revealed diffuse whitish velvet-like changes in several segments without apparent mucosal ulcerations ( Figure 1 ). Abdominal computed tomography without contrast showed hepatic lipomatosis ( Figure 2 ). As a result, diagnosis of Crohn’s disease cannot be supported in our patient. Hepatic lipomatosis might not be a usual cause of recurrent abdominal pain and vomiting in children. However, when associated with elevated free fatty acid, lactate and abnormal results of serum tandem mass spectrometry, metabolic disorders are of high suspicion. Endocrinology was consulted. Genomic DNA was extracted from the peripheral whole blood of the patient and parent using the Agilent SureSelectXT Human All Exon 50-Mb kit. Exome sequencing resulted in an average 100× coverage using the Illumina HiSeq2000/2500 sequencer (Illumina, San Diego, CA, USA). Sequence read alignments were completed using Novoalign (V2.07.18) against the human reference genome GRCh37.p10 ( http://www.novocraft.com ). The bioinformatics pipeline has been previously described ( 3 ). In brief, after quality control, variants were filtered by means of public databases, including Human Gene Mutation Database (HGMD) Professional, the Exome Aggregation Consortium (ExAC), and an in-house database. Sanger sequencing was performed with a Biosystems 3500 DNA Analyzer and analyzed by Mutation Surveyor V4.0.9. Trios exome sequencing showed that compound heterozygous mutations of c. + were identified in ETFDH, which was confirmed by Sanger sequencing ( Figure 3 ). This patient was diagnosed with late-onset MADD and treated with riboflavin with a dosage of 100 mg/day instead of mesalamine and azathioprine. She was symptom-free soon after initiation of treatment. In addition, she did not complain about any adverse effects of the treatment. We followed the patient for 2 years, and she did not report any attack of vomiting and abdominal pain. The parent refused endoscopy since the patient did not show any symptoms after treatment. The timeline of this case was shown in Figure 4 .'}
|
Eyes-Ears-Nose-Throat
|
EENT
|
[] |
test-2028
|
7882281
|
{'Case presentation': 'All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient’s parents. An 8-year-old girl of non-consanguineous parents from southern China with history of recurrent abdominal pain and vomiting since 4 years of age presented to the gastroenterology department. Colonoscopy was unremarkable, while multiple ulcers were identified in the small intestine on video capsule endoscopy. She was diagnosed with Crohn’s disease, and initially treated with exclusive enteral nutrition, mesalamine and azathioprine in a local hospital. She still complained of abdominal pain and had multiple episodes of vomiting and was referred to our unit. Apart from gastrointestinal symptoms, she also reported muscle weakness during attacks. On presentation, her physical examination was unremarkable. There was no sign of perianal diseases. Inflammatory markers, including C-reactive protein and erythrocyte sedimentation rate were within normal limits. Other laboratory investigations showed a lactate of 2.9 mmol/L, pH of 7.311, serum free fatty acid of 2.161 mmol/L. Considering the onset of age and recurrent vomiting, serum tandem mass spectrometry was performed, and showed C10 of 1.29 µM, C8 of 0.57 µM, C5/C3 of 0.362 µM. Upper endoscopy and colonoscopy were unremarkable. A repeat video capsule endoscopy revealed diffuse whitish velvet-like changes in several segments without apparent mucosal ulcerations ( Figure 1 ). Abdominal computed tomography without contrast showed hepatic lipomatosis ( Figure 2 ). As a result, diagnosis of Crohn’s disease cannot be supported in our patient. Hepatic lipomatosis might not be a usual cause of recurrent abdominal pain and vomiting in children. However, when associated with elevated free fatty acid, lactate and abnormal results of serum tandem mass spectrometry, metabolic disorders are of high suspicion. Endocrinology was consulted. Genomic DNA was extracted from the peripheral whole blood of the patient and parent using the Agilent SureSelectXT Human All Exon 50-Mb kit. Exome sequencing resulted in an average 100× coverage using the Illumina HiSeq2000/2500 sequencer (Illumina, San Diego, CA, USA). Sequence read alignments were completed using Novoalign (V2.07.18) against the human reference genome GRCh37.p10 ( http://www.novocraft.com ). The bioinformatics pipeline has been previously described ( 3 ). In brief, after quality control, variants were filtered by means of public databases, including Human Gene Mutation Database (HGMD) Professional, the Exome Aggregation Consortium (ExAC), and an in-house database. Sanger sequencing was performed with a Biosystems 3500 DNA Analyzer and analyzed by Mutation Surveyor V4.0.9. Trios exome sequencing showed that compound heterozygous mutations of c. + were identified in ETFDH, which was confirmed by Sanger sequencing ( Figure 3 ). This patient was diagnosed with late-onset MADD and treated with riboflavin with a dosage of 100 mg/day instead of mesalamine and azathioprine. She was symptom-free soon after initiation of treatment. In addition, she did not complain about any adverse effects of the treatment. We followed the patient for 2 years, and she did not report any attack of vomiting and abdominal pain. The parent refused endoscopy since the patient did not show any symptoms after treatment. The timeline of this case was shown in Figure 4 .'}
|
{'Case presentation': 'All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient’s parents. An 8-year-old girl of non-consanguineous parents from southern China with history of recurrent abdominal pain and vomiting since 4 years of age presented to the gastroenterology department. Colonoscopy was unremarkable, while multiple ulcers were identified in the small intestine on video capsule endoscopy. She was diagnosed with Crohn’s disease, and initially treated with exclusive enteral nutrition, mesalamine and azathioprine in a local hospital. She still complained of abdominal pain and had multiple episodes of vomiting and was referred to our unit. Apart from gastrointestinal symptoms, she also reported muscle weakness during attacks. On presentation, her physical examination was unremarkable. There was no sign of perianal diseases. Inflammatory markers, including C-reactive protein and erythrocyte sedimentation rate were within normal limits. Other laboratory investigations showed a lactate of 2.9 mmol/L, pH of 7.311, serum free fatty acid of 2.161 mmol/L. Considering the onset of age and recurrent vomiting, serum tandem mass spectrometry was performed, and showed C10 of 1.29 µM, C8 of 0.57 µM, C5/C3 of 0.362 µM. Upper endoscopy and colonoscopy were unremarkable. A repeat video capsule endoscopy revealed diffuse whitish velvet-like changes in several segments without apparent mucosal ulcerations ( Figure 1 ). Abdominal computed tomography without contrast showed hepatic lipomatosis ( Figure 2 ). As a result, diagnosis of Crohn’s disease cannot be supported in our patient. Hepatic lipomatosis might not be a usual cause of recurrent abdominal pain and vomiting in children. However, when associated with elevated free fatty acid, lactate and abnormal results of serum tandem mass spectrometry, metabolic disorders are of high suspicion. Endocrinology was consulted. Genomic DNA was extracted from the peripheral whole blood of the patient and parent using the Agilent SureSelectXT Human All Exon 50-Mb kit. Exome sequencing resulted in an average 100× coverage using the Illumina HiSeq2000/2500 sequencer (Illumina, San Diego, CA, USA). Sequence read alignments were completed using Novoalign (V2.07.18) against the human reference genome GRCh37.p10 ( http://www.novocraft.com ). The bioinformatics pipeline has been previously described ( 3 ). In brief, after quality control, variants were filtered by means of public databases, including Human Gene Mutation Database (HGMD) Professional, the Exome Aggregation Consortium (ExAC), and an in-house database. Sanger sequencing was performed with a Biosystems 3500 DNA Analyzer and analyzed by Mutation Surveyor V4.0.9. Trios exome sequencing showed that compound heterozygous mutations of c. + were identified in ETFDH, which was confirmed by Sanger sequencing ( Figure 3 ). This patient was diagnosed with late-onset MADD and treated with riboflavin with a dosage of 100 mg/day instead of mesalamine and azathioprine. She was symptom-free soon after initiation of treatment. In addition, she did not complain about any adverse effects of the treatment. We followed the patient for 2 years, and she did not report any attack of vomiting and abdominal pain. The parent refused endoscopy since the patient did not show any symptoms after treatment. The timeline of this case was shown in Figure 4 .'}
|
Dermatology
|
DERM
|
[] |
test-2029
|
7882281
|
{'Case presentation': 'All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient’s parents. An 8-year-old girl of non-consanguineous parents from southern China with history of recurrent abdominal pain and vomiting since 4 years of age presented to the gastroenterology department. Colonoscopy was unremarkable, while multiple ulcers were identified in the small intestine on video capsule endoscopy. She was diagnosed with Crohn’s disease, and initially treated with exclusive enteral nutrition, mesalamine and azathioprine in a local hospital. She still complained of abdominal pain and had multiple episodes of vomiting and was referred to our unit. Apart from gastrointestinal symptoms, she also reported muscle weakness during attacks. On presentation, her physical examination was unremarkable. There was no sign of perianal diseases. Inflammatory markers, including C-reactive protein and erythrocyte sedimentation rate were within normal limits. Other laboratory investigations showed a lactate of 2.9 mmol/L, pH of 7.311, serum free fatty acid of 2.161 mmol/L. Considering the onset of age and recurrent vomiting, serum tandem mass spectrometry was performed, and showed C10 of 1.29 µM, C8 of 0.57 µM, C5/C3 of 0.362 µM. Upper endoscopy and colonoscopy were unremarkable. A repeat video capsule endoscopy revealed diffuse whitish velvet-like changes in several segments without apparent mucosal ulcerations ( Figure 1 ). Abdominal computed tomography without contrast showed hepatic lipomatosis ( Figure 2 ). As a result, diagnosis of Crohn’s disease cannot be supported in our patient. Hepatic lipomatosis might not be a usual cause of recurrent abdominal pain and vomiting in children. However, when associated with elevated free fatty acid, lactate and abnormal results of serum tandem mass spectrometry, metabolic disorders are of high suspicion. Endocrinology was consulted. Genomic DNA was extracted from the peripheral whole blood of the patient and parent using the Agilent SureSelectXT Human All Exon 50-Mb kit. Exome sequencing resulted in an average 100× coverage using the Illumina HiSeq2000/2500 sequencer (Illumina, San Diego, CA, USA). Sequence read alignments were completed using Novoalign (V2.07.18) against the human reference genome GRCh37.p10 ( http://www.novocraft.com ). The bioinformatics pipeline has been previously described ( 3 ). In brief, after quality control, variants were filtered by means of public databases, including Human Gene Mutation Database (HGMD) Professional, the Exome Aggregation Consortium (ExAC), and an in-house database. Sanger sequencing was performed with a Biosystems 3500 DNA Analyzer and analyzed by Mutation Surveyor V4.0.9. Trios exome sequencing showed that compound heterozygous mutations of c. + were identified in ETFDH, which was confirmed by Sanger sequencing ( Figure 3 ). This patient was diagnosed with late-onset MADD and treated with riboflavin with a dosage of 100 mg/day instead of mesalamine and azathioprine. She was symptom-free soon after initiation of treatment. In addition, she did not complain about any adverse effects of the treatment. We followed the patient for 2 years, and she did not report any attack of vomiting and abdominal pain. The parent refused endoscopy since the patient did not show any symptoms after treatment. The timeline of this case was shown in Figure 4 .'}
|
{'Case presentation': 'All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient’s parents. An 8-year-old girl of non-consanguineous parents from southern China with history of recurrent abdominal pain and vomiting since 4 years of age presented to the gastroenterology department. Colonoscopy was unremarkable, while multiple ulcers were identified in the small intestine on video capsule endoscopy. She was diagnosed with Crohn’s disease, and initially treated with exclusive enteral nutrition, mesalamine and azathioprine in a local hospital. She still complained of abdominal pain and had multiple episodes of vomiting and was referred to our unit. Apart from gastrointestinal symptoms, she also reported muscle weakness during attacks. On presentation, her physical examination was unremarkable. There was no sign of perianal diseases. Inflammatory markers, including C-reactive protein and erythrocyte sedimentation rate were within normal limits. Other laboratory investigations showed a lactate of 2.9 mmol/L, pH of 7.311, serum free fatty acid of 2.161 mmol/L. Considering the onset of age and recurrent vomiting, serum tandem mass spectrometry was performed, and showed C10 of 1.29 µM, C8 of 0.57 µM, C5/C3 of 0.362 µM. Upper endoscopy and colonoscopy were unremarkable. A repeat video capsule endoscopy revealed diffuse whitish velvet-like changes in several segments without apparent mucosal ulcerations ( Figure 1 ). Abdominal computed tomography without contrast showed hepatic lipomatosis ( Figure 2 ). As a result, diagnosis of Crohn’s disease cannot be supported in our patient. Hepatic lipomatosis might not be a usual cause of recurrent abdominal pain and vomiting in children. However, when associated with elevated free fatty acid, lactate and abnormal results of serum tandem mass spectrometry, metabolic disorders are of high suspicion. Endocrinology was consulted. Genomic DNA was extracted from the peripheral whole blood of the patient and parent using the Agilent SureSelectXT Human All Exon 50-Mb kit. Exome sequencing resulted in an average 100× coverage using the Illumina HiSeq2000/2500 sequencer (Illumina, San Diego, CA, USA). Sequence read alignments were completed using Novoalign (V2.07.18) against the human reference genome GRCh37.p10 ( http://www.novocraft.com ). The bioinformatics pipeline has been previously described ( 3 ). In brief, after quality control, variants were filtered by means of public databases, including Human Gene Mutation Database (HGMD) Professional, the Exome Aggregation Consortium (ExAC), and an in-house database. Sanger sequencing was performed with a Biosystems 3500 DNA Analyzer and analyzed by Mutation Surveyor V4.0.9. Trios exome sequencing showed that compound heterozygous mutations of c. + were identified in ETFDH, which was confirmed by Sanger sequencing ( Figure 3 ). This patient was diagnosed with late-onset MADD and treated with riboflavin with a dosage of 100 mg/day instead of mesalamine and azathioprine. She was symptom-free soon after initiation of treatment. In addition, she did not complain about any adverse effects of the treatment. We followed the patient for 2 years, and she did not report any attack of vomiting and abdominal pain. The parent refused endoscopy since the patient did not show any symptoms after treatment. The timeline of this case was shown in Figure 4 .'}
|
Pregnancy
|
Pregnancy
|
[] |
test-2030
|
7882281
|
{'Case presentation': 'All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient’s parents. An 8-year-old girl of non-consanguineous parents from southern China with history of recurrent abdominal pain and vomiting since 4 years of age presented to the gastroenterology department. Colonoscopy was unremarkable, while multiple ulcers were identified in the small intestine on video capsule endoscopy. She was diagnosed with Crohn’s disease, and initially treated with exclusive enteral nutrition, mesalamine and azathioprine in a local hospital. She still complained of abdominal pain and had multiple episodes of vomiting and was referred to our unit. Apart from gastrointestinal symptoms, she also reported muscle weakness during attacks. On presentation, her physical examination was unremarkable. There was no sign of perianal diseases. Inflammatory markers, including C-reactive protein and erythrocyte sedimentation rate were within normal limits. Other laboratory investigations showed a lactate of 2.9 mmol/L, pH of 7.311, serum free fatty acid of 2.161 mmol/L. Considering the onset of age and recurrent vomiting, serum tandem mass spectrometry was performed, and showed C10 of 1.29 µM, C8 of 0.57 µM, C5/C3 of 0.362 µM. Upper endoscopy and colonoscopy were unremarkable. A repeat video capsule endoscopy revealed diffuse whitish velvet-like changes in several segments without apparent mucosal ulcerations ( Figure 1 ). Abdominal computed tomography without contrast showed hepatic lipomatosis ( Figure 2 ). As a result, diagnosis of Crohn’s disease cannot be supported in our patient. Hepatic lipomatosis might not be a usual cause of recurrent abdominal pain and vomiting in children. However, when associated with elevated free fatty acid, lactate and abnormal results of serum tandem mass spectrometry, metabolic disorders are of high suspicion. Endocrinology was consulted. Genomic DNA was extracted from the peripheral whole blood of the patient and parent using the Agilent SureSelectXT Human All Exon 50-Mb kit. Exome sequencing resulted in an average 100× coverage using the Illumina HiSeq2000/2500 sequencer (Illumina, San Diego, CA, USA). Sequence read alignments were completed using Novoalign (V2.07.18) against the human reference genome GRCh37.p10 ( http://www.novocraft.com ). The bioinformatics pipeline has been previously described ( 3 ). In brief, after quality control, variants were filtered by means of public databases, including Human Gene Mutation Database (HGMD) Professional, the Exome Aggregation Consortium (ExAC), and an in-house database. Sanger sequencing was performed with a Biosystems 3500 DNA Analyzer and analyzed by Mutation Surveyor V4.0.9. Trios exome sequencing showed that compound heterozygous mutations of c. + were identified in ETFDH, which was confirmed by Sanger sequencing ( Figure 3 ). This patient was diagnosed with late-onset MADD and treated with riboflavin with a dosage of 100 mg/day instead of mesalamine and azathioprine. She was symptom-free soon after initiation of treatment. In addition, she did not complain about any adverse effects of the treatment. We followed the patient for 2 years, and she did not report any attack of vomiting and abdominal pain. The parent refused endoscopy since the patient did not show any symptoms after treatment. The timeline of this case was shown in Figure 4 .'}
|
{'Case presentation': 'All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient’s parents. An 8-year-old girl of non-consanguineous parents from southern China with history of recurrent abdominal pain and vomiting since 4 years of age presented to the gastroenterology department. Colonoscopy was unremarkable, while multiple ulcers were identified in the small intestine on video capsule endoscopy. She was diagnosed with Crohn’s disease, and initially treated with exclusive enteral nutrition, mesalamine and azathioprine in a local hospital. She still complained of abdominal pain and had multiple episodes of vomiting and was referred to our unit. Apart from gastrointestinal symptoms, she also reported muscle weakness during attacks. On presentation, her physical examination was unremarkable. There was no sign of perianal diseases. Inflammatory markers, including C-reactive protein and erythrocyte sedimentation rate were within normal limits. Other laboratory investigations showed a lactate of 2.9 mmol/L, pH of 7.311, serum free fatty acid of 2.161 mmol/L. Considering the onset of age and recurrent vomiting, serum tandem mass spectrometry was performed, and showed C10 of 1.29 µM, C8 of 0.57 µM, C5/C3 of 0.362 µM. Upper endoscopy and colonoscopy were unremarkable. A repeat video capsule endoscopy revealed diffuse whitish velvet-like changes in several segments without apparent mucosal ulcerations ( Figure 1 ). Abdominal computed tomography without contrast showed hepatic lipomatosis ( Figure 2 ). As a result, diagnosis of Crohn’s disease cannot be supported in our patient. Hepatic lipomatosis might not be a usual cause of recurrent abdominal pain and vomiting in children. However, when associated with elevated free fatty acid, lactate and abnormal results of serum tandem mass spectrometry, metabolic disorders are of high suspicion. Endocrinology was consulted. Genomic DNA was extracted from the peripheral whole blood of the patient and parent using the Agilent SureSelectXT Human All Exon 50-Mb kit. Exome sequencing resulted in an average 100× coverage using the Illumina HiSeq2000/2500 sequencer (Illumina, San Diego, CA, USA). Sequence read alignments were completed using Novoalign (V2.07.18) against the human reference genome GRCh37.p10 ( http://www.novocraft.com ). The bioinformatics pipeline has been previously described ( 3 ). In brief, after quality control, variants were filtered by means of public databases, including Human Gene Mutation Database (HGMD) Professional, the Exome Aggregation Consortium (ExAC), and an in-house database. Sanger sequencing was performed with a Biosystems 3500 DNA Analyzer and analyzed by Mutation Surveyor V4.0.9. Trios exome sequencing showed that compound heterozygous mutations of c. + were identified in ETFDH, which was confirmed by Sanger sequencing ( Figure 3 ). This patient was diagnosed with late-onset MADD and treated with riboflavin with a dosage of 100 mg/day instead of mesalamine and azathioprine. She was symptom-free soon after initiation of treatment. In addition, she did not complain about any adverse effects of the treatment. We followed the patient for 2 years, and she did not report any attack of vomiting and abdominal pain. The parent refused endoscopy since the patient did not show any symptoms after treatment. The timeline of this case was shown in Figure 4 .'}
|
Lymphatic-System
|
LYMPH
|
[] |
test-2031
|
7882281
|
{'Case presentation': 'All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient’s parents. An 8-year-old girl of non-consanguineous parents from southern China with history of recurrent abdominal pain and vomiting since 4 years of age presented to the gastroenterology department. Colonoscopy was unremarkable, while multiple ulcers were identified in the small intestine on video capsule endoscopy. She was diagnosed with Crohn’s disease, and initially treated with exclusive enteral nutrition, mesalamine and azathioprine in a local hospital. She still complained of abdominal pain and had multiple episodes of vomiting and was referred to our unit. Apart from gastrointestinal symptoms, she also reported muscle weakness during attacks. On presentation, her physical examination was unremarkable. There was no sign of perianal diseases. Inflammatory markers, including C-reactive protein and erythrocyte sedimentation rate were within normal limits. Other laboratory investigations showed a lactate of 2.9 mmol/L, pH of 7.311, serum free fatty acid of 2.161 mmol/L. Considering the onset of age and recurrent vomiting, serum tandem mass spectrometry was performed, and showed C10 of 1.29 µM, C8 of 0.57 µM, C5/C3 of 0.362 µM. Upper endoscopy and colonoscopy were unremarkable. A repeat video capsule endoscopy revealed diffuse whitish velvet-like changes in several segments without apparent mucosal ulcerations ( Figure 1 ). Abdominal computed tomography without contrast showed hepatic lipomatosis ( Figure 2 ). As a result, diagnosis of Crohn’s disease cannot be supported in our patient. Hepatic lipomatosis might not be a usual cause of recurrent abdominal pain and vomiting in children. However, when associated with elevated free fatty acid, lactate and abnormal results of serum tandem mass spectrometry, metabolic disorders are of high suspicion. Endocrinology was consulted. Genomic DNA was extracted from the peripheral whole blood of the patient and parent using the Agilent SureSelectXT Human All Exon 50-Mb kit. Exome sequencing resulted in an average 100× coverage using the Illumina HiSeq2000/2500 sequencer (Illumina, San Diego, CA, USA). Sequence read alignments were completed using Novoalign (V2.07.18) against the human reference genome GRCh37.p10 ( http://www.novocraft.com ). The bioinformatics pipeline has been previously described ( 3 ). In brief, after quality control, variants were filtered by means of public databases, including Human Gene Mutation Database (HGMD) Professional, the Exome Aggregation Consortium (ExAC), and an in-house database. Sanger sequencing was performed with a Biosystems 3500 DNA Analyzer and analyzed by Mutation Surveyor V4.0.9. Trios exome sequencing showed that compound heterozygous mutations of c. + were identified in ETFDH, which was confirmed by Sanger sequencing ( Figure 3 ). This patient was diagnosed with late-onset MADD and treated with riboflavin with a dosage of 100 mg/day instead of mesalamine and azathioprine. She was symptom-free soon after initiation of treatment. In addition, she did not complain about any adverse effects of the treatment. We followed the patient for 2 years, and she did not report any attack of vomiting and abdominal pain. The parent refused endoscopy since the patient did not show any symptoms after treatment. The timeline of this case was shown in Figure 4 .'}
|
{'Case presentation': 'All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient’s parents. An 8-year-old girl of non-consanguineous parents from southern China with history of recurrent abdominal pain and vomiting since 4 years of age presented to the gastroenterology department. Colonoscopy was unremarkable, while multiple ulcers were identified in the small intestine on video capsule endoscopy. She was diagnosed with Crohn’s disease, and initially treated with exclusive enteral nutrition, mesalamine and azathioprine in a local hospital. She still complained of abdominal pain and had multiple episodes of vomiting and was referred to our unit. Apart from gastrointestinal symptoms, she also reported muscle weakness during attacks. On presentation, her physical examination was unremarkable. There was no sign of perianal diseases. Inflammatory markers, including C-reactive protein and erythrocyte sedimentation rate were within normal limits. Other laboratory investigations showed a lactate of 2.9 mmol/L, pH of 7.311, serum free fatty acid of 2.161 mmol/L. Considering the onset of age and recurrent vomiting, serum tandem mass spectrometry was performed, and showed C10 of 1.29 µM, C8 of 0.57 µM, C5/C3 of 0.362 µM. Upper endoscopy and colonoscopy were unremarkable. A repeat video capsule endoscopy revealed diffuse whitish velvet-like changes in several segments without apparent mucosal ulcerations ( Figure 1 ). Abdominal computed tomography without contrast showed hepatic lipomatosis ( Figure 2 ). As a result, diagnosis of Crohn’s disease cannot be supported in our patient. Hepatic lipomatosis might not be a usual cause of recurrent abdominal pain and vomiting in children. However, when associated with elevated free fatty acid, lactate and abnormal results of serum tandem mass spectrometry, metabolic disorders are of high suspicion. Endocrinology was consulted. Genomic DNA was extracted from the peripheral whole blood of the patient and parent using the Agilent SureSelectXT Human All Exon 50-Mb kit. Exome sequencing resulted in an average 100× coverage using the Illumina HiSeq2000/2500 sequencer (Illumina, San Diego, CA, USA). Sequence read alignments were completed using Novoalign (V2.07.18) against the human reference genome GRCh37.p10 ( http://www.novocraft.com ). The bioinformatics pipeline has been previously described ( 3 ). In brief, after quality control, variants were filtered by means of public databases, including Human Gene Mutation Database (HGMD) Professional, the Exome Aggregation Consortium (ExAC), and an in-house database. Sanger sequencing was performed with a Biosystems 3500 DNA Analyzer and analyzed by Mutation Surveyor V4.0.9. Trios exome sequencing showed that compound heterozygous mutations of c. + were identified in ETFDH, which was confirmed by Sanger sequencing ( Figure 3 ). This patient was diagnosed with late-onset MADD and treated with riboflavin with a dosage of 100 mg/day instead of mesalamine and azathioprine. She was symptom-free soon after initiation of treatment. In addition, she did not complain about any adverse effects of the treatment. We followed the patient for 2 years, and she did not report any attack of vomiting and abdominal pain. The parent refused endoscopy since the patient did not show any symptoms after treatment. The timeline of this case was shown in Figure 4 .'}
|
Age-at-Presentation
|
Age (at case presentation)
|
[
"8 - year - old"
] |
test-2032
|
7882281
|
{'Case presentation': 'All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient’s parents. An 8-year-old girl of non-consanguineous parents from southern China with history of recurrent abdominal pain and vomiting since 4 years of age presented to the gastroenterology department. Colonoscopy was unremarkable, while multiple ulcers were identified in the small intestine on video capsule endoscopy. She was diagnosed with Crohn’s disease, and initially treated with exclusive enteral nutrition, mesalamine and azathioprine in a local hospital. She still complained of abdominal pain and had multiple episodes of vomiting and was referred to our unit. Apart from gastrointestinal symptoms, she also reported muscle weakness during attacks. On presentation, her physical examination was unremarkable. There was no sign of perianal diseases. Inflammatory markers, including C-reactive protein and erythrocyte sedimentation rate were within normal limits. Other laboratory investigations showed a lactate of 2.9 mmol/L, pH of 7.311, serum free fatty acid of 2.161 mmol/L. Considering the onset of age and recurrent vomiting, serum tandem mass spectrometry was performed, and showed C10 of 1.29 µM, C8 of 0.57 µM, C5/C3 of 0.362 µM. Upper endoscopy and colonoscopy were unremarkable. A repeat video capsule endoscopy revealed diffuse whitish velvet-like changes in several segments without apparent mucosal ulcerations ( Figure 1 ). Abdominal computed tomography without contrast showed hepatic lipomatosis ( Figure 2 ). As a result, diagnosis of Crohn’s disease cannot be supported in our patient. Hepatic lipomatosis might not be a usual cause of recurrent abdominal pain and vomiting in children. However, when associated with elevated free fatty acid, lactate and abnormal results of serum tandem mass spectrometry, metabolic disorders are of high suspicion. Endocrinology was consulted. Genomic DNA was extracted from the peripheral whole blood of the patient and parent using the Agilent SureSelectXT Human All Exon 50-Mb kit. Exome sequencing resulted in an average 100× coverage using the Illumina HiSeq2000/2500 sequencer (Illumina, San Diego, CA, USA). Sequence read alignments were completed using Novoalign (V2.07.18) against the human reference genome GRCh37.p10 ( http://www.novocraft.com ). The bioinformatics pipeline has been previously described ( 3 ). In brief, after quality control, variants were filtered by means of public databases, including Human Gene Mutation Database (HGMD) Professional, the Exome Aggregation Consortium (ExAC), and an in-house database. Sanger sequencing was performed with a Biosystems 3500 DNA Analyzer and analyzed by Mutation Surveyor V4.0.9. Trios exome sequencing showed that compound heterozygous mutations of c. + were identified in ETFDH, which was confirmed by Sanger sequencing ( Figure 3 ). This patient was diagnosed with late-onset MADD and treated with riboflavin with a dosage of 100 mg/day instead of mesalamine and azathioprine. She was symptom-free soon after initiation of treatment. In addition, she did not complain about any adverse effects of the treatment. We followed the patient for 2 years, and she did not report any attack of vomiting and abdominal pain. The parent refused endoscopy since the patient did not show any symptoms after treatment. The timeline of this case was shown in Figure 4 .'}
|
{'Case presentation': 'All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient’s parents. An 8-year-old girl of non-consanguineous parents from southern China with history of recurrent abdominal pain and vomiting since 4 years of age presented to the gastroenterology department. Colonoscopy was unremarkable, while multiple ulcers were identified in the small intestine on video capsule endoscopy. She was diagnosed with Crohn’s disease, and initially treated with exclusive enteral nutrition, mesalamine and azathioprine in a local hospital. She still complained of abdominal pain and had multiple episodes of vomiting and was referred to our unit. Apart from gastrointestinal symptoms, she also reported muscle weakness during attacks. On presentation, her physical examination was unremarkable. There was no sign of perianal diseases. Inflammatory markers, including C-reactive protein and erythrocyte sedimentation rate were within normal limits. Other laboratory investigations showed a lactate of 2.9 mmol/L, pH of 7.311, serum free fatty acid of 2.161 mmol/L. Considering the onset of age and recurrent vomiting, serum tandem mass spectrometry was performed, and showed C10 of 1.29 µM, C8 of 0.57 µM, C5/C3 of 0.362 µM. Upper endoscopy and colonoscopy were unremarkable. A repeat video capsule endoscopy revealed diffuse whitish velvet-like changes in several segments without apparent mucosal ulcerations ( Figure 1 ). Abdominal computed tomography without contrast showed hepatic lipomatosis ( Figure 2 ). As a result, diagnosis of Crohn’s disease cannot be supported in our patient. Hepatic lipomatosis might not be a usual cause of recurrent abdominal pain and vomiting in children. However, when associated with elevated free fatty acid, lactate and abnormal results of serum tandem mass spectrometry, metabolic disorders are of high suspicion. Endocrinology was consulted. Genomic DNA was extracted from the peripheral whole blood of the patient and parent using the Agilent SureSelectXT Human All Exon 50-Mb kit. Exome sequencing resulted in an average 100× coverage using the Illumina HiSeq2000/2500 sequencer (Illumina, San Diego, CA, USA). Sequence read alignments were completed using Novoalign (V2.07.18) against the human reference genome GRCh37.p10 ( http://www.novocraft.com ). The bioinformatics pipeline has been previously described ( 3 ). In brief, after quality control, variants were filtered by means of public databases, including Human Gene Mutation Database (HGMD) Professional, the Exome Aggregation Consortium (ExAC), and an in-house database. Sanger sequencing was performed with a Biosystems 3500 DNA Analyzer and analyzed by Mutation Surveyor V4.0.9. Trios exome sequencing showed that compound heterozygous mutations of c. + were identified in ETFDH, which was confirmed by Sanger sequencing ( Figure 3 ). This patient was diagnosed with late-onset MADD and treated with riboflavin with a dosage of 100 mg/day instead of mesalamine and azathioprine. She was symptom-free soon after initiation of treatment. In addition, she did not complain about any adverse effects of the treatment. We followed the patient for 2 years, and she did not report any attack of vomiting and abdominal pain. The parent refused endoscopy since the patient did not show any symptoms after treatment. The timeline of this case was shown in Figure 4 .'}
|
Age-of-Onset
|
Age (of onset)
|
[
"4 years of age"
] |
test-2033
|
7882281
|
{'Case presentation': 'All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient’s parents. An 8-year-old girl of non-consanguineous parents from southern China with history of recurrent abdominal pain and vomiting since 4 years of age presented to the gastroenterology department. Colonoscopy was unremarkable, while multiple ulcers were identified in the small intestine on video capsule endoscopy. She was diagnosed with Crohn’s disease, and initially treated with exclusive enteral nutrition, mesalamine and azathioprine in a local hospital. She still complained of abdominal pain and had multiple episodes of vomiting and was referred to our unit. Apart from gastrointestinal symptoms, she also reported muscle weakness during attacks. On presentation, her physical examination was unremarkable. There was no sign of perianal diseases. Inflammatory markers, including C-reactive protein and erythrocyte sedimentation rate were within normal limits. Other laboratory investigations showed a lactate of 2.9 mmol/L, pH of 7.311, serum free fatty acid of 2.161 mmol/L. Considering the onset of age and recurrent vomiting, serum tandem mass spectrometry was performed, and showed C10 of 1.29 µM, C8 of 0.57 µM, C5/C3 of 0.362 µM. Upper endoscopy and colonoscopy were unremarkable. A repeat video capsule endoscopy revealed diffuse whitish velvet-like changes in several segments without apparent mucosal ulcerations ( Figure 1 ). Abdominal computed tomography without contrast showed hepatic lipomatosis ( Figure 2 ). As a result, diagnosis of Crohn’s disease cannot be supported in our patient. Hepatic lipomatosis might not be a usual cause of recurrent abdominal pain and vomiting in children. However, when associated with elevated free fatty acid, lactate and abnormal results of serum tandem mass spectrometry, metabolic disorders are of high suspicion. Endocrinology was consulted. Genomic DNA was extracted from the peripheral whole blood of the patient and parent using the Agilent SureSelectXT Human All Exon 50-Mb kit. Exome sequencing resulted in an average 100× coverage using the Illumina HiSeq2000/2500 sequencer (Illumina, San Diego, CA, USA). Sequence read alignments were completed using Novoalign (V2.07.18) against the human reference genome GRCh37.p10 ( http://www.novocraft.com ). The bioinformatics pipeline has been previously described ( 3 ). In brief, after quality control, variants were filtered by means of public databases, including Human Gene Mutation Database (HGMD) Professional, the Exome Aggregation Consortium (ExAC), and an in-house database. Sanger sequencing was performed with a Biosystems 3500 DNA Analyzer and analyzed by Mutation Surveyor V4.0.9. Trios exome sequencing showed that compound heterozygous mutations of c. + were identified in ETFDH, which was confirmed by Sanger sequencing ( Figure 3 ). This patient was diagnosed with late-onset MADD and treated with riboflavin with a dosage of 100 mg/day instead of mesalamine and azathioprine. She was symptom-free soon after initiation of treatment. In addition, she did not complain about any adverse effects of the treatment. We followed the patient for 2 years, and she did not report any attack of vomiting and abdominal pain. The parent refused endoscopy since the patient did not show any symptoms after treatment. The timeline of this case was shown in Figure 4 .'}
|
{'Case presentation': 'All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient’s parents. An 8-year-old girl of non-consanguineous parents from southern China with history of recurrent abdominal pain and vomiting since 4 years of age presented to the gastroenterology department. Colonoscopy was unremarkable, while multiple ulcers were identified in the small intestine on video capsule endoscopy. She was diagnosed with Crohn’s disease, and initially treated with exclusive enteral nutrition, mesalamine and azathioprine in a local hospital. She still complained of abdominal pain and had multiple episodes of vomiting and was referred to our unit. Apart from gastrointestinal symptoms, she also reported muscle weakness during attacks. On presentation, her physical examination was unremarkable. There was no sign of perianal diseases. Inflammatory markers, including C-reactive protein and erythrocyte sedimentation rate were within normal limits. Other laboratory investigations showed a lactate of 2.9 mmol/L, pH of 7.311, serum free fatty acid of 2.161 mmol/L. Considering the onset of age and recurrent vomiting, serum tandem mass spectrometry was performed, and showed C10 of 1.29 µM, C8 of 0.57 µM, C5/C3 of 0.362 µM. Upper endoscopy and colonoscopy were unremarkable. A repeat video capsule endoscopy revealed diffuse whitish velvet-like changes in several segments without apparent mucosal ulcerations ( Figure 1 ). Abdominal computed tomography without contrast showed hepatic lipomatosis ( Figure 2 ). As a result, diagnosis of Crohn’s disease cannot be supported in our patient. Hepatic lipomatosis might not be a usual cause of recurrent abdominal pain and vomiting in children. However, when associated with elevated free fatty acid, lactate and abnormal results of serum tandem mass spectrometry, metabolic disorders are of high suspicion. Endocrinology was consulted. Genomic DNA was extracted from the peripheral whole blood of the patient and parent using the Agilent SureSelectXT Human All Exon 50-Mb kit. Exome sequencing resulted in an average 100× coverage using the Illumina HiSeq2000/2500 sequencer (Illumina, San Diego, CA, USA). Sequence read alignments were completed using Novoalign (V2.07.18) against the human reference genome GRCh37.p10 ( http://www.novocraft.com ). The bioinformatics pipeline has been previously described ( 3 ). In brief, after quality control, variants were filtered by means of public databases, including Human Gene Mutation Database (HGMD) Professional, the Exome Aggregation Consortium (ExAC), and an in-house database. Sanger sequencing was performed with a Biosystems 3500 DNA Analyzer and analyzed by Mutation Surveyor V4.0.9. Trios exome sequencing showed that compound heterozygous mutations of c. + were identified in ETFDH, which was confirmed by Sanger sequencing ( Figure 3 ). This patient was diagnosed with late-onset MADD and treated with riboflavin with a dosage of 100 mg/day instead of mesalamine and azathioprine. She was symptom-free soon after initiation of treatment. In addition, she did not complain about any adverse effects of the treatment. We followed the patient for 2 years, and she did not report any attack of vomiting and abdominal pain. The parent refused endoscopy since the patient did not show any symptoms after treatment. The timeline of this case was shown in Figure 4 .'}
|
Confirmed-Diagnosis-IEM
|
Confirmed_Diagnosis(IEM)
|
[
"This patient was diagnosed with late - onset MADD"
] |
test-2034
|
7882281
|
{'Case presentation': 'All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient’s parents. An 8-year-old girl of non-consanguineous parents from southern China with history of recurrent abdominal pain and vomiting since 4 years of age presented to the gastroenterology department. Colonoscopy was unremarkable, while multiple ulcers were identified in the small intestine on video capsule endoscopy. She was diagnosed with Crohn’s disease, and initially treated with exclusive enteral nutrition, mesalamine and azathioprine in a local hospital. She still complained of abdominal pain and had multiple episodes of vomiting and was referred to our unit. Apart from gastrointestinal symptoms, she also reported muscle weakness during attacks. On presentation, her physical examination was unremarkable. There was no sign of perianal diseases. Inflammatory markers, including C-reactive protein and erythrocyte sedimentation rate were within normal limits. Other laboratory investigations showed a lactate of 2.9 mmol/L, pH of 7.311, serum free fatty acid of 2.161 mmol/L. Considering the onset of age and recurrent vomiting, serum tandem mass spectrometry was performed, and showed C10 of 1.29 µM, C8 of 0.57 µM, C5/C3 of 0.362 µM. Upper endoscopy and colonoscopy were unremarkable. A repeat video capsule endoscopy revealed diffuse whitish velvet-like changes in several segments without apparent mucosal ulcerations ( Figure 1 ). Abdominal computed tomography without contrast showed hepatic lipomatosis ( Figure 2 ). As a result, diagnosis of Crohn’s disease cannot be supported in our patient. Hepatic lipomatosis might not be a usual cause of recurrent abdominal pain and vomiting in children. However, when associated with elevated free fatty acid, lactate and abnormal results of serum tandem mass spectrometry, metabolic disorders are of high suspicion. Endocrinology was consulted. Genomic DNA was extracted from the peripheral whole blood of the patient and parent using the Agilent SureSelectXT Human All Exon 50-Mb kit. Exome sequencing resulted in an average 100× coverage using the Illumina HiSeq2000/2500 sequencer (Illumina, San Diego, CA, USA). Sequence read alignments were completed using Novoalign (V2.07.18) against the human reference genome GRCh37.p10 ( http://www.novocraft.com ). The bioinformatics pipeline has been previously described ( 3 ). In brief, after quality control, variants were filtered by means of public databases, including Human Gene Mutation Database (HGMD) Professional, the Exome Aggregation Consortium (ExAC), and an in-house database. Sanger sequencing was performed with a Biosystems 3500 DNA Analyzer and analyzed by Mutation Surveyor V4.0.9. Trios exome sequencing showed that compound heterozygous mutations of c. + were identified in ETFDH, which was confirmed by Sanger sequencing ( Figure 3 ). This patient was diagnosed with late-onset MADD and treated with riboflavin with a dosage of 100 mg/day instead of mesalamine and azathioprine. She was symptom-free soon after initiation of treatment. In addition, she did not complain about any adverse effects of the treatment. We followed the patient for 2 years, and she did not report any attack of vomiting and abdominal pain. The parent refused endoscopy since the patient did not show any symptoms after treatment. The timeline of this case was shown in Figure 4 .'}
|
{'Case presentation': 'All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient’s parents. An 8-year-old girl of non-consanguineous parents from southern China with history of recurrent abdominal pain and vomiting since 4 years of age presented to the gastroenterology department. Colonoscopy was unremarkable, while multiple ulcers were identified in the small intestine on video capsule endoscopy. She was diagnosed with Crohn’s disease, and initially treated with exclusive enteral nutrition, mesalamine and azathioprine in a local hospital. She still complained of abdominal pain and had multiple episodes of vomiting and was referred to our unit. Apart from gastrointestinal symptoms, she also reported muscle weakness during attacks. On presentation, her physical examination was unremarkable. There was no sign of perianal diseases. Inflammatory markers, including C-reactive protein and erythrocyte sedimentation rate were within normal limits. Other laboratory investigations showed a lactate of 2.9 mmol/L, pH of 7.311, serum free fatty acid of 2.161 mmol/L. Considering the onset of age and recurrent vomiting, serum tandem mass spectrometry was performed, and showed C10 of 1.29 µM, C8 of 0.57 µM, C5/C3 of 0.362 µM. Upper endoscopy and colonoscopy were unremarkable. A repeat video capsule endoscopy revealed diffuse whitish velvet-like changes in several segments without apparent mucosal ulcerations ( Figure 1 ). Abdominal computed tomography without contrast showed hepatic lipomatosis ( Figure 2 ). As a result, diagnosis of Crohn’s disease cannot be supported in our patient. Hepatic lipomatosis might not be a usual cause of recurrent abdominal pain and vomiting in children. However, when associated with elevated free fatty acid, lactate and abnormal results of serum tandem mass spectrometry, metabolic disorders are of high suspicion. Endocrinology was consulted. Genomic DNA was extracted from the peripheral whole blood of the patient and parent using the Agilent SureSelectXT Human All Exon 50-Mb kit. Exome sequencing resulted in an average 100× coverage using the Illumina HiSeq2000/2500 sequencer (Illumina, San Diego, CA, USA). Sequence read alignments were completed using Novoalign (V2.07.18) against the human reference genome GRCh37.p10 ( http://www.novocraft.com ). The bioinformatics pipeline has been previously described ( 3 ). In brief, after quality control, variants were filtered by means of public databases, including Human Gene Mutation Database (HGMD) Professional, the Exome Aggregation Consortium (ExAC), and an in-house database. Sanger sequencing was performed with a Biosystems 3500 DNA Analyzer and analyzed by Mutation Surveyor V4.0.9. Trios exome sequencing showed that compound heterozygous mutations of c. + were identified in ETFDH, which was confirmed by Sanger sequencing ( Figure 3 ). This patient was diagnosed with late-onset MADD and treated with riboflavin with a dosage of 100 mg/day instead of mesalamine and azathioprine. She was symptom-free soon after initiation of treatment. In addition, she did not complain about any adverse effects of the treatment. We followed the patient for 2 years, and she did not report any attack of vomiting and abdominal pain. The parent refused endoscopy since the patient did not show any symptoms after treatment. The timeline of this case was shown in Figure 4 .'}
|
IEM-Treatment
|
IEM_Treatment
|
[
"treated with riboflavin with a dosage of 100 mg / day"
] |
test-2035
|
7369454
|
{'Case report': "We present the case of a 65-year-old woman with a long-standing, biopsy-proven diagnosis of PXE. She had subtle yellowish skin papules coalescing into plaques on the lateral neck with skin laxity of the axilla ( Fig 1 ), face, neck, and groin. Noncutaneous history of PXE was significant for angioid streaks, atrophic retinal break of the right eye, angina pectoris, myocardial infarction, peripheral artery disease, coronary artery disease, vitreous degeneration, and bilateral posterior vitreous detachment. Fig 1 PXE in the patient's scanned, right axilla. Note the lax and redundant skin. Noninvasive imaging with MPM and OCT was performed to visualize any irregularities in dermal elastin and/or calcium deposits. The patient consented to the imaging procedure, which was approved by the Institutional Review Board. We imaged an area of lax skin on the right axilla with dynamic OCT (VivoSight Dx, Michelson Diagnostics Ltd, London, UK) and MPM tomography (MPTflex, JenLab GmbH, Jena, Germany) and processed images using the freely available ImageJ software (National Institutes of Heath, Bethesda, MD).", 'Optical coherence tomography': 'OCT imaging of the lax axilla skin displayed large areas of hyporeflective, homogeneous areas of attenuation, or signal loss, in the mid dermis ( Fig 3 ). In contrast to normal skin, which attenuates the image at about 0.7 to 0.9 mm, the depth of the PXE image exhibits relative superficial attenuation of 50% at 0.3 mm and near complete attenuation at a depth of about 0.53 mm. The observed changes may be associated with the noted abundance of elastin at and above this level on histology. Fig 3 OCT cross-section of PXE shows homogenous areas of premature signal loss ( yellow, dotted circle ), with 50% of total attenuation at 0.3 mm below the skin surface and near-complete attenuation at about 0.53 mm. The approximate depth of the MPM image at 30 μm below the DEJ is marked by the red line, and an approximation of the maximum depth MPM can penetrate is marked by the blue line.'}
|
{'Case report': "We present the case of a 65-year-old woman with a long-standing, biopsy-proven diagnosis of PXE. She had subtle yellowish skin papules coalescing into plaques on the lateral neck with skin laxity of the axilla ( Fig 1 ), face, neck, and groin. Noncutaneous history of PXE was significant for angioid streaks, atrophic retinal break of the right eye, angina pectoris, myocardial infarction, peripheral artery disease, coronary artery disease, vitreous degeneration, and bilateral posterior vitreous detachment. Fig 1 PXE in the patient's scanned, right axilla. Note the lax and redundant skin. Noninvasive imaging with MPM and OCT was performed to visualize any irregularities in dermal elastin and/or calcium deposits. The patient consented to the imaging procedure, which was approved by the Institutional Review Board. We imaged an area of lax skin on the right axilla with dynamic OCT (VivoSight Dx, Michelson Diagnostics Ltd, London, UK) and MPM tomography (MPTflex, JenLab GmbH, Jena, Germany) and processed images using the freely available ImageJ software (National Institutes of Heath, Bethesda, MD).", 'Optical coherence tomography': 'OCT imaging of the lax axilla skin displayed large areas of hyporeflective, homogeneous areas of attenuation, or signal loss, in the mid dermis ( Fig 3 ). In contrast to normal skin, which attenuates the image at about 0.7 to 0.9 mm, the depth of the PXE image exhibits relative superficial attenuation of 50% at 0.3 mm and near complete attenuation at a depth of about 0.53 mm. The observed changes may be associated with the noted abundance of elastin at and above this level on histology. Fig 3 OCT cross-section of PXE shows homogenous areas of premature signal loss ( yellow, dotted circle ), with 50% of total attenuation at 0.3 mm below the skin surface and near-complete attenuation at about 0.53 mm. The approximate depth of the MPM image at 30 μm below the DEJ is marked by the red line, and an approximation of the maximum depth MPM can penetrate is marked by the blue line.'}
|
Vitals-and-Hematology
|
Vitals_Hema
|
[] |
test-2036
|
7369454
|
{'Case report': "We present the case of a 65-year-old woman with a long-standing, biopsy-proven diagnosis of PXE. She had subtle yellowish skin papules coalescing into plaques on the lateral neck with skin laxity of the axilla ( Fig 1 ), face, neck, and groin. Noncutaneous history of PXE was significant for angioid streaks, atrophic retinal break of the right eye, angina pectoris, myocardial infarction, peripheral artery disease, coronary artery disease, vitreous degeneration, and bilateral posterior vitreous detachment. Fig 1 PXE in the patient's scanned, right axilla. Note the lax and redundant skin. Noninvasive imaging with MPM and OCT was performed to visualize any irregularities in dermal elastin and/or calcium deposits. The patient consented to the imaging procedure, which was approved by the Institutional Review Board. We imaged an area of lax skin on the right axilla with dynamic OCT (VivoSight Dx, Michelson Diagnostics Ltd, London, UK) and MPM tomography (MPTflex, JenLab GmbH, Jena, Germany) and processed images using the freely available ImageJ software (National Institutes of Heath, Bethesda, MD).", 'Optical coherence tomography': 'OCT imaging of the lax axilla skin displayed large areas of hyporeflective, homogeneous areas of attenuation, or signal loss, in the mid dermis ( Fig 3 ). In contrast to normal skin, which attenuates the image at about 0.7 to 0.9 mm, the depth of the PXE image exhibits relative superficial attenuation of 50% at 0.3 mm and near complete attenuation at a depth of about 0.53 mm. The observed changes may be associated with the noted abundance of elastin at and above this level on histology. Fig 3 OCT cross-section of PXE shows homogenous areas of premature signal loss ( yellow, dotted circle ), with 50% of total attenuation at 0.3 mm below the skin surface and near-complete attenuation at about 0.53 mm. The approximate depth of the MPM image at 30 μm below the DEJ is marked by the red line, and an approximation of the maximum depth MPM can penetrate is marked by the blue line.'}
|
{'Case report': "We present the case of a 65-year-old woman with a long-standing, biopsy-proven diagnosis of PXE. She had subtle yellowish skin papules coalescing into plaques on the lateral neck with skin laxity of the axilla ( Fig 1 ), face, neck, and groin. Noncutaneous history of PXE was significant for angioid streaks, atrophic retinal break of the right eye, angina pectoris, myocardial infarction, peripheral artery disease, coronary artery disease, vitreous degeneration, and bilateral posterior vitreous detachment. Fig 1 PXE in the patient's scanned, right axilla. Note the lax and redundant skin. Noninvasive imaging with MPM and OCT was performed to visualize any irregularities in dermal elastin and/or calcium deposits. The patient consented to the imaging procedure, which was approved by the Institutional Review Board. We imaged an area of lax skin on the right axilla with dynamic OCT (VivoSight Dx, Michelson Diagnostics Ltd, London, UK) and MPM tomography (MPTflex, JenLab GmbH, Jena, Germany) and processed images using the freely available ImageJ software (National Institutes of Heath, Bethesda, MD).", 'Optical coherence tomography': 'OCT imaging of the lax axilla skin displayed large areas of hyporeflective, homogeneous areas of attenuation, or signal loss, in the mid dermis ( Fig 3 ). In contrast to normal skin, which attenuates the image at about 0.7 to 0.9 mm, the depth of the PXE image exhibits relative superficial attenuation of 50% at 0.3 mm and near complete attenuation at a depth of about 0.53 mm. The observed changes may be associated with the noted abundance of elastin at and above this level on histology. Fig 3 OCT cross-section of PXE shows homogenous areas of premature signal loss ( yellow, dotted circle ), with 50% of total attenuation at 0.3 mm below the skin surface and near-complete attenuation at about 0.53 mm. The approximate depth of the MPM image at 30 μm below the DEJ is marked by the red line, and an approximation of the maximum depth MPM can penetrate is marked by the blue line.'}
|
Gastrointestinal-System
|
GI
|
[] |
test-2037
|
7369454
|
{'Case report': "We present the case of a 65-year-old woman with a long-standing, biopsy-proven diagnosis of PXE. She had subtle yellowish skin papules coalescing into plaques on the lateral neck with skin laxity of the axilla ( Fig 1 ), face, neck, and groin. Noncutaneous history of PXE was significant for angioid streaks, atrophic retinal break of the right eye, angina pectoris, myocardial infarction, peripheral artery disease, coronary artery disease, vitreous degeneration, and bilateral posterior vitreous detachment. Fig 1 PXE in the patient's scanned, right axilla. Note the lax and redundant skin. Noninvasive imaging with MPM and OCT was performed to visualize any irregularities in dermal elastin and/or calcium deposits. The patient consented to the imaging procedure, which was approved by the Institutional Review Board. We imaged an area of lax skin on the right axilla with dynamic OCT (VivoSight Dx, Michelson Diagnostics Ltd, London, UK) and MPM tomography (MPTflex, JenLab GmbH, Jena, Germany) and processed images using the freely available ImageJ software (National Institutes of Heath, Bethesda, MD).", 'Optical coherence tomography': 'OCT imaging of the lax axilla skin displayed large areas of hyporeflective, homogeneous areas of attenuation, or signal loss, in the mid dermis ( Fig 3 ). In contrast to normal skin, which attenuates the image at about 0.7 to 0.9 mm, the depth of the PXE image exhibits relative superficial attenuation of 50% at 0.3 mm and near complete attenuation at a depth of about 0.53 mm. The observed changes may be associated with the noted abundance of elastin at and above this level on histology. Fig 3 OCT cross-section of PXE shows homogenous areas of premature signal loss ( yellow, dotted circle ), with 50% of total attenuation at 0.3 mm below the skin surface and near-complete attenuation at about 0.53 mm. The approximate depth of the MPM image at 30 μm below the DEJ is marked by the red line, and an approximation of the maximum depth MPM can penetrate is marked by the blue line.'}
|
{'Case report': "We present the case of a 65-year-old woman with a long-standing, biopsy-proven diagnosis of PXE. She had subtle yellowish skin papules coalescing into plaques on the lateral neck with skin laxity of the axilla ( Fig 1 ), face, neck, and groin. Noncutaneous history of PXE was significant for angioid streaks, atrophic retinal break of the right eye, angina pectoris, myocardial infarction, peripheral artery disease, coronary artery disease, vitreous degeneration, and bilateral posterior vitreous detachment. Fig 1 PXE in the patient's scanned, right axilla. Note the lax and redundant skin. Noninvasive imaging with MPM and OCT was performed to visualize any irregularities in dermal elastin and/or calcium deposits. The patient consented to the imaging procedure, which was approved by the Institutional Review Board. We imaged an area of lax skin on the right axilla with dynamic OCT (VivoSight Dx, Michelson Diagnostics Ltd, London, UK) and MPM tomography (MPTflex, JenLab GmbH, Jena, Germany) and processed images using the freely available ImageJ software (National Institutes of Heath, Bethesda, MD).", 'Optical coherence tomography': 'OCT imaging of the lax axilla skin displayed large areas of hyporeflective, homogeneous areas of attenuation, or signal loss, in the mid dermis ( Fig 3 ). In contrast to normal skin, which attenuates the image at about 0.7 to 0.9 mm, the depth of the PXE image exhibits relative superficial attenuation of 50% at 0.3 mm and near complete attenuation at a depth of about 0.53 mm. The observed changes may be associated with the noted abundance of elastin at and above this level on histology. Fig 3 OCT cross-section of PXE shows homogenous areas of premature signal loss ( yellow, dotted circle ), with 50% of total attenuation at 0.3 mm below the skin surface and near-complete attenuation at about 0.53 mm. The approximate depth of the MPM image at 30 μm below the DEJ is marked by the red line, and an approximation of the maximum depth MPM can penetrate is marked by the blue line.'}
|
Patient-History
|
History
|
[
"angioid streaks, atrophic retinal break of the right eye, angina pectoris, myocardial infarction, peripheral artery disease, coronary artery disease, vitreous degeneration, and bilateral posterior vitreous detachment"
] |
test-2038
|
7369454
|
{'Case report': "We present the case of a 65-year-old woman with a long-standing, biopsy-proven diagnosis of PXE. She had subtle yellowish skin papules coalescing into plaques on the lateral neck with skin laxity of the axilla ( Fig 1 ), face, neck, and groin. Noncutaneous history of PXE was significant for angioid streaks, atrophic retinal break of the right eye, angina pectoris, myocardial infarction, peripheral artery disease, coronary artery disease, vitreous degeneration, and bilateral posterior vitreous detachment. Fig 1 PXE in the patient's scanned, right axilla. Note the lax and redundant skin. Noninvasive imaging with MPM and OCT was performed to visualize any irregularities in dermal elastin and/or calcium deposits. The patient consented to the imaging procedure, which was approved by the Institutional Review Board. We imaged an area of lax skin on the right axilla with dynamic OCT (VivoSight Dx, Michelson Diagnostics Ltd, London, UK) and MPM tomography (MPTflex, JenLab GmbH, Jena, Germany) and processed images using the freely available ImageJ software (National Institutes of Heath, Bethesda, MD).", 'Optical coherence tomography': 'OCT imaging of the lax axilla skin displayed large areas of hyporeflective, homogeneous areas of attenuation, or signal loss, in the mid dermis ( Fig 3 ). In contrast to normal skin, which attenuates the image at about 0.7 to 0.9 mm, the depth of the PXE image exhibits relative superficial attenuation of 50% at 0.3 mm and near complete attenuation at a depth of about 0.53 mm. The observed changes may be associated with the noted abundance of elastin at and above this level on histology. Fig 3 OCT cross-section of PXE shows homogenous areas of premature signal loss ( yellow, dotted circle ), with 50% of total attenuation at 0.3 mm below the skin surface and near-complete attenuation at about 0.53 mm. The approximate depth of the MPM image at 30 μm below the DEJ is marked by the red line, and an approximation of the maximum depth MPM can penetrate is marked by the blue line.'}
|
{'Case report': "We present the case of a 65-year-old woman with a long-standing, biopsy-proven diagnosis of PXE. She had subtle yellowish skin papules coalescing into plaques on the lateral neck with skin laxity of the axilla ( Fig 1 ), face, neck, and groin. Noncutaneous history of PXE was significant for angioid streaks, atrophic retinal break of the right eye, angina pectoris, myocardial infarction, peripheral artery disease, coronary artery disease, vitreous degeneration, and bilateral posterior vitreous detachment. Fig 1 PXE in the patient's scanned, right axilla. Note the lax and redundant skin. Noninvasive imaging with MPM and OCT was performed to visualize any irregularities in dermal elastin and/or calcium deposits. The patient consented to the imaging procedure, which was approved by the Institutional Review Board. We imaged an area of lax skin on the right axilla with dynamic OCT (VivoSight Dx, Michelson Diagnostics Ltd, London, UK) and MPM tomography (MPTflex, JenLab GmbH, Jena, Germany) and processed images using the freely available ImageJ software (National Institutes of Heath, Bethesda, MD).", 'Optical coherence tomography': 'OCT imaging of the lax axilla skin displayed large areas of hyporeflective, homogeneous areas of attenuation, or signal loss, in the mid dermis ( Fig 3 ). In contrast to normal skin, which attenuates the image at about 0.7 to 0.9 mm, the depth of the PXE image exhibits relative superficial attenuation of 50% at 0.3 mm and near complete attenuation at a depth of about 0.53 mm. The observed changes may be associated with the noted abundance of elastin at and above this level on histology. Fig 3 OCT cross-section of PXE shows homogenous areas of premature signal loss ( yellow, dotted circle ), with 50% of total attenuation at 0.3 mm below the skin surface and near-complete attenuation at about 0.53 mm. The approximate depth of the MPM image at 30 μm below the DEJ is marked by the red line, and an approximation of the maximum depth MPM can penetrate is marked by the blue line.'}
|
Neurology
|
Neuro
|
[] |
test-2039
|
7369454
|
{'Case report': "We present the case of a 65-year-old woman with a long-standing, biopsy-proven diagnosis of PXE. She had subtle yellowish skin papules coalescing into plaques on the lateral neck with skin laxity of the axilla ( Fig 1 ), face, neck, and groin. Noncutaneous history of PXE was significant for angioid streaks, atrophic retinal break of the right eye, angina pectoris, myocardial infarction, peripheral artery disease, coronary artery disease, vitreous degeneration, and bilateral posterior vitreous detachment. Fig 1 PXE in the patient's scanned, right axilla. Note the lax and redundant skin. Noninvasive imaging with MPM and OCT was performed to visualize any irregularities in dermal elastin and/or calcium deposits. The patient consented to the imaging procedure, which was approved by the Institutional Review Board. We imaged an area of lax skin on the right axilla with dynamic OCT (VivoSight Dx, Michelson Diagnostics Ltd, London, UK) and MPM tomography (MPTflex, JenLab GmbH, Jena, Germany) and processed images using the freely available ImageJ software (National Institutes of Heath, Bethesda, MD).", 'Optical coherence tomography': 'OCT imaging of the lax axilla skin displayed large areas of hyporeflective, homogeneous areas of attenuation, or signal loss, in the mid dermis ( Fig 3 ). In contrast to normal skin, which attenuates the image at about 0.7 to 0.9 mm, the depth of the PXE image exhibits relative superficial attenuation of 50% at 0.3 mm and near complete attenuation at a depth of about 0.53 mm. The observed changes may be associated with the noted abundance of elastin at and above this level on histology. Fig 3 OCT cross-section of PXE shows homogenous areas of premature signal loss ( yellow, dotted circle ), with 50% of total attenuation at 0.3 mm below the skin surface and near-complete attenuation at about 0.53 mm. The approximate depth of the MPM image at 30 μm below the DEJ is marked by the red line, and an approximation of the maximum depth MPM can penetrate is marked by the blue line.'}
|
{'Case report': "We present the case of a 65-year-old woman with a long-standing, biopsy-proven diagnosis of PXE. She had subtle yellowish skin papules coalescing into plaques on the lateral neck with skin laxity of the axilla ( Fig 1 ), face, neck, and groin. Noncutaneous history of PXE was significant for angioid streaks, atrophic retinal break of the right eye, angina pectoris, myocardial infarction, peripheral artery disease, coronary artery disease, vitreous degeneration, and bilateral posterior vitreous detachment. Fig 1 PXE in the patient's scanned, right axilla. Note the lax and redundant skin. Noninvasive imaging with MPM and OCT was performed to visualize any irregularities in dermal elastin and/or calcium deposits. The patient consented to the imaging procedure, which was approved by the Institutional Review Board. We imaged an area of lax skin on the right axilla with dynamic OCT (VivoSight Dx, Michelson Diagnostics Ltd, London, UK) and MPM tomography (MPTflex, JenLab GmbH, Jena, Germany) and processed images using the freely available ImageJ software (National Institutes of Heath, Bethesda, MD).", 'Optical coherence tomography': 'OCT imaging of the lax axilla skin displayed large areas of hyporeflective, homogeneous areas of attenuation, or signal loss, in the mid dermis ( Fig 3 ). In contrast to normal skin, which attenuates the image at about 0.7 to 0.9 mm, the depth of the PXE image exhibits relative superficial attenuation of 50% at 0.3 mm and near complete attenuation at a depth of about 0.53 mm. The observed changes may be associated with the noted abundance of elastin at and above this level on histology. Fig 3 OCT cross-section of PXE shows homogenous areas of premature signal loss ( yellow, dotted circle ), with 50% of total attenuation at 0.3 mm below the skin surface and near-complete attenuation at about 0.53 mm. The approximate depth of the MPM image at 30 μm below the DEJ is marked by the red line, and an approximation of the maximum depth MPM can penetrate is marked by the blue line.'}
|
Laboratory-and-Imaging
|
Lab_Image
|
[
"OCT imaging of the lax axilla skin displayed large areas of hyporeflective, homogeneous areas of attenuation, or signal loss, in the mid dermis ( Fig 3 ). In contrast to normal skin, which attenuates the image at about 0.7 to 0.9 mm, the depth of the PXE image exhibits relative superficial attenuation of 50 % at 0.3 mm and near complete attenuation at a depth of about 0.53 mm. The observed changes may be associated with the noted abundance of elastin at and above this level on histology. Fig 3 OCT cross - section of PXE shows homogenous areas of premature signal loss ( yellow, dotted circle ), with 50 % of total attenuation at 0.3 mm below the skin surface and near - complete attenuation at about 0.53 mm. The approximate depth of the MPM image at 30 μm below the DEJ is marked by the red line, and an approximation of the maximum depth MPM can penetrate is marked by the blue line"
] |
test-2040
|
7369454
|
{'Case report': "We present the case of a 65-year-old woman with a long-standing, biopsy-proven diagnosis of PXE. She had subtle yellowish skin papules coalescing into plaques on the lateral neck with skin laxity of the axilla ( Fig 1 ), face, neck, and groin. Noncutaneous history of PXE was significant for angioid streaks, atrophic retinal break of the right eye, angina pectoris, myocardial infarction, peripheral artery disease, coronary artery disease, vitreous degeneration, and bilateral posterior vitreous detachment. Fig 1 PXE in the patient's scanned, right axilla. Note the lax and redundant skin. Noninvasive imaging with MPM and OCT was performed to visualize any irregularities in dermal elastin and/or calcium deposits. The patient consented to the imaging procedure, which was approved by the Institutional Review Board. We imaged an area of lax skin on the right axilla with dynamic OCT (VivoSight Dx, Michelson Diagnostics Ltd, London, UK) and MPM tomography (MPTflex, JenLab GmbH, Jena, Germany) and processed images using the freely available ImageJ software (National Institutes of Heath, Bethesda, MD).", 'Optical coherence tomography': 'OCT imaging of the lax axilla skin displayed large areas of hyporeflective, homogeneous areas of attenuation, or signal loss, in the mid dermis ( Fig 3 ). In contrast to normal skin, which attenuates the image at about 0.7 to 0.9 mm, the depth of the PXE image exhibits relative superficial attenuation of 50% at 0.3 mm and near complete attenuation at a depth of about 0.53 mm. The observed changes may be associated with the noted abundance of elastin at and above this level on histology. Fig 3 OCT cross-section of PXE shows homogenous areas of premature signal loss ( yellow, dotted circle ), with 50% of total attenuation at 0.3 mm below the skin surface and near-complete attenuation at about 0.53 mm. The approximate depth of the MPM image at 30 μm below the DEJ is marked by the red line, and an approximation of the maximum depth MPM can penetrate is marked by the blue line.'}
|
{'Case report': "We present the case of a 65-year-old woman with a long-standing, biopsy-proven diagnosis of PXE. She had subtle yellowish skin papules coalescing into plaques on the lateral neck with skin laxity of the axilla ( Fig 1 ), face, neck, and groin. Noncutaneous history of PXE was significant for angioid streaks, atrophic retinal break of the right eye, angina pectoris, myocardial infarction, peripheral artery disease, coronary artery disease, vitreous degeneration, and bilateral posterior vitreous detachment. Fig 1 PXE in the patient's scanned, right axilla. Note the lax and redundant skin. Noninvasive imaging with MPM and OCT was performed to visualize any irregularities in dermal elastin and/or calcium deposits. The patient consented to the imaging procedure, which was approved by the Institutional Review Board. We imaged an area of lax skin on the right axilla with dynamic OCT (VivoSight Dx, Michelson Diagnostics Ltd, London, UK) and MPM tomography (MPTflex, JenLab GmbH, Jena, Germany) and processed images using the freely available ImageJ software (National Institutes of Heath, Bethesda, MD).", 'Optical coherence tomography': 'OCT imaging of the lax axilla skin displayed large areas of hyporeflective, homogeneous areas of attenuation, or signal loss, in the mid dermis ( Fig 3 ). In contrast to normal skin, which attenuates the image at about 0.7 to 0.9 mm, the depth of the PXE image exhibits relative superficial attenuation of 50% at 0.3 mm and near complete attenuation at a depth of about 0.53 mm. The observed changes may be associated with the noted abundance of elastin at and above this level on histology. Fig 3 OCT cross-section of PXE shows homogenous areas of premature signal loss ( yellow, dotted circle ), with 50% of total attenuation at 0.3 mm below the skin surface and near-complete attenuation at about 0.53 mm. The approximate depth of the MPM image at 30 μm below the DEJ is marked by the red line, and an approximation of the maximum depth MPM can penetrate is marked by the blue line.'}
|
Cardiovascular-System
|
CVS
|
[
"angina pectoris, myocardial infarction, peripheral artery disease, coronary artery disease"
] |
test-2041
|
7369454
|
{'Case report': "We present the case of a 65-year-old woman with a long-standing, biopsy-proven diagnosis of PXE. She had subtle yellowish skin papules coalescing into plaques on the lateral neck with skin laxity of the axilla ( Fig 1 ), face, neck, and groin. Noncutaneous history of PXE was significant for angioid streaks, atrophic retinal break of the right eye, angina pectoris, myocardial infarction, peripheral artery disease, coronary artery disease, vitreous degeneration, and bilateral posterior vitreous detachment. Fig 1 PXE in the patient's scanned, right axilla. Note the lax and redundant skin. Noninvasive imaging with MPM and OCT was performed to visualize any irregularities in dermal elastin and/or calcium deposits. The patient consented to the imaging procedure, which was approved by the Institutional Review Board. We imaged an area of lax skin on the right axilla with dynamic OCT (VivoSight Dx, Michelson Diagnostics Ltd, London, UK) and MPM tomography (MPTflex, JenLab GmbH, Jena, Germany) and processed images using the freely available ImageJ software (National Institutes of Heath, Bethesda, MD).", 'Optical coherence tomography': 'OCT imaging of the lax axilla skin displayed large areas of hyporeflective, homogeneous areas of attenuation, or signal loss, in the mid dermis ( Fig 3 ). In contrast to normal skin, which attenuates the image at about 0.7 to 0.9 mm, the depth of the PXE image exhibits relative superficial attenuation of 50% at 0.3 mm and near complete attenuation at a depth of about 0.53 mm. The observed changes may be associated with the noted abundance of elastin at and above this level on histology. Fig 3 OCT cross-section of PXE shows homogenous areas of premature signal loss ( yellow, dotted circle ), with 50% of total attenuation at 0.3 mm below the skin surface and near-complete attenuation at about 0.53 mm. The approximate depth of the MPM image at 30 μm below the DEJ is marked by the red line, and an approximation of the maximum depth MPM can penetrate is marked by the blue line.'}
|
{'Case report': "We present the case of a 65-year-old woman with a long-standing, biopsy-proven diagnosis of PXE. She had subtle yellowish skin papules coalescing into plaques on the lateral neck with skin laxity of the axilla ( Fig 1 ), face, neck, and groin. Noncutaneous history of PXE was significant for angioid streaks, atrophic retinal break of the right eye, angina pectoris, myocardial infarction, peripheral artery disease, coronary artery disease, vitreous degeneration, and bilateral posterior vitreous detachment. Fig 1 PXE in the patient's scanned, right axilla. Note the lax and redundant skin. Noninvasive imaging with MPM and OCT was performed to visualize any irregularities in dermal elastin and/or calcium deposits. The patient consented to the imaging procedure, which was approved by the Institutional Review Board. We imaged an area of lax skin on the right axilla with dynamic OCT (VivoSight Dx, Michelson Diagnostics Ltd, London, UK) and MPM tomography (MPTflex, JenLab GmbH, Jena, Germany) and processed images using the freely available ImageJ software (National Institutes of Heath, Bethesda, MD).", 'Optical coherence tomography': 'OCT imaging of the lax axilla skin displayed large areas of hyporeflective, homogeneous areas of attenuation, or signal loss, in the mid dermis ( Fig 3 ). In contrast to normal skin, which attenuates the image at about 0.7 to 0.9 mm, the depth of the PXE image exhibits relative superficial attenuation of 50% at 0.3 mm and near complete attenuation at a depth of about 0.53 mm. The observed changes may be associated with the noted abundance of elastin at and above this level on histology. Fig 3 OCT cross-section of PXE shows homogenous areas of premature signal loss ( yellow, dotted circle ), with 50% of total attenuation at 0.3 mm below the skin surface and near-complete attenuation at about 0.53 mm. The approximate depth of the MPM image at 30 μm below the DEJ is marked by the red line, and an approximation of the maximum depth MPM can penetrate is marked by the blue line.'}
|
Endocrinology
|
ENDO
|
[] |
test-2042
|
7369454
|
{'Case report': "We present the case of a 65-year-old woman with a long-standing, biopsy-proven diagnosis of PXE. She had subtle yellowish skin papules coalescing into plaques on the lateral neck with skin laxity of the axilla ( Fig 1 ), face, neck, and groin. Noncutaneous history of PXE was significant for angioid streaks, atrophic retinal break of the right eye, angina pectoris, myocardial infarction, peripheral artery disease, coronary artery disease, vitreous degeneration, and bilateral posterior vitreous detachment. Fig 1 PXE in the patient's scanned, right axilla. Note the lax and redundant skin. Noninvasive imaging with MPM and OCT was performed to visualize any irregularities in dermal elastin and/or calcium deposits. The patient consented to the imaging procedure, which was approved by the Institutional Review Board. We imaged an area of lax skin on the right axilla with dynamic OCT (VivoSight Dx, Michelson Diagnostics Ltd, London, UK) and MPM tomography (MPTflex, JenLab GmbH, Jena, Germany) and processed images using the freely available ImageJ software (National Institutes of Heath, Bethesda, MD).", 'Optical coherence tomography': 'OCT imaging of the lax axilla skin displayed large areas of hyporeflective, homogeneous areas of attenuation, or signal loss, in the mid dermis ( Fig 3 ). In contrast to normal skin, which attenuates the image at about 0.7 to 0.9 mm, the depth of the PXE image exhibits relative superficial attenuation of 50% at 0.3 mm and near complete attenuation at a depth of about 0.53 mm. The observed changes may be associated with the noted abundance of elastin at and above this level on histology. Fig 3 OCT cross-section of PXE shows homogenous areas of premature signal loss ( yellow, dotted circle ), with 50% of total attenuation at 0.3 mm below the skin surface and near-complete attenuation at about 0.53 mm. The approximate depth of the MPM image at 30 μm below the DEJ is marked by the red line, and an approximation of the maximum depth MPM can penetrate is marked by the blue line.'}
|
{'Case report': "We present the case of a 65-year-old woman with a long-standing, biopsy-proven diagnosis of PXE. She had subtle yellowish skin papules coalescing into plaques on the lateral neck with skin laxity of the axilla ( Fig 1 ), face, neck, and groin. Noncutaneous history of PXE was significant for angioid streaks, atrophic retinal break of the right eye, angina pectoris, myocardial infarction, peripheral artery disease, coronary artery disease, vitreous degeneration, and bilateral posterior vitreous detachment. Fig 1 PXE in the patient's scanned, right axilla. Note the lax and redundant skin. Noninvasive imaging with MPM and OCT was performed to visualize any irregularities in dermal elastin and/or calcium deposits. The patient consented to the imaging procedure, which was approved by the Institutional Review Board. We imaged an area of lax skin on the right axilla with dynamic OCT (VivoSight Dx, Michelson Diagnostics Ltd, London, UK) and MPM tomography (MPTflex, JenLab GmbH, Jena, Germany) and processed images using the freely available ImageJ software (National Institutes of Heath, Bethesda, MD).", 'Optical coherence tomography': 'OCT imaging of the lax axilla skin displayed large areas of hyporeflective, homogeneous areas of attenuation, or signal loss, in the mid dermis ( Fig 3 ). In contrast to normal skin, which attenuates the image at about 0.7 to 0.9 mm, the depth of the PXE image exhibits relative superficial attenuation of 50% at 0.3 mm and near complete attenuation at a depth of about 0.53 mm. The observed changes may be associated with the noted abundance of elastin at and above this level on histology. Fig 3 OCT cross-section of PXE shows homogenous areas of premature signal loss ( yellow, dotted circle ), with 50% of total attenuation at 0.3 mm below the skin surface and near-complete attenuation at about 0.53 mm. The approximate depth of the MPM image at 30 μm below the DEJ is marked by the red line, and an approximation of the maximum depth MPM can penetrate is marked by the blue line.'}
|
Genitourinary-System
|
GU
|
[] |
test-2043
|
7369454
|
{'Case report': "We present the case of a 65-year-old woman with a long-standing, biopsy-proven diagnosis of PXE. She had subtle yellowish skin papules coalescing into plaques on the lateral neck with skin laxity of the axilla ( Fig 1 ), face, neck, and groin. Noncutaneous history of PXE was significant for angioid streaks, atrophic retinal break of the right eye, angina pectoris, myocardial infarction, peripheral artery disease, coronary artery disease, vitreous degeneration, and bilateral posterior vitreous detachment. Fig 1 PXE in the patient's scanned, right axilla. Note the lax and redundant skin. Noninvasive imaging with MPM and OCT was performed to visualize any irregularities in dermal elastin and/or calcium deposits. The patient consented to the imaging procedure, which was approved by the Institutional Review Board. We imaged an area of lax skin on the right axilla with dynamic OCT (VivoSight Dx, Michelson Diagnostics Ltd, London, UK) and MPM tomography (MPTflex, JenLab GmbH, Jena, Germany) and processed images using the freely available ImageJ software (National Institutes of Heath, Bethesda, MD).", 'Optical coherence tomography': 'OCT imaging of the lax axilla skin displayed large areas of hyporeflective, homogeneous areas of attenuation, or signal loss, in the mid dermis ( Fig 3 ). In contrast to normal skin, which attenuates the image at about 0.7 to 0.9 mm, the depth of the PXE image exhibits relative superficial attenuation of 50% at 0.3 mm and near complete attenuation at a depth of about 0.53 mm. The observed changes may be associated with the noted abundance of elastin at and above this level on histology. Fig 3 OCT cross-section of PXE shows homogenous areas of premature signal loss ( yellow, dotted circle ), with 50% of total attenuation at 0.3 mm below the skin surface and near-complete attenuation at about 0.53 mm. The approximate depth of the MPM image at 30 μm below the DEJ is marked by the red line, and an approximation of the maximum depth MPM can penetrate is marked by the blue line.'}
|
{'Case report': "We present the case of a 65-year-old woman with a long-standing, biopsy-proven diagnosis of PXE. She had subtle yellowish skin papules coalescing into plaques on the lateral neck with skin laxity of the axilla ( Fig 1 ), face, neck, and groin. Noncutaneous history of PXE was significant for angioid streaks, atrophic retinal break of the right eye, angina pectoris, myocardial infarction, peripheral artery disease, coronary artery disease, vitreous degeneration, and bilateral posterior vitreous detachment. Fig 1 PXE in the patient's scanned, right axilla. Note the lax and redundant skin. Noninvasive imaging with MPM and OCT was performed to visualize any irregularities in dermal elastin and/or calcium deposits. The patient consented to the imaging procedure, which was approved by the Institutional Review Board. We imaged an area of lax skin on the right axilla with dynamic OCT (VivoSight Dx, Michelson Diagnostics Ltd, London, UK) and MPM tomography (MPTflex, JenLab GmbH, Jena, Germany) and processed images using the freely available ImageJ software (National Institutes of Heath, Bethesda, MD).", 'Optical coherence tomography': 'OCT imaging of the lax axilla skin displayed large areas of hyporeflective, homogeneous areas of attenuation, or signal loss, in the mid dermis ( Fig 3 ). In contrast to normal skin, which attenuates the image at about 0.7 to 0.9 mm, the depth of the PXE image exhibits relative superficial attenuation of 50% at 0.3 mm and near complete attenuation at a depth of about 0.53 mm. The observed changes may be associated with the noted abundance of elastin at and above this level on histology. Fig 3 OCT cross-section of PXE shows homogenous areas of premature signal loss ( yellow, dotted circle ), with 50% of total attenuation at 0.3 mm below the skin surface and near-complete attenuation at about 0.53 mm. The approximate depth of the MPM image at 30 μm below the DEJ is marked by the red line, and an approximation of the maximum depth MPM can penetrate is marked by the blue line.'}
|
Respiratory-System
|
RESP
|
[] |
test-2044
|
7369454
|
{'Case report': "We present the case of a 65-year-old woman with a long-standing, biopsy-proven diagnosis of PXE. She had subtle yellowish skin papules coalescing into plaques on the lateral neck with skin laxity of the axilla ( Fig 1 ), face, neck, and groin. Noncutaneous history of PXE was significant for angioid streaks, atrophic retinal break of the right eye, angina pectoris, myocardial infarction, peripheral artery disease, coronary artery disease, vitreous degeneration, and bilateral posterior vitreous detachment. Fig 1 PXE in the patient's scanned, right axilla. Note the lax and redundant skin. Noninvasive imaging with MPM and OCT was performed to visualize any irregularities in dermal elastin and/or calcium deposits. The patient consented to the imaging procedure, which was approved by the Institutional Review Board. We imaged an area of lax skin on the right axilla with dynamic OCT (VivoSight Dx, Michelson Diagnostics Ltd, London, UK) and MPM tomography (MPTflex, JenLab GmbH, Jena, Germany) and processed images using the freely available ImageJ software (National Institutes of Heath, Bethesda, MD).", 'Optical coherence tomography': 'OCT imaging of the lax axilla skin displayed large areas of hyporeflective, homogeneous areas of attenuation, or signal loss, in the mid dermis ( Fig 3 ). In contrast to normal skin, which attenuates the image at about 0.7 to 0.9 mm, the depth of the PXE image exhibits relative superficial attenuation of 50% at 0.3 mm and near complete attenuation at a depth of about 0.53 mm. The observed changes may be associated with the noted abundance of elastin at and above this level on histology. Fig 3 OCT cross-section of PXE shows homogenous areas of premature signal loss ( yellow, dotted circle ), with 50% of total attenuation at 0.3 mm below the skin surface and near-complete attenuation at about 0.53 mm. The approximate depth of the MPM image at 30 μm below the DEJ is marked by the red line, and an approximation of the maximum depth MPM can penetrate is marked by the blue line.'}
|
{'Case report': "We present the case of a 65-year-old woman with a long-standing, biopsy-proven diagnosis of PXE. She had subtle yellowish skin papules coalescing into plaques on the lateral neck with skin laxity of the axilla ( Fig 1 ), face, neck, and groin. Noncutaneous history of PXE was significant for angioid streaks, atrophic retinal break of the right eye, angina pectoris, myocardial infarction, peripheral artery disease, coronary artery disease, vitreous degeneration, and bilateral posterior vitreous detachment. Fig 1 PXE in the patient's scanned, right axilla. Note the lax and redundant skin. Noninvasive imaging with MPM and OCT was performed to visualize any irregularities in dermal elastin and/or calcium deposits. The patient consented to the imaging procedure, which was approved by the Institutional Review Board. We imaged an area of lax skin on the right axilla with dynamic OCT (VivoSight Dx, Michelson Diagnostics Ltd, London, UK) and MPM tomography (MPTflex, JenLab GmbH, Jena, Germany) and processed images using the freely available ImageJ software (National Institutes of Heath, Bethesda, MD).", 'Optical coherence tomography': 'OCT imaging of the lax axilla skin displayed large areas of hyporeflective, homogeneous areas of attenuation, or signal loss, in the mid dermis ( Fig 3 ). In contrast to normal skin, which attenuates the image at about 0.7 to 0.9 mm, the depth of the PXE image exhibits relative superficial attenuation of 50% at 0.3 mm and near complete attenuation at a depth of about 0.53 mm. The observed changes may be associated with the noted abundance of elastin at and above this level on histology. Fig 3 OCT cross-section of PXE shows homogenous areas of premature signal loss ( yellow, dotted circle ), with 50% of total attenuation at 0.3 mm below the skin surface and near-complete attenuation at about 0.53 mm. The approximate depth of the MPM image at 30 μm below the DEJ is marked by the red line, and an approximation of the maximum depth MPM can penetrate is marked by the blue line.'}
|
Musculoskeletal-System
|
MSK
|
[] |
test-2045
|
7369454
|
{'Case report': "We present the case of a 65-year-old woman with a long-standing, biopsy-proven diagnosis of PXE. She had subtle yellowish skin papules coalescing into plaques on the lateral neck with skin laxity of the axilla ( Fig 1 ), face, neck, and groin. Noncutaneous history of PXE was significant for angioid streaks, atrophic retinal break of the right eye, angina pectoris, myocardial infarction, peripheral artery disease, coronary artery disease, vitreous degeneration, and bilateral posterior vitreous detachment. Fig 1 PXE in the patient's scanned, right axilla. Note the lax and redundant skin. Noninvasive imaging with MPM and OCT was performed to visualize any irregularities in dermal elastin and/or calcium deposits. The patient consented to the imaging procedure, which was approved by the Institutional Review Board. We imaged an area of lax skin on the right axilla with dynamic OCT (VivoSight Dx, Michelson Diagnostics Ltd, London, UK) and MPM tomography (MPTflex, JenLab GmbH, Jena, Germany) and processed images using the freely available ImageJ software (National Institutes of Heath, Bethesda, MD).", 'Optical coherence tomography': 'OCT imaging of the lax axilla skin displayed large areas of hyporeflective, homogeneous areas of attenuation, or signal loss, in the mid dermis ( Fig 3 ). In contrast to normal skin, which attenuates the image at about 0.7 to 0.9 mm, the depth of the PXE image exhibits relative superficial attenuation of 50% at 0.3 mm and near complete attenuation at a depth of about 0.53 mm. The observed changes may be associated with the noted abundance of elastin at and above this level on histology. Fig 3 OCT cross-section of PXE shows homogenous areas of premature signal loss ( yellow, dotted circle ), with 50% of total attenuation at 0.3 mm below the skin surface and near-complete attenuation at about 0.53 mm. The approximate depth of the MPM image at 30 μm below the DEJ is marked by the red line, and an approximation of the maximum depth MPM can penetrate is marked by the blue line.'}
|
{'Case report': "We present the case of a 65-year-old woman with a long-standing, biopsy-proven diagnosis of PXE. She had subtle yellowish skin papules coalescing into plaques on the lateral neck with skin laxity of the axilla ( Fig 1 ), face, neck, and groin. Noncutaneous history of PXE was significant for angioid streaks, atrophic retinal break of the right eye, angina pectoris, myocardial infarction, peripheral artery disease, coronary artery disease, vitreous degeneration, and bilateral posterior vitreous detachment. Fig 1 PXE in the patient's scanned, right axilla. Note the lax and redundant skin. Noninvasive imaging with MPM and OCT was performed to visualize any irregularities in dermal elastin and/or calcium deposits. The patient consented to the imaging procedure, which was approved by the Institutional Review Board. We imaged an area of lax skin on the right axilla with dynamic OCT (VivoSight Dx, Michelson Diagnostics Ltd, London, UK) and MPM tomography (MPTflex, JenLab GmbH, Jena, Germany) and processed images using the freely available ImageJ software (National Institutes of Heath, Bethesda, MD).", 'Optical coherence tomography': 'OCT imaging of the lax axilla skin displayed large areas of hyporeflective, homogeneous areas of attenuation, or signal loss, in the mid dermis ( Fig 3 ). In contrast to normal skin, which attenuates the image at about 0.7 to 0.9 mm, the depth of the PXE image exhibits relative superficial attenuation of 50% at 0.3 mm and near complete attenuation at a depth of about 0.53 mm. The observed changes may be associated with the noted abundance of elastin at and above this level on histology. Fig 3 OCT cross-section of PXE shows homogenous areas of premature signal loss ( yellow, dotted circle ), with 50% of total attenuation at 0.3 mm below the skin surface and near-complete attenuation at about 0.53 mm. The approximate depth of the MPM image at 30 μm below the DEJ is marked by the red line, and an approximation of the maximum depth MPM can penetrate is marked by the blue line.'}
|
Eyes-Ears-Nose-Throat
|
EENT
|
[
"angioid streaks, atrophic retinal break of the right eye,",
"vitreous degeneration, and bilateral posterior vitreous detachment"
] |
test-2046
|
7369454
|
{'Case report': "We present the case of a 65-year-old woman with a long-standing, biopsy-proven diagnosis of PXE. She had subtle yellowish skin papules coalescing into plaques on the lateral neck with skin laxity of the axilla ( Fig 1 ), face, neck, and groin. Noncutaneous history of PXE was significant for angioid streaks, atrophic retinal break of the right eye, angina pectoris, myocardial infarction, peripheral artery disease, coronary artery disease, vitreous degeneration, and bilateral posterior vitreous detachment. Fig 1 PXE in the patient's scanned, right axilla. Note the lax and redundant skin. Noninvasive imaging with MPM and OCT was performed to visualize any irregularities in dermal elastin and/or calcium deposits. The patient consented to the imaging procedure, which was approved by the Institutional Review Board. We imaged an area of lax skin on the right axilla with dynamic OCT (VivoSight Dx, Michelson Diagnostics Ltd, London, UK) and MPM tomography (MPTflex, JenLab GmbH, Jena, Germany) and processed images using the freely available ImageJ software (National Institutes of Heath, Bethesda, MD).", 'Optical coherence tomography': 'OCT imaging of the lax axilla skin displayed large areas of hyporeflective, homogeneous areas of attenuation, or signal loss, in the mid dermis ( Fig 3 ). In contrast to normal skin, which attenuates the image at about 0.7 to 0.9 mm, the depth of the PXE image exhibits relative superficial attenuation of 50% at 0.3 mm and near complete attenuation at a depth of about 0.53 mm. The observed changes may be associated with the noted abundance of elastin at and above this level on histology. Fig 3 OCT cross-section of PXE shows homogenous areas of premature signal loss ( yellow, dotted circle ), with 50% of total attenuation at 0.3 mm below the skin surface and near-complete attenuation at about 0.53 mm. The approximate depth of the MPM image at 30 μm below the DEJ is marked by the red line, and an approximation of the maximum depth MPM can penetrate is marked by the blue line.'}
|
{'Case report': "We present the case of a 65-year-old woman with a long-standing, biopsy-proven diagnosis of PXE. She had subtle yellowish skin papules coalescing into plaques on the lateral neck with skin laxity of the axilla ( Fig 1 ), face, neck, and groin. Noncutaneous history of PXE was significant for angioid streaks, atrophic retinal break of the right eye, angina pectoris, myocardial infarction, peripheral artery disease, coronary artery disease, vitreous degeneration, and bilateral posterior vitreous detachment. Fig 1 PXE in the patient's scanned, right axilla. Note the lax and redundant skin. Noninvasive imaging with MPM and OCT was performed to visualize any irregularities in dermal elastin and/or calcium deposits. The patient consented to the imaging procedure, which was approved by the Institutional Review Board. We imaged an area of lax skin on the right axilla with dynamic OCT (VivoSight Dx, Michelson Diagnostics Ltd, London, UK) and MPM tomography (MPTflex, JenLab GmbH, Jena, Germany) and processed images using the freely available ImageJ software (National Institutes of Heath, Bethesda, MD).", 'Optical coherence tomography': 'OCT imaging of the lax axilla skin displayed large areas of hyporeflective, homogeneous areas of attenuation, or signal loss, in the mid dermis ( Fig 3 ). In contrast to normal skin, which attenuates the image at about 0.7 to 0.9 mm, the depth of the PXE image exhibits relative superficial attenuation of 50% at 0.3 mm and near complete attenuation at a depth of about 0.53 mm. The observed changes may be associated with the noted abundance of elastin at and above this level on histology. Fig 3 OCT cross-section of PXE shows homogenous areas of premature signal loss ( yellow, dotted circle ), with 50% of total attenuation at 0.3 mm below the skin surface and near-complete attenuation at about 0.53 mm. The approximate depth of the MPM image at 30 μm below the DEJ is marked by the red line, and an approximation of the maximum depth MPM can penetrate is marked by the blue line.'}
|
Dermatology
|
DERM
|
[
"yellowish skin papules coalescing into plaques on the lateral neck with skin laxity of the axilla ( Fig 1 ), face, neck, and groin.",
"lax and redundant skin",
"OCT imaging of the lax axilla skin displayed large areas of hyporeflective, homogeneous areas of attenuation, or signal loss, in the mid dermis ( Fig 3 ). In contrast to normal skin, which attenuates the image at about 0.7 to 0.9 mm, the depth of the PXE image exhibits relative superficial attenuation of 50 % at 0.3 mm and near complete attenuation at a depth of about 0.53 mm. The observed changes may be associated with the noted abundance of elastin at and above this level on histology. Fig 3 OCT cross - section of PXE shows homogenous areas of premature signal loss ( yellow, dotted circle ), with 50 % of total attenuation at 0.3 mm below the skin surface and near - complete attenuation at about 0.53 mm. The approximate depth of the MPM image at 30 μm below the DEJ is marked by the red line, and an approximation of the maximum depth MPM can penetrate is marked by the blue line."
] |
test-2047
|
7369454
|
{'Case report': "We present the case of a 65-year-old woman with a long-standing, biopsy-proven diagnosis of PXE. She had subtle yellowish skin papules coalescing into plaques on the lateral neck with skin laxity of the axilla ( Fig 1 ), face, neck, and groin. Noncutaneous history of PXE was significant for angioid streaks, atrophic retinal break of the right eye, angina pectoris, myocardial infarction, peripheral artery disease, coronary artery disease, vitreous degeneration, and bilateral posterior vitreous detachment. Fig 1 PXE in the patient's scanned, right axilla. Note the lax and redundant skin. Noninvasive imaging with MPM and OCT was performed to visualize any irregularities in dermal elastin and/or calcium deposits. The patient consented to the imaging procedure, which was approved by the Institutional Review Board. We imaged an area of lax skin on the right axilla with dynamic OCT (VivoSight Dx, Michelson Diagnostics Ltd, London, UK) and MPM tomography (MPTflex, JenLab GmbH, Jena, Germany) and processed images using the freely available ImageJ software (National Institutes of Heath, Bethesda, MD).", 'Optical coherence tomography': 'OCT imaging of the lax axilla skin displayed large areas of hyporeflective, homogeneous areas of attenuation, or signal loss, in the mid dermis ( Fig 3 ). In contrast to normal skin, which attenuates the image at about 0.7 to 0.9 mm, the depth of the PXE image exhibits relative superficial attenuation of 50% at 0.3 mm and near complete attenuation at a depth of about 0.53 mm. The observed changes may be associated with the noted abundance of elastin at and above this level on histology. Fig 3 OCT cross-section of PXE shows homogenous areas of premature signal loss ( yellow, dotted circle ), with 50% of total attenuation at 0.3 mm below the skin surface and near-complete attenuation at about 0.53 mm. The approximate depth of the MPM image at 30 μm below the DEJ is marked by the red line, and an approximation of the maximum depth MPM can penetrate is marked by the blue line.'}
|
{'Case report': "We present the case of a 65-year-old woman with a long-standing, biopsy-proven diagnosis of PXE. She had subtle yellowish skin papules coalescing into plaques on the lateral neck with skin laxity of the axilla ( Fig 1 ), face, neck, and groin. Noncutaneous history of PXE was significant for angioid streaks, atrophic retinal break of the right eye, angina pectoris, myocardial infarction, peripheral artery disease, coronary artery disease, vitreous degeneration, and bilateral posterior vitreous detachment. Fig 1 PXE in the patient's scanned, right axilla. Note the lax and redundant skin. Noninvasive imaging with MPM and OCT was performed to visualize any irregularities in dermal elastin and/or calcium deposits. The patient consented to the imaging procedure, which was approved by the Institutional Review Board. We imaged an area of lax skin on the right axilla with dynamic OCT (VivoSight Dx, Michelson Diagnostics Ltd, London, UK) and MPM tomography (MPTflex, JenLab GmbH, Jena, Germany) and processed images using the freely available ImageJ software (National Institutes of Heath, Bethesda, MD).", 'Optical coherence tomography': 'OCT imaging of the lax axilla skin displayed large areas of hyporeflective, homogeneous areas of attenuation, or signal loss, in the mid dermis ( Fig 3 ). In contrast to normal skin, which attenuates the image at about 0.7 to 0.9 mm, the depth of the PXE image exhibits relative superficial attenuation of 50% at 0.3 mm and near complete attenuation at a depth of about 0.53 mm. The observed changes may be associated with the noted abundance of elastin at and above this level on histology. Fig 3 OCT cross-section of PXE shows homogenous areas of premature signal loss ( yellow, dotted circle ), with 50% of total attenuation at 0.3 mm below the skin surface and near-complete attenuation at about 0.53 mm. The approximate depth of the MPM image at 30 μm below the DEJ is marked by the red line, and an approximation of the maximum depth MPM can penetrate is marked by the blue line.'}
|
Pregnancy
|
Pregnancy
|
[] |
test-2048
|
7369454
|
{'Case report': "We present the case of a 65-year-old woman with a long-standing, biopsy-proven diagnosis of PXE. She had subtle yellowish skin papules coalescing into plaques on the lateral neck with skin laxity of the axilla ( Fig 1 ), face, neck, and groin. Noncutaneous history of PXE was significant for angioid streaks, atrophic retinal break of the right eye, angina pectoris, myocardial infarction, peripheral artery disease, coronary artery disease, vitreous degeneration, and bilateral posterior vitreous detachment. Fig 1 PXE in the patient's scanned, right axilla. Note the lax and redundant skin. Noninvasive imaging with MPM and OCT was performed to visualize any irregularities in dermal elastin and/or calcium deposits. The patient consented to the imaging procedure, which was approved by the Institutional Review Board. We imaged an area of lax skin on the right axilla with dynamic OCT (VivoSight Dx, Michelson Diagnostics Ltd, London, UK) and MPM tomography (MPTflex, JenLab GmbH, Jena, Germany) and processed images using the freely available ImageJ software (National Institutes of Heath, Bethesda, MD).", 'Optical coherence tomography': 'OCT imaging of the lax axilla skin displayed large areas of hyporeflective, homogeneous areas of attenuation, or signal loss, in the mid dermis ( Fig 3 ). In contrast to normal skin, which attenuates the image at about 0.7 to 0.9 mm, the depth of the PXE image exhibits relative superficial attenuation of 50% at 0.3 mm and near complete attenuation at a depth of about 0.53 mm. The observed changes may be associated with the noted abundance of elastin at and above this level on histology. Fig 3 OCT cross-section of PXE shows homogenous areas of premature signal loss ( yellow, dotted circle ), with 50% of total attenuation at 0.3 mm below the skin surface and near-complete attenuation at about 0.53 mm. The approximate depth of the MPM image at 30 μm below the DEJ is marked by the red line, and an approximation of the maximum depth MPM can penetrate is marked by the blue line.'}
|
{'Case report': "We present the case of a 65-year-old woman with a long-standing, biopsy-proven diagnosis of PXE. She had subtle yellowish skin papules coalescing into plaques on the lateral neck with skin laxity of the axilla ( Fig 1 ), face, neck, and groin. Noncutaneous history of PXE was significant for angioid streaks, atrophic retinal break of the right eye, angina pectoris, myocardial infarction, peripheral artery disease, coronary artery disease, vitreous degeneration, and bilateral posterior vitreous detachment. Fig 1 PXE in the patient's scanned, right axilla. Note the lax and redundant skin. Noninvasive imaging with MPM and OCT was performed to visualize any irregularities in dermal elastin and/or calcium deposits. The patient consented to the imaging procedure, which was approved by the Institutional Review Board. We imaged an area of lax skin on the right axilla with dynamic OCT (VivoSight Dx, Michelson Diagnostics Ltd, London, UK) and MPM tomography (MPTflex, JenLab GmbH, Jena, Germany) and processed images using the freely available ImageJ software (National Institutes of Heath, Bethesda, MD).", 'Optical coherence tomography': 'OCT imaging of the lax axilla skin displayed large areas of hyporeflective, homogeneous areas of attenuation, or signal loss, in the mid dermis ( Fig 3 ). In contrast to normal skin, which attenuates the image at about 0.7 to 0.9 mm, the depth of the PXE image exhibits relative superficial attenuation of 50% at 0.3 mm and near complete attenuation at a depth of about 0.53 mm. The observed changes may be associated with the noted abundance of elastin at and above this level on histology. Fig 3 OCT cross-section of PXE shows homogenous areas of premature signal loss ( yellow, dotted circle ), with 50% of total attenuation at 0.3 mm below the skin surface and near-complete attenuation at about 0.53 mm. The approximate depth of the MPM image at 30 μm below the DEJ is marked by the red line, and an approximation of the maximum depth MPM can penetrate is marked by the blue line.'}
|
Lymphatic-System
|
LYMPH
|
[] |
test-2049
|
7369454
|
{'Case report': "We present the case of a 65-year-old woman with a long-standing, biopsy-proven diagnosis of PXE. She had subtle yellowish skin papules coalescing into plaques on the lateral neck with skin laxity of the axilla ( Fig 1 ), face, neck, and groin. Noncutaneous history of PXE was significant for angioid streaks, atrophic retinal break of the right eye, angina pectoris, myocardial infarction, peripheral artery disease, coronary artery disease, vitreous degeneration, and bilateral posterior vitreous detachment. Fig 1 PXE in the patient's scanned, right axilla. Note the lax and redundant skin. Noninvasive imaging with MPM and OCT was performed to visualize any irregularities in dermal elastin and/or calcium deposits. The patient consented to the imaging procedure, which was approved by the Institutional Review Board. We imaged an area of lax skin on the right axilla with dynamic OCT (VivoSight Dx, Michelson Diagnostics Ltd, London, UK) and MPM tomography (MPTflex, JenLab GmbH, Jena, Germany) and processed images using the freely available ImageJ software (National Institutes of Heath, Bethesda, MD).", 'Optical coherence tomography': 'OCT imaging of the lax axilla skin displayed large areas of hyporeflective, homogeneous areas of attenuation, or signal loss, in the mid dermis ( Fig 3 ). In contrast to normal skin, which attenuates the image at about 0.7 to 0.9 mm, the depth of the PXE image exhibits relative superficial attenuation of 50% at 0.3 mm and near complete attenuation at a depth of about 0.53 mm. The observed changes may be associated with the noted abundance of elastin at and above this level on histology. Fig 3 OCT cross-section of PXE shows homogenous areas of premature signal loss ( yellow, dotted circle ), with 50% of total attenuation at 0.3 mm below the skin surface and near-complete attenuation at about 0.53 mm. The approximate depth of the MPM image at 30 μm below the DEJ is marked by the red line, and an approximation of the maximum depth MPM can penetrate is marked by the blue line.'}
|
{'Case report': "We present the case of a 65-year-old woman with a long-standing, biopsy-proven diagnosis of PXE. She had subtle yellowish skin papules coalescing into plaques on the lateral neck with skin laxity of the axilla ( Fig 1 ), face, neck, and groin. Noncutaneous history of PXE was significant for angioid streaks, atrophic retinal break of the right eye, angina pectoris, myocardial infarction, peripheral artery disease, coronary artery disease, vitreous degeneration, and bilateral posterior vitreous detachment. Fig 1 PXE in the patient's scanned, right axilla. Note the lax and redundant skin. Noninvasive imaging with MPM and OCT was performed to visualize any irregularities in dermal elastin and/or calcium deposits. The patient consented to the imaging procedure, which was approved by the Institutional Review Board. We imaged an area of lax skin on the right axilla with dynamic OCT (VivoSight Dx, Michelson Diagnostics Ltd, London, UK) and MPM tomography (MPTflex, JenLab GmbH, Jena, Germany) and processed images using the freely available ImageJ software (National Institutes of Heath, Bethesda, MD).", 'Optical coherence tomography': 'OCT imaging of the lax axilla skin displayed large areas of hyporeflective, homogeneous areas of attenuation, or signal loss, in the mid dermis ( Fig 3 ). In contrast to normal skin, which attenuates the image at about 0.7 to 0.9 mm, the depth of the PXE image exhibits relative superficial attenuation of 50% at 0.3 mm and near complete attenuation at a depth of about 0.53 mm. The observed changes may be associated with the noted abundance of elastin at and above this level on histology. Fig 3 OCT cross-section of PXE shows homogenous areas of premature signal loss ( yellow, dotted circle ), with 50% of total attenuation at 0.3 mm below the skin surface and near-complete attenuation at about 0.53 mm. The approximate depth of the MPM image at 30 μm below the DEJ is marked by the red line, and an approximation of the maximum depth MPM can penetrate is marked by the blue line.'}
|
Age-at-Presentation
|
Age (at case presentation)
|
[
"65 - year - old"
] |
test-2050
|
7369454
|
{'Case report': "We present the case of a 65-year-old woman with a long-standing, biopsy-proven diagnosis of PXE. She had subtle yellowish skin papules coalescing into plaques on the lateral neck with skin laxity of the axilla ( Fig 1 ), face, neck, and groin. Noncutaneous history of PXE was significant for angioid streaks, atrophic retinal break of the right eye, angina pectoris, myocardial infarction, peripheral artery disease, coronary artery disease, vitreous degeneration, and bilateral posterior vitreous detachment. Fig 1 PXE in the patient's scanned, right axilla. Note the lax and redundant skin. Noninvasive imaging with MPM and OCT was performed to visualize any irregularities in dermal elastin and/or calcium deposits. The patient consented to the imaging procedure, which was approved by the Institutional Review Board. We imaged an area of lax skin on the right axilla with dynamic OCT (VivoSight Dx, Michelson Diagnostics Ltd, London, UK) and MPM tomography (MPTflex, JenLab GmbH, Jena, Germany) and processed images using the freely available ImageJ software (National Institutes of Heath, Bethesda, MD).", 'Optical coherence tomography': 'OCT imaging of the lax axilla skin displayed large areas of hyporeflective, homogeneous areas of attenuation, or signal loss, in the mid dermis ( Fig 3 ). In contrast to normal skin, which attenuates the image at about 0.7 to 0.9 mm, the depth of the PXE image exhibits relative superficial attenuation of 50% at 0.3 mm and near complete attenuation at a depth of about 0.53 mm. The observed changes may be associated with the noted abundance of elastin at and above this level on histology. Fig 3 OCT cross-section of PXE shows homogenous areas of premature signal loss ( yellow, dotted circle ), with 50% of total attenuation at 0.3 mm below the skin surface and near-complete attenuation at about 0.53 mm. The approximate depth of the MPM image at 30 μm below the DEJ is marked by the red line, and an approximation of the maximum depth MPM can penetrate is marked by the blue line.'}
|
{'Case report': "We present the case of a 65-year-old woman with a long-standing, biopsy-proven diagnosis of PXE. She had subtle yellowish skin papules coalescing into plaques on the lateral neck with skin laxity of the axilla ( Fig 1 ), face, neck, and groin. Noncutaneous history of PXE was significant for angioid streaks, atrophic retinal break of the right eye, angina pectoris, myocardial infarction, peripheral artery disease, coronary artery disease, vitreous degeneration, and bilateral posterior vitreous detachment. Fig 1 PXE in the patient's scanned, right axilla. Note the lax and redundant skin. Noninvasive imaging with MPM and OCT was performed to visualize any irregularities in dermal elastin and/or calcium deposits. The patient consented to the imaging procedure, which was approved by the Institutional Review Board. We imaged an area of lax skin on the right axilla with dynamic OCT (VivoSight Dx, Michelson Diagnostics Ltd, London, UK) and MPM tomography (MPTflex, JenLab GmbH, Jena, Germany) and processed images using the freely available ImageJ software (National Institutes of Heath, Bethesda, MD).", 'Optical coherence tomography': 'OCT imaging of the lax axilla skin displayed large areas of hyporeflective, homogeneous areas of attenuation, or signal loss, in the mid dermis ( Fig 3 ). In contrast to normal skin, which attenuates the image at about 0.7 to 0.9 mm, the depth of the PXE image exhibits relative superficial attenuation of 50% at 0.3 mm and near complete attenuation at a depth of about 0.53 mm. The observed changes may be associated with the noted abundance of elastin at and above this level on histology. Fig 3 OCT cross-section of PXE shows homogenous areas of premature signal loss ( yellow, dotted circle ), with 50% of total attenuation at 0.3 mm below the skin surface and near-complete attenuation at about 0.53 mm. The approximate depth of the MPM image at 30 μm below the DEJ is marked by the red line, and an approximation of the maximum depth MPM can penetrate is marked by the blue line.'}
|
Age-of-Onset
|
Age (of onset)
|
[] |
test-2051
|
7369454
|
{'Case report': "We present the case of a 65-year-old woman with a long-standing, biopsy-proven diagnosis of PXE. She had subtle yellowish skin papules coalescing into plaques on the lateral neck with skin laxity of the axilla ( Fig 1 ), face, neck, and groin. Noncutaneous history of PXE was significant for angioid streaks, atrophic retinal break of the right eye, angina pectoris, myocardial infarction, peripheral artery disease, coronary artery disease, vitreous degeneration, and bilateral posterior vitreous detachment. Fig 1 PXE in the patient's scanned, right axilla. Note the lax and redundant skin. Noninvasive imaging with MPM and OCT was performed to visualize any irregularities in dermal elastin and/or calcium deposits. The patient consented to the imaging procedure, which was approved by the Institutional Review Board. We imaged an area of lax skin on the right axilla with dynamic OCT (VivoSight Dx, Michelson Diagnostics Ltd, London, UK) and MPM tomography (MPTflex, JenLab GmbH, Jena, Germany) and processed images using the freely available ImageJ software (National Institutes of Heath, Bethesda, MD).", 'Optical coherence tomography': 'OCT imaging of the lax axilla skin displayed large areas of hyporeflective, homogeneous areas of attenuation, or signal loss, in the mid dermis ( Fig 3 ). In contrast to normal skin, which attenuates the image at about 0.7 to 0.9 mm, the depth of the PXE image exhibits relative superficial attenuation of 50% at 0.3 mm and near complete attenuation at a depth of about 0.53 mm. The observed changes may be associated with the noted abundance of elastin at and above this level on histology. Fig 3 OCT cross-section of PXE shows homogenous areas of premature signal loss ( yellow, dotted circle ), with 50% of total attenuation at 0.3 mm below the skin surface and near-complete attenuation at about 0.53 mm. The approximate depth of the MPM image at 30 μm below the DEJ is marked by the red line, and an approximation of the maximum depth MPM can penetrate is marked by the blue line.'}
|
{'Case report': "We present the case of a 65-year-old woman with a long-standing, biopsy-proven diagnosis of PXE. She had subtle yellowish skin papules coalescing into plaques on the lateral neck with skin laxity of the axilla ( Fig 1 ), face, neck, and groin. Noncutaneous history of PXE was significant for angioid streaks, atrophic retinal break of the right eye, angina pectoris, myocardial infarction, peripheral artery disease, coronary artery disease, vitreous degeneration, and bilateral posterior vitreous detachment. Fig 1 PXE in the patient's scanned, right axilla. Note the lax and redundant skin. Noninvasive imaging with MPM and OCT was performed to visualize any irregularities in dermal elastin and/or calcium deposits. The patient consented to the imaging procedure, which was approved by the Institutional Review Board. We imaged an area of lax skin on the right axilla with dynamic OCT (VivoSight Dx, Michelson Diagnostics Ltd, London, UK) and MPM tomography (MPTflex, JenLab GmbH, Jena, Germany) and processed images using the freely available ImageJ software (National Institutes of Heath, Bethesda, MD).", 'Optical coherence tomography': 'OCT imaging of the lax axilla skin displayed large areas of hyporeflective, homogeneous areas of attenuation, or signal loss, in the mid dermis ( Fig 3 ). In contrast to normal skin, which attenuates the image at about 0.7 to 0.9 mm, the depth of the PXE image exhibits relative superficial attenuation of 50% at 0.3 mm and near complete attenuation at a depth of about 0.53 mm. The observed changes may be associated with the noted abundance of elastin at and above this level on histology. Fig 3 OCT cross-section of PXE shows homogenous areas of premature signal loss ( yellow, dotted circle ), with 50% of total attenuation at 0.3 mm below the skin surface and near-complete attenuation at about 0.53 mm. The approximate depth of the MPM image at 30 μm below the DEJ is marked by the red line, and an approximation of the maximum depth MPM can penetrate is marked by the blue line.'}
|
Confirmed-Diagnosis-IEM
|
Confirmed_Diagnosis(IEM)
|
[
"long - standing , biopsy - proven diagnosis of PXE"
] |
test-2052
|
7369454
|
{'Case report': "We present the case of a 65-year-old woman with a long-standing, biopsy-proven diagnosis of PXE. She had subtle yellowish skin papules coalescing into plaques on the lateral neck with skin laxity of the axilla ( Fig 1 ), face, neck, and groin. Noncutaneous history of PXE was significant for angioid streaks, atrophic retinal break of the right eye, angina pectoris, myocardial infarction, peripheral artery disease, coronary artery disease, vitreous degeneration, and bilateral posterior vitreous detachment. Fig 1 PXE in the patient's scanned, right axilla. Note the lax and redundant skin. Noninvasive imaging with MPM and OCT was performed to visualize any irregularities in dermal elastin and/or calcium deposits. The patient consented to the imaging procedure, which was approved by the Institutional Review Board. We imaged an area of lax skin on the right axilla with dynamic OCT (VivoSight Dx, Michelson Diagnostics Ltd, London, UK) and MPM tomography (MPTflex, JenLab GmbH, Jena, Germany) and processed images using the freely available ImageJ software (National Institutes of Heath, Bethesda, MD).", 'Optical coherence tomography': 'OCT imaging of the lax axilla skin displayed large areas of hyporeflective, homogeneous areas of attenuation, or signal loss, in the mid dermis ( Fig 3 ). In contrast to normal skin, which attenuates the image at about 0.7 to 0.9 mm, the depth of the PXE image exhibits relative superficial attenuation of 50% at 0.3 mm and near complete attenuation at a depth of about 0.53 mm. The observed changes may be associated with the noted abundance of elastin at and above this level on histology. Fig 3 OCT cross-section of PXE shows homogenous areas of premature signal loss ( yellow, dotted circle ), with 50% of total attenuation at 0.3 mm below the skin surface and near-complete attenuation at about 0.53 mm. The approximate depth of the MPM image at 30 μm below the DEJ is marked by the red line, and an approximation of the maximum depth MPM can penetrate is marked by the blue line.'}
|
{'Case report': "We present the case of a 65-year-old woman with a long-standing, biopsy-proven diagnosis of PXE. She had subtle yellowish skin papules coalescing into plaques on the lateral neck with skin laxity of the axilla ( Fig 1 ), face, neck, and groin. Noncutaneous history of PXE was significant for angioid streaks, atrophic retinal break of the right eye, angina pectoris, myocardial infarction, peripheral artery disease, coronary artery disease, vitreous degeneration, and bilateral posterior vitreous detachment. Fig 1 PXE in the patient's scanned, right axilla. Note the lax and redundant skin. Noninvasive imaging with MPM and OCT was performed to visualize any irregularities in dermal elastin and/or calcium deposits. The patient consented to the imaging procedure, which was approved by the Institutional Review Board. We imaged an area of lax skin on the right axilla with dynamic OCT (VivoSight Dx, Michelson Diagnostics Ltd, London, UK) and MPM tomography (MPTflex, JenLab GmbH, Jena, Germany) and processed images using the freely available ImageJ software (National Institutes of Heath, Bethesda, MD).", 'Optical coherence tomography': 'OCT imaging of the lax axilla skin displayed large areas of hyporeflective, homogeneous areas of attenuation, or signal loss, in the mid dermis ( Fig 3 ). In contrast to normal skin, which attenuates the image at about 0.7 to 0.9 mm, the depth of the PXE image exhibits relative superficial attenuation of 50% at 0.3 mm and near complete attenuation at a depth of about 0.53 mm. The observed changes may be associated with the noted abundance of elastin at and above this level on histology. Fig 3 OCT cross-section of PXE shows homogenous areas of premature signal loss ( yellow, dotted circle ), with 50% of total attenuation at 0.3 mm below the skin surface and near-complete attenuation at about 0.53 mm. The approximate depth of the MPM image at 30 μm below the DEJ is marked by the red line, and an approximation of the maximum depth MPM can penetrate is marked by the blue line.'}
|
IEM-Treatment
|
IEM_Treatment
|
[] |
test-2053
|
7695813
|
{'Case 2': 'A woman in her 40s, who had 2 family members with CTX, struggled with irregular bowel movements from an early age. She developed cataracts at the age of 11 years and was diagnosed with CTX at age 27. The diagnosis was confirmed by genetic testing, with the prompt initiation of chenodiol therapy. She has been on chenodiol consistently since the diagnosis at age 27. During adolescence, she developed tendon xanthomas on the fingers and toes, which required debulking, as well as plantar and Achilles xanthomas. She reported no new xanthomas and no changes in the existing xanthomas over 10 years. She was followed-up by neurologic examinations, and the most recent imaging showed cerebellar lesions; however, the patient did not have neurologic deficits. She had no known cardiovascular involvement. She has one daughter, who does not have the genetic mutation for CTX.', 'Case 3': 'A woman in her 50s, who has 2 family members formally diagnosed with CTX, had loose stools from childhood. She was diagnosed with cataracts at the age of 20 years and with CTX at 38 years, which was confirmed by genetic testing. She started chenodiol at the time of the diagnosis but had a 10-year interruption in the therapy. She restarted chenodiol at the age of 48 years and has since remained on the medication without further interruption. She acquired xanthomas of the Achilles, knee, and elbow. Her existing xanthomas have remained stable, with no new xanthomas. Significant neurologic involvement developed in the patient, which progressively led to her becoming nonambulatory and wheelchair-bound. The patient is cared for by her mother. The patient has severe cognitive decline and visual impairment. She has no known cardiovascular disease.', 'Case 1': 'A woman in her 30s, with no reported family history of CTX, first experienced symptoms with an early onset of frequent diarrhea in infancy. She developed cataracts by the age of 6 years. At the age of 14 years, she was formally diagnosed with CTX, which was confirmed by genetic testing. Chenodiol (chenodeoxycholic acid) therapy was initiated at diagnosis, and she has remained on chenodiol since that time. Tendon xanthomas required surgical debulking by the age of 17 years. She has had xanthomas of the Achilles, elbow, and plantar foot and extensor tendons of the fingers and toes. She reported minimal increases in the left Achilles xanthoma over 8 years, with no new xanthomas. The most recent magnetic resonance imaging of the brain showed a mild increased T2 signal within the dentate nucleus, which can be seen in CTX. Despite these findings, she has not clinically expressed any neurologic motor deficits. She has reported a significant cognitive delay. She has no known cardiovascular disease.'}
|
{'Case 2': 'A woman in her 40s, who had 2 family members with CTX, struggled with irregular bowel movements from an early age. She developed cataracts at the age of 11 years and was diagnosed with CTX at age 27. The diagnosis was confirmed by genetic testing, with the prompt initiation of chenodiol therapy. She has been on chenodiol consistently since the diagnosis at age 27. During adolescence, she developed tendon xanthomas on the fingers and toes, which required debulking, as well as plantar and Achilles xanthomas. She reported no new xanthomas and no changes in the existing xanthomas over 10 years. She was followed-up by neurologic examinations, and the most recent imaging showed cerebellar lesions; however, the patient did not have neurologic deficits. She had no known cardiovascular involvement. She has one daughter, who does not have the genetic mutation for CTX.', 'Case 3': 'A woman in her 50s, who has 2 family members formally diagnosed with CTX, had loose stools from childhood. She was diagnosed with cataracts at the age of 20 years and with CTX at 38 years, which was confirmed by genetic testing. She started chenodiol at the time of the diagnosis but had a 10-year interruption in the therapy. She restarted chenodiol at the age of 48 years and has since remained on the medication without further interruption. She acquired xanthomas of the Achilles, knee, and elbow. Her existing xanthomas have remained stable, with no new xanthomas. Significant neurologic involvement developed in the patient, which progressively led to her becoming nonambulatory and wheelchair-bound. The patient is cared for by her mother. The patient has severe cognitive decline and visual impairment. She has no known cardiovascular disease.', 'Case 1': 'A woman in her 30s, with no reported family history of CTX, first experienced symptoms with an early onset of frequent diarrhea in infancy. She developed cataracts by the age of 6 years. At the age of 14 years, she was formally diagnosed with CTX, which was confirmed by genetic testing. Chenodiol (chenodeoxycholic acid) therapy was initiated at diagnosis, and she has remained on chenodiol since that time. Tendon xanthomas required surgical debulking by the age of 17 years. She has had xanthomas of the Achilles, elbow, and plantar foot and extensor tendons of the fingers and toes. She reported minimal increases in the left Achilles xanthoma over 8 years, with no new xanthomas. The most recent magnetic resonance imaging of the brain showed a mild increased T2 signal within the dentate nucleus, which can be seen in CTX. Despite these findings, she has not clinically expressed any neurologic motor deficits. She has reported a significant cognitive delay. She has no known cardiovascular disease.'}
|
Vitals-and-Hematology
|
Vitals_Hema
|
[] |
test-2054
|
7695813
|
{'Case 2': 'A woman in her 40s, who had 2 family members with CTX, struggled with irregular bowel movements from an early age. She developed cataracts at the age of 11 years and was diagnosed with CTX at age 27. The diagnosis was confirmed by genetic testing, with the prompt initiation of chenodiol therapy. She has been on chenodiol consistently since the diagnosis at age 27. During adolescence, she developed tendon xanthomas on the fingers and toes, which required debulking, as well as plantar and Achilles xanthomas. She reported no new xanthomas and no changes in the existing xanthomas over 10 years. She was followed-up by neurologic examinations, and the most recent imaging showed cerebellar lesions; however, the patient did not have neurologic deficits. She had no known cardiovascular involvement. She has one daughter, who does not have the genetic mutation for CTX.', 'Case 3': 'A woman in her 50s, who has 2 family members formally diagnosed with CTX, had loose stools from childhood. She was diagnosed with cataracts at the age of 20 years and with CTX at 38 years, which was confirmed by genetic testing. She started chenodiol at the time of the diagnosis but had a 10-year interruption in the therapy. She restarted chenodiol at the age of 48 years and has since remained on the medication without further interruption. She acquired xanthomas of the Achilles, knee, and elbow. Her existing xanthomas have remained stable, with no new xanthomas. Significant neurologic involvement developed in the patient, which progressively led to her becoming nonambulatory and wheelchair-bound. The patient is cared for by her mother. The patient has severe cognitive decline and visual impairment. She has no known cardiovascular disease.', 'Case 1': 'A woman in her 30s, with no reported family history of CTX, first experienced symptoms with an early onset of frequent diarrhea in infancy. She developed cataracts by the age of 6 years. At the age of 14 years, she was formally diagnosed with CTX, which was confirmed by genetic testing. Chenodiol (chenodeoxycholic acid) therapy was initiated at diagnosis, and she has remained on chenodiol since that time. Tendon xanthomas required surgical debulking by the age of 17 years. She has had xanthomas of the Achilles, elbow, and plantar foot and extensor tendons of the fingers and toes. She reported minimal increases in the left Achilles xanthoma over 8 years, with no new xanthomas. The most recent magnetic resonance imaging of the brain showed a mild increased T2 signal within the dentate nucleus, which can be seen in CTX. Despite these findings, she has not clinically expressed any neurologic motor deficits. She has reported a significant cognitive delay. She has no known cardiovascular disease.'}
|
{'Case 2': 'A woman in her 40s, who had 2 family members with CTX, struggled with irregular bowel movements from an early age. She developed cataracts at the age of 11 years and was diagnosed with CTX at age 27. The diagnosis was confirmed by genetic testing, with the prompt initiation of chenodiol therapy. She has been on chenodiol consistently since the diagnosis at age 27. During adolescence, she developed tendon xanthomas on the fingers and toes, which required debulking, as well as plantar and Achilles xanthomas. She reported no new xanthomas and no changes in the existing xanthomas over 10 years. She was followed-up by neurologic examinations, and the most recent imaging showed cerebellar lesions; however, the patient did not have neurologic deficits. She had no known cardiovascular involvement. She has one daughter, who does not have the genetic mutation for CTX.', 'Case 3': 'A woman in her 50s, who has 2 family members formally diagnosed with CTX, had loose stools from childhood. She was diagnosed with cataracts at the age of 20 years and with CTX at 38 years, which was confirmed by genetic testing. She started chenodiol at the time of the diagnosis but had a 10-year interruption in the therapy. She restarted chenodiol at the age of 48 years and has since remained on the medication without further interruption. She acquired xanthomas of the Achilles, knee, and elbow. Her existing xanthomas have remained stable, with no new xanthomas. Significant neurologic involvement developed in the patient, which progressively led to her becoming nonambulatory and wheelchair-bound. The patient is cared for by her mother. The patient has severe cognitive decline and visual impairment. She has no known cardiovascular disease.', 'Case 1': 'A woman in her 30s, with no reported family history of CTX, first experienced symptoms with an early onset of frequent diarrhea in infancy. She developed cataracts by the age of 6 years. At the age of 14 years, she was formally diagnosed with CTX, which was confirmed by genetic testing. Chenodiol (chenodeoxycholic acid) therapy was initiated at diagnosis, and she has remained on chenodiol since that time. Tendon xanthomas required surgical debulking by the age of 17 years. She has had xanthomas of the Achilles, elbow, and plantar foot and extensor tendons of the fingers and toes. She reported minimal increases in the left Achilles xanthoma over 8 years, with no new xanthomas. The most recent magnetic resonance imaging of the brain showed a mild increased T2 signal within the dentate nucleus, which can be seen in CTX. Despite these findings, she has not clinically expressed any neurologic motor deficits. She has reported a significant cognitive delay. She has no known cardiovascular disease.'}
|
Gastrointestinal-System
|
GI
|
[
"irregular bowel movements",
"loose stools",
"early onset of frequent diarrhea"
] |
test-2055
|
7695813
|
{'Case 2': 'A woman in her 40s, who had 2 family members with CTX, struggled with irregular bowel movements from an early age. She developed cataracts at the age of 11 years and was diagnosed with CTX at age 27. The diagnosis was confirmed by genetic testing, with the prompt initiation of chenodiol therapy. She has been on chenodiol consistently since the diagnosis at age 27. During adolescence, she developed tendon xanthomas on the fingers and toes, which required debulking, as well as plantar and Achilles xanthomas. She reported no new xanthomas and no changes in the existing xanthomas over 10 years. She was followed-up by neurologic examinations, and the most recent imaging showed cerebellar lesions; however, the patient did not have neurologic deficits. She had no known cardiovascular involvement. She has one daughter, who does not have the genetic mutation for CTX.', 'Case 3': 'A woman in her 50s, who has 2 family members formally diagnosed with CTX, had loose stools from childhood. She was diagnosed with cataracts at the age of 20 years and with CTX at 38 years, which was confirmed by genetic testing. She started chenodiol at the time of the diagnosis but had a 10-year interruption in the therapy. She restarted chenodiol at the age of 48 years and has since remained on the medication without further interruption. She acquired xanthomas of the Achilles, knee, and elbow. Her existing xanthomas have remained stable, with no new xanthomas. Significant neurologic involvement developed in the patient, which progressively led to her becoming nonambulatory and wheelchair-bound. The patient is cared for by her mother. The patient has severe cognitive decline and visual impairment. She has no known cardiovascular disease.', 'Case 1': 'A woman in her 30s, with no reported family history of CTX, first experienced symptoms with an early onset of frequent diarrhea in infancy. She developed cataracts by the age of 6 years. At the age of 14 years, she was formally diagnosed with CTX, which was confirmed by genetic testing. Chenodiol (chenodeoxycholic acid) therapy was initiated at diagnosis, and she has remained on chenodiol since that time. Tendon xanthomas required surgical debulking by the age of 17 years. She has had xanthomas of the Achilles, elbow, and plantar foot and extensor tendons of the fingers and toes. She reported minimal increases in the left Achilles xanthoma over 8 years, with no new xanthomas. The most recent magnetic resonance imaging of the brain showed a mild increased T2 signal within the dentate nucleus, which can be seen in CTX. Despite these findings, she has not clinically expressed any neurologic motor deficits. She has reported a significant cognitive delay. She has no known cardiovascular disease.'}
|
{'Case 2': 'A woman in her 40s, who had 2 family members with CTX, struggled with irregular bowel movements from an early age. She developed cataracts at the age of 11 years and was diagnosed with CTX at age 27. The diagnosis was confirmed by genetic testing, with the prompt initiation of chenodiol therapy. She has been on chenodiol consistently since the diagnosis at age 27. During adolescence, she developed tendon xanthomas on the fingers and toes, which required debulking, as well as plantar and Achilles xanthomas. She reported no new xanthomas and no changes in the existing xanthomas over 10 years. She was followed-up by neurologic examinations, and the most recent imaging showed cerebellar lesions; however, the patient did not have neurologic deficits. She had no known cardiovascular involvement. She has one daughter, who does not have the genetic mutation for CTX.', 'Case 3': 'A woman in her 50s, who has 2 family members formally diagnosed with CTX, had loose stools from childhood. She was diagnosed with cataracts at the age of 20 years and with CTX at 38 years, which was confirmed by genetic testing. She started chenodiol at the time of the diagnosis but had a 10-year interruption in the therapy. She restarted chenodiol at the age of 48 years and has since remained on the medication without further interruption. She acquired xanthomas of the Achilles, knee, and elbow. Her existing xanthomas have remained stable, with no new xanthomas. Significant neurologic involvement developed in the patient, which progressively led to her becoming nonambulatory and wheelchair-bound. The patient is cared for by her mother. The patient has severe cognitive decline and visual impairment. She has no known cardiovascular disease.', 'Case 1': 'A woman in her 30s, with no reported family history of CTX, first experienced symptoms with an early onset of frequent diarrhea in infancy. She developed cataracts by the age of 6 years. At the age of 14 years, she was formally diagnosed with CTX, which was confirmed by genetic testing. Chenodiol (chenodeoxycholic acid) therapy was initiated at diagnosis, and she has remained on chenodiol since that time. Tendon xanthomas required surgical debulking by the age of 17 years. She has had xanthomas of the Achilles, elbow, and plantar foot and extensor tendons of the fingers and toes. She reported minimal increases in the left Achilles xanthoma over 8 years, with no new xanthomas. The most recent magnetic resonance imaging of the brain showed a mild increased T2 signal within the dentate nucleus, which can be seen in CTX. Despite these findings, she has not clinically expressed any neurologic motor deficits. She has reported a significant cognitive delay. She has no known cardiovascular disease.'}
|
Patient-History
|
History
|
[
"A woman in her 40s, who had 2 family members with CTX, struggled with irregular bowel movements from an early age. She developed cataracts at the age of 11 years and was diagnosed with CTX at age 27",
"A woman in her 50s, who has 2 family members formally diagnosed with CTX, had loose stools from childhood. She was diagnosed with cataracts at the age of 20 years and with CTX at 38 years",
"A woman in her 30s, with no reported family history of CTX, first experienced symptoms with an early onset of frequent diarrhea in infancy. She developed cataracts by the age of 6 years",
"Tendon xanthomas required surgical debulking by the age of 17 years"
] |
test-2056
|
7695813
|
{'Case 2': 'A woman in her 40s, who had 2 family members with CTX, struggled with irregular bowel movements from an early age. She developed cataracts at the age of 11 years and was diagnosed with CTX at age 27. The diagnosis was confirmed by genetic testing, with the prompt initiation of chenodiol therapy. She has been on chenodiol consistently since the diagnosis at age 27. During adolescence, she developed tendon xanthomas on the fingers and toes, which required debulking, as well as plantar and Achilles xanthomas. She reported no new xanthomas and no changes in the existing xanthomas over 10 years. She was followed-up by neurologic examinations, and the most recent imaging showed cerebellar lesions; however, the patient did not have neurologic deficits. She had no known cardiovascular involvement. She has one daughter, who does not have the genetic mutation for CTX.', 'Case 3': 'A woman in her 50s, who has 2 family members formally diagnosed with CTX, had loose stools from childhood. She was diagnosed with cataracts at the age of 20 years and with CTX at 38 years, which was confirmed by genetic testing. She started chenodiol at the time of the diagnosis but had a 10-year interruption in the therapy. She restarted chenodiol at the age of 48 years and has since remained on the medication without further interruption. She acquired xanthomas of the Achilles, knee, and elbow. Her existing xanthomas have remained stable, with no new xanthomas. Significant neurologic involvement developed in the patient, which progressively led to her becoming nonambulatory and wheelchair-bound. The patient is cared for by her mother. The patient has severe cognitive decline and visual impairment. She has no known cardiovascular disease.', 'Case 1': 'A woman in her 30s, with no reported family history of CTX, first experienced symptoms with an early onset of frequent diarrhea in infancy. She developed cataracts by the age of 6 years. At the age of 14 years, she was formally diagnosed with CTX, which was confirmed by genetic testing. Chenodiol (chenodeoxycholic acid) therapy was initiated at diagnosis, and she has remained on chenodiol since that time. Tendon xanthomas required surgical debulking by the age of 17 years. She has had xanthomas of the Achilles, elbow, and plantar foot and extensor tendons of the fingers and toes. She reported minimal increases in the left Achilles xanthoma over 8 years, with no new xanthomas. The most recent magnetic resonance imaging of the brain showed a mild increased T2 signal within the dentate nucleus, which can be seen in CTX. Despite these findings, she has not clinically expressed any neurologic motor deficits. She has reported a significant cognitive delay. She has no known cardiovascular disease.'}
|
{'Case 2': 'A woman in her 40s, who had 2 family members with CTX, struggled with irregular bowel movements from an early age. She developed cataracts at the age of 11 years and was diagnosed with CTX at age 27. The diagnosis was confirmed by genetic testing, with the prompt initiation of chenodiol therapy. She has been on chenodiol consistently since the diagnosis at age 27. During adolescence, she developed tendon xanthomas on the fingers and toes, which required debulking, as well as plantar and Achilles xanthomas. She reported no new xanthomas and no changes in the existing xanthomas over 10 years. She was followed-up by neurologic examinations, and the most recent imaging showed cerebellar lesions; however, the patient did not have neurologic deficits. She had no known cardiovascular involvement. She has one daughter, who does not have the genetic mutation for CTX.', 'Case 3': 'A woman in her 50s, who has 2 family members formally diagnosed with CTX, had loose stools from childhood. She was diagnosed with cataracts at the age of 20 years and with CTX at 38 years, which was confirmed by genetic testing. She started chenodiol at the time of the diagnosis but had a 10-year interruption in the therapy. She restarted chenodiol at the age of 48 years and has since remained on the medication without further interruption. She acquired xanthomas of the Achilles, knee, and elbow. Her existing xanthomas have remained stable, with no new xanthomas. Significant neurologic involvement developed in the patient, which progressively led to her becoming nonambulatory and wheelchair-bound. The patient is cared for by her mother. The patient has severe cognitive decline and visual impairment. She has no known cardiovascular disease.', 'Case 1': 'A woman in her 30s, with no reported family history of CTX, first experienced symptoms with an early onset of frequent diarrhea in infancy. She developed cataracts by the age of 6 years. At the age of 14 years, she was formally diagnosed with CTX, which was confirmed by genetic testing. Chenodiol (chenodeoxycholic acid) therapy was initiated at diagnosis, and she has remained on chenodiol since that time. Tendon xanthomas required surgical debulking by the age of 17 years. She has had xanthomas of the Achilles, elbow, and plantar foot and extensor tendons of the fingers and toes. She reported minimal increases in the left Achilles xanthoma over 8 years, with no new xanthomas. The most recent magnetic resonance imaging of the brain showed a mild increased T2 signal within the dentate nucleus, which can be seen in CTX. Despite these findings, she has not clinically expressed any neurologic motor deficits. She has reported a significant cognitive delay. She has no known cardiovascular disease.'}
|
Neurology
|
Neuro
|
[
"cerebellar lesions",
"patient did not have neurologic deficits",
"Significant neurologic involvement developed in the patient, which progressively led to her becoming nonambulatory and wheelchair - bound",
"severe cognitive decline",
"magnetic resonance imaging of the brain showed a mild increased T2 signal within the dentate nucleus",
"she has not clinically expressed any neurologic motor deficits",
"significant cognitive delay"
] |
test-2057
|
7695813
|
{'Case 2': 'A woman in her 40s, who had 2 family members with CTX, struggled with irregular bowel movements from an early age. She developed cataracts at the age of 11 years and was diagnosed with CTX at age 27. The diagnosis was confirmed by genetic testing, with the prompt initiation of chenodiol therapy. She has been on chenodiol consistently since the diagnosis at age 27. During adolescence, she developed tendon xanthomas on the fingers and toes, which required debulking, as well as plantar and Achilles xanthomas. She reported no new xanthomas and no changes in the existing xanthomas over 10 years. She was followed-up by neurologic examinations, and the most recent imaging showed cerebellar lesions; however, the patient did not have neurologic deficits. She had no known cardiovascular involvement. She has one daughter, who does not have the genetic mutation for CTX.', 'Case 3': 'A woman in her 50s, who has 2 family members formally diagnosed with CTX, had loose stools from childhood. She was diagnosed with cataracts at the age of 20 years and with CTX at 38 years, which was confirmed by genetic testing. She started chenodiol at the time of the diagnosis but had a 10-year interruption in the therapy. She restarted chenodiol at the age of 48 years and has since remained on the medication without further interruption. She acquired xanthomas of the Achilles, knee, and elbow. Her existing xanthomas have remained stable, with no new xanthomas. Significant neurologic involvement developed in the patient, which progressively led to her becoming nonambulatory and wheelchair-bound. The patient is cared for by her mother. The patient has severe cognitive decline and visual impairment. She has no known cardiovascular disease.', 'Case 1': 'A woman in her 30s, with no reported family history of CTX, first experienced symptoms with an early onset of frequent diarrhea in infancy. She developed cataracts by the age of 6 years. At the age of 14 years, she was formally diagnosed with CTX, which was confirmed by genetic testing. Chenodiol (chenodeoxycholic acid) therapy was initiated at diagnosis, and she has remained on chenodiol since that time. Tendon xanthomas required surgical debulking by the age of 17 years. She has had xanthomas of the Achilles, elbow, and plantar foot and extensor tendons of the fingers and toes. She reported minimal increases in the left Achilles xanthoma over 8 years, with no new xanthomas. The most recent magnetic resonance imaging of the brain showed a mild increased T2 signal within the dentate nucleus, which can be seen in CTX. Despite these findings, she has not clinically expressed any neurologic motor deficits. She has reported a significant cognitive delay. She has no known cardiovascular disease.'}
|
{'Case 2': 'A woman in her 40s, who had 2 family members with CTX, struggled with irregular bowel movements from an early age. She developed cataracts at the age of 11 years and was diagnosed with CTX at age 27. The diagnosis was confirmed by genetic testing, with the prompt initiation of chenodiol therapy. She has been on chenodiol consistently since the diagnosis at age 27. During adolescence, she developed tendon xanthomas on the fingers and toes, which required debulking, as well as plantar and Achilles xanthomas. She reported no new xanthomas and no changes in the existing xanthomas over 10 years. She was followed-up by neurologic examinations, and the most recent imaging showed cerebellar lesions; however, the patient did not have neurologic deficits. She had no known cardiovascular involvement. She has one daughter, who does not have the genetic mutation for CTX.', 'Case 3': 'A woman in her 50s, who has 2 family members formally diagnosed with CTX, had loose stools from childhood. She was diagnosed with cataracts at the age of 20 years and with CTX at 38 years, which was confirmed by genetic testing. She started chenodiol at the time of the diagnosis but had a 10-year interruption in the therapy. She restarted chenodiol at the age of 48 years and has since remained on the medication without further interruption. She acquired xanthomas of the Achilles, knee, and elbow. Her existing xanthomas have remained stable, with no new xanthomas. Significant neurologic involvement developed in the patient, which progressively led to her becoming nonambulatory and wheelchair-bound. The patient is cared for by her mother. The patient has severe cognitive decline and visual impairment. She has no known cardiovascular disease.', 'Case 1': 'A woman in her 30s, with no reported family history of CTX, first experienced symptoms with an early onset of frequent diarrhea in infancy. She developed cataracts by the age of 6 years. At the age of 14 years, she was formally diagnosed with CTX, which was confirmed by genetic testing. Chenodiol (chenodeoxycholic acid) therapy was initiated at diagnosis, and she has remained on chenodiol since that time. Tendon xanthomas required surgical debulking by the age of 17 years. She has had xanthomas of the Achilles, elbow, and plantar foot and extensor tendons of the fingers and toes. She reported minimal increases in the left Achilles xanthoma over 8 years, with no new xanthomas. The most recent magnetic resonance imaging of the brain showed a mild increased T2 signal within the dentate nucleus, which can be seen in CTX. Despite these findings, she has not clinically expressed any neurologic motor deficits. She has reported a significant cognitive delay. She has no known cardiovascular disease.'}
|
Laboratory-and-Imaging
|
Lab_Image
|
[
"most recent imaging showed cerebellar lesions",
"magnetic resonance imaging of the brain showed a mild increased T2 signal within the dentate nucleus"
] |
test-2058
|
7695813
|
{'Case 2': 'A woman in her 40s, who had 2 family members with CTX, struggled with irregular bowel movements from an early age. She developed cataracts at the age of 11 years and was diagnosed with CTX at age 27. The diagnosis was confirmed by genetic testing, with the prompt initiation of chenodiol therapy. She has been on chenodiol consistently since the diagnosis at age 27. During adolescence, she developed tendon xanthomas on the fingers and toes, which required debulking, as well as plantar and Achilles xanthomas. She reported no new xanthomas and no changes in the existing xanthomas over 10 years. She was followed-up by neurologic examinations, and the most recent imaging showed cerebellar lesions; however, the patient did not have neurologic deficits. She had no known cardiovascular involvement. She has one daughter, who does not have the genetic mutation for CTX.', 'Case 3': 'A woman in her 50s, who has 2 family members formally diagnosed with CTX, had loose stools from childhood. She was diagnosed with cataracts at the age of 20 years and with CTX at 38 years, which was confirmed by genetic testing. She started chenodiol at the time of the diagnosis but had a 10-year interruption in the therapy. She restarted chenodiol at the age of 48 years and has since remained on the medication without further interruption. She acquired xanthomas of the Achilles, knee, and elbow. Her existing xanthomas have remained stable, with no new xanthomas. Significant neurologic involvement developed in the patient, which progressively led to her becoming nonambulatory and wheelchair-bound. The patient is cared for by her mother. The patient has severe cognitive decline and visual impairment. She has no known cardiovascular disease.', 'Case 1': 'A woman in her 30s, with no reported family history of CTX, first experienced symptoms with an early onset of frequent diarrhea in infancy. She developed cataracts by the age of 6 years. At the age of 14 years, she was formally diagnosed with CTX, which was confirmed by genetic testing. Chenodiol (chenodeoxycholic acid) therapy was initiated at diagnosis, and she has remained on chenodiol since that time. Tendon xanthomas required surgical debulking by the age of 17 years. She has had xanthomas of the Achilles, elbow, and plantar foot and extensor tendons of the fingers and toes. She reported minimal increases in the left Achilles xanthoma over 8 years, with no new xanthomas. The most recent magnetic resonance imaging of the brain showed a mild increased T2 signal within the dentate nucleus, which can be seen in CTX. Despite these findings, she has not clinically expressed any neurologic motor deficits. She has reported a significant cognitive delay. She has no known cardiovascular disease.'}
|
{'Case 2': 'A woman in her 40s, who had 2 family members with CTX, struggled with irregular bowel movements from an early age. She developed cataracts at the age of 11 years and was diagnosed with CTX at age 27. The diagnosis was confirmed by genetic testing, with the prompt initiation of chenodiol therapy. She has been on chenodiol consistently since the diagnosis at age 27. During adolescence, she developed tendon xanthomas on the fingers and toes, which required debulking, as well as plantar and Achilles xanthomas. She reported no new xanthomas and no changes in the existing xanthomas over 10 years. She was followed-up by neurologic examinations, and the most recent imaging showed cerebellar lesions; however, the patient did not have neurologic deficits. She had no known cardiovascular involvement. She has one daughter, who does not have the genetic mutation for CTX.', 'Case 3': 'A woman in her 50s, who has 2 family members formally diagnosed with CTX, had loose stools from childhood. She was diagnosed with cataracts at the age of 20 years and with CTX at 38 years, which was confirmed by genetic testing. She started chenodiol at the time of the diagnosis but had a 10-year interruption in the therapy. She restarted chenodiol at the age of 48 years and has since remained on the medication without further interruption. She acquired xanthomas of the Achilles, knee, and elbow. Her existing xanthomas have remained stable, with no new xanthomas. Significant neurologic involvement developed in the patient, which progressively led to her becoming nonambulatory and wheelchair-bound. The patient is cared for by her mother. The patient has severe cognitive decline and visual impairment. She has no known cardiovascular disease.', 'Case 1': 'A woman in her 30s, with no reported family history of CTX, first experienced symptoms with an early onset of frequent diarrhea in infancy. She developed cataracts by the age of 6 years. At the age of 14 years, she was formally diagnosed with CTX, which was confirmed by genetic testing. Chenodiol (chenodeoxycholic acid) therapy was initiated at diagnosis, and she has remained on chenodiol since that time. Tendon xanthomas required surgical debulking by the age of 17 years. She has had xanthomas of the Achilles, elbow, and plantar foot and extensor tendons of the fingers and toes. She reported minimal increases in the left Achilles xanthoma over 8 years, with no new xanthomas. The most recent magnetic resonance imaging of the brain showed a mild increased T2 signal within the dentate nucleus, which can be seen in CTX. Despite these findings, she has not clinically expressed any neurologic motor deficits. She has reported a significant cognitive delay. She has no known cardiovascular disease.'}
|
Cardiovascular-System
|
CVS
|
[
"no known cardiovascular involvement",
"no known cardiovascular disease",
"no known cardiovascular disease"
] |
test-2059
|
7695813
|
{'Case 2': 'A woman in her 40s, who had 2 family members with CTX, struggled with irregular bowel movements from an early age. She developed cataracts at the age of 11 years and was diagnosed with CTX at age 27. The diagnosis was confirmed by genetic testing, with the prompt initiation of chenodiol therapy. She has been on chenodiol consistently since the diagnosis at age 27. During adolescence, she developed tendon xanthomas on the fingers and toes, which required debulking, as well as plantar and Achilles xanthomas. She reported no new xanthomas and no changes in the existing xanthomas over 10 years. She was followed-up by neurologic examinations, and the most recent imaging showed cerebellar lesions; however, the patient did not have neurologic deficits. She had no known cardiovascular involvement. She has one daughter, who does not have the genetic mutation for CTX.', 'Case 3': 'A woman in her 50s, who has 2 family members formally diagnosed with CTX, had loose stools from childhood. She was diagnosed with cataracts at the age of 20 years and with CTX at 38 years, which was confirmed by genetic testing. She started chenodiol at the time of the diagnosis but had a 10-year interruption in the therapy. She restarted chenodiol at the age of 48 years and has since remained on the medication without further interruption. She acquired xanthomas of the Achilles, knee, and elbow. Her existing xanthomas have remained stable, with no new xanthomas. Significant neurologic involvement developed in the patient, which progressively led to her becoming nonambulatory and wheelchair-bound. The patient is cared for by her mother. The patient has severe cognitive decline and visual impairment. She has no known cardiovascular disease.', 'Case 1': 'A woman in her 30s, with no reported family history of CTX, first experienced symptoms with an early onset of frequent diarrhea in infancy. She developed cataracts by the age of 6 years. At the age of 14 years, she was formally diagnosed with CTX, which was confirmed by genetic testing. Chenodiol (chenodeoxycholic acid) therapy was initiated at diagnosis, and she has remained on chenodiol since that time. Tendon xanthomas required surgical debulking by the age of 17 years. She has had xanthomas of the Achilles, elbow, and plantar foot and extensor tendons of the fingers and toes. She reported minimal increases in the left Achilles xanthoma over 8 years, with no new xanthomas. The most recent magnetic resonance imaging of the brain showed a mild increased T2 signal within the dentate nucleus, which can be seen in CTX. Despite these findings, she has not clinically expressed any neurologic motor deficits. She has reported a significant cognitive delay. She has no known cardiovascular disease.'}
|
{'Case 2': 'A woman in her 40s, who had 2 family members with CTX, struggled with irregular bowel movements from an early age. She developed cataracts at the age of 11 years and was diagnosed with CTX at age 27. The diagnosis was confirmed by genetic testing, with the prompt initiation of chenodiol therapy. She has been on chenodiol consistently since the diagnosis at age 27. During adolescence, she developed tendon xanthomas on the fingers and toes, which required debulking, as well as plantar and Achilles xanthomas. She reported no new xanthomas and no changes in the existing xanthomas over 10 years. She was followed-up by neurologic examinations, and the most recent imaging showed cerebellar lesions; however, the patient did not have neurologic deficits. She had no known cardiovascular involvement. She has one daughter, who does not have the genetic mutation for CTX.', 'Case 3': 'A woman in her 50s, who has 2 family members formally diagnosed with CTX, had loose stools from childhood. She was diagnosed with cataracts at the age of 20 years and with CTX at 38 years, which was confirmed by genetic testing. She started chenodiol at the time of the diagnosis but had a 10-year interruption in the therapy. She restarted chenodiol at the age of 48 years and has since remained on the medication without further interruption. She acquired xanthomas of the Achilles, knee, and elbow. Her existing xanthomas have remained stable, with no new xanthomas. Significant neurologic involvement developed in the patient, which progressively led to her becoming nonambulatory and wheelchair-bound. The patient is cared for by her mother. The patient has severe cognitive decline and visual impairment. She has no known cardiovascular disease.', 'Case 1': 'A woman in her 30s, with no reported family history of CTX, first experienced symptoms with an early onset of frequent diarrhea in infancy. She developed cataracts by the age of 6 years. At the age of 14 years, she was formally diagnosed with CTX, which was confirmed by genetic testing. Chenodiol (chenodeoxycholic acid) therapy was initiated at diagnosis, and she has remained on chenodiol since that time. Tendon xanthomas required surgical debulking by the age of 17 years. She has had xanthomas of the Achilles, elbow, and plantar foot and extensor tendons of the fingers and toes. She reported minimal increases in the left Achilles xanthoma over 8 years, with no new xanthomas. The most recent magnetic resonance imaging of the brain showed a mild increased T2 signal within the dentate nucleus, which can be seen in CTX. Despite these findings, she has not clinically expressed any neurologic motor deficits. She has reported a significant cognitive delay. She has no known cardiovascular disease.'}
|
Endocrinology
|
ENDO
|
[] |
test-2060
|
7695813
|
{'Case 2': 'A woman in her 40s, who had 2 family members with CTX, struggled with irregular bowel movements from an early age. She developed cataracts at the age of 11 years and was diagnosed with CTX at age 27. The diagnosis was confirmed by genetic testing, with the prompt initiation of chenodiol therapy. She has been on chenodiol consistently since the diagnosis at age 27. During adolescence, she developed tendon xanthomas on the fingers and toes, which required debulking, as well as plantar and Achilles xanthomas. She reported no new xanthomas and no changes in the existing xanthomas over 10 years. She was followed-up by neurologic examinations, and the most recent imaging showed cerebellar lesions; however, the patient did not have neurologic deficits. She had no known cardiovascular involvement. She has one daughter, who does not have the genetic mutation for CTX.', 'Case 3': 'A woman in her 50s, who has 2 family members formally diagnosed with CTX, had loose stools from childhood. She was diagnosed with cataracts at the age of 20 years and with CTX at 38 years, which was confirmed by genetic testing. She started chenodiol at the time of the diagnosis but had a 10-year interruption in the therapy. She restarted chenodiol at the age of 48 years and has since remained on the medication without further interruption. She acquired xanthomas of the Achilles, knee, and elbow. Her existing xanthomas have remained stable, with no new xanthomas. Significant neurologic involvement developed in the patient, which progressively led to her becoming nonambulatory and wheelchair-bound. The patient is cared for by her mother. The patient has severe cognitive decline and visual impairment. She has no known cardiovascular disease.', 'Case 1': 'A woman in her 30s, with no reported family history of CTX, first experienced symptoms with an early onset of frequent diarrhea in infancy. She developed cataracts by the age of 6 years. At the age of 14 years, she was formally diagnosed with CTX, which was confirmed by genetic testing. Chenodiol (chenodeoxycholic acid) therapy was initiated at diagnosis, and she has remained on chenodiol since that time. Tendon xanthomas required surgical debulking by the age of 17 years. She has had xanthomas of the Achilles, elbow, and plantar foot and extensor tendons of the fingers and toes. She reported minimal increases in the left Achilles xanthoma over 8 years, with no new xanthomas. The most recent magnetic resonance imaging of the brain showed a mild increased T2 signal within the dentate nucleus, which can be seen in CTX. Despite these findings, she has not clinically expressed any neurologic motor deficits. She has reported a significant cognitive delay. She has no known cardiovascular disease.'}
|
{'Case 2': 'A woman in her 40s, who had 2 family members with CTX, struggled with irregular bowel movements from an early age. She developed cataracts at the age of 11 years and was diagnosed with CTX at age 27. The diagnosis was confirmed by genetic testing, with the prompt initiation of chenodiol therapy. She has been on chenodiol consistently since the diagnosis at age 27. During adolescence, she developed tendon xanthomas on the fingers and toes, which required debulking, as well as plantar and Achilles xanthomas. She reported no new xanthomas and no changes in the existing xanthomas over 10 years. She was followed-up by neurologic examinations, and the most recent imaging showed cerebellar lesions; however, the patient did not have neurologic deficits. She had no known cardiovascular involvement. She has one daughter, who does not have the genetic mutation for CTX.', 'Case 3': 'A woman in her 50s, who has 2 family members formally diagnosed with CTX, had loose stools from childhood. She was diagnosed with cataracts at the age of 20 years and with CTX at 38 years, which was confirmed by genetic testing. She started chenodiol at the time of the diagnosis but had a 10-year interruption in the therapy. She restarted chenodiol at the age of 48 years and has since remained on the medication without further interruption. She acquired xanthomas of the Achilles, knee, and elbow. Her existing xanthomas have remained stable, with no new xanthomas. Significant neurologic involvement developed in the patient, which progressively led to her becoming nonambulatory and wheelchair-bound. The patient is cared for by her mother. The patient has severe cognitive decline and visual impairment. She has no known cardiovascular disease.', 'Case 1': 'A woman in her 30s, with no reported family history of CTX, first experienced symptoms with an early onset of frequent diarrhea in infancy. She developed cataracts by the age of 6 years. At the age of 14 years, she was formally diagnosed with CTX, which was confirmed by genetic testing. Chenodiol (chenodeoxycholic acid) therapy was initiated at diagnosis, and she has remained on chenodiol since that time. Tendon xanthomas required surgical debulking by the age of 17 years. She has had xanthomas of the Achilles, elbow, and plantar foot and extensor tendons of the fingers and toes. She reported minimal increases in the left Achilles xanthoma over 8 years, with no new xanthomas. The most recent magnetic resonance imaging of the brain showed a mild increased T2 signal within the dentate nucleus, which can be seen in CTX. Despite these findings, she has not clinically expressed any neurologic motor deficits. She has reported a significant cognitive delay. She has no known cardiovascular disease.'}
|
Genitourinary-System
|
GU
|
[] |
test-2061
|
7695813
|
{'Case 2': 'A woman in her 40s, who had 2 family members with CTX, struggled with irregular bowel movements from an early age. She developed cataracts at the age of 11 years and was diagnosed with CTX at age 27. The diagnosis was confirmed by genetic testing, with the prompt initiation of chenodiol therapy. She has been on chenodiol consistently since the diagnosis at age 27. During adolescence, she developed tendon xanthomas on the fingers and toes, which required debulking, as well as plantar and Achilles xanthomas. She reported no new xanthomas and no changes in the existing xanthomas over 10 years. She was followed-up by neurologic examinations, and the most recent imaging showed cerebellar lesions; however, the patient did not have neurologic deficits. She had no known cardiovascular involvement. She has one daughter, who does not have the genetic mutation for CTX.', 'Case 3': 'A woman in her 50s, who has 2 family members formally diagnosed with CTX, had loose stools from childhood. She was diagnosed with cataracts at the age of 20 years and with CTX at 38 years, which was confirmed by genetic testing. She started chenodiol at the time of the diagnosis but had a 10-year interruption in the therapy. She restarted chenodiol at the age of 48 years and has since remained on the medication without further interruption. She acquired xanthomas of the Achilles, knee, and elbow. Her existing xanthomas have remained stable, with no new xanthomas. Significant neurologic involvement developed in the patient, which progressively led to her becoming nonambulatory and wheelchair-bound. The patient is cared for by her mother. The patient has severe cognitive decline and visual impairment. She has no known cardiovascular disease.', 'Case 1': 'A woman in her 30s, with no reported family history of CTX, first experienced symptoms with an early onset of frequent diarrhea in infancy. She developed cataracts by the age of 6 years. At the age of 14 years, she was formally diagnosed with CTX, which was confirmed by genetic testing. Chenodiol (chenodeoxycholic acid) therapy was initiated at diagnosis, and she has remained on chenodiol since that time. Tendon xanthomas required surgical debulking by the age of 17 years. She has had xanthomas of the Achilles, elbow, and plantar foot and extensor tendons of the fingers and toes. She reported minimal increases in the left Achilles xanthoma over 8 years, with no new xanthomas. The most recent magnetic resonance imaging of the brain showed a mild increased T2 signal within the dentate nucleus, which can be seen in CTX. Despite these findings, she has not clinically expressed any neurologic motor deficits. She has reported a significant cognitive delay. She has no known cardiovascular disease.'}
|
{'Case 2': 'A woman in her 40s, who had 2 family members with CTX, struggled with irregular bowel movements from an early age. She developed cataracts at the age of 11 years and was diagnosed with CTX at age 27. The diagnosis was confirmed by genetic testing, with the prompt initiation of chenodiol therapy. She has been on chenodiol consistently since the diagnosis at age 27. During adolescence, she developed tendon xanthomas on the fingers and toes, which required debulking, as well as plantar and Achilles xanthomas. She reported no new xanthomas and no changes in the existing xanthomas over 10 years. She was followed-up by neurologic examinations, and the most recent imaging showed cerebellar lesions; however, the patient did not have neurologic deficits. She had no known cardiovascular involvement. She has one daughter, who does not have the genetic mutation for CTX.', 'Case 3': 'A woman in her 50s, who has 2 family members formally diagnosed with CTX, had loose stools from childhood. She was diagnosed with cataracts at the age of 20 years and with CTX at 38 years, which was confirmed by genetic testing. She started chenodiol at the time of the diagnosis but had a 10-year interruption in the therapy. She restarted chenodiol at the age of 48 years and has since remained on the medication without further interruption. She acquired xanthomas of the Achilles, knee, and elbow. Her existing xanthomas have remained stable, with no new xanthomas. Significant neurologic involvement developed in the patient, which progressively led to her becoming nonambulatory and wheelchair-bound. The patient is cared for by her mother. The patient has severe cognitive decline and visual impairment. She has no known cardiovascular disease.', 'Case 1': 'A woman in her 30s, with no reported family history of CTX, first experienced symptoms with an early onset of frequent diarrhea in infancy. She developed cataracts by the age of 6 years. At the age of 14 years, she was formally diagnosed with CTX, which was confirmed by genetic testing. Chenodiol (chenodeoxycholic acid) therapy was initiated at diagnosis, and she has remained on chenodiol since that time. Tendon xanthomas required surgical debulking by the age of 17 years. She has had xanthomas of the Achilles, elbow, and plantar foot and extensor tendons of the fingers and toes. She reported minimal increases in the left Achilles xanthoma over 8 years, with no new xanthomas. The most recent magnetic resonance imaging of the brain showed a mild increased T2 signal within the dentate nucleus, which can be seen in CTX. Despite these findings, she has not clinically expressed any neurologic motor deficits. She has reported a significant cognitive delay. She has no known cardiovascular disease.'}
|
Respiratory-System
|
RESP
|
[] |
test-2062
|
7695813
|
{'Case 2': 'A woman in her 40s, who had 2 family members with CTX, struggled with irregular bowel movements from an early age. She developed cataracts at the age of 11 years and was diagnosed with CTX at age 27. The diagnosis was confirmed by genetic testing, with the prompt initiation of chenodiol therapy. She has been on chenodiol consistently since the diagnosis at age 27. During adolescence, she developed tendon xanthomas on the fingers and toes, which required debulking, as well as plantar and Achilles xanthomas. She reported no new xanthomas and no changes in the existing xanthomas over 10 years. She was followed-up by neurologic examinations, and the most recent imaging showed cerebellar lesions; however, the patient did not have neurologic deficits. She had no known cardiovascular involvement. She has one daughter, who does not have the genetic mutation for CTX.', 'Case 3': 'A woman in her 50s, who has 2 family members formally diagnosed with CTX, had loose stools from childhood. She was diagnosed with cataracts at the age of 20 years and with CTX at 38 years, which was confirmed by genetic testing. She started chenodiol at the time of the diagnosis but had a 10-year interruption in the therapy. She restarted chenodiol at the age of 48 years and has since remained on the medication without further interruption. She acquired xanthomas of the Achilles, knee, and elbow. Her existing xanthomas have remained stable, with no new xanthomas. Significant neurologic involvement developed in the patient, which progressively led to her becoming nonambulatory and wheelchair-bound. The patient is cared for by her mother. The patient has severe cognitive decline and visual impairment. She has no known cardiovascular disease.', 'Case 1': 'A woman in her 30s, with no reported family history of CTX, first experienced symptoms with an early onset of frequent diarrhea in infancy. She developed cataracts by the age of 6 years. At the age of 14 years, she was formally diagnosed with CTX, which was confirmed by genetic testing. Chenodiol (chenodeoxycholic acid) therapy was initiated at diagnosis, and she has remained on chenodiol since that time. Tendon xanthomas required surgical debulking by the age of 17 years. She has had xanthomas of the Achilles, elbow, and plantar foot and extensor tendons of the fingers and toes. She reported minimal increases in the left Achilles xanthoma over 8 years, with no new xanthomas. The most recent magnetic resonance imaging of the brain showed a mild increased T2 signal within the dentate nucleus, which can be seen in CTX. Despite these findings, she has not clinically expressed any neurologic motor deficits. She has reported a significant cognitive delay. She has no known cardiovascular disease.'}
|
{'Case 2': 'A woman in her 40s, who had 2 family members with CTX, struggled with irregular bowel movements from an early age. She developed cataracts at the age of 11 years and was diagnosed with CTX at age 27. The diagnosis was confirmed by genetic testing, with the prompt initiation of chenodiol therapy. She has been on chenodiol consistently since the diagnosis at age 27. During adolescence, she developed tendon xanthomas on the fingers and toes, which required debulking, as well as plantar and Achilles xanthomas. She reported no new xanthomas and no changes in the existing xanthomas over 10 years. She was followed-up by neurologic examinations, and the most recent imaging showed cerebellar lesions; however, the patient did not have neurologic deficits. She had no known cardiovascular involvement. She has one daughter, who does not have the genetic mutation for CTX.', 'Case 3': 'A woman in her 50s, who has 2 family members formally diagnosed with CTX, had loose stools from childhood. She was diagnosed with cataracts at the age of 20 years and with CTX at 38 years, which was confirmed by genetic testing. She started chenodiol at the time of the diagnosis but had a 10-year interruption in the therapy. She restarted chenodiol at the age of 48 years and has since remained on the medication without further interruption. She acquired xanthomas of the Achilles, knee, and elbow. Her existing xanthomas have remained stable, with no new xanthomas. Significant neurologic involvement developed in the patient, which progressively led to her becoming nonambulatory and wheelchair-bound. The patient is cared for by her mother. The patient has severe cognitive decline and visual impairment. She has no known cardiovascular disease.', 'Case 1': 'A woman in her 30s, with no reported family history of CTX, first experienced symptoms with an early onset of frequent diarrhea in infancy. She developed cataracts by the age of 6 years. At the age of 14 years, she was formally diagnosed with CTX, which was confirmed by genetic testing. Chenodiol (chenodeoxycholic acid) therapy was initiated at diagnosis, and she has remained on chenodiol since that time. Tendon xanthomas required surgical debulking by the age of 17 years. She has had xanthomas of the Achilles, elbow, and plantar foot and extensor tendons of the fingers and toes. She reported minimal increases in the left Achilles xanthoma over 8 years, with no new xanthomas. The most recent magnetic resonance imaging of the brain showed a mild increased T2 signal within the dentate nucleus, which can be seen in CTX. Despite these findings, she has not clinically expressed any neurologic motor deficits. She has reported a significant cognitive delay. She has no known cardiovascular disease.'}
|
Musculoskeletal-System
|
MSK
|
[
"tendon xanthomas on the fingers and toes, which required debulking, as well as plantar and Achilles xanthomas. She reported no new xanthomas and no changes in the existing xanthomas over 10 years",
"acquired xanthomas of the Achilles, knee, and elbow. Her existing xanthomas have remained stable, with no new xanthomas",
"Tendon xanthomas",
"xanthomas of the Achilles, elbow, and plantar foot and extensor tendons of the fingers and toes. She reported minimal increases in the left Achilles xanthoma over 8 years, with no new xanthomas"
] |
test-2063
|
7695813
|
{'Case 2': 'A woman in her 40s, who had 2 family members with CTX, struggled with irregular bowel movements from an early age. She developed cataracts at the age of 11 years and was diagnosed with CTX at age 27. The diagnosis was confirmed by genetic testing, with the prompt initiation of chenodiol therapy. She has been on chenodiol consistently since the diagnosis at age 27. During adolescence, she developed tendon xanthomas on the fingers and toes, which required debulking, as well as plantar and Achilles xanthomas. She reported no new xanthomas and no changes in the existing xanthomas over 10 years. She was followed-up by neurologic examinations, and the most recent imaging showed cerebellar lesions; however, the patient did not have neurologic deficits. She had no known cardiovascular involvement. She has one daughter, who does not have the genetic mutation for CTX.', 'Case 3': 'A woman in her 50s, who has 2 family members formally diagnosed with CTX, had loose stools from childhood. She was diagnosed with cataracts at the age of 20 years and with CTX at 38 years, which was confirmed by genetic testing. She started chenodiol at the time of the diagnosis but had a 10-year interruption in the therapy. She restarted chenodiol at the age of 48 years and has since remained on the medication without further interruption. She acquired xanthomas of the Achilles, knee, and elbow. Her existing xanthomas have remained stable, with no new xanthomas. Significant neurologic involvement developed in the patient, which progressively led to her becoming nonambulatory and wheelchair-bound. The patient is cared for by her mother. The patient has severe cognitive decline and visual impairment. She has no known cardiovascular disease.', 'Case 1': 'A woman in her 30s, with no reported family history of CTX, first experienced symptoms with an early onset of frequent diarrhea in infancy. She developed cataracts by the age of 6 years. At the age of 14 years, she was formally diagnosed with CTX, which was confirmed by genetic testing. Chenodiol (chenodeoxycholic acid) therapy was initiated at diagnosis, and she has remained on chenodiol since that time. Tendon xanthomas required surgical debulking by the age of 17 years. She has had xanthomas of the Achilles, elbow, and plantar foot and extensor tendons of the fingers and toes. She reported minimal increases in the left Achilles xanthoma over 8 years, with no new xanthomas. The most recent magnetic resonance imaging of the brain showed a mild increased T2 signal within the dentate nucleus, which can be seen in CTX. Despite these findings, she has not clinically expressed any neurologic motor deficits. She has reported a significant cognitive delay. She has no known cardiovascular disease.'}
|
{'Case 2': 'A woman in her 40s, who had 2 family members with CTX, struggled with irregular bowel movements from an early age. She developed cataracts at the age of 11 years and was diagnosed with CTX at age 27. The diagnosis was confirmed by genetic testing, with the prompt initiation of chenodiol therapy. She has been on chenodiol consistently since the diagnosis at age 27. During adolescence, she developed tendon xanthomas on the fingers and toes, which required debulking, as well as plantar and Achilles xanthomas. She reported no new xanthomas and no changes in the existing xanthomas over 10 years. She was followed-up by neurologic examinations, and the most recent imaging showed cerebellar lesions; however, the patient did not have neurologic deficits. She had no known cardiovascular involvement. She has one daughter, who does not have the genetic mutation for CTX.', 'Case 3': 'A woman in her 50s, who has 2 family members formally diagnosed with CTX, had loose stools from childhood. She was diagnosed with cataracts at the age of 20 years and with CTX at 38 years, which was confirmed by genetic testing. She started chenodiol at the time of the diagnosis but had a 10-year interruption in the therapy. She restarted chenodiol at the age of 48 years and has since remained on the medication without further interruption. She acquired xanthomas of the Achilles, knee, and elbow. Her existing xanthomas have remained stable, with no new xanthomas. Significant neurologic involvement developed in the patient, which progressively led to her becoming nonambulatory and wheelchair-bound. The patient is cared for by her mother. The patient has severe cognitive decline and visual impairment. She has no known cardiovascular disease.', 'Case 1': 'A woman in her 30s, with no reported family history of CTX, first experienced symptoms with an early onset of frequent diarrhea in infancy. She developed cataracts by the age of 6 years. At the age of 14 years, she was formally diagnosed with CTX, which was confirmed by genetic testing. Chenodiol (chenodeoxycholic acid) therapy was initiated at diagnosis, and she has remained on chenodiol since that time. Tendon xanthomas required surgical debulking by the age of 17 years. She has had xanthomas of the Achilles, elbow, and plantar foot and extensor tendons of the fingers and toes. She reported minimal increases in the left Achilles xanthoma over 8 years, with no new xanthomas. The most recent magnetic resonance imaging of the brain showed a mild increased T2 signal within the dentate nucleus, which can be seen in CTX. Despite these findings, she has not clinically expressed any neurologic motor deficits. She has reported a significant cognitive delay. She has no known cardiovascular disease.'}
|
Eyes-Ears-Nose-Throat
|
EENT
|
[
"cataracts",
"cataracts",
"visual impairment",
"cataracts"
] |
test-2064
|
7695813
|
{'Case 2': 'A woman in her 40s, who had 2 family members with CTX, struggled with irregular bowel movements from an early age. She developed cataracts at the age of 11 years and was diagnosed with CTX at age 27. The diagnosis was confirmed by genetic testing, with the prompt initiation of chenodiol therapy. She has been on chenodiol consistently since the diagnosis at age 27. During adolescence, she developed tendon xanthomas on the fingers and toes, which required debulking, as well as plantar and Achilles xanthomas. She reported no new xanthomas and no changes in the existing xanthomas over 10 years. She was followed-up by neurologic examinations, and the most recent imaging showed cerebellar lesions; however, the patient did not have neurologic deficits. She had no known cardiovascular involvement. She has one daughter, who does not have the genetic mutation for CTX.', 'Case 3': 'A woman in her 50s, who has 2 family members formally diagnosed with CTX, had loose stools from childhood. She was diagnosed with cataracts at the age of 20 years and with CTX at 38 years, which was confirmed by genetic testing. She started chenodiol at the time of the diagnosis but had a 10-year interruption in the therapy. She restarted chenodiol at the age of 48 years and has since remained on the medication without further interruption. She acquired xanthomas of the Achilles, knee, and elbow. Her existing xanthomas have remained stable, with no new xanthomas. Significant neurologic involvement developed in the patient, which progressively led to her becoming nonambulatory and wheelchair-bound. The patient is cared for by her mother. The patient has severe cognitive decline and visual impairment. She has no known cardiovascular disease.', 'Case 1': 'A woman in her 30s, with no reported family history of CTX, first experienced symptoms with an early onset of frequent diarrhea in infancy. She developed cataracts by the age of 6 years. At the age of 14 years, she was formally diagnosed with CTX, which was confirmed by genetic testing. Chenodiol (chenodeoxycholic acid) therapy was initiated at diagnosis, and she has remained on chenodiol since that time. Tendon xanthomas required surgical debulking by the age of 17 years. She has had xanthomas of the Achilles, elbow, and plantar foot and extensor tendons of the fingers and toes. She reported minimal increases in the left Achilles xanthoma over 8 years, with no new xanthomas. The most recent magnetic resonance imaging of the brain showed a mild increased T2 signal within the dentate nucleus, which can be seen in CTX. Despite these findings, she has not clinically expressed any neurologic motor deficits. She has reported a significant cognitive delay. She has no known cardiovascular disease.'}
|
{'Case 2': 'A woman in her 40s, who had 2 family members with CTX, struggled with irregular bowel movements from an early age. She developed cataracts at the age of 11 years and was diagnosed with CTX at age 27. The diagnosis was confirmed by genetic testing, with the prompt initiation of chenodiol therapy. She has been on chenodiol consistently since the diagnosis at age 27. During adolescence, she developed tendon xanthomas on the fingers and toes, which required debulking, as well as plantar and Achilles xanthomas. She reported no new xanthomas and no changes in the existing xanthomas over 10 years. She was followed-up by neurologic examinations, and the most recent imaging showed cerebellar lesions; however, the patient did not have neurologic deficits. She had no known cardiovascular involvement. She has one daughter, who does not have the genetic mutation for CTX.', 'Case 3': 'A woman in her 50s, who has 2 family members formally diagnosed with CTX, had loose stools from childhood. She was diagnosed with cataracts at the age of 20 years and with CTX at 38 years, which was confirmed by genetic testing. She started chenodiol at the time of the diagnosis but had a 10-year interruption in the therapy. She restarted chenodiol at the age of 48 years and has since remained on the medication without further interruption. She acquired xanthomas of the Achilles, knee, and elbow. Her existing xanthomas have remained stable, with no new xanthomas. Significant neurologic involvement developed in the patient, which progressively led to her becoming nonambulatory and wheelchair-bound. The patient is cared for by her mother. The patient has severe cognitive decline and visual impairment. She has no known cardiovascular disease.', 'Case 1': 'A woman in her 30s, with no reported family history of CTX, first experienced symptoms with an early onset of frequent diarrhea in infancy. She developed cataracts by the age of 6 years. At the age of 14 years, she was formally diagnosed with CTX, which was confirmed by genetic testing. Chenodiol (chenodeoxycholic acid) therapy was initiated at diagnosis, and she has remained on chenodiol since that time. Tendon xanthomas required surgical debulking by the age of 17 years. She has had xanthomas of the Achilles, elbow, and plantar foot and extensor tendons of the fingers and toes. She reported minimal increases in the left Achilles xanthoma over 8 years, with no new xanthomas. The most recent magnetic resonance imaging of the brain showed a mild increased T2 signal within the dentate nucleus, which can be seen in CTX. Despite these findings, she has not clinically expressed any neurologic motor deficits. She has reported a significant cognitive delay. She has no known cardiovascular disease.'}
|
Dermatology
|
DERM
|
[] |
test-2065
|
7695813
|
{'Case 2': 'A woman in her 40s, who had 2 family members with CTX, struggled with irregular bowel movements from an early age. She developed cataracts at the age of 11 years and was diagnosed with CTX at age 27. The diagnosis was confirmed by genetic testing, with the prompt initiation of chenodiol therapy. She has been on chenodiol consistently since the diagnosis at age 27. During adolescence, she developed tendon xanthomas on the fingers and toes, which required debulking, as well as plantar and Achilles xanthomas. She reported no new xanthomas and no changes in the existing xanthomas over 10 years. She was followed-up by neurologic examinations, and the most recent imaging showed cerebellar lesions; however, the patient did not have neurologic deficits. She had no known cardiovascular involvement. She has one daughter, who does not have the genetic mutation for CTX.', 'Case 3': 'A woman in her 50s, who has 2 family members formally diagnosed with CTX, had loose stools from childhood. She was diagnosed with cataracts at the age of 20 years and with CTX at 38 years, which was confirmed by genetic testing. She started chenodiol at the time of the diagnosis but had a 10-year interruption in the therapy. She restarted chenodiol at the age of 48 years and has since remained on the medication without further interruption. She acquired xanthomas of the Achilles, knee, and elbow. Her existing xanthomas have remained stable, with no new xanthomas. Significant neurologic involvement developed in the patient, which progressively led to her becoming nonambulatory and wheelchair-bound. The patient is cared for by her mother. The patient has severe cognitive decline and visual impairment. She has no known cardiovascular disease.', 'Case 1': 'A woman in her 30s, with no reported family history of CTX, first experienced symptoms with an early onset of frequent diarrhea in infancy. She developed cataracts by the age of 6 years. At the age of 14 years, she was formally diagnosed with CTX, which was confirmed by genetic testing. Chenodiol (chenodeoxycholic acid) therapy was initiated at diagnosis, and she has remained on chenodiol since that time. Tendon xanthomas required surgical debulking by the age of 17 years. She has had xanthomas of the Achilles, elbow, and plantar foot and extensor tendons of the fingers and toes. She reported minimal increases in the left Achilles xanthoma over 8 years, with no new xanthomas. The most recent magnetic resonance imaging of the brain showed a mild increased T2 signal within the dentate nucleus, which can be seen in CTX. Despite these findings, she has not clinically expressed any neurologic motor deficits. She has reported a significant cognitive delay. She has no known cardiovascular disease.'}
|
{'Case 2': 'A woman in her 40s, who had 2 family members with CTX, struggled with irregular bowel movements from an early age. She developed cataracts at the age of 11 years and was diagnosed with CTX at age 27. The diagnosis was confirmed by genetic testing, with the prompt initiation of chenodiol therapy. She has been on chenodiol consistently since the diagnosis at age 27. During adolescence, she developed tendon xanthomas on the fingers and toes, which required debulking, as well as plantar and Achilles xanthomas. She reported no new xanthomas and no changes in the existing xanthomas over 10 years. She was followed-up by neurologic examinations, and the most recent imaging showed cerebellar lesions; however, the patient did not have neurologic deficits. She had no known cardiovascular involvement. She has one daughter, who does not have the genetic mutation for CTX.', 'Case 3': 'A woman in her 50s, who has 2 family members formally diagnosed with CTX, had loose stools from childhood. She was diagnosed with cataracts at the age of 20 years and with CTX at 38 years, which was confirmed by genetic testing. She started chenodiol at the time of the diagnosis but had a 10-year interruption in the therapy. She restarted chenodiol at the age of 48 years and has since remained on the medication without further interruption. She acquired xanthomas of the Achilles, knee, and elbow. Her existing xanthomas have remained stable, with no new xanthomas. Significant neurologic involvement developed in the patient, which progressively led to her becoming nonambulatory and wheelchair-bound. The patient is cared for by her mother. The patient has severe cognitive decline and visual impairment. She has no known cardiovascular disease.', 'Case 1': 'A woman in her 30s, with no reported family history of CTX, first experienced symptoms with an early onset of frequent diarrhea in infancy. She developed cataracts by the age of 6 years. At the age of 14 years, she was formally diagnosed with CTX, which was confirmed by genetic testing. Chenodiol (chenodeoxycholic acid) therapy was initiated at diagnosis, and she has remained on chenodiol since that time. Tendon xanthomas required surgical debulking by the age of 17 years. She has had xanthomas of the Achilles, elbow, and plantar foot and extensor tendons of the fingers and toes. She reported minimal increases in the left Achilles xanthoma over 8 years, with no new xanthomas. The most recent magnetic resonance imaging of the brain showed a mild increased T2 signal within the dentate nucleus, which can be seen in CTX. Despite these findings, she has not clinically expressed any neurologic motor deficits. She has reported a significant cognitive delay. She has no known cardiovascular disease.'}
|
Pregnancy
|
Pregnancy
|
[] |
test-2066
|
7695813
|
{'Case 2': 'A woman in her 40s, who had 2 family members with CTX, struggled with irregular bowel movements from an early age. She developed cataracts at the age of 11 years and was diagnosed with CTX at age 27. The diagnosis was confirmed by genetic testing, with the prompt initiation of chenodiol therapy. She has been on chenodiol consistently since the diagnosis at age 27. During adolescence, she developed tendon xanthomas on the fingers and toes, which required debulking, as well as plantar and Achilles xanthomas. She reported no new xanthomas and no changes in the existing xanthomas over 10 years. She was followed-up by neurologic examinations, and the most recent imaging showed cerebellar lesions; however, the patient did not have neurologic deficits. She had no known cardiovascular involvement. She has one daughter, who does not have the genetic mutation for CTX.', 'Case 3': 'A woman in her 50s, who has 2 family members formally diagnosed with CTX, had loose stools from childhood. She was diagnosed with cataracts at the age of 20 years and with CTX at 38 years, which was confirmed by genetic testing. She started chenodiol at the time of the diagnosis but had a 10-year interruption in the therapy. She restarted chenodiol at the age of 48 years and has since remained on the medication without further interruption. She acquired xanthomas of the Achilles, knee, and elbow. Her existing xanthomas have remained stable, with no new xanthomas. Significant neurologic involvement developed in the patient, which progressively led to her becoming nonambulatory and wheelchair-bound. The patient is cared for by her mother. The patient has severe cognitive decline and visual impairment. She has no known cardiovascular disease.', 'Case 1': 'A woman in her 30s, with no reported family history of CTX, first experienced symptoms with an early onset of frequent diarrhea in infancy. She developed cataracts by the age of 6 years. At the age of 14 years, she was formally diagnosed with CTX, which was confirmed by genetic testing. Chenodiol (chenodeoxycholic acid) therapy was initiated at diagnosis, and she has remained on chenodiol since that time. Tendon xanthomas required surgical debulking by the age of 17 years. She has had xanthomas of the Achilles, elbow, and plantar foot and extensor tendons of the fingers and toes. She reported minimal increases in the left Achilles xanthoma over 8 years, with no new xanthomas. The most recent magnetic resonance imaging of the brain showed a mild increased T2 signal within the dentate nucleus, which can be seen in CTX. Despite these findings, she has not clinically expressed any neurologic motor deficits. She has reported a significant cognitive delay. She has no known cardiovascular disease.'}
|
{'Case 2': 'A woman in her 40s, who had 2 family members with CTX, struggled with irregular bowel movements from an early age. She developed cataracts at the age of 11 years and was diagnosed with CTX at age 27. The diagnosis was confirmed by genetic testing, with the prompt initiation of chenodiol therapy. She has been on chenodiol consistently since the diagnosis at age 27. During adolescence, she developed tendon xanthomas on the fingers and toes, which required debulking, as well as plantar and Achilles xanthomas. She reported no new xanthomas and no changes in the existing xanthomas over 10 years. She was followed-up by neurologic examinations, and the most recent imaging showed cerebellar lesions; however, the patient did not have neurologic deficits. She had no known cardiovascular involvement. She has one daughter, who does not have the genetic mutation for CTX.', 'Case 3': 'A woman in her 50s, who has 2 family members formally diagnosed with CTX, had loose stools from childhood. She was diagnosed with cataracts at the age of 20 years and with CTX at 38 years, which was confirmed by genetic testing. She started chenodiol at the time of the diagnosis but had a 10-year interruption in the therapy. She restarted chenodiol at the age of 48 years and has since remained on the medication without further interruption. She acquired xanthomas of the Achilles, knee, and elbow. Her existing xanthomas have remained stable, with no new xanthomas. Significant neurologic involvement developed in the patient, which progressively led to her becoming nonambulatory and wheelchair-bound. The patient is cared for by her mother. The patient has severe cognitive decline and visual impairment. She has no known cardiovascular disease.', 'Case 1': 'A woman in her 30s, with no reported family history of CTX, first experienced symptoms with an early onset of frequent diarrhea in infancy. She developed cataracts by the age of 6 years. At the age of 14 years, she was formally diagnosed with CTX, which was confirmed by genetic testing. Chenodiol (chenodeoxycholic acid) therapy was initiated at diagnosis, and she has remained on chenodiol since that time. Tendon xanthomas required surgical debulking by the age of 17 years. She has had xanthomas of the Achilles, elbow, and plantar foot and extensor tendons of the fingers and toes. She reported minimal increases in the left Achilles xanthoma over 8 years, with no new xanthomas. The most recent magnetic resonance imaging of the brain showed a mild increased T2 signal within the dentate nucleus, which can be seen in CTX. Despite these findings, she has not clinically expressed any neurologic motor deficits. She has reported a significant cognitive delay. She has no known cardiovascular disease.'}
|
Lymphatic-System
|
LYMPH
|
[] |
test-2067
|
7695813
|
{'Case 2': 'A woman in her 40s, who had 2 family members with CTX, struggled with irregular bowel movements from an early age. She developed cataracts at the age of 11 years and was diagnosed with CTX at age 27. The diagnosis was confirmed by genetic testing, with the prompt initiation of chenodiol therapy. She has been on chenodiol consistently since the diagnosis at age 27. During adolescence, she developed tendon xanthomas on the fingers and toes, which required debulking, as well as plantar and Achilles xanthomas. She reported no new xanthomas and no changes in the existing xanthomas over 10 years. She was followed-up by neurologic examinations, and the most recent imaging showed cerebellar lesions; however, the patient did not have neurologic deficits. She had no known cardiovascular involvement. She has one daughter, who does not have the genetic mutation for CTX.', 'Case 3': 'A woman in her 50s, who has 2 family members formally diagnosed with CTX, had loose stools from childhood. She was diagnosed with cataracts at the age of 20 years and with CTX at 38 years, which was confirmed by genetic testing. She started chenodiol at the time of the diagnosis but had a 10-year interruption in the therapy. She restarted chenodiol at the age of 48 years and has since remained on the medication without further interruption. She acquired xanthomas of the Achilles, knee, and elbow. Her existing xanthomas have remained stable, with no new xanthomas. Significant neurologic involvement developed in the patient, which progressively led to her becoming nonambulatory and wheelchair-bound. The patient is cared for by her mother. The patient has severe cognitive decline and visual impairment. She has no known cardiovascular disease.', 'Case 1': 'A woman in her 30s, with no reported family history of CTX, first experienced symptoms with an early onset of frequent diarrhea in infancy. She developed cataracts by the age of 6 years. At the age of 14 years, she was formally diagnosed with CTX, which was confirmed by genetic testing. Chenodiol (chenodeoxycholic acid) therapy was initiated at diagnosis, and she has remained on chenodiol since that time. Tendon xanthomas required surgical debulking by the age of 17 years. She has had xanthomas of the Achilles, elbow, and plantar foot and extensor tendons of the fingers and toes. She reported minimal increases in the left Achilles xanthoma over 8 years, with no new xanthomas. The most recent magnetic resonance imaging of the brain showed a mild increased T2 signal within the dentate nucleus, which can be seen in CTX. Despite these findings, she has not clinically expressed any neurologic motor deficits. She has reported a significant cognitive delay. She has no known cardiovascular disease.'}
|
{'Case 2': 'A woman in her 40s, who had 2 family members with CTX, struggled with irregular bowel movements from an early age. She developed cataracts at the age of 11 years and was diagnosed with CTX at age 27. The diagnosis was confirmed by genetic testing, with the prompt initiation of chenodiol therapy. She has been on chenodiol consistently since the diagnosis at age 27. During adolescence, she developed tendon xanthomas on the fingers and toes, which required debulking, as well as plantar and Achilles xanthomas. She reported no new xanthomas and no changes in the existing xanthomas over 10 years. She was followed-up by neurologic examinations, and the most recent imaging showed cerebellar lesions; however, the patient did not have neurologic deficits. She had no known cardiovascular involvement. She has one daughter, who does not have the genetic mutation for CTX.', 'Case 3': 'A woman in her 50s, who has 2 family members formally diagnosed with CTX, had loose stools from childhood. She was diagnosed with cataracts at the age of 20 years and with CTX at 38 years, which was confirmed by genetic testing. She started chenodiol at the time of the diagnosis but had a 10-year interruption in the therapy. She restarted chenodiol at the age of 48 years and has since remained on the medication without further interruption. She acquired xanthomas of the Achilles, knee, and elbow. Her existing xanthomas have remained stable, with no new xanthomas. Significant neurologic involvement developed in the patient, which progressively led to her becoming nonambulatory and wheelchair-bound. The patient is cared for by her mother. The patient has severe cognitive decline and visual impairment. She has no known cardiovascular disease.', 'Case 1': 'A woman in her 30s, with no reported family history of CTX, first experienced symptoms with an early onset of frequent diarrhea in infancy. She developed cataracts by the age of 6 years. At the age of 14 years, she was formally diagnosed with CTX, which was confirmed by genetic testing. Chenodiol (chenodeoxycholic acid) therapy was initiated at diagnosis, and she has remained on chenodiol since that time. Tendon xanthomas required surgical debulking by the age of 17 years. She has had xanthomas of the Achilles, elbow, and plantar foot and extensor tendons of the fingers and toes. She reported minimal increases in the left Achilles xanthoma over 8 years, with no new xanthomas. The most recent magnetic resonance imaging of the brain showed a mild increased T2 signal within the dentate nucleus, which can be seen in CTX. Despite these findings, she has not clinically expressed any neurologic motor deficits. She has reported a significant cognitive delay. She has no known cardiovascular disease.'}
|
Age-at-Presentation
|
Age (at case presentation)
|
[
"her 40s",
"in her 50s",
"her 30s"
] |
test-2068
|
7695813
|
{'Case 2': 'A woman in her 40s, who had 2 family members with CTX, struggled with irregular bowel movements from an early age. She developed cataracts at the age of 11 years and was diagnosed with CTX at age 27. The diagnosis was confirmed by genetic testing, with the prompt initiation of chenodiol therapy. She has been on chenodiol consistently since the diagnosis at age 27. During adolescence, she developed tendon xanthomas on the fingers and toes, which required debulking, as well as plantar and Achilles xanthomas. She reported no new xanthomas and no changes in the existing xanthomas over 10 years. She was followed-up by neurologic examinations, and the most recent imaging showed cerebellar lesions; however, the patient did not have neurologic deficits. She had no known cardiovascular involvement. She has one daughter, who does not have the genetic mutation for CTX.', 'Case 3': 'A woman in her 50s, who has 2 family members formally diagnosed with CTX, had loose stools from childhood. She was diagnosed with cataracts at the age of 20 years and with CTX at 38 years, which was confirmed by genetic testing. She started chenodiol at the time of the diagnosis but had a 10-year interruption in the therapy. She restarted chenodiol at the age of 48 years and has since remained on the medication without further interruption. She acquired xanthomas of the Achilles, knee, and elbow. Her existing xanthomas have remained stable, with no new xanthomas. Significant neurologic involvement developed in the patient, which progressively led to her becoming nonambulatory and wheelchair-bound. The patient is cared for by her mother. The patient has severe cognitive decline and visual impairment. She has no known cardiovascular disease.', 'Case 1': 'A woman in her 30s, with no reported family history of CTX, first experienced symptoms with an early onset of frequent diarrhea in infancy. She developed cataracts by the age of 6 years. At the age of 14 years, she was formally diagnosed with CTX, which was confirmed by genetic testing. Chenodiol (chenodeoxycholic acid) therapy was initiated at diagnosis, and she has remained on chenodiol since that time. Tendon xanthomas required surgical debulking by the age of 17 years. She has had xanthomas of the Achilles, elbow, and plantar foot and extensor tendons of the fingers and toes. She reported minimal increases in the left Achilles xanthoma over 8 years, with no new xanthomas. The most recent magnetic resonance imaging of the brain showed a mild increased T2 signal within the dentate nucleus, which can be seen in CTX. Despite these findings, she has not clinically expressed any neurologic motor deficits. She has reported a significant cognitive delay. She has no known cardiovascular disease.'}
|
{'Case 2': 'A woman in her 40s, who had 2 family members with CTX, struggled with irregular bowel movements from an early age. She developed cataracts at the age of 11 years and was diagnosed with CTX at age 27. The diagnosis was confirmed by genetic testing, with the prompt initiation of chenodiol therapy. She has been on chenodiol consistently since the diagnosis at age 27. During adolescence, she developed tendon xanthomas on the fingers and toes, which required debulking, as well as plantar and Achilles xanthomas. She reported no new xanthomas and no changes in the existing xanthomas over 10 years. She was followed-up by neurologic examinations, and the most recent imaging showed cerebellar lesions; however, the patient did not have neurologic deficits. She had no known cardiovascular involvement. She has one daughter, who does not have the genetic mutation for CTX.', 'Case 3': 'A woman in her 50s, who has 2 family members formally diagnosed with CTX, had loose stools from childhood. She was diagnosed with cataracts at the age of 20 years and with CTX at 38 years, which was confirmed by genetic testing. She started chenodiol at the time of the diagnosis but had a 10-year interruption in the therapy. She restarted chenodiol at the age of 48 years and has since remained on the medication without further interruption. She acquired xanthomas of the Achilles, knee, and elbow. Her existing xanthomas have remained stable, with no new xanthomas. Significant neurologic involvement developed in the patient, which progressively led to her becoming nonambulatory and wheelchair-bound. The patient is cared for by her mother. The patient has severe cognitive decline and visual impairment. She has no known cardiovascular disease.', 'Case 1': 'A woman in her 30s, with no reported family history of CTX, first experienced symptoms with an early onset of frequent diarrhea in infancy. She developed cataracts by the age of 6 years. At the age of 14 years, she was formally diagnosed with CTX, which was confirmed by genetic testing. Chenodiol (chenodeoxycholic acid) therapy was initiated at diagnosis, and she has remained on chenodiol since that time. Tendon xanthomas required surgical debulking by the age of 17 years. She has had xanthomas of the Achilles, elbow, and plantar foot and extensor tendons of the fingers and toes. She reported minimal increases in the left Achilles xanthoma over 8 years, with no new xanthomas. The most recent magnetic resonance imaging of the brain showed a mild increased T2 signal within the dentate nucleus, which can be seen in CTX. Despite these findings, she has not clinically expressed any neurologic motor deficits. She has reported a significant cognitive delay. She has no known cardiovascular disease.'}
|
Age-of-Onset
|
Age (of onset)
|
[
"early age",
"childhood",
"infancy"
] |
test-2069
|
7695813
|
{'Case 2': 'A woman in her 40s, who had 2 family members with CTX, struggled with irregular bowel movements from an early age. She developed cataracts at the age of 11 years and was diagnosed with CTX at age 27. The diagnosis was confirmed by genetic testing, with the prompt initiation of chenodiol therapy. She has been on chenodiol consistently since the diagnosis at age 27. During adolescence, she developed tendon xanthomas on the fingers and toes, which required debulking, as well as plantar and Achilles xanthomas. She reported no new xanthomas and no changes in the existing xanthomas over 10 years. She was followed-up by neurologic examinations, and the most recent imaging showed cerebellar lesions; however, the patient did not have neurologic deficits. She had no known cardiovascular involvement. She has one daughter, who does not have the genetic mutation for CTX.', 'Case 3': 'A woman in her 50s, who has 2 family members formally diagnosed with CTX, had loose stools from childhood. She was diagnosed with cataracts at the age of 20 years and with CTX at 38 years, which was confirmed by genetic testing. She started chenodiol at the time of the diagnosis but had a 10-year interruption in the therapy. She restarted chenodiol at the age of 48 years and has since remained on the medication without further interruption. She acquired xanthomas of the Achilles, knee, and elbow. Her existing xanthomas have remained stable, with no new xanthomas. Significant neurologic involvement developed in the patient, which progressively led to her becoming nonambulatory and wheelchair-bound. The patient is cared for by her mother. The patient has severe cognitive decline and visual impairment. She has no known cardiovascular disease.', 'Case 1': 'A woman in her 30s, with no reported family history of CTX, first experienced symptoms with an early onset of frequent diarrhea in infancy. She developed cataracts by the age of 6 years. At the age of 14 years, she was formally diagnosed with CTX, which was confirmed by genetic testing. Chenodiol (chenodeoxycholic acid) therapy was initiated at diagnosis, and she has remained on chenodiol since that time. Tendon xanthomas required surgical debulking by the age of 17 years. She has had xanthomas of the Achilles, elbow, and plantar foot and extensor tendons of the fingers and toes. She reported minimal increases in the left Achilles xanthoma over 8 years, with no new xanthomas. The most recent magnetic resonance imaging of the brain showed a mild increased T2 signal within the dentate nucleus, which can be seen in CTX. Despite these findings, she has not clinically expressed any neurologic motor deficits. She has reported a significant cognitive delay. She has no known cardiovascular disease.'}
|
{'Case 2': 'A woman in her 40s, who had 2 family members with CTX, struggled with irregular bowel movements from an early age. She developed cataracts at the age of 11 years and was diagnosed with CTX at age 27. The diagnosis was confirmed by genetic testing, with the prompt initiation of chenodiol therapy. She has been on chenodiol consistently since the diagnosis at age 27. During adolescence, she developed tendon xanthomas on the fingers and toes, which required debulking, as well as plantar and Achilles xanthomas. She reported no new xanthomas and no changes in the existing xanthomas over 10 years. She was followed-up by neurologic examinations, and the most recent imaging showed cerebellar lesions; however, the patient did not have neurologic deficits. She had no known cardiovascular involvement. She has one daughter, who does not have the genetic mutation for CTX.', 'Case 3': 'A woman in her 50s, who has 2 family members formally diagnosed with CTX, had loose stools from childhood. She was diagnosed with cataracts at the age of 20 years and with CTX at 38 years, which was confirmed by genetic testing. She started chenodiol at the time of the diagnosis but had a 10-year interruption in the therapy. She restarted chenodiol at the age of 48 years and has since remained on the medication without further interruption. She acquired xanthomas of the Achilles, knee, and elbow. Her existing xanthomas have remained stable, with no new xanthomas. Significant neurologic involvement developed in the patient, which progressively led to her becoming nonambulatory and wheelchair-bound. The patient is cared for by her mother. The patient has severe cognitive decline and visual impairment. She has no known cardiovascular disease.', 'Case 1': 'A woman in her 30s, with no reported family history of CTX, first experienced symptoms with an early onset of frequent diarrhea in infancy. She developed cataracts by the age of 6 years. At the age of 14 years, she was formally diagnosed with CTX, which was confirmed by genetic testing. Chenodiol (chenodeoxycholic acid) therapy was initiated at diagnosis, and she has remained on chenodiol since that time. Tendon xanthomas required surgical debulking by the age of 17 years. She has had xanthomas of the Achilles, elbow, and plantar foot and extensor tendons of the fingers and toes. She reported minimal increases in the left Achilles xanthoma over 8 years, with no new xanthomas. The most recent magnetic resonance imaging of the brain showed a mild increased T2 signal within the dentate nucleus, which can be seen in CTX. Despite these findings, she has not clinically expressed any neurologic motor deficits. She has reported a significant cognitive delay. She has no known cardiovascular disease.'}
|
Confirmed-Diagnosis-IEM
|
Confirmed_Diagnosis(IEM)
|
[
"diagnosed with CTX at age 27",
"CTX at 38 years , which was confirmed by genetic testing .",
"At the age of 14 years , she was formally diagnosed with CTX , which was confirmed by genetic testing ."
] |
test-2070
|
7695813
|
{'Case 2': 'A woman in her 40s, who had 2 family members with CTX, struggled with irregular bowel movements from an early age. She developed cataracts at the age of 11 years and was diagnosed with CTX at age 27. The diagnosis was confirmed by genetic testing, with the prompt initiation of chenodiol therapy. She has been on chenodiol consistently since the diagnosis at age 27. During adolescence, she developed tendon xanthomas on the fingers and toes, which required debulking, as well as plantar and Achilles xanthomas. She reported no new xanthomas and no changes in the existing xanthomas over 10 years. She was followed-up by neurologic examinations, and the most recent imaging showed cerebellar lesions; however, the patient did not have neurologic deficits. She had no known cardiovascular involvement. She has one daughter, who does not have the genetic mutation for CTX.', 'Case 3': 'A woman in her 50s, who has 2 family members formally diagnosed with CTX, had loose stools from childhood. She was diagnosed with cataracts at the age of 20 years and with CTX at 38 years, which was confirmed by genetic testing. She started chenodiol at the time of the diagnosis but had a 10-year interruption in the therapy. She restarted chenodiol at the age of 48 years and has since remained on the medication without further interruption. She acquired xanthomas of the Achilles, knee, and elbow. Her existing xanthomas have remained stable, with no new xanthomas. Significant neurologic involvement developed in the patient, which progressively led to her becoming nonambulatory and wheelchair-bound. The patient is cared for by her mother. The patient has severe cognitive decline and visual impairment. She has no known cardiovascular disease.', 'Case 1': 'A woman in her 30s, with no reported family history of CTX, first experienced symptoms with an early onset of frequent diarrhea in infancy. She developed cataracts by the age of 6 years. At the age of 14 years, she was formally diagnosed with CTX, which was confirmed by genetic testing. Chenodiol (chenodeoxycholic acid) therapy was initiated at diagnosis, and she has remained on chenodiol since that time. Tendon xanthomas required surgical debulking by the age of 17 years. She has had xanthomas of the Achilles, elbow, and plantar foot and extensor tendons of the fingers and toes. She reported minimal increases in the left Achilles xanthoma over 8 years, with no new xanthomas. The most recent magnetic resonance imaging of the brain showed a mild increased T2 signal within the dentate nucleus, which can be seen in CTX. Despite these findings, she has not clinically expressed any neurologic motor deficits. She has reported a significant cognitive delay. She has no known cardiovascular disease.'}
|
{'Case 2': 'A woman in her 40s, who had 2 family members with CTX, struggled with irregular bowel movements from an early age. She developed cataracts at the age of 11 years and was diagnosed with CTX at age 27. The diagnosis was confirmed by genetic testing, with the prompt initiation of chenodiol therapy. She has been on chenodiol consistently since the diagnosis at age 27. During adolescence, she developed tendon xanthomas on the fingers and toes, which required debulking, as well as plantar and Achilles xanthomas. She reported no new xanthomas and no changes in the existing xanthomas over 10 years. She was followed-up by neurologic examinations, and the most recent imaging showed cerebellar lesions; however, the patient did not have neurologic deficits. She had no known cardiovascular involvement. She has one daughter, who does not have the genetic mutation for CTX.', 'Case 3': 'A woman in her 50s, who has 2 family members formally diagnosed with CTX, had loose stools from childhood. She was diagnosed with cataracts at the age of 20 years and with CTX at 38 years, which was confirmed by genetic testing. She started chenodiol at the time of the diagnosis but had a 10-year interruption in the therapy. She restarted chenodiol at the age of 48 years and has since remained on the medication without further interruption. She acquired xanthomas of the Achilles, knee, and elbow. Her existing xanthomas have remained stable, with no new xanthomas. Significant neurologic involvement developed in the patient, which progressively led to her becoming nonambulatory and wheelchair-bound. The patient is cared for by her mother. The patient has severe cognitive decline and visual impairment. She has no known cardiovascular disease.', 'Case 1': 'A woman in her 30s, with no reported family history of CTX, first experienced symptoms with an early onset of frequent diarrhea in infancy. She developed cataracts by the age of 6 years. At the age of 14 years, she was formally diagnosed with CTX, which was confirmed by genetic testing. Chenodiol (chenodeoxycholic acid) therapy was initiated at diagnosis, and she has remained on chenodiol since that time. Tendon xanthomas required surgical debulking by the age of 17 years. She has had xanthomas of the Achilles, elbow, and plantar foot and extensor tendons of the fingers and toes. She reported minimal increases in the left Achilles xanthoma over 8 years, with no new xanthomas. The most recent magnetic resonance imaging of the brain showed a mild increased T2 signal within the dentate nucleus, which can be seen in CTX. Despite these findings, she has not clinically expressed any neurologic motor deficits. She has reported a significant cognitive delay. She has no known cardiovascular disease.'}
|
IEM-Treatment
|
IEM_Treatment
|
[
"prompt initiation of chenodiol therapy . She has been on chenodiol consistently since the diagnosis at age 27 .",
"She started chenodiol at the time of the diagnosis",
"Chenodiol ( chenodeoxycholic acid ) therapy was initiated at diagnosis , and she has remained on chenodiol since that time"
] |
test-2071
|
7809922
|
{'Case report': 'A 37-year-old woman presented to the surgical unit of a general teaching hospital with abdominal pain that she experienced while walking to the hospital (May 2019). Her symptoms had started 4 months previously (January 2019). The initial symptoms included recurring abdominal pain and bloating (almost once per month). During this period, the patient visited her local clinic several times, without obtaining a clear diagnosis. The patient received Chinese medicine over a long period of time and also received symptomatic treatments (e.g., enema, tramadol as analgesia), but her condition did not improve considerably. She had a history of a cesarean section in 2013, and no other notable medical history or family history of disease. On her admission assessment, an abdominal flat plate X-ray showed incomplete intestinal obstruction ( Figure 1a ), but no obvious abnormalities were observed in any other inspections. Forty-eight hours after admission, the patient suddenly developed dyspnea, muscle weakness, and a disorder of consciousness, with uncorrectable hypoxemia (SPO 2 86%), tachycardia (130 bpm), and hypotension (blood pressure 80/59 mmHg). She was transferred to the intensive care unit (ICU) for further management. Urgent arterial blood gas analysis on ICU admission indicated severe hypoxemia and respiratory acidosis (pH: 7.153, PO 2 : 66 mmHg, PCO 2 : 50.2 mmHg, and PO 2 /FiO 2 : 110 mmHg); tracheal intubation was then performed. On day 2 of ICU admission, the patient’s awareness gradually recovered and her abdominal pain spontaneously disappeared. Further examination revealed stubborn respiratory failure, meaning that the patient was unable to be removed from the ventilator. Muscle power of the limbs was 0/5 proximally and 2/5 distally. Furthermore, sensation and cranial nerve examinations were normal. Cranial computed tomography (CT) and abdominal CT did not indicate any abnormalities ( Figure 1b ), although the chest CT showed patchy exudation of the lower lungs, which did not explain the patient’s respiratory failure. Bedside ultrasound revealed that diaphragm displacement during spontaneous breathing mode was 5.4 mm, whereas normal displacement is considered to be greater than 10 mm. Blood tests showed that serum creatinine was elevated at 350.5 µmol/L (normal range: 44–133 µmol/L), and urea nitrogen was elevated at 22.23 mmol/L (normal range: 2.9–7.5 mmol/L), although these levels returned to normal soon after hemodialysis. The initial cerebrospinal fluid (CSF) examination was within the normal range, and anti-ganglioside antibodies, such as GM1 and GD1a, were negative. Furthermore, electromyography findings showed unspecific peripheral nerve damage ( Figure 2 ). The patient was treated with a course of intravenous immunoglobulin for a probable diagnosis of Guillain–Barré syndrome (GBS), but no relief was achieved. The patient’s condition continued to worsen, and on day 14 after ICU admission, her abdominal pain and constipation returned, along with changes in her neurological examination. Her overall weakness worsened, with muscle power of 0/5 (absolutely no movement) in all four limbs. Furthermore, a cranial nerve examination showed new nasal and labial asymmetry, and her eyelids were unable to close. Abdominal CT at this time showed extensive colonic expansion ( Figure 1c ). Another CSF examination was performed, but the results remained normal, with no cytoalbuminologic dissociation. It was also noted that the color of the patient’s urine turned visibly reddish on exposure to sunlight ( Figure 3 ). A diagnosis of AIP was finally confirmed by genetic analysis, which identified a missense mutation: c.541C>T, encoding p. Gln181 in the HMBS gene ( Figure 4 ). Targeted mutation analysis was then performed in her two children, but neither of them carried the disease-causing gene. Because heme arginate is not available in mainland China, the patient was treated with intravenous glucose infusion (50%). Twenty-four hours after glucose medication, her abdominal pain was alleviated and her urine returned to a normal color; however, her peripheral neuropathy did not markedly improve. After 2 weeks of treatment, the tracheal tube was removed. The patient was then transferred back to her local hospital for rehabilitation training because of the poor muscle strength in her limbs. At the 1-year follow-up, her overall muscle power had gradually improved to grade 3/5, and she was able to walk with the aid of a rehabilitation walking assistance vehicle. To date, the patient has not experienced any other AIP attacks, but she still has severe neurological sequelae.'}
|
{'Case report': 'A 37-year-old woman presented to the surgical unit of a general teaching hospital with abdominal pain that she experienced while walking to the hospital (May 2019). Her symptoms had started 4 months previously (January 2019). The initial symptoms included recurring abdominal pain and bloating (almost once per month). During this period, the patient visited her local clinic several times, without obtaining a clear diagnosis. The patient received Chinese medicine over a long period of time and also received symptomatic treatments (e.g., enema, tramadol as analgesia), but her condition did not improve considerably. She had a history of a cesarean section in 2013, and no other notable medical history or family history of disease. On her admission assessment, an abdominal flat plate X-ray showed incomplete intestinal obstruction ( Figure 1a ), but no obvious abnormalities were observed in any other inspections. Forty-eight hours after admission, the patient suddenly developed dyspnea, muscle weakness, and a disorder of consciousness, with uncorrectable hypoxemia (SPO 2 86%), tachycardia (130 bpm), and hypotension (blood pressure 80/59 mmHg). She was transferred to the intensive care unit (ICU) for further management. Urgent arterial blood gas analysis on ICU admission indicated severe hypoxemia and respiratory acidosis (pH: 7.153, PO 2 : 66 mmHg, PCO 2 : 50.2 mmHg, and PO 2 /FiO 2 : 110 mmHg); tracheal intubation was then performed. On day 2 of ICU admission, the patient’s awareness gradually recovered and her abdominal pain spontaneously disappeared. Further examination revealed stubborn respiratory failure, meaning that the patient was unable to be removed from the ventilator. Muscle power of the limbs was 0/5 proximally and 2/5 distally. Furthermore, sensation and cranial nerve examinations were normal. Cranial computed tomography (CT) and abdominal CT did not indicate any abnormalities ( Figure 1b ), although the chest CT showed patchy exudation of the lower lungs, which did not explain the patient’s respiratory failure. Bedside ultrasound revealed that diaphragm displacement during spontaneous breathing mode was 5.4 mm, whereas normal displacement is considered to be greater than 10 mm. Blood tests showed that serum creatinine was elevated at 350.5 µmol/L (normal range: 44–133 µmol/L), and urea nitrogen was elevated at 22.23 mmol/L (normal range: 2.9–7.5 mmol/L), although these levels returned to normal soon after hemodialysis. The initial cerebrospinal fluid (CSF) examination was within the normal range, and anti-ganglioside antibodies, such as GM1 and GD1a, were negative. Furthermore, electromyography findings showed unspecific peripheral nerve damage ( Figure 2 ). The patient was treated with a course of intravenous immunoglobulin for a probable diagnosis of Guillain–Barré syndrome (GBS), but no relief was achieved. The patient’s condition continued to worsen, and on day 14 after ICU admission, her abdominal pain and constipation returned, along with changes in her neurological examination. Her overall weakness worsened, with muscle power of 0/5 (absolutely no movement) in all four limbs. Furthermore, a cranial nerve examination showed new nasal and labial asymmetry, and her eyelids were unable to close. Abdominal CT at this time showed extensive colonic expansion ( Figure 1c ). Another CSF examination was performed, but the results remained normal, with no cytoalbuminologic dissociation. It was also noted that the color of the patient’s urine turned visibly reddish on exposure to sunlight ( Figure 3 ). A diagnosis of AIP was finally confirmed by genetic analysis, which identified a missense mutation: c.541C>T, encoding p. Gln181 in the HMBS gene ( Figure 4 ). Targeted mutation analysis was then performed in her two children, but neither of them carried the disease-causing gene. Because heme arginate is not available in mainland China, the patient was treated with intravenous glucose infusion (50%). Twenty-four hours after glucose medication, her abdominal pain was alleviated and her urine returned to a normal color; however, her peripheral neuropathy did not markedly improve. After 2 weeks of treatment, the tracheal tube was removed. The patient was then transferred back to her local hospital for rehabilitation training because of the poor muscle strength in her limbs. At the 1-year follow-up, her overall muscle power had gradually improved to grade 3/5, and she was able to walk with the aid of a rehabilitation walking assistance vehicle. To date, the patient has not experienced any other AIP attacks, but she still has severe neurological sequelae.'}
|
Vitals-and-Hematology
|
Vitals_Hema
|
[
"SPO 2 86 %",
"130 bpm",
"blood pressure 80/59 mmHg"
] |
test-2072
|
7809922
|
{'Case report': 'A 37-year-old woman presented to the surgical unit of a general teaching hospital with abdominal pain that she experienced while walking to the hospital (May 2019). Her symptoms had started 4 months previously (January 2019). The initial symptoms included recurring abdominal pain and bloating (almost once per month). During this period, the patient visited her local clinic several times, without obtaining a clear diagnosis. The patient received Chinese medicine over a long period of time and also received symptomatic treatments (e.g., enema, tramadol as analgesia), but her condition did not improve considerably. She had a history of a cesarean section in 2013, and no other notable medical history or family history of disease. On her admission assessment, an abdominal flat plate X-ray showed incomplete intestinal obstruction ( Figure 1a ), but no obvious abnormalities were observed in any other inspections. Forty-eight hours after admission, the patient suddenly developed dyspnea, muscle weakness, and a disorder of consciousness, with uncorrectable hypoxemia (SPO 2 86%), tachycardia (130 bpm), and hypotension (blood pressure 80/59 mmHg). She was transferred to the intensive care unit (ICU) for further management. Urgent arterial blood gas analysis on ICU admission indicated severe hypoxemia and respiratory acidosis (pH: 7.153, PO 2 : 66 mmHg, PCO 2 : 50.2 mmHg, and PO 2 /FiO 2 : 110 mmHg); tracheal intubation was then performed. On day 2 of ICU admission, the patient’s awareness gradually recovered and her abdominal pain spontaneously disappeared. Further examination revealed stubborn respiratory failure, meaning that the patient was unable to be removed from the ventilator. Muscle power of the limbs was 0/5 proximally and 2/5 distally. Furthermore, sensation and cranial nerve examinations were normal. Cranial computed tomography (CT) and abdominal CT did not indicate any abnormalities ( Figure 1b ), although the chest CT showed patchy exudation of the lower lungs, which did not explain the patient’s respiratory failure. Bedside ultrasound revealed that diaphragm displacement during spontaneous breathing mode was 5.4 mm, whereas normal displacement is considered to be greater than 10 mm. Blood tests showed that serum creatinine was elevated at 350.5 µmol/L (normal range: 44–133 µmol/L), and urea nitrogen was elevated at 22.23 mmol/L (normal range: 2.9–7.5 mmol/L), although these levels returned to normal soon after hemodialysis. The initial cerebrospinal fluid (CSF) examination was within the normal range, and anti-ganglioside antibodies, such as GM1 and GD1a, were negative. Furthermore, electromyography findings showed unspecific peripheral nerve damage ( Figure 2 ). The patient was treated with a course of intravenous immunoglobulin for a probable diagnosis of Guillain–Barré syndrome (GBS), but no relief was achieved. The patient’s condition continued to worsen, and on day 14 after ICU admission, her abdominal pain and constipation returned, along with changes in her neurological examination. Her overall weakness worsened, with muscle power of 0/5 (absolutely no movement) in all four limbs. Furthermore, a cranial nerve examination showed new nasal and labial asymmetry, and her eyelids were unable to close. Abdominal CT at this time showed extensive colonic expansion ( Figure 1c ). Another CSF examination was performed, but the results remained normal, with no cytoalbuminologic dissociation. It was also noted that the color of the patient’s urine turned visibly reddish on exposure to sunlight ( Figure 3 ). A diagnosis of AIP was finally confirmed by genetic analysis, which identified a missense mutation: c.541C>T, encoding p. Gln181 in the HMBS gene ( Figure 4 ). Targeted mutation analysis was then performed in her two children, but neither of them carried the disease-causing gene. Because heme arginate is not available in mainland China, the patient was treated with intravenous glucose infusion (50%). Twenty-four hours after glucose medication, her abdominal pain was alleviated and her urine returned to a normal color; however, her peripheral neuropathy did not markedly improve. After 2 weeks of treatment, the tracheal tube was removed. The patient was then transferred back to her local hospital for rehabilitation training because of the poor muscle strength in her limbs. At the 1-year follow-up, her overall muscle power had gradually improved to grade 3/5, and she was able to walk with the aid of a rehabilitation walking assistance vehicle. To date, the patient has not experienced any other AIP attacks, but she still has severe neurological sequelae.'}
|
{'Case report': 'A 37-year-old woman presented to the surgical unit of a general teaching hospital with abdominal pain that she experienced while walking to the hospital (May 2019). Her symptoms had started 4 months previously (January 2019). The initial symptoms included recurring abdominal pain and bloating (almost once per month). During this period, the patient visited her local clinic several times, without obtaining a clear diagnosis. The patient received Chinese medicine over a long period of time and also received symptomatic treatments (e.g., enema, tramadol as analgesia), but her condition did not improve considerably. She had a history of a cesarean section in 2013, and no other notable medical history or family history of disease. On her admission assessment, an abdominal flat plate X-ray showed incomplete intestinal obstruction ( Figure 1a ), but no obvious abnormalities were observed in any other inspections. Forty-eight hours after admission, the patient suddenly developed dyspnea, muscle weakness, and a disorder of consciousness, with uncorrectable hypoxemia (SPO 2 86%), tachycardia (130 bpm), and hypotension (blood pressure 80/59 mmHg). She was transferred to the intensive care unit (ICU) for further management. Urgent arterial blood gas analysis on ICU admission indicated severe hypoxemia and respiratory acidosis (pH: 7.153, PO 2 : 66 mmHg, PCO 2 : 50.2 mmHg, and PO 2 /FiO 2 : 110 mmHg); tracheal intubation was then performed. On day 2 of ICU admission, the patient’s awareness gradually recovered and her abdominal pain spontaneously disappeared. Further examination revealed stubborn respiratory failure, meaning that the patient was unable to be removed from the ventilator. Muscle power of the limbs was 0/5 proximally and 2/5 distally. Furthermore, sensation and cranial nerve examinations were normal. Cranial computed tomography (CT) and abdominal CT did not indicate any abnormalities ( Figure 1b ), although the chest CT showed patchy exudation of the lower lungs, which did not explain the patient’s respiratory failure. Bedside ultrasound revealed that diaphragm displacement during spontaneous breathing mode was 5.4 mm, whereas normal displacement is considered to be greater than 10 mm. Blood tests showed that serum creatinine was elevated at 350.5 µmol/L (normal range: 44–133 µmol/L), and urea nitrogen was elevated at 22.23 mmol/L (normal range: 2.9–7.5 mmol/L), although these levels returned to normal soon after hemodialysis. The initial cerebrospinal fluid (CSF) examination was within the normal range, and anti-ganglioside antibodies, such as GM1 and GD1a, were negative. Furthermore, electromyography findings showed unspecific peripheral nerve damage ( Figure 2 ). The patient was treated with a course of intravenous immunoglobulin for a probable diagnosis of Guillain–Barré syndrome (GBS), but no relief was achieved. The patient’s condition continued to worsen, and on day 14 after ICU admission, her abdominal pain and constipation returned, along with changes in her neurological examination. Her overall weakness worsened, with muscle power of 0/5 (absolutely no movement) in all four limbs. Furthermore, a cranial nerve examination showed new nasal and labial asymmetry, and her eyelids were unable to close. Abdominal CT at this time showed extensive colonic expansion ( Figure 1c ). Another CSF examination was performed, but the results remained normal, with no cytoalbuminologic dissociation. It was also noted that the color of the patient’s urine turned visibly reddish on exposure to sunlight ( Figure 3 ). A diagnosis of AIP was finally confirmed by genetic analysis, which identified a missense mutation: c.541C>T, encoding p. Gln181 in the HMBS gene ( Figure 4 ). Targeted mutation analysis was then performed in her two children, but neither of them carried the disease-causing gene. Because heme arginate is not available in mainland China, the patient was treated with intravenous glucose infusion (50%). Twenty-four hours after glucose medication, her abdominal pain was alleviated and her urine returned to a normal color; however, her peripheral neuropathy did not markedly improve. After 2 weeks of treatment, the tracheal tube was removed. The patient was then transferred back to her local hospital for rehabilitation training because of the poor muscle strength in her limbs. At the 1-year follow-up, her overall muscle power had gradually improved to grade 3/5, and she was able to walk with the aid of a rehabilitation walking assistance vehicle. To date, the patient has not experienced any other AIP attacks, but she still has severe neurological sequelae.'}
|
Gastrointestinal-System
|
GI
|
[
"abdominal pain",
"recurring abdominal pain and bloating ( almost once per month )",
"incomplete intestinal obstruction",
"abdominal pain spontaneously disappeared",
"abdominal pain and constipation returned"
] |
test-2073
|
7809922
|
{'Case report': 'A 37-year-old woman presented to the surgical unit of a general teaching hospital with abdominal pain that she experienced while walking to the hospital (May 2019). Her symptoms had started 4 months previously (January 2019). The initial symptoms included recurring abdominal pain and bloating (almost once per month). During this period, the patient visited her local clinic several times, without obtaining a clear diagnosis. The patient received Chinese medicine over a long period of time and also received symptomatic treatments (e.g., enema, tramadol as analgesia), but her condition did not improve considerably. She had a history of a cesarean section in 2013, and no other notable medical history or family history of disease. On her admission assessment, an abdominal flat plate X-ray showed incomplete intestinal obstruction ( Figure 1a ), but no obvious abnormalities were observed in any other inspections. Forty-eight hours after admission, the patient suddenly developed dyspnea, muscle weakness, and a disorder of consciousness, with uncorrectable hypoxemia (SPO 2 86%), tachycardia (130 bpm), and hypotension (blood pressure 80/59 mmHg). She was transferred to the intensive care unit (ICU) for further management. Urgent arterial blood gas analysis on ICU admission indicated severe hypoxemia and respiratory acidosis (pH: 7.153, PO 2 : 66 mmHg, PCO 2 : 50.2 mmHg, and PO 2 /FiO 2 : 110 mmHg); tracheal intubation was then performed. On day 2 of ICU admission, the patient’s awareness gradually recovered and her abdominal pain spontaneously disappeared. Further examination revealed stubborn respiratory failure, meaning that the patient was unable to be removed from the ventilator. Muscle power of the limbs was 0/5 proximally and 2/5 distally. Furthermore, sensation and cranial nerve examinations were normal. Cranial computed tomography (CT) and abdominal CT did not indicate any abnormalities ( Figure 1b ), although the chest CT showed patchy exudation of the lower lungs, which did not explain the patient’s respiratory failure. Bedside ultrasound revealed that diaphragm displacement during spontaneous breathing mode was 5.4 mm, whereas normal displacement is considered to be greater than 10 mm. Blood tests showed that serum creatinine was elevated at 350.5 µmol/L (normal range: 44–133 µmol/L), and urea nitrogen was elevated at 22.23 mmol/L (normal range: 2.9–7.5 mmol/L), although these levels returned to normal soon after hemodialysis. The initial cerebrospinal fluid (CSF) examination was within the normal range, and anti-ganglioside antibodies, such as GM1 and GD1a, were negative. Furthermore, electromyography findings showed unspecific peripheral nerve damage ( Figure 2 ). The patient was treated with a course of intravenous immunoglobulin for a probable diagnosis of Guillain–Barré syndrome (GBS), but no relief was achieved. The patient’s condition continued to worsen, and on day 14 after ICU admission, her abdominal pain and constipation returned, along with changes in her neurological examination. Her overall weakness worsened, with muscle power of 0/5 (absolutely no movement) in all four limbs. Furthermore, a cranial nerve examination showed new nasal and labial asymmetry, and her eyelids were unable to close. Abdominal CT at this time showed extensive colonic expansion ( Figure 1c ). Another CSF examination was performed, but the results remained normal, with no cytoalbuminologic dissociation. It was also noted that the color of the patient’s urine turned visibly reddish on exposure to sunlight ( Figure 3 ). A diagnosis of AIP was finally confirmed by genetic analysis, which identified a missense mutation: c.541C>T, encoding p. Gln181 in the HMBS gene ( Figure 4 ). Targeted mutation analysis was then performed in her two children, but neither of them carried the disease-causing gene. Because heme arginate is not available in mainland China, the patient was treated with intravenous glucose infusion (50%). Twenty-four hours after glucose medication, her abdominal pain was alleviated and her urine returned to a normal color; however, her peripheral neuropathy did not markedly improve. After 2 weeks of treatment, the tracheal tube was removed. The patient was then transferred back to her local hospital for rehabilitation training because of the poor muscle strength in her limbs. At the 1-year follow-up, her overall muscle power had gradually improved to grade 3/5, and she was able to walk with the aid of a rehabilitation walking assistance vehicle. To date, the patient has not experienced any other AIP attacks, but she still has severe neurological sequelae.'}
|
{'Case report': 'A 37-year-old woman presented to the surgical unit of a general teaching hospital with abdominal pain that she experienced while walking to the hospital (May 2019). Her symptoms had started 4 months previously (January 2019). The initial symptoms included recurring abdominal pain and bloating (almost once per month). During this period, the patient visited her local clinic several times, without obtaining a clear diagnosis. The patient received Chinese medicine over a long period of time and also received symptomatic treatments (e.g., enema, tramadol as analgesia), but her condition did not improve considerably. She had a history of a cesarean section in 2013, and no other notable medical history or family history of disease. On her admission assessment, an abdominal flat plate X-ray showed incomplete intestinal obstruction ( Figure 1a ), but no obvious abnormalities were observed in any other inspections. Forty-eight hours after admission, the patient suddenly developed dyspnea, muscle weakness, and a disorder of consciousness, with uncorrectable hypoxemia (SPO 2 86%), tachycardia (130 bpm), and hypotension (blood pressure 80/59 mmHg). She was transferred to the intensive care unit (ICU) for further management. Urgent arterial blood gas analysis on ICU admission indicated severe hypoxemia and respiratory acidosis (pH: 7.153, PO 2 : 66 mmHg, PCO 2 : 50.2 mmHg, and PO 2 /FiO 2 : 110 mmHg); tracheal intubation was then performed. On day 2 of ICU admission, the patient’s awareness gradually recovered and her abdominal pain spontaneously disappeared. Further examination revealed stubborn respiratory failure, meaning that the patient was unable to be removed from the ventilator. Muscle power of the limbs was 0/5 proximally and 2/5 distally. Furthermore, sensation and cranial nerve examinations were normal. Cranial computed tomography (CT) and abdominal CT did not indicate any abnormalities ( Figure 1b ), although the chest CT showed patchy exudation of the lower lungs, which did not explain the patient’s respiratory failure. Bedside ultrasound revealed that diaphragm displacement during spontaneous breathing mode was 5.4 mm, whereas normal displacement is considered to be greater than 10 mm. Blood tests showed that serum creatinine was elevated at 350.5 µmol/L (normal range: 44–133 µmol/L), and urea nitrogen was elevated at 22.23 mmol/L (normal range: 2.9–7.5 mmol/L), although these levels returned to normal soon after hemodialysis. The initial cerebrospinal fluid (CSF) examination was within the normal range, and anti-ganglioside antibodies, such as GM1 and GD1a, were negative. Furthermore, electromyography findings showed unspecific peripheral nerve damage ( Figure 2 ). The patient was treated with a course of intravenous immunoglobulin for a probable diagnosis of Guillain–Barré syndrome (GBS), but no relief was achieved. The patient’s condition continued to worsen, and on day 14 after ICU admission, her abdominal pain and constipation returned, along with changes in her neurological examination. Her overall weakness worsened, with muscle power of 0/5 (absolutely no movement) in all four limbs. Furthermore, a cranial nerve examination showed new nasal and labial asymmetry, and her eyelids were unable to close. Abdominal CT at this time showed extensive colonic expansion ( Figure 1c ). Another CSF examination was performed, but the results remained normal, with no cytoalbuminologic dissociation. It was also noted that the color of the patient’s urine turned visibly reddish on exposure to sunlight ( Figure 3 ). A diagnosis of AIP was finally confirmed by genetic analysis, which identified a missense mutation: c.541C>T, encoding p. Gln181 in the HMBS gene ( Figure 4 ). Targeted mutation analysis was then performed in her two children, but neither of them carried the disease-causing gene. Because heme arginate is not available in mainland China, the patient was treated with intravenous glucose infusion (50%). Twenty-four hours after glucose medication, her abdominal pain was alleviated and her urine returned to a normal color; however, her peripheral neuropathy did not markedly improve. After 2 weeks of treatment, the tracheal tube was removed. The patient was then transferred back to her local hospital for rehabilitation training because of the poor muscle strength in her limbs. At the 1-year follow-up, her overall muscle power had gradually improved to grade 3/5, and she was able to walk with the aid of a rehabilitation walking assistance vehicle. To date, the patient has not experienced any other AIP attacks, but she still has severe neurological sequelae.'}
|
Patient-History
|
History
|
[
"A 37 - year - old woman presented to the surgical unit of a general teaching hospital with abdominal pain that she experienced while walking to the hospital ( May 2019 ). Her symptoms had started 4 months previously ( January 2019 ). The initial symptoms included recurring abdominal pain and bloating ( almost once per month ). During this period, the patient visited her local clinic several times, without obtaining a clear diagnosis",
"She had a history of a cesarean section in 2013, and no other notable medical history or family history of disease",
"Targeted mutation analysis was then performed in her two children, but neither of them carried the disease - causing gene"
] |
test-2074
|
7809922
|
{'Case report': 'A 37-year-old woman presented to the surgical unit of a general teaching hospital with abdominal pain that she experienced while walking to the hospital (May 2019). Her symptoms had started 4 months previously (January 2019). The initial symptoms included recurring abdominal pain and bloating (almost once per month). During this period, the patient visited her local clinic several times, without obtaining a clear diagnosis. The patient received Chinese medicine over a long period of time and also received symptomatic treatments (e.g., enema, tramadol as analgesia), but her condition did not improve considerably. She had a history of a cesarean section in 2013, and no other notable medical history or family history of disease. On her admission assessment, an abdominal flat plate X-ray showed incomplete intestinal obstruction ( Figure 1a ), but no obvious abnormalities were observed in any other inspections. Forty-eight hours after admission, the patient suddenly developed dyspnea, muscle weakness, and a disorder of consciousness, with uncorrectable hypoxemia (SPO 2 86%), tachycardia (130 bpm), and hypotension (blood pressure 80/59 mmHg). She was transferred to the intensive care unit (ICU) for further management. Urgent arterial blood gas analysis on ICU admission indicated severe hypoxemia and respiratory acidosis (pH: 7.153, PO 2 : 66 mmHg, PCO 2 : 50.2 mmHg, and PO 2 /FiO 2 : 110 mmHg); tracheal intubation was then performed. On day 2 of ICU admission, the patient’s awareness gradually recovered and her abdominal pain spontaneously disappeared. Further examination revealed stubborn respiratory failure, meaning that the patient was unable to be removed from the ventilator. Muscle power of the limbs was 0/5 proximally and 2/5 distally. Furthermore, sensation and cranial nerve examinations were normal. Cranial computed tomography (CT) and abdominal CT did not indicate any abnormalities ( Figure 1b ), although the chest CT showed patchy exudation of the lower lungs, which did not explain the patient’s respiratory failure. Bedside ultrasound revealed that diaphragm displacement during spontaneous breathing mode was 5.4 mm, whereas normal displacement is considered to be greater than 10 mm. Blood tests showed that serum creatinine was elevated at 350.5 µmol/L (normal range: 44–133 µmol/L), and urea nitrogen was elevated at 22.23 mmol/L (normal range: 2.9–7.5 mmol/L), although these levels returned to normal soon after hemodialysis. The initial cerebrospinal fluid (CSF) examination was within the normal range, and anti-ganglioside antibodies, such as GM1 and GD1a, were negative. Furthermore, electromyography findings showed unspecific peripheral nerve damage ( Figure 2 ). The patient was treated with a course of intravenous immunoglobulin for a probable diagnosis of Guillain–Barré syndrome (GBS), but no relief was achieved. The patient’s condition continued to worsen, and on day 14 after ICU admission, her abdominal pain and constipation returned, along with changes in her neurological examination. Her overall weakness worsened, with muscle power of 0/5 (absolutely no movement) in all four limbs. Furthermore, a cranial nerve examination showed new nasal and labial asymmetry, and her eyelids were unable to close. Abdominal CT at this time showed extensive colonic expansion ( Figure 1c ). Another CSF examination was performed, but the results remained normal, with no cytoalbuminologic dissociation. It was also noted that the color of the patient’s urine turned visibly reddish on exposure to sunlight ( Figure 3 ). A diagnosis of AIP was finally confirmed by genetic analysis, which identified a missense mutation: c.541C>T, encoding p. Gln181 in the HMBS gene ( Figure 4 ). Targeted mutation analysis was then performed in her two children, but neither of them carried the disease-causing gene. Because heme arginate is not available in mainland China, the patient was treated with intravenous glucose infusion (50%). Twenty-four hours after glucose medication, her abdominal pain was alleviated and her urine returned to a normal color; however, her peripheral neuropathy did not markedly improve. After 2 weeks of treatment, the tracheal tube was removed. The patient was then transferred back to her local hospital for rehabilitation training because of the poor muscle strength in her limbs. At the 1-year follow-up, her overall muscle power had gradually improved to grade 3/5, and she was able to walk with the aid of a rehabilitation walking assistance vehicle. To date, the patient has not experienced any other AIP attacks, but she still has severe neurological sequelae.'}
|
{'Case report': 'A 37-year-old woman presented to the surgical unit of a general teaching hospital with abdominal pain that she experienced while walking to the hospital (May 2019). Her symptoms had started 4 months previously (January 2019). The initial symptoms included recurring abdominal pain and bloating (almost once per month). During this period, the patient visited her local clinic several times, without obtaining a clear diagnosis. The patient received Chinese medicine over a long period of time and also received symptomatic treatments (e.g., enema, tramadol as analgesia), but her condition did not improve considerably. She had a history of a cesarean section in 2013, and no other notable medical history or family history of disease. On her admission assessment, an abdominal flat plate X-ray showed incomplete intestinal obstruction ( Figure 1a ), but no obvious abnormalities were observed in any other inspections. Forty-eight hours after admission, the patient suddenly developed dyspnea, muscle weakness, and a disorder of consciousness, with uncorrectable hypoxemia (SPO 2 86%), tachycardia (130 bpm), and hypotension (blood pressure 80/59 mmHg). She was transferred to the intensive care unit (ICU) for further management. Urgent arterial blood gas analysis on ICU admission indicated severe hypoxemia and respiratory acidosis (pH: 7.153, PO 2 : 66 mmHg, PCO 2 : 50.2 mmHg, and PO 2 /FiO 2 : 110 mmHg); tracheal intubation was then performed. On day 2 of ICU admission, the patient’s awareness gradually recovered and her abdominal pain spontaneously disappeared. Further examination revealed stubborn respiratory failure, meaning that the patient was unable to be removed from the ventilator. Muscle power of the limbs was 0/5 proximally and 2/5 distally. Furthermore, sensation and cranial nerve examinations were normal. Cranial computed tomography (CT) and abdominal CT did not indicate any abnormalities ( Figure 1b ), although the chest CT showed patchy exudation of the lower lungs, which did not explain the patient’s respiratory failure. Bedside ultrasound revealed that diaphragm displacement during spontaneous breathing mode was 5.4 mm, whereas normal displacement is considered to be greater than 10 mm. Blood tests showed that serum creatinine was elevated at 350.5 µmol/L (normal range: 44–133 µmol/L), and urea nitrogen was elevated at 22.23 mmol/L (normal range: 2.9–7.5 mmol/L), although these levels returned to normal soon after hemodialysis. The initial cerebrospinal fluid (CSF) examination was within the normal range, and anti-ganglioside antibodies, such as GM1 and GD1a, were negative. Furthermore, electromyography findings showed unspecific peripheral nerve damage ( Figure 2 ). The patient was treated with a course of intravenous immunoglobulin for a probable diagnosis of Guillain–Barré syndrome (GBS), but no relief was achieved. The patient’s condition continued to worsen, and on day 14 after ICU admission, her abdominal pain and constipation returned, along with changes in her neurological examination. Her overall weakness worsened, with muscle power of 0/5 (absolutely no movement) in all four limbs. Furthermore, a cranial nerve examination showed new nasal and labial asymmetry, and her eyelids were unable to close. Abdominal CT at this time showed extensive colonic expansion ( Figure 1c ). Another CSF examination was performed, but the results remained normal, with no cytoalbuminologic dissociation. It was also noted that the color of the patient’s urine turned visibly reddish on exposure to sunlight ( Figure 3 ). A diagnosis of AIP was finally confirmed by genetic analysis, which identified a missense mutation: c.541C>T, encoding p. Gln181 in the HMBS gene ( Figure 4 ). Targeted mutation analysis was then performed in her two children, but neither of them carried the disease-causing gene. Because heme arginate is not available in mainland China, the patient was treated with intravenous glucose infusion (50%). Twenty-four hours after glucose medication, her abdominal pain was alleviated and her urine returned to a normal color; however, her peripheral neuropathy did not markedly improve. After 2 weeks of treatment, the tracheal tube was removed. The patient was then transferred back to her local hospital for rehabilitation training because of the poor muscle strength in her limbs. At the 1-year follow-up, her overall muscle power had gradually improved to grade 3/5, and she was able to walk with the aid of a rehabilitation walking assistance vehicle. To date, the patient has not experienced any other AIP attacks, but she still has severe neurological sequelae.'}
|
Neurology
|
Neuro
|
[
"muscle weakness, and a disorder of consciousness",
"patient ’s awareness gradually recovered",
"Muscle power of the limbs was 0/5 proximally and 2/5 distally. Furthermore, sensation and cranial nerve examinations were normal",
"Cranial computed tomography ( CT ) and abdominal CT did not indicate any abnormalities",
"The initial cerebrospinal fluid ( CSF ) examination was within the normal range, and anti - ganglioside antibodies, such as GM1 and GD1a, were negative",
"electromyography findings showed unspecific peripheral nerve damage",
"changes in her neurological examination. Her overall weakness worsened, with muscle power of 0/5 ( absolutely no movement ) in all four limbs. Furthermore, a cranial nerve examination showed new nasal and labial asymmetry, and her eyelids were unable to close",
"Another CSF examination was performed, but the results remained normal, with no cytoalbuminologic dissociation",
"peripheral neuropathy did not markedly improve",
"poor muscle strength in her limbs",
"her overall muscle power had gradually improved to grade 3/5, and she was able to walk with the aid of a rehabilitation walking assistance vehicle",
"severe neurological sequelae"
] |
test-2075
|
7809922
|
{'Case report': 'A 37-year-old woman presented to the surgical unit of a general teaching hospital with abdominal pain that she experienced while walking to the hospital (May 2019). Her symptoms had started 4 months previously (January 2019). The initial symptoms included recurring abdominal pain and bloating (almost once per month). During this period, the patient visited her local clinic several times, without obtaining a clear diagnosis. The patient received Chinese medicine over a long period of time and also received symptomatic treatments (e.g., enema, tramadol as analgesia), but her condition did not improve considerably. She had a history of a cesarean section in 2013, and no other notable medical history or family history of disease. On her admission assessment, an abdominal flat plate X-ray showed incomplete intestinal obstruction ( Figure 1a ), but no obvious abnormalities were observed in any other inspections. Forty-eight hours after admission, the patient suddenly developed dyspnea, muscle weakness, and a disorder of consciousness, with uncorrectable hypoxemia (SPO 2 86%), tachycardia (130 bpm), and hypotension (blood pressure 80/59 mmHg). She was transferred to the intensive care unit (ICU) for further management. Urgent arterial blood gas analysis on ICU admission indicated severe hypoxemia and respiratory acidosis (pH: 7.153, PO 2 : 66 mmHg, PCO 2 : 50.2 mmHg, and PO 2 /FiO 2 : 110 mmHg); tracheal intubation was then performed. On day 2 of ICU admission, the patient’s awareness gradually recovered and her abdominal pain spontaneously disappeared. Further examination revealed stubborn respiratory failure, meaning that the patient was unable to be removed from the ventilator. Muscle power of the limbs was 0/5 proximally and 2/5 distally. Furthermore, sensation and cranial nerve examinations were normal. Cranial computed tomography (CT) and abdominal CT did not indicate any abnormalities ( Figure 1b ), although the chest CT showed patchy exudation of the lower lungs, which did not explain the patient’s respiratory failure. Bedside ultrasound revealed that diaphragm displacement during spontaneous breathing mode was 5.4 mm, whereas normal displacement is considered to be greater than 10 mm. Blood tests showed that serum creatinine was elevated at 350.5 µmol/L (normal range: 44–133 µmol/L), and urea nitrogen was elevated at 22.23 mmol/L (normal range: 2.9–7.5 mmol/L), although these levels returned to normal soon after hemodialysis. The initial cerebrospinal fluid (CSF) examination was within the normal range, and anti-ganglioside antibodies, such as GM1 and GD1a, were negative. Furthermore, electromyography findings showed unspecific peripheral nerve damage ( Figure 2 ). The patient was treated with a course of intravenous immunoglobulin for a probable diagnosis of Guillain–Barré syndrome (GBS), but no relief was achieved. The patient’s condition continued to worsen, and on day 14 after ICU admission, her abdominal pain and constipation returned, along with changes in her neurological examination. Her overall weakness worsened, with muscle power of 0/5 (absolutely no movement) in all four limbs. Furthermore, a cranial nerve examination showed new nasal and labial asymmetry, and her eyelids were unable to close. Abdominal CT at this time showed extensive colonic expansion ( Figure 1c ). Another CSF examination was performed, but the results remained normal, with no cytoalbuminologic dissociation. It was also noted that the color of the patient’s urine turned visibly reddish on exposure to sunlight ( Figure 3 ). A diagnosis of AIP was finally confirmed by genetic analysis, which identified a missense mutation: c.541C>T, encoding p. Gln181 in the HMBS gene ( Figure 4 ). Targeted mutation analysis was then performed in her two children, but neither of them carried the disease-causing gene. Because heme arginate is not available in mainland China, the patient was treated with intravenous glucose infusion (50%). Twenty-four hours after glucose medication, her abdominal pain was alleviated and her urine returned to a normal color; however, her peripheral neuropathy did not markedly improve. After 2 weeks of treatment, the tracheal tube was removed. The patient was then transferred back to her local hospital for rehabilitation training because of the poor muscle strength in her limbs. At the 1-year follow-up, her overall muscle power had gradually improved to grade 3/5, and she was able to walk with the aid of a rehabilitation walking assistance vehicle. To date, the patient has not experienced any other AIP attacks, but she still has severe neurological sequelae.'}
|
{'Case report': 'A 37-year-old woman presented to the surgical unit of a general teaching hospital with abdominal pain that she experienced while walking to the hospital (May 2019). Her symptoms had started 4 months previously (January 2019). The initial symptoms included recurring abdominal pain and bloating (almost once per month). During this period, the patient visited her local clinic several times, without obtaining a clear diagnosis. The patient received Chinese medicine over a long period of time and also received symptomatic treatments (e.g., enema, tramadol as analgesia), but her condition did not improve considerably. She had a history of a cesarean section in 2013, and no other notable medical history or family history of disease. On her admission assessment, an abdominal flat plate X-ray showed incomplete intestinal obstruction ( Figure 1a ), but no obvious abnormalities were observed in any other inspections. Forty-eight hours after admission, the patient suddenly developed dyspnea, muscle weakness, and a disorder of consciousness, with uncorrectable hypoxemia (SPO 2 86%), tachycardia (130 bpm), and hypotension (blood pressure 80/59 mmHg). She was transferred to the intensive care unit (ICU) for further management. Urgent arterial blood gas analysis on ICU admission indicated severe hypoxemia and respiratory acidosis (pH: 7.153, PO 2 : 66 mmHg, PCO 2 : 50.2 mmHg, and PO 2 /FiO 2 : 110 mmHg); tracheal intubation was then performed. On day 2 of ICU admission, the patient’s awareness gradually recovered and her abdominal pain spontaneously disappeared. Further examination revealed stubborn respiratory failure, meaning that the patient was unable to be removed from the ventilator. Muscle power of the limbs was 0/5 proximally and 2/5 distally. Furthermore, sensation and cranial nerve examinations were normal. Cranial computed tomography (CT) and abdominal CT did not indicate any abnormalities ( Figure 1b ), although the chest CT showed patchy exudation of the lower lungs, which did not explain the patient’s respiratory failure. Bedside ultrasound revealed that diaphragm displacement during spontaneous breathing mode was 5.4 mm, whereas normal displacement is considered to be greater than 10 mm. Blood tests showed that serum creatinine was elevated at 350.5 µmol/L (normal range: 44–133 µmol/L), and urea nitrogen was elevated at 22.23 mmol/L (normal range: 2.9–7.5 mmol/L), although these levels returned to normal soon after hemodialysis. The initial cerebrospinal fluid (CSF) examination was within the normal range, and anti-ganglioside antibodies, such as GM1 and GD1a, were negative. Furthermore, electromyography findings showed unspecific peripheral nerve damage ( Figure 2 ). The patient was treated with a course of intravenous immunoglobulin for a probable diagnosis of Guillain–Barré syndrome (GBS), but no relief was achieved. The patient’s condition continued to worsen, and on day 14 after ICU admission, her abdominal pain and constipation returned, along with changes in her neurological examination. Her overall weakness worsened, with muscle power of 0/5 (absolutely no movement) in all four limbs. Furthermore, a cranial nerve examination showed new nasal and labial asymmetry, and her eyelids were unable to close. Abdominal CT at this time showed extensive colonic expansion ( Figure 1c ). Another CSF examination was performed, but the results remained normal, with no cytoalbuminologic dissociation. It was also noted that the color of the patient’s urine turned visibly reddish on exposure to sunlight ( Figure 3 ). A diagnosis of AIP was finally confirmed by genetic analysis, which identified a missense mutation: c.541C>T, encoding p. Gln181 in the HMBS gene ( Figure 4 ). Targeted mutation analysis was then performed in her two children, but neither of them carried the disease-causing gene. Because heme arginate is not available in mainland China, the patient was treated with intravenous glucose infusion (50%). Twenty-four hours after glucose medication, her abdominal pain was alleviated and her urine returned to a normal color; however, her peripheral neuropathy did not markedly improve. After 2 weeks of treatment, the tracheal tube was removed. The patient was then transferred back to her local hospital for rehabilitation training because of the poor muscle strength in her limbs. At the 1-year follow-up, her overall muscle power had gradually improved to grade 3/5, and she was able to walk with the aid of a rehabilitation walking assistance vehicle. To date, the patient has not experienced any other AIP attacks, but she still has severe neurological sequelae.'}
|
Laboratory-and-Imaging
|
Lab_Image
|
[
"an abdominal flat plate X - ray showed incomplete intestinal obstruction",
"Urgent arterial blood gas analysis on ICU admission indicated severe hypoxemia and respiratory acidosis ( pH : 7.153, PO 2 : 66 mmHg, PCO 2 : 50.2 mmHg, and PO 2 /FiO 2 : 110 mmHg );",
"Cranial computed tomography ( CT ) and abdominal CT did not indicate any abnormalities ( Figure 1b ), although the chest CT showed patchy exudation of the lower lungs, which did not explain the patient ’s respiratory failure. Bedside ultrasound revealed that diaphragm displacement during spontaneous breathing mode was 5.4 mm, whereas normal displacement is considered to be greater than 10 mm",
"Blood tests showed that serum creatinine was elevated at 350.5 µmol / L ( normal range : 44–133 µmol / L ), and urea nitrogen was elevated at 22.23 mmol / L ( normal range : 2.9–7.5 mmol / L )",
"The initial cerebrospinal fluid ( CSF ) examination was within the normal range, and anti - ganglioside antibodies, such as GM1 and GD1a, were negative",
"Abdominal CT at this time showed extensive colonic expansion ( Figure 1c ). Another CSF examination was performed, but the results remained normal, with no cytoalbuminologic dissociation.",
"genetic analysis, which identified a missense mutation : c.541C > T, encoding p. Gln181 in the HMBS gene"
] |
test-2076
|
7809922
|
{'Case report': 'A 37-year-old woman presented to the surgical unit of a general teaching hospital with abdominal pain that she experienced while walking to the hospital (May 2019). Her symptoms had started 4 months previously (January 2019). The initial symptoms included recurring abdominal pain and bloating (almost once per month). During this period, the patient visited her local clinic several times, without obtaining a clear diagnosis. The patient received Chinese medicine over a long period of time and also received symptomatic treatments (e.g., enema, tramadol as analgesia), but her condition did not improve considerably. She had a history of a cesarean section in 2013, and no other notable medical history or family history of disease. On her admission assessment, an abdominal flat plate X-ray showed incomplete intestinal obstruction ( Figure 1a ), but no obvious abnormalities were observed in any other inspections. Forty-eight hours after admission, the patient suddenly developed dyspnea, muscle weakness, and a disorder of consciousness, with uncorrectable hypoxemia (SPO 2 86%), tachycardia (130 bpm), and hypotension (blood pressure 80/59 mmHg). She was transferred to the intensive care unit (ICU) for further management. Urgent arterial blood gas analysis on ICU admission indicated severe hypoxemia and respiratory acidosis (pH: 7.153, PO 2 : 66 mmHg, PCO 2 : 50.2 mmHg, and PO 2 /FiO 2 : 110 mmHg); tracheal intubation was then performed. On day 2 of ICU admission, the patient’s awareness gradually recovered and her abdominal pain spontaneously disappeared. Further examination revealed stubborn respiratory failure, meaning that the patient was unable to be removed from the ventilator. Muscle power of the limbs was 0/5 proximally and 2/5 distally. Furthermore, sensation and cranial nerve examinations were normal. Cranial computed tomography (CT) and abdominal CT did not indicate any abnormalities ( Figure 1b ), although the chest CT showed patchy exudation of the lower lungs, which did not explain the patient’s respiratory failure. Bedside ultrasound revealed that diaphragm displacement during spontaneous breathing mode was 5.4 mm, whereas normal displacement is considered to be greater than 10 mm. Blood tests showed that serum creatinine was elevated at 350.5 µmol/L (normal range: 44–133 µmol/L), and urea nitrogen was elevated at 22.23 mmol/L (normal range: 2.9–7.5 mmol/L), although these levels returned to normal soon after hemodialysis. The initial cerebrospinal fluid (CSF) examination was within the normal range, and anti-ganglioside antibodies, such as GM1 and GD1a, were negative. Furthermore, electromyography findings showed unspecific peripheral nerve damage ( Figure 2 ). The patient was treated with a course of intravenous immunoglobulin for a probable diagnosis of Guillain–Barré syndrome (GBS), but no relief was achieved. The patient’s condition continued to worsen, and on day 14 after ICU admission, her abdominal pain and constipation returned, along with changes in her neurological examination. Her overall weakness worsened, with muscle power of 0/5 (absolutely no movement) in all four limbs. Furthermore, a cranial nerve examination showed new nasal and labial asymmetry, and her eyelids were unable to close. Abdominal CT at this time showed extensive colonic expansion ( Figure 1c ). Another CSF examination was performed, but the results remained normal, with no cytoalbuminologic dissociation. It was also noted that the color of the patient’s urine turned visibly reddish on exposure to sunlight ( Figure 3 ). A diagnosis of AIP was finally confirmed by genetic analysis, which identified a missense mutation: c.541C>T, encoding p. Gln181 in the HMBS gene ( Figure 4 ). Targeted mutation analysis was then performed in her two children, but neither of them carried the disease-causing gene. Because heme arginate is not available in mainland China, the patient was treated with intravenous glucose infusion (50%). Twenty-four hours after glucose medication, her abdominal pain was alleviated and her urine returned to a normal color; however, her peripheral neuropathy did not markedly improve. After 2 weeks of treatment, the tracheal tube was removed. The patient was then transferred back to her local hospital for rehabilitation training because of the poor muscle strength in her limbs. At the 1-year follow-up, her overall muscle power had gradually improved to grade 3/5, and she was able to walk with the aid of a rehabilitation walking assistance vehicle. To date, the patient has not experienced any other AIP attacks, but she still has severe neurological sequelae.'}
|
{'Case report': 'A 37-year-old woman presented to the surgical unit of a general teaching hospital with abdominal pain that she experienced while walking to the hospital (May 2019). Her symptoms had started 4 months previously (January 2019). The initial symptoms included recurring abdominal pain and bloating (almost once per month). During this period, the patient visited her local clinic several times, without obtaining a clear diagnosis. The patient received Chinese medicine over a long period of time and also received symptomatic treatments (e.g., enema, tramadol as analgesia), but her condition did not improve considerably. She had a history of a cesarean section in 2013, and no other notable medical history or family history of disease. On her admission assessment, an abdominal flat plate X-ray showed incomplete intestinal obstruction ( Figure 1a ), but no obvious abnormalities were observed in any other inspections. Forty-eight hours after admission, the patient suddenly developed dyspnea, muscle weakness, and a disorder of consciousness, with uncorrectable hypoxemia (SPO 2 86%), tachycardia (130 bpm), and hypotension (blood pressure 80/59 mmHg). She was transferred to the intensive care unit (ICU) for further management. Urgent arterial blood gas analysis on ICU admission indicated severe hypoxemia and respiratory acidosis (pH: 7.153, PO 2 : 66 mmHg, PCO 2 : 50.2 mmHg, and PO 2 /FiO 2 : 110 mmHg); tracheal intubation was then performed. On day 2 of ICU admission, the patient’s awareness gradually recovered and her abdominal pain spontaneously disappeared. Further examination revealed stubborn respiratory failure, meaning that the patient was unable to be removed from the ventilator. Muscle power of the limbs was 0/5 proximally and 2/5 distally. Furthermore, sensation and cranial nerve examinations were normal. Cranial computed tomography (CT) and abdominal CT did not indicate any abnormalities ( Figure 1b ), although the chest CT showed patchy exudation of the lower lungs, which did not explain the patient’s respiratory failure. Bedside ultrasound revealed that diaphragm displacement during spontaneous breathing mode was 5.4 mm, whereas normal displacement is considered to be greater than 10 mm. Blood tests showed that serum creatinine was elevated at 350.5 µmol/L (normal range: 44–133 µmol/L), and urea nitrogen was elevated at 22.23 mmol/L (normal range: 2.9–7.5 mmol/L), although these levels returned to normal soon after hemodialysis. The initial cerebrospinal fluid (CSF) examination was within the normal range, and anti-ganglioside antibodies, such as GM1 and GD1a, were negative. Furthermore, electromyography findings showed unspecific peripheral nerve damage ( Figure 2 ). The patient was treated with a course of intravenous immunoglobulin for a probable diagnosis of Guillain–Barré syndrome (GBS), but no relief was achieved. The patient’s condition continued to worsen, and on day 14 after ICU admission, her abdominal pain and constipation returned, along with changes in her neurological examination. Her overall weakness worsened, with muscle power of 0/5 (absolutely no movement) in all four limbs. Furthermore, a cranial nerve examination showed new nasal and labial asymmetry, and her eyelids were unable to close. Abdominal CT at this time showed extensive colonic expansion ( Figure 1c ). Another CSF examination was performed, but the results remained normal, with no cytoalbuminologic dissociation. It was also noted that the color of the patient’s urine turned visibly reddish on exposure to sunlight ( Figure 3 ). A diagnosis of AIP was finally confirmed by genetic analysis, which identified a missense mutation: c.541C>T, encoding p. Gln181 in the HMBS gene ( Figure 4 ). Targeted mutation analysis was then performed in her two children, but neither of them carried the disease-causing gene. Because heme arginate is not available in mainland China, the patient was treated with intravenous glucose infusion (50%). Twenty-four hours after glucose medication, her abdominal pain was alleviated and her urine returned to a normal color; however, her peripheral neuropathy did not markedly improve. After 2 weeks of treatment, the tracheal tube was removed. The patient was then transferred back to her local hospital for rehabilitation training because of the poor muscle strength in her limbs. At the 1-year follow-up, her overall muscle power had gradually improved to grade 3/5, and she was able to walk with the aid of a rehabilitation walking assistance vehicle. To date, the patient has not experienced any other AIP attacks, but she still has severe neurological sequelae.'}
|
Cardiovascular-System
|
CVS
|
[
"uncorrectable hypoxemia ( SPO 2 86 % ), tachycardia ( 130 bpm ), and hypotension ( blood pressure 80/59 mmHg )"
] |
test-2077
|
7809922
|
{'Case report': 'A 37-year-old woman presented to the surgical unit of a general teaching hospital with abdominal pain that she experienced while walking to the hospital (May 2019). Her symptoms had started 4 months previously (January 2019). The initial symptoms included recurring abdominal pain and bloating (almost once per month). During this period, the patient visited her local clinic several times, without obtaining a clear diagnosis. The patient received Chinese medicine over a long period of time and also received symptomatic treatments (e.g., enema, tramadol as analgesia), but her condition did not improve considerably. She had a history of a cesarean section in 2013, and no other notable medical history or family history of disease. On her admission assessment, an abdominal flat plate X-ray showed incomplete intestinal obstruction ( Figure 1a ), but no obvious abnormalities were observed in any other inspections. Forty-eight hours after admission, the patient suddenly developed dyspnea, muscle weakness, and a disorder of consciousness, with uncorrectable hypoxemia (SPO 2 86%), tachycardia (130 bpm), and hypotension (blood pressure 80/59 mmHg). She was transferred to the intensive care unit (ICU) for further management. Urgent arterial blood gas analysis on ICU admission indicated severe hypoxemia and respiratory acidosis (pH: 7.153, PO 2 : 66 mmHg, PCO 2 : 50.2 mmHg, and PO 2 /FiO 2 : 110 mmHg); tracheal intubation was then performed. On day 2 of ICU admission, the patient’s awareness gradually recovered and her abdominal pain spontaneously disappeared. Further examination revealed stubborn respiratory failure, meaning that the patient was unable to be removed from the ventilator. Muscle power of the limbs was 0/5 proximally and 2/5 distally. Furthermore, sensation and cranial nerve examinations were normal. Cranial computed tomography (CT) and abdominal CT did not indicate any abnormalities ( Figure 1b ), although the chest CT showed patchy exudation of the lower lungs, which did not explain the patient’s respiratory failure. Bedside ultrasound revealed that diaphragm displacement during spontaneous breathing mode was 5.4 mm, whereas normal displacement is considered to be greater than 10 mm. Blood tests showed that serum creatinine was elevated at 350.5 µmol/L (normal range: 44–133 µmol/L), and urea nitrogen was elevated at 22.23 mmol/L (normal range: 2.9–7.5 mmol/L), although these levels returned to normal soon after hemodialysis. The initial cerebrospinal fluid (CSF) examination was within the normal range, and anti-ganglioside antibodies, such as GM1 and GD1a, were negative. Furthermore, electromyography findings showed unspecific peripheral nerve damage ( Figure 2 ). The patient was treated with a course of intravenous immunoglobulin for a probable diagnosis of Guillain–Barré syndrome (GBS), but no relief was achieved. The patient’s condition continued to worsen, and on day 14 after ICU admission, her abdominal pain and constipation returned, along with changes in her neurological examination. Her overall weakness worsened, with muscle power of 0/5 (absolutely no movement) in all four limbs. Furthermore, a cranial nerve examination showed new nasal and labial asymmetry, and her eyelids were unable to close. Abdominal CT at this time showed extensive colonic expansion ( Figure 1c ). Another CSF examination was performed, but the results remained normal, with no cytoalbuminologic dissociation. It was also noted that the color of the patient’s urine turned visibly reddish on exposure to sunlight ( Figure 3 ). A diagnosis of AIP was finally confirmed by genetic analysis, which identified a missense mutation: c.541C>T, encoding p. Gln181 in the HMBS gene ( Figure 4 ). Targeted mutation analysis was then performed in her two children, but neither of them carried the disease-causing gene. Because heme arginate is not available in mainland China, the patient was treated with intravenous glucose infusion (50%). Twenty-four hours after glucose medication, her abdominal pain was alleviated and her urine returned to a normal color; however, her peripheral neuropathy did not markedly improve. After 2 weeks of treatment, the tracheal tube was removed. The patient was then transferred back to her local hospital for rehabilitation training because of the poor muscle strength in her limbs. At the 1-year follow-up, her overall muscle power had gradually improved to grade 3/5, and she was able to walk with the aid of a rehabilitation walking assistance vehicle. To date, the patient has not experienced any other AIP attacks, but she still has severe neurological sequelae.'}
|
{'Case report': 'A 37-year-old woman presented to the surgical unit of a general teaching hospital with abdominal pain that she experienced while walking to the hospital (May 2019). Her symptoms had started 4 months previously (January 2019). The initial symptoms included recurring abdominal pain and bloating (almost once per month). During this period, the patient visited her local clinic several times, without obtaining a clear diagnosis. The patient received Chinese medicine over a long period of time and also received symptomatic treatments (e.g., enema, tramadol as analgesia), but her condition did not improve considerably. She had a history of a cesarean section in 2013, and no other notable medical history or family history of disease. On her admission assessment, an abdominal flat plate X-ray showed incomplete intestinal obstruction ( Figure 1a ), but no obvious abnormalities were observed in any other inspections. Forty-eight hours after admission, the patient suddenly developed dyspnea, muscle weakness, and a disorder of consciousness, with uncorrectable hypoxemia (SPO 2 86%), tachycardia (130 bpm), and hypotension (blood pressure 80/59 mmHg). She was transferred to the intensive care unit (ICU) for further management. Urgent arterial blood gas analysis on ICU admission indicated severe hypoxemia and respiratory acidosis (pH: 7.153, PO 2 : 66 mmHg, PCO 2 : 50.2 mmHg, and PO 2 /FiO 2 : 110 mmHg); tracheal intubation was then performed. On day 2 of ICU admission, the patient’s awareness gradually recovered and her abdominal pain spontaneously disappeared. Further examination revealed stubborn respiratory failure, meaning that the patient was unable to be removed from the ventilator. Muscle power of the limbs was 0/5 proximally and 2/5 distally. Furthermore, sensation and cranial nerve examinations were normal. Cranial computed tomography (CT) and abdominal CT did not indicate any abnormalities ( Figure 1b ), although the chest CT showed patchy exudation of the lower lungs, which did not explain the patient’s respiratory failure. Bedside ultrasound revealed that diaphragm displacement during spontaneous breathing mode was 5.4 mm, whereas normal displacement is considered to be greater than 10 mm. Blood tests showed that serum creatinine was elevated at 350.5 µmol/L (normal range: 44–133 µmol/L), and urea nitrogen was elevated at 22.23 mmol/L (normal range: 2.9–7.5 mmol/L), although these levels returned to normal soon after hemodialysis. The initial cerebrospinal fluid (CSF) examination was within the normal range, and anti-ganglioside antibodies, such as GM1 and GD1a, were negative. Furthermore, electromyography findings showed unspecific peripheral nerve damage ( Figure 2 ). The patient was treated with a course of intravenous immunoglobulin for a probable diagnosis of Guillain–Barré syndrome (GBS), but no relief was achieved. The patient’s condition continued to worsen, and on day 14 after ICU admission, her abdominal pain and constipation returned, along with changes in her neurological examination. Her overall weakness worsened, with muscle power of 0/5 (absolutely no movement) in all four limbs. Furthermore, a cranial nerve examination showed new nasal and labial asymmetry, and her eyelids were unable to close. Abdominal CT at this time showed extensive colonic expansion ( Figure 1c ). Another CSF examination was performed, but the results remained normal, with no cytoalbuminologic dissociation. It was also noted that the color of the patient’s urine turned visibly reddish on exposure to sunlight ( Figure 3 ). A diagnosis of AIP was finally confirmed by genetic analysis, which identified a missense mutation: c.541C>T, encoding p. Gln181 in the HMBS gene ( Figure 4 ). Targeted mutation analysis was then performed in her two children, but neither of them carried the disease-causing gene. Because heme arginate is not available in mainland China, the patient was treated with intravenous glucose infusion (50%). Twenty-four hours after glucose medication, her abdominal pain was alleviated and her urine returned to a normal color; however, her peripheral neuropathy did not markedly improve. After 2 weeks of treatment, the tracheal tube was removed. The patient was then transferred back to her local hospital for rehabilitation training because of the poor muscle strength in her limbs. At the 1-year follow-up, her overall muscle power had gradually improved to grade 3/5, and she was able to walk with the aid of a rehabilitation walking assistance vehicle. To date, the patient has not experienced any other AIP attacks, but she still has severe neurological sequelae.'}
|
Endocrinology
|
ENDO
|
[] |
test-2078
|
7809922
|
{'Case report': 'A 37-year-old woman presented to the surgical unit of a general teaching hospital with abdominal pain that she experienced while walking to the hospital (May 2019). Her symptoms had started 4 months previously (January 2019). The initial symptoms included recurring abdominal pain and bloating (almost once per month). During this period, the patient visited her local clinic several times, without obtaining a clear diagnosis. The patient received Chinese medicine over a long period of time and also received symptomatic treatments (e.g., enema, tramadol as analgesia), but her condition did not improve considerably. She had a history of a cesarean section in 2013, and no other notable medical history or family history of disease. On her admission assessment, an abdominal flat plate X-ray showed incomplete intestinal obstruction ( Figure 1a ), but no obvious abnormalities were observed in any other inspections. Forty-eight hours after admission, the patient suddenly developed dyspnea, muscle weakness, and a disorder of consciousness, with uncorrectable hypoxemia (SPO 2 86%), tachycardia (130 bpm), and hypotension (blood pressure 80/59 mmHg). She was transferred to the intensive care unit (ICU) for further management. Urgent arterial blood gas analysis on ICU admission indicated severe hypoxemia and respiratory acidosis (pH: 7.153, PO 2 : 66 mmHg, PCO 2 : 50.2 mmHg, and PO 2 /FiO 2 : 110 mmHg); tracheal intubation was then performed. On day 2 of ICU admission, the patient’s awareness gradually recovered and her abdominal pain spontaneously disappeared. Further examination revealed stubborn respiratory failure, meaning that the patient was unable to be removed from the ventilator. Muscle power of the limbs was 0/5 proximally and 2/5 distally. Furthermore, sensation and cranial nerve examinations were normal. Cranial computed tomography (CT) and abdominal CT did not indicate any abnormalities ( Figure 1b ), although the chest CT showed patchy exudation of the lower lungs, which did not explain the patient’s respiratory failure. Bedside ultrasound revealed that diaphragm displacement during spontaneous breathing mode was 5.4 mm, whereas normal displacement is considered to be greater than 10 mm. Blood tests showed that serum creatinine was elevated at 350.5 µmol/L (normal range: 44–133 µmol/L), and urea nitrogen was elevated at 22.23 mmol/L (normal range: 2.9–7.5 mmol/L), although these levels returned to normal soon after hemodialysis. The initial cerebrospinal fluid (CSF) examination was within the normal range, and anti-ganglioside antibodies, such as GM1 and GD1a, were negative. Furthermore, electromyography findings showed unspecific peripheral nerve damage ( Figure 2 ). The patient was treated with a course of intravenous immunoglobulin for a probable diagnosis of Guillain–Barré syndrome (GBS), but no relief was achieved. The patient’s condition continued to worsen, and on day 14 after ICU admission, her abdominal pain and constipation returned, along with changes in her neurological examination. Her overall weakness worsened, with muscle power of 0/5 (absolutely no movement) in all four limbs. Furthermore, a cranial nerve examination showed new nasal and labial asymmetry, and her eyelids were unable to close. Abdominal CT at this time showed extensive colonic expansion ( Figure 1c ). Another CSF examination was performed, but the results remained normal, with no cytoalbuminologic dissociation. It was also noted that the color of the patient’s urine turned visibly reddish on exposure to sunlight ( Figure 3 ). A diagnosis of AIP was finally confirmed by genetic analysis, which identified a missense mutation: c.541C>T, encoding p. Gln181 in the HMBS gene ( Figure 4 ). Targeted mutation analysis was then performed in her two children, but neither of them carried the disease-causing gene. Because heme arginate is not available in mainland China, the patient was treated with intravenous glucose infusion (50%). Twenty-four hours after glucose medication, her abdominal pain was alleviated and her urine returned to a normal color; however, her peripheral neuropathy did not markedly improve. After 2 weeks of treatment, the tracheal tube was removed. The patient was then transferred back to her local hospital for rehabilitation training because of the poor muscle strength in her limbs. At the 1-year follow-up, her overall muscle power had gradually improved to grade 3/5, and she was able to walk with the aid of a rehabilitation walking assistance vehicle. To date, the patient has not experienced any other AIP attacks, but she still has severe neurological sequelae.'}
|
{'Case report': 'A 37-year-old woman presented to the surgical unit of a general teaching hospital with abdominal pain that she experienced while walking to the hospital (May 2019). Her symptoms had started 4 months previously (January 2019). The initial symptoms included recurring abdominal pain and bloating (almost once per month). During this period, the patient visited her local clinic several times, without obtaining a clear diagnosis. The patient received Chinese medicine over a long period of time and also received symptomatic treatments (e.g., enema, tramadol as analgesia), but her condition did not improve considerably. She had a history of a cesarean section in 2013, and no other notable medical history or family history of disease. On her admission assessment, an abdominal flat plate X-ray showed incomplete intestinal obstruction ( Figure 1a ), but no obvious abnormalities were observed in any other inspections. Forty-eight hours after admission, the patient suddenly developed dyspnea, muscle weakness, and a disorder of consciousness, with uncorrectable hypoxemia (SPO 2 86%), tachycardia (130 bpm), and hypotension (blood pressure 80/59 mmHg). She was transferred to the intensive care unit (ICU) for further management. Urgent arterial blood gas analysis on ICU admission indicated severe hypoxemia and respiratory acidosis (pH: 7.153, PO 2 : 66 mmHg, PCO 2 : 50.2 mmHg, and PO 2 /FiO 2 : 110 mmHg); tracheal intubation was then performed. On day 2 of ICU admission, the patient’s awareness gradually recovered and her abdominal pain spontaneously disappeared. Further examination revealed stubborn respiratory failure, meaning that the patient was unable to be removed from the ventilator. Muscle power of the limbs was 0/5 proximally and 2/5 distally. Furthermore, sensation and cranial nerve examinations were normal. Cranial computed tomography (CT) and abdominal CT did not indicate any abnormalities ( Figure 1b ), although the chest CT showed patchy exudation of the lower lungs, which did not explain the patient’s respiratory failure. Bedside ultrasound revealed that diaphragm displacement during spontaneous breathing mode was 5.4 mm, whereas normal displacement is considered to be greater than 10 mm. Blood tests showed that serum creatinine was elevated at 350.5 µmol/L (normal range: 44–133 µmol/L), and urea nitrogen was elevated at 22.23 mmol/L (normal range: 2.9–7.5 mmol/L), although these levels returned to normal soon after hemodialysis. The initial cerebrospinal fluid (CSF) examination was within the normal range, and anti-ganglioside antibodies, such as GM1 and GD1a, were negative. Furthermore, electromyography findings showed unspecific peripheral nerve damage ( Figure 2 ). The patient was treated with a course of intravenous immunoglobulin for a probable diagnosis of Guillain–Barré syndrome (GBS), but no relief was achieved. The patient’s condition continued to worsen, and on day 14 after ICU admission, her abdominal pain and constipation returned, along with changes in her neurological examination. Her overall weakness worsened, with muscle power of 0/5 (absolutely no movement) in all four limbs. Furthermore, a cranial nerve examination showed new nasal and labial asymmetry, and her eyelids were unable to close. Abdominal CT at this time showed extensive colonic expansion ( Figure 1c ). Another CSF examination was performed, but the results remained normal, with no cytoalbuminologic dissociation. It was also noted that the color of the patient’s urine turned visibly reddish on exposure to sunlight ( Figure 3 ). A diagnosis of AIP was finally confirmed by genetic analysis, which identified a missense mutation: c.541C>T, encoding p. Gln181 in the HMBS gene ( Figure 4 ). Targeted mutation analysis was then performed in her two children, but neither of them carried the disease-causing gene. Because heme arginate is not available in mainland China, the patient was treated with intravenous glucose infusion (50%). Twenty-four hours after glucose medication, her abdominal pain was alleviated and her urine returned to a normal color; however, her peripheral neuropathy did not markedly improve. After 2 weeks of treatment, the tracheal tube was removed. The patient was then transferred back to her local hospital for rehabilitation training because of the poor muscle strength in her limbs. At the 1-year follow-up, her overall muscle power had gradually improved to grade 3/5, and she was able to walk with the aid of a rehabilitation walking assistance vehicle. To date, the patient has not experienced any other AIP attacks, but she still has severe neurological sequelae.'}
|
Genitourinary-System
|
GU
|
[
"serum creatinine was elevated at 350.5 µmol / L ( normal range : 44–133 µmol / L ), and urea nitrogen was elevated at 22.23 mmol / L ( normal range : 2.9–7.5 mmol / L )",
"color of the patient ’s urine turned visibly reddish on exposure to sunlight",
"urine returned to a normal color"
] |
test-2079
|
7809922
|
{'Case report': 'A 37-year-old woman presented to the surgical unit of a general teaching hospital with abdominal pain that she experienced while walking to the hospital (May 2019). Her symptoms had started 4 months previously (January 2019). The initial symptoms included recurring abdominal pain and bloating (almost once per month). During this period, the patient visited her local clinic several times, without obtaining a clear diagnosis. The patient received Chinese medicine over a long period of time and also received symptomatic treatments (e.g., enema, tramadol as analgesia), but her condition did not improve considerably. She had a history of a cesarean section in 2013, and no other notable medical history or family history of disease. On her admission assessment, an abdominal flat plate X-ray showed incomplete intestinal obstruction ( Figure 1a ), but no obvious abnormalities were observed in any other inspections. Forty-eight hours after admission, the patient suddenly developed dyspnea, muscle weakness, and a disorder of consciousness, with uncorrectable hypoxemia (SPO 2 86%), tachycardia (130 bpm), and hypotension (blood pressure 80/59 mmHg). She was transferred to the intensive care unit (ICU) for further management. Urgent arterial blood gas analysis on ICU admission indicated severe hypoxemia and respiratory acidosis (pH: 7.153, PO 2 : 66 mmHg, PCO 2 : 50.2 mmHg, and PO 2 /FiO 2 : 110 mmHg); tracheal intubation was then performed. On day 2 of ICU admission, the patient’s awareness gradually recovered and her abdominal pain spontaneously disappeared. Further examination revealed stubborn respiratory failure, meaning that the patient was unable to be removed from the ventilator. Muscle power of the limbs was 0/5 proximally and 2/5 distally. Furthermore, sensation and cranial nerve examinations were normal. Cranial computed tomography (CT) and abdominal CT did not indicate any abnormalities ( Figure 1b ), although the chest CT showed patchy exudation of the lower lungs, which did not explain the patient’s respiratory failure. Bedside ultrasound revealed that diaphragm displacement during spontaneous breathing mode was 5.4 mm, whereas normal displacement is considered to be greater than 10 mm. Blood tests showed that serum creatinine was elevated at 350.5 µmol/L (normal range: 44–133 µmol/L), and urea nitrogen was elevated at 22.23 mmol/L (normal range: 2.9–7.5 mmol/L), although these levels returned to normal soon after hemodialysis. The initial cerebrospinal fluid (CSF) examination was within the normal range, and anti-ganglioside antibodies, such as GM1 and GD1a, were negative. Furthermore, electromyography findings showed unspecific peripheral nerve damage ( Figure 2 ). The patient was treated with a course of intravenous immunoglobulin for a probable diagnosis of Guillain–Barré syndrome (GBS), but no relief was achieved. The patient’s condition continued to worsen, and on day 14 after ICU admission, her abdominal pain and constipation returned, along with changes in her neurological examination. Her overall weakness worsened, with muscle power of 0/5 (absolutely no movement) in all four limbs. Furthermore, a cranial nerve examination showed new nasal and labial asymmetry, and her eyelids were unable to close. Abdominal CT at this time showed extensive colonic expansion ( Figure 1c ). Another CSF examination was performed, but the results remained normal, with no cytoalbuminologic dissociation. It was also noted that the color of the patient’s urine turned visibly reddish on exposure to sunlight ( Figure 3 ). A diagnosis of AIP was finally confirmed by genetic analysis, which identified a missense mutation: c.541C>T, encoding p. Gln181 in the HMBS gene ( Figure 4 ). Targeted mutation analysis was then performed in her two children, but neither of them carried the disease-causing gene. Because heme arginate is not available in mainland China, the patient was treated with intravenous glucose infusion (50%). Twenty-four hours after glucose medication, her abdominal pain was alleviated and her urine returned to a normal color; however, her peripheral neuropathy did not markedly improve. After 2 weeks of treatment, the tracheal tube was removed. The patient was then transferred back to her local hospital for rehabilitation training because of the poor muscle strength in her limbs. At the 1-year follow-up, her overall muscle power had gradually improved to grade 3/5, and she was able to walk with the aid of a rehabilitation walking assistance vehicle. To date, the patient has not experienced any other AIP attacks, but she still has severe neurological sequelae.'}
|
{'Case report': 'A 37-year-old woman presented to the surgical unit of a general teaching hospital with abdominal pain that she experienced while walking to the hospital (May 2019). Her symptoms had started 4 months previously (January 2019). The initial symptoms included recurring abdominal pain and bloating (almost once per month). During this period, the patient visited her local clinic several times, without obtaining a clear diagnosis. The patient received Chinese medicine over a long period of time and also received symptomatic treatments (e.g., enema, tramadol as analgesia), but her condition did not improve considerably. She had a history of a cesarean section in 2013, and no other notable medical history or family history of disease. On her admission assessment, an abdominal flat plate X-ray showed incomplete intestinal obstruction ( Figure 1a ), but no obvious abnormalities were observed in any other inspections. Forty-eight hours after admission, the patient suddenly developed dyspnea, muscle weakness, and a disorder of consciousness, with uncorrectable hypoxemia (SPO 2 86%), tachycardia (130 bpm), and hypotension (blood pressure 80/59 mmHg). She was transferred to the intensive care unit (ICU) for further management. Urgent arterial blood gas analysis on ICU admission indicated severe hypoxemia and respiratory acidosis (pH: 7.153, PO 2 : 66 mmHg, PCO 2 : 50.2 mmHg, and PO 2 /FiO 2 : 110 mmHg); tracheal intubation was then performed. On day 2 of ICU admission, the patient’s awareness gradually recovered and her abdominal pain spontaneously disappeared. Further examination revealed stubborn respiratory failure, meaning that the patient was unable to be removed from the ventilator. Muscle power of the limbs was 0/5 proximally and 2/5 distally. Furthermore, sensation and cranial nerve examinations were normal. Cranial computed tomography (CT) and abdominal CT did not indicate any abnormalities ( Figure 1b ), although the chest CT showed patchy exudation of the lower lungs, which did not explain the patient’s respiratory failure. Bedside ultrasound revealed that diaphragm displacement during spontaneous breathing mode was 5.4 mm, whereas normal displacement is considered to be greater than 10 mm. Blood tests showed that serum creatinine was elevated at 350.5 µmol/L (normal range: 44–133 µmol/L), and urea nitrogen was elevated at 22.23 mmol/L (normal range: 2.9–7.5 mmol/L), although these levels returned to normal soon after hemodialysis. The initial cerebrospinal fluid (CSF) examination was within the normal range, and anti-ganglioside antibodies, such as GM1 and GD1a, were negative. Furthermore, electromyography findings showed unspecific peripheral nerve damage ( Figure 2 ). The patient was treated with a course of intravenous immunoglobulin for a probable diagnosis of Guillain–Barré syndrome (GBS), but no relief was achieved. The patient’s condition continued to worsen, and on day 14 after ICU admission, her abdominal pain and constipation returned, along with changes in her neurological examination. Her overall weakness worsened, with muscle power of 0/5 (absolutely no movement) in all four limbs. Furthermore, a cranial nerve examination showed new nasal and labial asymmetry, and her eyelids were unable to close. Abdominal CT at this time showed extensive colonic expansion ( Figure 1c ). Another CSF examination was performed, but the results remained normal, with no cytoalbuminologic dissociation. It was also noted that the color of the patient’s urine turned visibly reddish on exposure to sunlight ( Figure 3 ). A diagnosis of AIP was finally confirmed by genetic analysis, which identified a missense mutation: c.541C>T, encoding p. Gln181 in the HMBS gene ( Figure 4 ). Targeted mutation analysis was then performed in her two children, but neither of them carried the disease-causing gene. Because heme arginate is not available in mainland China, the patient was treated with intravenous glucose infusion (50%). Twenty-four hours after glucose medication, her abdominal pain was alleviated and her urine returned to a normal color; however, her peripheral neuropathy did not markedly improve. After 2 weeks of treatment, the tracheal tube was removed. The patient was then transferred back to her local hospital for rehabilitation training because of the poor muscle strength in her limbs. At the 1-year follow-up, her overall muscle power had gradually improved to grade 3/5, and she was able to walk with the aid of a rehabilitation walking assistance vehicle. To date, the patient has not experienced any other AIP attacks, but she still has severe neurological sequelae.'}
|
Respiratory-System
|
RESP
|
[
"dyspnea,",
"uncorrectable hypoxemia ( SPO 2 86 % )",
"severe hypoxemia and respiratory acidosis",
"stubborn respiratory failure",
"patient was unable to be removed from the ventilator",
"chest CT showed patchy exudation of the lower lungs",
"diaphragm displacement during spontaneous breathing mode was 5.4 mm, whereas normal displacement is considered to be greater than 10 mm"
] |
test-2080
|
7809922
|
{'Case report': 'A 37-year-old woman presented to the surgical unit of a general teaching hospital with abdominal pain that she experienced while walking to the hospital (May 2019). Her symptoms had started 4 months previously (January 2019). The initial symptoms included recurring abdominal pain and bloating (almost once per month). During this period, the patient visited her local clinic several times, without obtaining a clear diagnosis. The patient received Chinese medicine over a long period of time and also received symptomatic treatments (e.g., enema, tramadol as analgesia), but her condition did not improve considerably. She had a history of a cesarean section in 2013, and no other notable medical history or family history of disease. On her admission assessment, an abdominal flat plate X-ray showed incomplete intestinal obstruction ( Figure 1a ), but no obvious abnormalities were observed in any other inspections. Forty-eight hours after admission, the patient suddenly developed dyspnea, muscle weakness, and a disorder of consciousness, with uncorrectable hypoxemia (SPO 2 86%), tachycardia (130 bpm), and hypotension (blood pressure 80/59 mmHg). She was transferred to the intensive care unit (ICU) for further management. Urgent arterial blood gas analysis on ICU admission indicated severe hypoxemia and respiratory acidosis (pH: 7.153, PO 2 : 66 mmHg, PCO 2 : 50.2 mmHg, and PO 2 /FiO 2 : 110 mmHg); tracheal intubation was then performed. On day 2 of ICU admission, the patient’s awareness gradually recovered and her abdominal pain spontaneously disappeared. Further examination revealed stubborn respiratory failure, meaning that the patient was unable to be removed from the ventilator. Muscle power of the limbs was 0/5 proximally and 2/5 distally. Furthermore, sensation and cranial nerve examinations were normal. Cranial computed tomography (CT) and abdominal CT did not indicate any abnormalities ( Figure 1b ), although the chest CT showed patchy exudation of the lower lungs, which did not explain the patient’s respiratory failure. Bedside ultrasound revealed that diaphragm displacement during spontaneous breathing mode was 5.4 mm, whereas normal displacement is considered to be greater than 10 mm. Blood tests showed that serum creatinine was elevated at 350.5 µmol/L (normal range: 44–133 µmol/L), and urea nitrogen was elevated at 22.23 mmol/L (normal range: 2.9–7.5 mmol/L), although these levels returned to normal soon after hemodialysis. The initial cerebrospinal fluid (CSF) examination was within the normal range, and anti-ganglioside antibodies, such as GM1 and GD1a, were negative. Furthermore, electromyography findings showed unspecific peripheral nerve damage ( Figure 2 ). The patient was treated with a course of intravenous immunoglobulin for a probable diagnosis of Guillain–Barré syndrome (GBS), but no relief was achieved. The patient’s condition continued to worsen, and on day 14 after ICU admission, her abdominal pain and constipation returned, along with changes in her neurological examination. Her overall weakness worsened, with muscle power of 0/5 (absolutely no movement) in all four limbs. Furthermore, a cranial nerve examination showed new nasal and labial asymmetry, and her eyelids were unable to close. Abdominal CT at this time showed extensive colonic expansion ( Figure 1c ). Another CSF examination was performed, but the results remained normal, with no cytoalbuminologic dissociation. It was also noted that the color of the patient’s urine turned visibly reddish on exposure to sunlight ( Figure 3 ). A diagnosis of AIP was finally confirmed by genetic analysis, which identified a missense mutation: c.541C>T, encoding p. Gln181 in the HMBS gene ( Figure 4 ). Targeted mutation analysis was then performed in her two children, but neither of them carried the disease-causing gene. Because heme arginate is not available in mainland China, the patient was treated with intravenous glucose infusion (50%). Twenty-four hours after glucose medication, her abdominal pain was alleviated and her urine returned to a normal color; however, her peripheral neuropathy did not markedly improve. After 2 weeks of treatment, the tracheal tube was removed. The patient was then transferred back to her local hospital for rehabilitation training because of the poor muscle strength in her limbs. At the 1-year follow-up, her overall muscle power had gradually improved to grade 3/5, and she was able to walk with the aid of a rehabilitation walking assistance vehicle. To date, the patient has not experienced any other AIP attacks, but she still has severe neurological sequelae.'}
|
{'Case report': 'A 37-year-old woman presented to the surgical unit of a general teaching hospital with abdominal pain that she experienced while walking to the hospital (May 2019). Her symptoms had started 4 months previously (January 2019). The initial symptoms included recurring abdominal pain and bloating (almost once per month). During this period, the patient visited her local clinic several times, without obtaining a clear diagnosis. The patient received Chinese medicine over a long period of time and also received symptomatic treatments (e.g., enema, tramadol as analgesia), but her condition did not improve considerably. She had a history of a cesarean section in 2013, and no other notable medical history or family history of disease. On her admission assessment, an abdominal flat plate X-ray showed incomplete intestinal obstruction ( Figure 1a ), but no obvious abnormalities were observed in any other inspections. Forty-eight hours after admission, the patient suddenly developed dyspnea, muscle weakness, and a disorder of consciousness, with uncorrectable hypoxemia (SPO 2 86%), tachycardia (130 bpm), and hypotension (blood pressure 80/59 mmHg). She was transferred to the intensive care unit (ICU) for further management. Urgent arterial blood gas analysis on ICU admission indicated severe hypoxemia and respiratory acidosis (pH: 7.153, PO 2 : 66 mmHg, PCO 2 : 50.2 mmHg, and PO 2 /FiO 2 : 110 mmHg); tracheal intubation was then performed. On day 2 of ICU admission, the patient’s awareness gradually recovered and her abdominal pain spontaneously disappeared. Further examination revealed stubborn respiratory failure, meaning that the patient was unable to be removed from the ventilator. Muscle power of the limbs was 0/5 proximally and 2/5 distally. Furthermore, sensation and cranial nerve examinations were normal. Cranial computed tomography (CT) and abdominal CT did not indicate any abnormalities ( Figure 1b ), although the chest CT showed patchy exudation of the lower lungs, which did not explain the patient’s respiratory failure. Bedside ultrasound revealed that diaphragm displacement during spontaneous breathing mode was 5.4 mm, whereas normal displacement is considered to be greater than 10 mm. Blood tests showed that serum creatinine was elevated at 350.5 µmol/L (normal range: 44–133 µmol/L), and urea nitrogen was elevated at 22.23 mmol/L (normal range: 2.9–7.5 mmol/L), although these levels returned to normal soon after hemodialysis. The initial cerebrospinal fluid (CSF) examination was within the normal range, and anti-ganglioside antibodies, such as GM1 and GD1a, were negative. Furthermore, electromyography findings showed unspecific peripheral nerve damage ( Figure 2 ). The patient was treated with a course of intravenous immunoglobulin for a probable diagnosis of Guillain–Barré syndrome (GBS), but no relief was achieved. The patient’s condition continued to worsen, and on day 14 after ICU admission, her abdominal pain and constipation returned, along with changes in her neurological examination. Her overall weakness worsened, with muscle power of 0/5 (absolutely no movement) in all four limbs. Furthermore, a cranial nerve examination showed new nasal and labial asymmetry, and her eyelids were unable to close. Abdominal CT at this time showed extensive colonic expansion ( Figure 1c ). Another CSF examination was performed, but the results remained normal, with no cytoalbuminologic dissociation. It was also noted that the color of the patient’s urine turned visibly reddish on exposure to sunlight ( Figure 3 ). A diagnosis of AIP was finally confirmed by genetic analysis, which identified a missense mutation: c.541C>T, encoding p. Gln181 in the HMBS gene ( Figure 4 ). Targeted mutation analysis was then performed in her two children, but neither of them carried the disease-causing gene. Because heme arginate is not available in mainland China, the patient was treated with intravenous glucose infusion (50%). Twenty-four hours after glucose medication, her abdominal pain was alleviated and her urine returned to a normal color; however, her peripheral neuropathy did not markedly improve. After 2 weeks of treatment, the tracheal tube was removed. The patient was then transferred back to her local hospital for rehabilitation training because of the poor muscle strength in her limbs. At the 1-year follow-up, her overall muscle power had gradually improved to grade 3/5, and she was able to walk with the aid of a rehabilitation walking assistance vehicle. To date, the patient has not experienced any other AIP attacks, but she still has severe neurological sequelae.'}
|
Musculoskeletal-System
|
MSK
|
[] |
test-2081
|
7809922
|
{'Case report': 'A 37-year-old woman presented to the surgical unit of a general teaching hospital with abdominal pain that she experienced while walking to the hospital (May 2019). Her symptoms had started 4 months previously (January 2019). The initial symptoms included recurring abdominal pain and bloating (almost once per month). During this period, the patient visited her local clinic several times, without obtaining a clear diagnosis. The patient received Chinese medicine over a long period of time and also received symptomatic treatments (e.g., enema, tramadol as analgesia), but her condition did not improve considerably. She had a history of a cesarean section in 2013, and no other notable medical history or family history of disease. On her admission assessment, an abdominal flat plate X-ray showed incomplete intestinal obstruction ( Figure 1a ), but no obvious abnormalities were observed in any other inspections. Forty-eight hours after admission, the patient suddenly developed dyspnea, muscle weakness, and a disorder of consciousness, with uncorrectable hypoxemia (SPO 2 86%), tachycardia (130 bpm), and hypotension (blood pressure 80/59 mmHg). She was transferred to the intensive care unit (ICU) for further management. Urgent arterial blood gas analysis on ICU admission indicated severe hypoxemia and respiratory acidosis (pH: 7.153, PO 2 : 66 mmHg, PCO 2 : 50.2 mmHg, and PO 2 /FiO 2 : 110 mmHg); tracheal intubation was then performed. On day 2 of ICU admission, the patient’s awareness gradually recovered and her abdominal pain spontaneously disappeared. Further examination revealed stubborn respiratory failure, meaning that the patient was unable to be removed from the ventilator. Muscle power of the limbs was 0/5 proximally and 2/5 distally. Furthermore, sensation and cranial nerve examinations were normal. Cranial computed tomography (CT) and abdominal CT did not indicate any abnormalities ( Figure 1b ), although the chest CT showed patchy exudation of the lower lungs, which did not explain the patient’s respiratory failure. Bedside ultrasound revealed that diaphragm displacement during spontaneous breathing mode was 5.4 mm, whereas normal displacement is considered to be greater than 10 mm. Blood tests showed that serum creatinine was elevated at 350.5 µmol/L (normal range: 44–133 µmol/L), and urea nitrogen was elevated at 22.23 mmol/L (normal range: 2.9–7.5 mmol/L), although these levels returned to normal soon after hemodialysis. The initial cerebrospinal fluid (CSF) examination was within the normal range, and anti-ganglioside antibodies, such as GM1 and GD1a, were negative. Furthermore, electromyography findings showed unspecific peripheral nerve damage ( Figure 2 ). The patient was treated with a course of intravenous immunoglobulin for a probable diagnosis of Guillain–Barré syndrome (GBS), but no relief was achieved. The patient’s condition continued to worsen, and on day 14 after ICU admission, her abdominal pain and constipation returned, along with changes in her neurological examination. Her overall weakness worsened, with muscle power of 0/5 (absolutely no movement) in all four limbs. Furthermore, a cranial nerve examination showed new nasal and labial asymmetry, and her eyelids were unable to close. Abdominal CT at this time showed extensive colonic expansion ( Figure 1c ). Another CSF examination was performed, but the results remained normal, with no cytoalbuminologic dissociation. It was also noted that the color of the patient’s urine turned visibly reddish on exposure to sunlight ( Figure 3 ). A diagnosis of AIP was finally confirmed by genetic analysis, which identified a missense mutation: c.541C>T, encoding p. Gln181 in the HMBS gene ( Figure 4 ). Targeted mutation analysis was then performed in her two children, but neither of them carried the disease-causing gene. Because heme arginate is not available in mainland China, the patient was treated with intravenous glucose infusion (50%). Twenty-four hours after glucose medication, her abdominal pain was alleviated and her urine returned to a normal color; however, her peripheral neuropathy did not markedly improve. After 2 weeks of treatment, the tracheal tube was removed. The patient was then transferred back to her local hospital for rehabilitation training because of the poor muscle strength in her limbs. At the 1-year follow-up, her overall muscle power had gradually improved to grade 3/5, and she was able to walk with the aid of a rehabilitation walking assistance vehicle. To date, the patient has not experienced any other AIP attacks, but she still has severe neurological sequelae.'}
|
{'Case report': 'A 37-year-old woman presented to the surgical unit of a general teaching hospital with abdominal pain that she experienced while walking to the hospital (May 2019). Her symptoms had started 4 months previously (January 2019). The initial symptoms included recurring abdominal pain and bloating (almost once per month). During this period, the patient visited her local clinic several times, without obtaining a clear diagnosis. The patient received Chinese medicine over a long period of time and also received symptomatic treatments (e.g., enema, tramadol as analgesia), but her condition did not improve considerably. She had a history of a cesarean section in 2013, and no other notable medical history or family history of disease. On her admission assessment, an abdominal flat plate X-ray showed incomplete intestinal obstruction ( Figure 1a ), but no obvious abnormalities were observed in any other inspections. Forty-eight hours after admission, the patient suddenly developed dyspnea, muscle weakness, and a disorder of consciousness, with uncorrectable hypoxemia (SPO 2 86%), tachycardia (130 bpm), and hypotension (blood pressure 80/59 mmHg). She was transferred to the intensive care unit (ICU) for further management. Urgent arterial blood gas analysis on ICU admission indicated severe hypoxemia and respiratory acidosis (pH: 7.153, PO 2 : 66 mmHg, PCO 2 : 50.2 mmHg, and PO 2 /FiO 2 : 110 mmHg); tracheal intubation was then performed. On day 2 of ICU admission, the patient’s awareness gradually recovered and her abdominal pain spontaneously disappeared. Further examination revealed stubborn respiratory failure, meaning that the patient was unable to be removed from the ventilator. Muscle power of the limbs was 0/5 proximally and 2/5 distally. Furthermore, sensation and cranial nerve examinations were normal. Cranial computed tomography (CT) and abdominal CT did not indicate any abnormalities ( Figure 1b ), although the chest CT showed patchy exudation of the lower lungs, which did not explain the patient’s respiratory failure. Bedside ultrasound revealed that diaphragm displacement during spontaneous breathing mode was 5.4 mm, whereas normal displacement is considered to be greater than 10 mm. Blood tests showed that serum creatinine was elevated at 350.5 µmol/L (normal range: 44–133 µmol/L), and urea nitrogen was elevated at 22.23 mmol/L (normal range: 2.9–7.5 mmol/L), although these levels returned to normal soon after hemodialysis. The initial cerebrospinal fluid (CSF) examination was within the normal range, and anti-ganglioside antibodies, such as GM1 and GD1a, were negative. Furthermore, electromyography findings showed unspecific peripheral nerve damage ( Figure 2 ). The patient was treated with a course of intravenous immunoglobulin for a probable diagnosis of Guillain–Barré syndrome (GBS), but no relief was achieved. The patient’s condition continued to worsen, and on day 14 after ICU admission, her abdominal pain and constipation returned, along with changes in her neurological examination. Her overall weakness worsened, with muscle power of 0/5 (absolutely no movement) in all four limbs. Furthermore, a cranial nerve examination showed new nasal and labial asymmetry, and her eyelids were unable to close. Abdominal CT at this time showed extensive colonic expansion ( Figure 1c ). Another CSF examination was performed, but the results remained normal, with no cytoalbuminologic dissociation. It was also noted that the color of the patient’s urine turned visibly reddish on exposure to sunlight ( Figure 3 ). A diagnosis of AIP was finally confirmed by genetic analysis, which identified a missense mutation: c.541C>T, encoding p. Gln181 in the HMBS gene ( Figure 4 ). Targeted mutation analysis was then performed in her two children, but neither of them carried the disease-causing gene. Because heme arginate is not available in mainland China, the patient was treated with intravenous glucose infusion (50%). Twenty-four hours after glucose medication, her abdominal pain was alleviated and her urine returned to a normal color; however, her peripheral neuropathy did not markedly improve. After 2 weeks of treatment, the tracheal tube was removed. The patient was then transferred back to her local hospital for rehabilitation training because of the poor muscle strength in her limbs. At the 1-year follow-up, her overall muscle power had gradually improved to grade 3/5, and she was able to walk with the aid of a rehabilitation walking assistance vehicle. To date, the patient has not experienced any other AIP attacks, but she still has severe neurological sequelae.'}
|
Eyes-Ears-Nose-Throat
|
EENT
|
[] |
test-2082
|
7809922
|
{'Case report': 'A 37-year-old woman presented to the surgical unit of a general teaching hospital with abdominal pain that she experienced while walking to the hospital (May 2019). Her symptoms had started 4 months previously (January 2019). The initial symptoms included recurring abdominal pain and bloating (almost once per month). During this period, the patient visited her local clinic several times, without obtaining a clear diagnosis. The patient received Chinese medicine over a long period of time and also received symptomatic treatments (e.g., enema, tramadol as analgesia), but her condition did not improve considerably. She had a history of a cesarean section in 2013, and no other notable medical history or family history of disease. On her admission assessment, an abdominal flat plate X-ray showed incomplete intestinal obstruction ( Figure 1a ), but no obvious abnormalities were observed in any other inspections. Forty-eight hours after admission, the patient suddenly developed dyspnea, muscle weakness, and a disorder of consciousness, with uncorrectable hypoxemia (SPO 2 86%), tachycardia (130 bpm), and hypotension (blood pressure 80/59 mmHg). She was transferred to the intensive care unit (ICU) for further management. Urgent arterial blood gas analysis on ICU admission indicated severe hypoxemia and respiratory acidosis (pH: 7.153, PO 2 : 66 mmHg, PCO 2 : 50.2 mmHg, and PO 2 /FiO 2 : 110 mmHg); tracheal intubation was then performed. On day 2 of ICU admission, the patient’s awareness gradually recovered and her abdominal pain spontaneously disappeared. Further examination revealed stubborn respiratory failure, meaning that the patient was unable to be removed from the ventilator. Muscle power of the limbs was 0/5 proximally and 2/5 distally. Furthermore, sensation and cranial nerve examinations were normal. Cranial computed tomography (CT) and abdominal CT did not indicate any abnormalities ( Figure 1b ), although the chest CT showed patchy exudation of the lower lungs, which did not explain the patient’s respiratory failure. Bedside ultrasound revealed that diaphragm displacement during spontaneous breathing mode was 5.4 mm, whereas normal displacement is considered to be greater than 10 mm. Blood tests showed that serum creatinine was elevated at 350.5 µmol/L (normal range: 44–133 µmol/L), and urea nitrogen was elevated at 22.23 mmol/L (normal range: 2.9–7.5 mmol/L), although these levels returned to normal soon after hemodialysis. The initial cerebrospinal fluid (CSF) examination was within the normal range, and anti-ganglioside antibodies, such as GM1 and GD1a, were negative. Furthermore, electromyography findings showed unspecific peripheral nerve damage ( Figure 2 ). The patient was treated with a course of intravenous immunoglobulin for a probable diagnosis of Guillain–Barré syndrome (GBS), but no relief was achieved. The patient’s condition continued to worsen, and on day 14 after ICU admission, her abdominal pain and constipation returned, along with changes in her neurological examination. Her overall weakness worsened, with muscle power of 0/5 (absolutely no movement) in all four limbs. Furthermore, a cranial nerve examination showed new nasal and labial asymmetry, and her eyelids were unable to close. Abdominal CT at this time showed extensive colonic expansion ( Figure 1c ). Another CSF examination was performed, but the results remained normal, with no cytoalbuminologic dissociation. It was also noted that the color of the patient’s urine turned visibly reddish on exposure to sunlight ( Figure 3 ). A diagnosis of AIP was finally confirmed by genetic analysis, which identified a missense mutation: c.541C>T, encoding p. Gln181 in the HMBS gene ( Figure 4 ). Targeted mutation analysis was then performed in her two children, but neither of them carried the disease-causing gene. Because heme arginate is not available in mainland China, the patient was treated with intravenous glucose infusion (50%). Twenty-four hours after glucose medication, her abdominal pain was alleviated and her urine returned to a normal color; however, her peripheral neuropathy did not markedly improve. After 2 weeks of treatment, the tracheal tube was removed. The patient was then transferred back to her local hospital for rehabilitation training because of the poor muscle strength in her limbs. At the 1-year follow-up, her overall muscle power had gradually improved to grade 3/5, and she was able to walk with the aid of a rehabilitation walking assistance vehicle. To date, the patient has not experienced any other AIP attacks, but she still has severe neurological sequelae.'}
|
{'Case report': 'A 37-year-old woman presented to the surgical unit of a general teaching hospital with abdominal pain that she experienced while walking to the hospital (May 2019). Her symptoms had started 4 months previously (January 2019). The initial symptoms included recurring abdominal pain and bloating (almost once per month). During this period, the patient visited her local clinic several times, without obtaining a clear diagnosis. The patient received Chinese medicine over a long period of time and also received symptomatic treatments (e.g., enema, tramadol as analgesia), but her condition did not improve considerably. She had a history of a cesarean section in 2013, and no other notable medical history or family history of disease. On her admission assessment, an abdominal flat plate X-ray showed incomplete intestinal obstruction ( Figure 1a ), but no obvious abnormalities were observed in any other inspections. Forty-eight hours after admission, the patient suddenly developed dyspnea, muscle weakness, and a disorder of consciousness, with uncorrectable hypoxemia (SPO 2 86%), tachycardia (130 bpm), and hypotension (blood pressure 80/59 mmHg). She was transferred to the intensive care unit (ICU) for further management. Urgent arterial blood gas analysis on ICU admission indicated severe hypoxemia and respiratory acidosis (pH: 7.153, PO 2 : 66 mmHg, PCO 2 : 50.2 mmHg, and PO 2 /FiO 2 : 110 mmHg); tracheal intubation was then performed. On day 2 of ICU admission, the patient’s awareness gradually recovered and her abdominal pain spontaneously disappeared. Further examination revealed stubborn respiratory failure, meaning that the patient was unable to be removed from the ventilator. Muscle power of the limbs was 0/5 proximally and 2/5 distally. Furthermore, sensation and cranial nerve examinations were normal. Cranial computed tomography (CT) and abdominal CT did not indicate any abnormalities ( Figure 1b ), although the chest CT showed patchy exudation of the lower lungs, which did not explain the patient’s respiratory failure. Bedside ultrasound revealed that diaphragm displacement during spontaneous breathing mode was 5.4 mm, whereas normal displacement is considered to be greater than 10 mm. Blood tests showed that serum creatinine was elevated at 350.5 µmol/L (normal range: 44–133 µmol/L), and urea nitrogen was elevated at 22.23 mmol/L (normal range: 2.9–7.5 mmol/L), although these levels returned to normal soon after hemodialysis. The initial cerebrospinal fluid (CSF) examination was within the normal range, and anti-ganglioside antibodies, such as GM1 and GD1a, were negative. Furthermore, electromyography findings showed unspecific peripheral nerve damage ( Figure 2 ). The patient was treated with a course of intravenous immunoglobulin for a probable diagnosis of Guillain–Barré syndrome (GBS), but no relief was achieved. The patient’s condition continued to worsen, and on day 14 after ICU admission, her abdominal pain and constipation returned, along with changes in her neurological examination. Her overall weakness worsened, with muscle power of 0/5 (absolutely no movement) in all four limbs. Furthermore, a cranial nerve examination showed new nasal and labial asymmetry, and her eyelids were unable to close. Abdominal CT at this time showed extensive colonic expansion ( Figure 1c ). Another CSF examination was performed, but the results remained normal, with no cytoalbuminologic dissociation. It was also noted that the color of the patient’s urine turned visibly reddish on exposure to sunlight ( Figure 3 ). A diagnosis of AIP was finally confirmed by genetic analysis, which identified a missense mutation: c.541C>T, encoding p. Gln181 in the HMBS gene ( Figure 4 ). Targeted mutation analysis was then performed in her two children, but neither of them carried the disease-causing gene. Because heme arginate is not available in mainland China, the patient was treated with intravenous glucose infusion (50%). Twenty-four hours after glucose medication, her abdominal pain was alleviated and her urine returned to a normal color; however, her peripheral neuropathy did not markedly improve. After 2 weeks of treatment, the tracheal tube was removed. The patient was then transferred back to her local hospital for rehabilitation training because of the poor muscle strength in her limbs. At the 1-year follow-up, her overall muscle power had gradually improved to grade 3/5, and she was able to walk with the aid of a rehabilitation walking assistance vehicle. To date, the patient has not experienced any other AIP attacks, but she still has severe neurological sequelae.'}
|
Dermatology
|
DERM
|
[] |
test-2083
|
7809922
|
{'Case report': 'A 37-year-old woman presented to the surgical unit of a general teaching hospital with abdominal pain that she experienced while walking to the hospital (May 2019). Her symptoms had started 4 months previously (January 2019). The initial symptoms included recurring abdominal pain and bloating (almost once per month). During this period, the patient visited her local clinic several times, without obtaining a clear diagnosis. The patient received Chinese medicine over a long period of time and also received symptomatic treatments (e.g., enema, tramadol as analgesia), but her condition did not improve considerably. She had a history of a cesarean section in 2013, and no other notable medical history or family history of disease. On her admission assessment, an abdominal flat plate X-ray showed incomplete intestinal obstruction ( Figure 1a ), but no obvious abnormalities were observed in any other inspections. Forty-eight hours after admission, the patient suddenly developed dyspnea, muscle weakness, and a disorder of consciousness, with uncorrectable hypoxemia (SPO 2 86%), tachycardia (130 bpm), and hypotension (blood pressure 80/59 mmHg). She was transferred to the intensive care unit (ICU) for further management. Urgent arterial blood gas analysis on ICU admission indicated severe hypoxemia and respiratory acidosis (pH: 7.153, PO 2 : 66 mmHg, PCO 2 : 50.2 mmHg, and PO 2 /FiO 2 : 110 mmHg); tracheal intubation was then performed. On day 2 of ICU admission, the patient’s awareness gradually recovered and her abdominal pain spontaneously disappeared. Further examination revealed stubborn respiratory failure, meaning that the patient was unable to be removed from the ventilator. Muscle power of the limbs was 0/5 proximally and 2/5 distally. Furthermore, sensation and cranial nerve examinations were normal. Cranial computed tomography (CT) and abdominal CT did not indicate any abnormalities ( Figure 1b ), although the chest CT showed patchy exudation of the lower lungs, which did not explain the patient’s respiratory failure. Bedside ultrasound revealed that diaphragm displacement during spontaneous breathing mode was 5.4 mm, whereas normal displacement is considered to be greater than 10 mm. Blood tests showed that serum creatinine was elevated at 350.5 µmol/L (normal range: 44–133 µmol/L), and urea nitrogen was elevated at 22.23 mmol/L (normal range: 2.9–7.5 mmol/L), although these levels returned to normal soon after hemodialysis. The initial cerebrospinal fluid (CSF) examination was within the normal range, and anti-ganglioside antibodies, such as GM1 and GD1a, were negative. Furthermore, electromyography findings showed unspecific peripheral nerve damage ( Figure 2 ). The patient was treated with a course of intravenous immunoglobulin for a probable diagnosis of Guillain–Barré syndrome (GBS), but no relief was achieved. The patient’s condition continued to worsen, and on day 14 after ICU admission, her abdominal pain and constipation returned, along with changes in her neurological examination. Her overall weakness worsened, with muscle power of 0/5 (absolutely no movement) in all four limbs. Furthermore, a cranial nerve examination showed new nasal and labial asymmetry, and her eyelids were unable to close. Abdominal CT at this time showed extensive colonic expansion ( Figure 1c ). Another CSF examination was performed, but the results remained normal, with no cytoalbuminologic dissociation. It was also noted that the color of the patient’s urine turned visibly reddish on exposure to sunlight ( Figure 3 ). A diagnosis of AIP was finally confirmed by genetic analysis, which identified a missense mutation: c.541C>T, encoding p. Gln181 in the HMBS gene ( Figure 4 ). Targeted mutation analysis was then performed in her two children, but neither of them carried the disease-causing gene. Because heme arginate is not available in mainland China, the patient was treated with intravenous glucose infusion (50%). Twenty-four hours after glucose medication, her abdominal pain was alleviated and her urine returned to a normal color; however, her peripheral neuropathy did not markedly improve. After 2 weeks of treatment, the tracheal tube was removed. The patient was then transferred back to her local hospital for rehabilitation training because of the poor muscle strength in her limbs. At the 1-year follow-up, her overall muscle power had gradually improved to grade 3/5, and she was able to walk with the aid of a rehabilitation walking assistance vehicle. To date, the patient has not experienced any other AIP attacks, but she still has severe neurological sequelae.'}
|
{'Case report': 'A 37-year-old woman presented to the surgical unit of a general teaching hospital with abdominal pain that she experienced while walking to the hospital (May 2019). Her symptoms had started 4 months previously (January 2019). The initial symptoms included recurring abdominal pain and bloating (almost once per month). During this period, the patient visited her local clinic several times, without obtaining a clear diagnosis. The patient received Chinese medicine over a long period of time and also received symptomatic treatments (e.g., enema, tramadol as analgesia), but her condition did not improve considerably. She had a history of a cesarean section in 2013, and no other notable medical history or family history of disease. On her admission assessment, an abdominal flat plate X-ray showed incomplete intestinal obstruction ( Figure 1a ), but no obvious abnormalities were observed in any other inspections. Forty-eight hours after admission, the patient suddenly developed dyspnea, muscle weakness, and a disorder of consciousness, with uncorrectable hypoxemia (SPO 2 86%), tachycardia (130 bpm), and hypotension (blood pressure 80/59 mmHg). She was transferred to the intensive care unit (ICU) for further management. Urgent arterial blood gas analysis on ICU admission indicated severe hypoxemia and respiratory acidosis (pH: 7.153, PO 2 : 66 mmHg, PCO 2 : 50.2 mmHg, and PO 2 /FiO 2 : 110 mmHg); tracheal intubation was then performed. On day 2 of ICU admission, the patient’s awareness gradually recovered and her abdominal pain spontaneously disappeared. Further examination revealed stubborn respiratory failure, meaning that the patient was unable to be removed from the ventilator. Muscle power of the limbs was 0/5 proximally and 2/5 distally. Furthermore, sensation and cranial nerve examinations were normal. Cranial computed tomography (CT) and abdominal CT did not indicate any abnormalities ( Figure 1b ), although the chest CT showed patchy exudation of the lower lungs, which did not explain the patient’s respiratory failure. Bedside ultrasound revealed that diaphragm displacement during spontaneous breathing mode was 5.4 mm, whereas normal displacement is considered to be greater than 10 mm. Blood tests showed that serum creatinine was elevated at 350.5 µmol/L (normal range: 44–133 µmol/L), and urea nitrogen was elevated at 22.23 mmol/L (normal range: 2.9–7.5 mmol/L), although these levels returned to normal soon after hemodialysis. The initial cerebrospinal fluid (CSF) examination was within the normal range, and anti-ganglioside antibodies, such as GM1 and GD1a, were negative. Furthermore, electromyography findings showed unspecific peripheral nerve damage ( Figure 2 ). The patient was treated with a course of intravenous immunoglobulin for a probable diagnosis of Guillain–Barré syndrome (GBS), but no relief was achieved. The patient’s condition continued to worsen, and on day 14 after ICU admission, her abdominal pain and constipation returned, along with changes in her neurological examination. Her overall weakness worsened, with muscle power of 0/5 (absolutely no movement) in all four limbs. Furthermore, a cranial nerve examination showed new nasal and labial asymmetry, and her eyelids were unable to close. Abdominal CT at this time showed extensive colonic expansion ( Figure 1c ). Another CSF examination was performed, but the results remained normal, with no cytoalbuminologic dissociation. It was also noted that the color of the patient’s urine turned visibly reddish on exposure to sunlight ( Figure 3 ). A diagnosis of AIP was finally confirmed by genetic analysis, which identified a missense mutation: c.541C>T, encoding p. Gln181 in the HMBS gene ( Figure 4 ). Targeted mutation analysis was then performed in her two children, but neither of them carried the disease-causing gene. Because heme arginate is not available in mainland China, the patient was treated with intravenous glucose infusion (50%). Twenty-four hours after glucose medication, her abdominal pain was alleviated and her urine returned to a normal color; however, her peripheral neuropathy did not markedly improve. After 2 weeks of treatment, the tracheal tube was removed. The patient was then transferred back to her local hospital for rehabilitation training because of the poor muscle strength in her limbs. At the 1-year follow-up, her overall muscle power had gradually improved to grade 3/5, and she was able to walk with the aid of a rehabilitation walking assistance vehicle. To date, the patient has not experienced any other AIP attacks, but she still has severe neurological sequelae.'}
|
Pregnancy
|
Pregnancy
|
[] |
test-2084
|
7809922
|
{'Case report': 'A 37-year-old woman presented to the surgical unit of a general teaching hospital with abdominal pain that she experienced while walking to the hospital (May 2019). Her symptoms had started 4 months previously (January 2019). The initial symptoms included recurring abdominal pain and bloating (almost once per month). During this period, the patient visited her local clinic several times, without obtaining a clear diagnosis. The patient received Chinese medicine over a long period of time and also received symptomatic treatments (e.g., enema, tramadol as analgesia), but her condition did not improve considerably. She had a history of a cesarean section in 2013, and no other notable medical history or family history of disease. On her admission assessment, an abdominal flat plate X-ray showed incomplete intestinal obstruction ( Figure 1a ), but no obvious abnormalities were observed in any other inspections. Forty-eight hours after admission, the patient suddenly developed dyspnea, muscle weakness, and a disorder of consciousness, with uncorrectable hypoxemia (SPO 2 86%), tachycardia (130 bpm), and hypotension (blood pressure 80/59 mmHg). She was transferred to the intensive care unit (ICU) for further management. Urgent arterial blood gas analysis on ICU admission indicated severe hypoxemia and respiratory acidosis (pH: 7.153, PO 2 : 66 mmHg, PCO 2 : 50.2 mmHg, and PO 2 /FiO 2 : 110 mmHg); tracheal intubation was then performed. On day 2 of ICU admission, the patient’s awareness gradually recovered and her abdominal pain spontaneously disappeared. Further examination revealed stubborn respiratory failure, meaning that the patient was unable to be removed from the ventilator. Muscle power of the limbs was 0/5 proximally and 2/5 distally. Furthermore, sensation and cranial nerve examinations were normal. Cranial computed tomography (CT) and abdominal CT did not indicate any abnormalities ( Figure 1b ), although the chest CT showed patchy exudation of the lower lungs, which did not explain the patient’s respiratory failure. Bedside ultrasound revealed that diaphragm displacement during spontaneous breathing mode was 5.4 mm, whereas normal displacement is considered to be greater than 10 mm. Blood tests showed that serum creatinine was elevated at 350.5 µmol/L (normal range: 44–133 µmol/L), and urea nitrogen was elevated at 22.23 mmol/L (normal range: 2.9–7.5 mmol/L), although these levels returned to normal soon after hemodialysis. The initial cerebrospinal fluid (CSF) examination was within the normal range, and anti-ganglioside antibodies, such as GM1 and GD1a, were negative. Furthermore, electromyography findings showed unspecific peripheral nerve damage ( Figure 2 ). The patient was treated with a course of intravenous immunoglobulin for a probable diagnosis of Guillain–Barré syndrome (GBS), but no relief was achieved. The patient’s condition continued to worsen, and on day 14 after ICU admission, her abdominal pain and constipation returned, along with changes in her neurological examination. Her overall weakness worsened, with muscle power of 0/5 (absolutely no movement) in all four limbs. Furthermore, a cranial nerve examination showed new nasal and labial asymmetry, and her eyelids were unable to close. Abdominal CT at this time showed extensive colonic expansion ( Figure 1c ). Another CSF examination was performed, but the results remained normal, with no cytoalbuminologic dissociation. It was also noted that the color of the patient’s urine turned visibly reddish on exposure to sunlight ( Figure 3 ). A diagnosis of AIP was finally confirmed by genetic analysis, which identified a missense mutation: c.541C>T, encoding p. Gln181 in the HMBS gene ( Figure 4 ). Targeted mutation analysis was then performed in her two children, but neither of them carried the disease-causing gene. Because heme arginate is not available in mainland China, the patient was treated with intravenous glucose infusion (50%). Twenty-four hours after glucose medication, her abdominal pain was alleviated and her urine returned to a normal color; however, her peripheral neuropathy did not markedly improve. After 2 weeks of treatment, the tracheal tube was removed. The patient was then transferred back to her local hospital for rehabilitation training because of the poor muscle strength in her limbs. At the 1-year follow-up, her overall muscle power had gradually improved to grade 3/5, and she was able to walk with the aid of a rehabilitation walking assistance vehicle. To date, the patient has not experienced any other AIP attacks, but she still has severe neurological sequelae.'}
|
{'Case report': 'A 37-year-old woman presented to the surgical unit of a general teaching hospital with abdominal pain that she experienced while walking to the hospital (May 2019). Her symptoms had started 4 months previously (January 2019). The initial symptoms included recurring abdominal pain and bloating (almost once per month). During this period, the patient visited her local clinic several times, without obtaining a clear diagnosis. The patient received Chinese medicine over a long period of time and also received symptomatic treatments (e.g., enema, tramadol as analgesia), but her condition did not improve considerably. She had a history of a cesarean section in 2013, and no other notable medical history or family history of disease. On her admission assessment, an abdominal flat plate X-ray showed incomplete intestinal obstruction ( Figure 1a ), but no obvious abnormalities were observed in any other inspections. Forty-eight hours after admission, the patient suddenly developed dyspnea, muscle weakness, and a disorder of consciousness, with uncorrectable hypoxemia (SPO 2 86%), tachycardia (130 bpm), and hypotension (blood pressure 80/59 mmHg). She was transferred to the intensive care unit (ICU) for further management. Urgent arterial blood gas analysis on ICU admission indicated severe hypoxemia and respiratory acidosis (pH: 7.153, PO 2 : 66 mmHg, PCO 2 : 50.2 mmHg, and PO 2 /FiO 2 : 110 mmHg); tracheal intubation was then performed. On day 2 of ICU admission, the patient’s awareness gradually recovered and her abdominal pain spontaneously disappeared. Further examination revealed stubborn respiratory failure, meaning that the patient was unable to be removed from the ventilator. Muscle power of the limbs was 0/5 proximally and 2/5 distally. Furthermore, sensation and cranial nerve examinations were normal. Cranial computed tomography (CT) and abdominal CT did not indicate any abnormalities ( Figure 1b ), although the chest CT showed patchy exudation of the lower lungs, which did not explain the patient’s respiratory failure. Bedside ultrasound revealed that diaphragm displacement during spontaneous breathing mode was 5.4 mm, whereas normal displacement is considered to be greater than 10 mm. Blood tests showed that serum creatinine was elevated at 350.5 µmol/L (normal range: 44–133 µmol/L), and urea nitrogen was elevated at 22.23 mmol/L (normal range: 2.9–7.5 mmol/L), although these levels returned to normal soon after hemodialysis. The initial cerebrospinal fluid (CSF) examination was within the normal range, and anti-ganglioside antibodies, such as GM1 and GD1a, were negative. Furthermore, electromyography findings showed unspecific peripheral nerve damage ( Figure 2 ). The patient was treated with a course of intravenous immunoglobulin for a probable diagnosis of Guillain–Barré syndrome (GBS), but no relief was achieved. The patient’s condition continued to worsen, and on day 14 after ICU admission, her abdominal pain and constipation returned, along with changes in her neurological examination. Her overall weakness worsened, with muscle power of 0/5 (absolutely no movement) in all four limbs. Furthermore, a cranial nerve examination showed new nasal and labial asymmetry, and her eyelids were unable to close. Abdominal CT at this time showed extensive colonic expansion ( Figure 1c ). Another CSF examination was performed, but the results remained normal, with no cytoalbuminologic dissociation. It was also noted that the color of the patient’s urine turned visibly reddish on exposure to sunlight ( Figure 3 ). A diagnosis of AIP was finally confirmed by genetic analysis, which identified a missense mutation: c.541C>T, encoding p. Gln181 in the HMBS gene ( Figure 4 ). Targeted mutation analysis was then performed in her two children, but neither of them carried the disease-causing gene. Because heme arginate is not available in mainland China, the patient was treated with intravenous glucose infusion (50%). Twenty-four hours after glucose medication, her abdominal pain was alleviated and her urine returned to a normal color; however, her peripheral neuropathy did not markedly improve. After 2 weeks of treatment, the tracheal tube was removed. The patient was then transferred back to her local hospital for rehabilitation training because of the poor muscle strength in her limbs. At the 1-year follow-up, her overall muscle power had gradually improved to grade 3/5, and she was able to walk with the aid of a rehabilitation walking assistance vehicle. To date, the patient has not experienced any other AIP attacks, but she still has severe neurological sequelae.'}
|
Lymphatic-System
|
LYMPH
|
[] |
test-2085
|
7809922
|
{'Case report': 'A 37-year-old woman presented to the surgical unit of a general teaching hospital with abdominal pain that she experienced while walking to the hospital (May 2019). Her symptoms had started 4 months previously (January 2019). The initial symptoms included recurring abdominal pain and bloating (almost once per month). During this period, the patient visited her local clinic several times, without obtaining a clear diagnosis. The patient received Chinese medicine over a long period of time and also received symptomatic treatments (e.g., enema, tramadol as analgesia), but her condition did not improve considerably. She had a history of a cesarean section in 2013, and no other notable medical history or family history of disease. On her admission assessment, an abdominal flat plate X-ray showed incomplete intestinal obstruction ( Figure 1a ), but no obvious abnormalities were observed in any other inspections. Forty-eight hours after admission, the patient suddenly developed dyspnea, muscle weakness, and a disorder of consciousness, with uncorrectable hypoxemia (SPO 2 86%), tachycardia (130 bpm), and hypotension (blood pressure 80/59 mmHg). She was transferred to the intensive care unit (ICU) for further management. Urgent arterial blood gas analysis on ICU admission indicated severe hypoxemia and respiratory acidosis (pH: 7.153, PO 2 : 66 mmHg, PCO 2 : 50.2 mmHg, and PO 2 /FiO 2 : 110 mmHg); tracheal intubation was then performed. On day 2 of ICU admission, the patient’s awareness gradually recovered and her abdominal pain spontaneously disappeared. Further examination revealed stubborn respiratory failure, meaning that the patient was unable to be removed from the ventilator. Muscle power of the limbs was 0/5 proximally and 2/5 distally. Furthermore, sensation and cranial nerve examinations were normal. Cranial computed tomography (CT) and abdominal CT did not indicate any abnormalities ( Figure 1b ), although the chest CT showed patchy exudation of the lower lungs, which did not explain the patient’s respiratory failure. Bedside ultrasound revealed that diaphragm displacement during spontaneous breathing mode was 5.4 mm, whereas normal displacement is considered to be greater than 10 mm. Blood tests showed that serum creatinine was elevated at 350.5 µmol/L (normal range: 44–133 µmol/L), and urea nitrogen was elevated at 22.23 mmol/L (normal range: 2.9–7.5 mmol/L), although these levels returned to normal soon after hemodialysis. The initial cerebrospinal fluid (CSF) examination was within the normal range, and anti-ganglioside antibodies, such as GM1 and GD1a, were negative. Furthermore, electromyography findings showed unspecific peripheral nerve damage ( Figure 2 ). The patient was treated with a course of intravenous immunoglobulin for a probable diagnosis of Guillain–Barré syndrome (GBS), but no relief was achieved. The patient’s condition continued to worsen, and on day 14 after ICU admission, her abdominal pain and constipation returned, along with changes in her neurological examination. Her overall weakness worsened, with muscle power of 0/5 (absolutely no movement) in all four limbs. Furthermore, a cranial nerve examination showed new nasal and labial asymmetry, and her eyelids were unable to close. Abdominal CT at this time showed extensive colonic expansion ( Figure 1c ). Another CSF examination was performed, but the results remained normal, with no cytoalbuminologic dissociation. It was also noted that the color of the patient’s urine turned visibly reddish on exposure to sunlight ( Figure 3 ). A diagnosis of AIP was finally confirmed by genetic analysis, which identified a missense mutation: c.541C>T, encoding p. Gln181 in the HMBS gene ( Figure 4 ). Targeted mutation analysis was then performed in her two children, but neither of them carried the disease-causing gene. Because heme arginate is not available in mainland China, the patient was treated with intravenous glucose infusion (50%). Twenty-four hours after glucose medication, her abdominal pain was alleviated and her urine returned to a normal color; however, her peripheral neuropathy did not markedly improve. After 2 weeks of treatment, the tracheal tube was removed. The patient was then transferred back to her local hospital for rehabilitation training because of the poor muscle strength in her limbs. At the 1-year follow-up, her overall muscle power had gradually improved to grade 3/5, and she was able to walk with the aid of a rehabilitation walking assistance vehicle. To date, the patient has not experienced any other AIP attacks, but she still has severe neurological sequelae.'}
|
{'Case report': 'A 37-year-old woman presented to the surgical unit of a general teaching hospital with abdominal pain that she experienced while walking to the hospital (May 2019). Her symptoms had started 4 months previously (January 2019). The initial symptoms included recurring abdominal pain and bloating (almost once per month). During this period, the patient visited her local clinic several times, without obtaining a clear diagnosis. The patient received Chinese medicine over a long period of time and also received symptomatic treatments (e.g., enema, tramadol as analgesia), but her condition did not improve considerably. She had a history of a cesarean section in 2013, and no other notable medical history or family history of disease. On her admission assessment, an abdominal flat plate X-ray showed incomplete intestinal obstruction ( Figure 1a ), but no obvious abnormalities were observed in any other inspections. Forty-eight hours after admission, the patient suddenly developed dyspnea, muscle weakness, and a disorder of consciousness, with uncorrectable hypoxemia (SPO 2 86%), tachycardia (130 bpm), and hypotension (blood pressure 80/59 mmHg). She was transferred to the intensive care unit (ICU) for further management. Urgent arterial blood gas analysis on ICU admission indicated severe hypoxemia and respiratory acidosis (pH: 7.153, PO 2 : 66 mmHg, PCO 2 : 50.2 mmHg, and PO 2 /FiO 2 : 110 mmHg); tracheal intubation was then performed. On day 2 of ICU admission, the patient’s awareness gradually recovered and her abdominal pain spontaneously disappeared. Further examination revealed stubborn respiratory failure, meaning that the patient was unable to be removed from the ventilator. Muscle power of the limbs was 0/5 proximally and 2/5 distally. Furthermore, sensation and cranial nerve examinations were normal. Cranial computed tomography (CT) and abdominal CT did not indicate any abnormalities ( Figure 1b ), although the chest CT showed patchy exudation of the lower lungs, which did not explain the patient’s respiratory failure. Bedside ultrasound revealed that diaphragm displacement during spontaneous breathing mode was 5.4 mm, whereas normal displacement is considered to be greater than 10 mm. Blood tests showed that serum creatinine was elevated at 350.5 µmol/L (normal range: 44–133 µmol/L), and urea nitrogen was elevated at 22.23 mmol/L (normal range: 2.9–7.5 mmol/L), although these levels returned to normal soon after hemodialysis. The initial cerebrospinal fluid (CSF) examination was within the normal range, and anti-ganglioside antibodies, such as GM1 and GD1a, were negative. Furthermore, electromyography findings showed unspecific peripheral nerve damage ( Figure 2 ). The patient was treated with a course of intravenous immunoglobulin for a probable diagnosis of Guillain–Barré syndrome (GBS), but no relief was achieved. The patient’s condition continued to worsen, and on day 14 after ICU admission, her abdominal pain and constipation returned, along with changes in her neurological examination. Her overall weakness worsened, with muscle power of 0/5 (absolutely no movement) in all four limbs. Furthermore, a cranial nerve examination showed new nasal and labial asymmetry, and her eyelids were unable to close. Abdominal CT at this time showed extensive colonic expansion ( Figure 1c ). Another CSF examination was performed, but the results remained normal, with no cytoalbuminologic dissociation. It was also noted that the color of the patient’s urine turned visibly reddish on exposure to sunlight ( Figure 3 ). A diagnosis of AIP was finally confirmed by genetic analysis, which identified a missense mutation: c.541C>T, encoding p. Gln181 in the HMBS gene ( Figure 4 ). Targeted mutation analysis was then performed in her two children, but neither of them carried the disease-causing gene. Because heme arginate is not available in mainland China, the patient was treated with intravenous glucose infusion (50%). Twenty-four hours after glucose medication, her abdominal pain was alleviated and her urine returned to a normal color; however, her peripheral neuropathy did not markedly improve. After 2 weeks of treatment, the tracheal tube was removed. The patient was then transferred back to her local hospital for rehabilitation training because of the poor muscle strength in her limbs. At the 1-year follow-up, her overall muscle power had gradually improved to grade 3/5, and she was able to walk with the aid of a rehabilitation walking assistance vehicle. To date, the patient has not experienced any other AIP attacks, but she still has severe neurological sequelae.'}
|
Age-at-Presentation
|
Age (at case presentation)
|
[
"37 - year - old"
] |
test-2086
|
7809922
|
{'Case report': 'A 37-year-old woman presented to the surgical unit of a general teaching hospital with abdominal pain that she experienced while walking to the hospital (May 2019). Her symptoms had started 4 months previously (January 2019). The initial symptoms included recurring abdominal pain and bloating (almost once per month). During this period, the patient visited her local clinic several times, without obtaining a clear diagnosis. The patient received Chinese medicine over a long period of time and also received symptomatic treatments (e.g., enema, tramadol as analgesia), but her condition did not improve considerably. She had a history of a cesarean section in 2013, and no other notable medical history or family history of disease. On her admission assessment, an abdominal flat plate X-ray showed incomplete intestinal obstruction ( Figure 1a ), but no obvious abnormalities were observed in any other inspections. Forty-eight hours after admission, the patient suddenly developed dyspnea, muscle weakness, and a disorder of consciousness, with uncorrectable hypoxemia (SPO 2 86%), tachycardia (130 bpm), and hypotension (blood pressure 80/59 mmHg). She was transferred to the intensive care unit (ICU) for further management. Urgent arterial blood gas analysis on ICU admission indicated severe hypoxemia and respiratory acidosis (pH: 7.153, PO 2 : 66 mmHg, PCO 2 : 50.2 mmHg, and PO 2 /FiO 2 : 110 mmHg); tracheal intubation was then performed. On day 2 of ICU admission, the patient’s awareness gradually recovered and her abdominal pain spontaneously disappeared. Further examination revealed stubborn respiratory failure, meaning that the patient was unable to be removed from the ventilator. Muscle power of the limbs was 0/5 proximally and 2/5 distally. Furthermore, sensation and cranial nerve examinations were normal. Cranial computed tomography (CT) and abdominal CT did not indicate any abnormalities ( Figure 1b ), although the chest CT showed patchy exudation of the lower lungs, which did not explain the patient’s respiratory failure. Bedside ultrasound revealed that diaphragm displacement during spontaneous breathing mode was 5.4 mm, whereas normal displacement is considered to be greater than 10 mm. Blood tests showed that serum creatinine was elevated at 350.5 µmol/L (normal range: 44–133 µmol/L), and urea nitrogen was elevated at 22.23 mmol/L (normal range: 2.9–7.5 mmol/L), although these levels returned to normal soon after hemodialysis. The initial cerebrospinal fluid (CSF) examination was within the normal range, and anti-ganglioside antibodies, such as GM1 and GD1a, were negative. Furthermore, electromyography findings showed unspecific peripheral nerve damage ( Figure 2 ). The patient was treated with a course of intravenous immunoglobulin for a probable diagnosis of Guillain–Barré syndrome (GBS), but no relief was achieved. The patient’s condition continued to worsen, and on day 14 after ICU admission, her abdominal pain and constipation returned, along with changes in her neurological examination. Her overall weakness worsened, with muscle power of 0/5 (absolutely no movement) in all four limbs. Furthermore, a cranial nerve examination showed new nasal and labial asymmetry, and her eyelids were unable to close. Abdominal CT at this time showed extensive colonic expansion ( Figure 1c ). Another CSF examination was performed, but the results remained normal, with no cytoalbuminologic dissociation. It was also noted that the color of the patient’s urine turned visibly reddish on exposure to sunlight ( Figure 3 ). A diagnosis of AIP was finally confirmed by genetic analysis, which identified a missense mutation: c.541C>T, encoding p. Gln181 in the HMBS gene ( Figure 4 ). Targeted mutation analysis was then performed in her two children, but neither of them carried the disease-causing gene. Because heme arginate is not available in mainland China, the patient was treated with intravenous glucose infusion (50%). Twenty-four hours after glucose medication, her abdominal pain was alleviated and her urine returned to a normal color; however, her peripheral neuropathy did not markedly improve. After 2 weeks of treatment, the tracheal tube was removed. The patient was then transferred back to her local hospital for rehabilitation training because of the poor muscle strength in her limbs. At the 1-year follow-up, her overall muscle power had gradually improved to grade 3/5, and she was able to walk with the aid of a rehabilitation walking assistance vehicle. To date, the patient has not experienced any other AIP attacks, but she still has severe neurological sequelae.'}
|
{'Case report': 'A 37-year-old woman presented to the surgical unit of a general teaching hospital with abdominal pain that she experienced while walking to the hospital (May 2019). Her symptoms had started 4 months previously (January 2019). The initial symptoms included recurring abdominal pain and bloating (almost once per month). During this period, the patient visited her local clinic several times, without obtaining a clear diagnosis. The patient received Chinese medicine over a long period of time and also received symptomatic treatments (e.g., enema, tramadol as analgesia), but her condition did not improve considerably. She had a history of a cesarean section in 2013, and no other notable medical history or family history of disease. On her admission assessment, an abdominal flat plate X-ray showed incomplete intestinal obstruction ( Figure 1a ), but no obvious abnormalities were observed in any other inspections. Forty-eight hours after admission, the patient suddenly developed dyspnea, muscle weakness, and a disorder of consciousness, with uncorrectable hypoxemia (SPO 2 86%), tachycardia (130 bpm), and hypotension (blood pressure 80/59 mmHg). She was transferred to the intensive care unit (ICU) for further management. Urgent arterial blood gas analysis on ICU admission indicated severe hypoxemia and respiratory acidosis (pH: 7.153, PO 2 : 66 mmHg, PCO 2 : 50.2 mmHg, and PO 2 /FiO 2 : 110 mmHg); tracheal intubation was then performed. On day 2 of ICU admission, the patient’s awareness gradually recovered and her abdominal pain spontaneously disappeared. Further examination revealed stubborn respiratory failure, meaning that the patient was unable to be removed from the ventilator. Muscle power of the limbs was 0/5 proximally and 2/5 distally. Furthermore, sensation and cranial nerve examinations were normal. Cranial computed tomography (CT) and abdominal CT did not indicate any abnormalities ( Figure 1b ), although the chest CT showed patchy exudation of the lower lungs, which did not explain the patient’s respiratory failure. Bedside ultrasound revealed that diaphragm displacement during spontaneous breathing mode was 5.4 mm, whereas normal displacement is considered to be greater than 10 mm. Blood tests showed that serum creatinine was elevated at 350.5 µmol/L (normal range: 44–133 µmol/L), and urea nitrogen was elevated at 22.23 mmol/L (normal range: 2.9–7.5 mmol/L), although these levels returned to normal soon after hemodialysis. The initial cerebrospinal fluid (CSF) examination was within the normal range, and anti-ganglioside antibodies, such as GM1 and GD1a, were negative. Furthermore, electromyography findings showed unspecific peripheral nerve damage ( Figure 2 ). The patient was treated with a course of intravenous immunoglobulin for a probable diagnosis of Guillain–Barré syndrome (GBS), but no relief was achieved. The patient’s condition continued to worsen, and on day 14 after ICU admission, her abdominal pain and constipation returned, along with changes in her neurological examination. Her overall weakness worsened, with muscle power of 0/5 (absolutely no movement) in all four limbs. Furthermore, a cranial nerve examination showed new nasal and labial asymmetry, and her eyelids were unable to close. Abdominal CT at this time showed extensive colonic expansion ( Figure 1c ). Another CSF examination was performed, but the results remained normal, with no cytoalbuminologic dissociation. It was also noted that the color of the patient’s urine turned visibly reddish on exposure to sunlight ( Figure 3 ). A diagnosis of AIP was finally confirmed by genetic analysis, which identified a missense mutation: c.541C>T, encoding p. Gln181 in the HMBS gene ( Figure 4 ). Targeted mutation analysis was then performed in her two children, but neither of them carried the disease-causing gene. Because heme arginate is not available in mainland China, the patient was treated with intravenous glucose infusion (50%). Twenty-four hours after glucose medication, her abdominal pain was alleviated and her urine returned to a normal color; however, her peripheral neuropathy did not markedly improve. After 2 weeks of treatment, the tracheal tube was removed. The patient was then transferred back to her local hospital for rehabilitation training because of the poor muscle strength in her limbs. At the 1-year follow-up, her overall muscle power had gradually improved to grade 3/5, and she was able to walk with the aid of a rehabilitation walking assistance vehicle. To date, the patient has not experienced any other AIP attacks, but she still has severe neurological sequelae.'}
|
Age-of-Onset
|
Age (of onset)
|
[] |
test-2087
|
7809922
|
{'Case report': 'A 37-year-old woman presented to the surgical unit of a general teaching hospital with abdominal pain that she experienced while walking to the hospital (May 2019). Her symptoms had started 4 months previously (January 2019). The initial symptoms included recurring abdominal pain and bloating (almost once per month). During this period, the patient visited her local clinic several times, without obtaining a clear diagnosis. The patient received Chinese medicine over a long period of time and also received symptomatic treatments (e.g., enema, tramadol as analgesia), but her condition did not improve considerably. She had a history of a cesarean section in 2013, and no other notable medical history or family history of disease. On her admission assessment, an abdominal flat plate X-ray showed incomplete intestinal obstruction ( Figure 1a ), but no obvious abnormalities were observed in any other inspections. Forty-eight hours after admission, the patient suddenly developed dyspnea, muscle weakness, and a disorder of consciousness, with uncorrectable hypoxemia (SPO 2 86%), tachycardia (130 bpm), and hypotension (blood pressure 80/59 mmHg). She was transferred to the intensive care unit (ICU) for further management. Urgent arterial blood gas analysis on ICU admission indicated severe hypoxemia and respiratory acidosis (pH: 7.153, PO 2 : 66 mmHg, PCO 2 : 50.2 mmHg, and PO 2 /FiO 2 : 110 mmHg); tracheal intubation was then performed. On day 2 of ICU admission, the patient’s awareness gradually recovered and her abdominal pain spontaneously disappeared. Further examination revealed stubborn respiratory failure, meaning that the patient was unable to be removed from the ventilator. Muscle power of the limbs was 0/5 proximally and 2/5 distally. Furthermore, sensation and cranial nerve examinations were normal. Cranial computed tomography (CT) and abdominal CT did not indicate any abnormalities ( Figure 1b ), although the chest CT showed patchy exudation of the lower lungs, which did not explain the patient’s respiratory failure. Bedside ultrasound revealed that diaphragm displacement during spontaneous breathing mode was 5.4 mm, whereas normal displacement is considered to be greater than 10 mm. Blood tests showed that serum creatinine was elevated at 350.5 µmol/L (normal range: 44–133 µmol/L), and urea nitrogen was elevated at 22.23 mmol/L (normal range: 2.9–7.5 mmol/L), although these levels returned to normal soon after hemodialysis. The initial cerebrospinal fluid (CSF) examination was within the normal range, and anti-ganglioside antibodies, such as GM1 and GD1a, were negative. Furthermore, electromyography findings showed unspecific peripheral nerve damage ( Figure 2 ). The patient was treated with a course of intravenous immunoglobulin for a probable diagnosis of Guillain–Barré syndrome (GBS), but no relief was achieved. The patient’s condition continued to worsen, and on day 14 after ICU admission, her abdominal pain and constipation returned, along with changes in her neurological examination. Her overall weakness worsened, with muscle power of 0/5 (absolutely no movement) in all four limbs. Furthermore, a cranial nerve examination showed new nasal and labial asymmetry, and her eyelids were unable to close. Abdominal CT at this time showed extensive colonic expansion ( Figure 1c ). Another CSF examination was performed, but the results remained normal, with no cytoalbuminologic dissociation. It was also noted that the color of the patient’s urine turned visibly reddish on exposure to sunlight ( Figure 3 ). A diagnosis of AIP was finally confirmed by genetic analysis, which identified a missense mutation: c.541C>T, encoding p. Gln181 in the HMBS gene ( Figure 4 ). Targeted mutation analysis was then performed in her two children, but neither of them carried the disease-causing gene. Because heme arginate is not available in mainland China, the patient was treated with intravenous glucose infusion (50%). Twenty-four hours after glucose medication, her abdominal pain was alleviated and her urine returned to a normal color; however, her peripheral neuropathy did not markedly improve. After 2 weeks of treatment, the tracheal tube was removed. The patient was then transferred back to her local hospital for rehabilitation training because of the poor muscle strength in her limbs. At the 1-year follow-up, her overall muscle power had gradually improved to grade 3/5, and she was able to walk with the aid of a rehabilitation walking assistance vehicle. To date, the patient has not experienced any other AIP attacks, but she still has severe neurological sequelae.'}
|
{'Case report': 'A 37-year-old woman presented to the surgical unit of a general teaching hospital with abdominal pain that she experienced while walking to the hospital (May 2019). Her symptoms had started 4 months previously (January 2019). The initial symptoms included recurring abdominal pain and bloating (almost once per month). During this period, the patient visited her local clinic several times, without obtaining a clear diagnosis. The patient received Chinese medicine over a long period of time and also received symptomatic treatments (e.g., enema, tramadol as analgesia), but her condition did not improve considerably. She had a history of a cesarean section in 2013, and no other notable medical history or family history of disease. On her admission assessment, an abdominal flat plate X-ray showed incomplete intestinal obstruction ( Figure 1a ), but no obvious abnormalities were observed in any other inspections. Forty-eight hours after admission, the patient suddenly developed dyspnea, muscle weakness, and a disorder of consciousness, with uncorrectable hypoxemia (SPO 2 86%), tachycardia (130 bpm), and hypotension (blood pressure 80/59 mmHg). She was transferred to the intensive care unit (ICU) for further management. Urgent arterial blood gas analysis on ICU admission indicated severe hypoxemia and respiratory acidosis (pH: 7.153, PO 2 : 66 mmHg, PCO 2 : 50.2 mmHg, and PO 2 /FiO 2 : 110 mmHg); tracheal intubation was then performed. On day 2 of ICU admission, the patient’s awareness gradually recovered and her abdominal pain spontaneously disappeared. Further examination revealed stubborn respiratory failure, meaning that the patient was unable to be removed from the ventilator. Muscle power of the limbs was 0/5 proximally and 2/5 distally. Furthermore, sensation and cranial nerve examinations were normal. Cranial computed tomography (CT) and abdominal CT did not indicate any abnormalities ( Figure 1b ), although the chest CT showed patchy exudation of the lower lungs, which did not explain the patient’s respiratory failure. Bedside ultrasound revealed that diaphragm displacement during spontaneous breathing mode was 5.4 mm, whereas normal displacement is considered to be greater than 10 mm. Blood tests showed that serum creatinine was elevated at 350.5 µmol/L (normal range: 44–133 µmol/L), and urea nitrogen was elevated at 22.23 mmol/L (normal range: 2.9–7.5 mmol/L), although these levels returned to normal soon after hemodialysis. The initial cerebrospinal fluid (CSF) examination was within the normal range, and anti-ganglioside antibodies, such as GM1 and GD1a, were negative. Furthermore, electromyography findings showed unspecific peripheral nerve damage ( Figure 2 ). The patient was treated with a course of intravenous immunoglobulin for a probable diagnosis of Guillain–Barré syndrome (GBS), but no relief was achieved. The patient’s condition continued to worsen, and on day 14 after ICU admission, her abdominal pain and constipation returned, along with changes in her neurological examination. Her overall weakness worsened, with muscle power of 0/5 (absolutely no movement) in all four limbs. Furthermore, a cranial nerve examination showed new nasal and labial asymmetry, and her eyelids were unable to close. Abdominal CT at this time showed extensive colonic expansion ( Figure 1c ). Another CSF examination was performed, but the results remained normal, with no cytoalbuminologic dissociation. It was also noted that the color of the patient’s urine turned visibly reddish on exposure to sunlight ( Figure 3 ). A diagnosis of AIP was finally confirmed by genetic analysis, which identified a missense mutation: c.541C>T, encoding p. Gln181 in the HMBS gene ( Figure 4 ). Targeted mutation analysis was then performed in her two children, but neither of them carried the disease-causing gene. Because heme arginate is not available in mainland China, the patient was treated with intravenous glucose infusion (50%). Twenty-four hours after glucose medication, her abdominal pain was alleviated and her urine returned to a normal color; however, her peripheral neuropathy did not markedly improve. After 2 weeks of treatment, the tracheal tube was removed. The patient was then transferred back to her local hospital for rehabilitation training because of the poor muscle strength in her limbs. At the 1-year follow-up, her overall muscle power had gradually improved to grade 3/5, and she was able to walk with the aid of a rehabilitation walking assistance vehicle. To date, the patient has not experienced any other AIP attacks, but she still has severe neurological sequelae.'}
|
Confirmed-Diagnosis-IEM
|
Confirmed_Diagnosis(IEM)
|
[
". A diagnosis of AIP was finally confirmed by genetic analysis"
] |
test-2088
|
7809922
|
{'Case report': 'A 37-year-old woman presented to the surgical unit of a general teaching hospital with abdominal pain that she experienced while walking to the hospital (May 2019). Her symptoms had started 4 months previously (January 2019). The initial symptoms included recurring abdominal pain and bloating (almost once per month). During this period, the patient visited her local clinic several times, without obtaining a clear diagnosis. The patient received Chinese medicine over a long period of time and also received symptomatic treatments (e.g., enema, tramadol as analgesia), but her condition did not improve considerably. She had a history of a cesarean section in 2013, and no other notable medical history or family history of disease. On her admission assessment, an abdominal flat plate X-ray showed incomplete intestinal obstruction ( Figure 1a ), but no obvious abnormalities were observed in any other inspections. Forty-eight hours after admission, the patient suddenly developed dyspnea, muscle weakness, and a disorder of consciousness, with uncorrectable hypoxemia (SPO 2 86%), tachycardia (130 bpm), and hypotension (blood pressure 80/59 mmHg). She was transferred to the intensive care unit (ICU) for further management. Urgent arterial blood gas analysis on ICU admission indicated severe hypoxemia and respiratory acidosis (pH: 7.153, PO 2 : 66 mmHg, PCO 2 : 50.2 mmHg, and PO 2 /FiO 2 : 110 mmHg); tracheal intubation was then performed. On day 2 of ICU admission, the patient’s awareness gradually recovered and her abdominal pain spontaneously disappeared. Further examination revealed stubborn respiratory failure, meaning that the patient was unable to be removed from the ventilator. Muscle power of the limbs was 0/5 proximally and 2/5 distally. Furthermore, sensation and cranial nerve examinations were normal. Cranial computed tomography (CT) and abdominal CT did not indicate any abnormalities ( Figure 1b ), although the chest CT showed patchy exudation of the lower lungs, which did not explain the patient’s respiratory failure. Bedside ultrasound revealed that diaphragm displacement during spontaneous breathing mode was 5.4 mm, whereas normal displacement is considered to be greater than 10 mm. Blood tests showed that serum creatinine was elevated at 350.5 µmol/L (normal range: 44–133 µmol/L), and urea nitrogen was elevated at 22.23 mmol/L (normal range: 2.9–7.5 mmol/L), although these levels returned to normal soon after hemodialysis. The initial cerebrospinal fluid (CSF) examination was within the normal range, and anti-ganglioside antibodies, such as GM1 and GD1a, were negative. Furthermore, electromyography findings showed unspecific peripheral nerve damage ( Figure 2 ). The patient was treated with a course of intravenous immunoglobulin for a probable diagnosis of Guillain–Barré syndrome (GBS), but no relief was achieved. The patient’s condition continued to worsen, and on day 14 after ICU admission, her abdominal pain and constipation returned, along with changes in her neurological examination. Her overall weakness worsened, with muscle power of 0/5 (absolutely no movement) in all four limbs. Furthermore, a cranial nerve examination showed new nasal and labial asymmetry, and her eyelids were unable to close. Abdominal CT at this time showed extensive colonic expansion ( Figure 1c ). Another CSF examination was performed, but the results remained normal, with no cytoalbuminologic dissociation. It was also noted that the color of the patient’s urine turned visibly reddish on exposure to sunlight ( Figure 3 ). A diagnosis of AIP was finally confirmed by genetic analysis, which identified a missense mutation: c.541C>T, encoding p. Gln181 in the HMBS gene ( Figure 4 ). Targeted mutation analysis was then performed in her two children, but neither of them carried the disease-causing gene. Because heme arginate is not available in mainland China, the patient was treated with intravenous glucose infusion (50%). Twenty-four hours after glucose medication, her abdominal pain was alleviated and her urine returned to a normal color; however, her peripheral neuropathy did not markedly improve. After 2 weeks of treatment, the tracheal tube was removed. The patient was then transferred back to her local hospital for rehabilitation training because of the poor muscle strength in her limbs. At the 1-year follow-up, her overall muscle power had gradually improved to grade 3/5, and she was able to walk with the aid of a rehabilitation walking assistance vehicle. To date, the patient has not experienced any other AIP attacks, but she still has severe neurological sequelae.'}
|
{'Case report': 'A 37-year-old woman presented to the surgical unit of a general teaching hospital with abdominal pain that she experienced while walking to the hospital (May 2019). Her symptoms had started 4 months previously (January 2019). The initial symptoms included recurring abdominal pain and bloating (almost once per month). During this period, the patient visited her local clinic several times, without obtaining a clear diagnosis. The patient received Chinese medicine over a long period of time and also received symptomatic treatments (e.g., enema, tramadol as analgesia), but her condition did not improve considerably. She had a history of a cesarean section in 2013, and no other notable medical history or family history of disease. On her admission assessment, an abdominal flat plate X-ray showed incomplete intestinal obstruction ( Figure 1a ), but no obvious abnormalities were observed in any other inspections. Forty-eight hours after admission, the patient suddenly developed dyspnea, muscle weakness, and a disorder of consciousness, with uncorrectable hypoxemia (SPO 2 86%), tachycardia (130 bpm), and hypotension (blood pressure 80/59 mmHg). She was transferred to the intensive care unit (ICU) for further management. Urgent arterial blood gas analysis on ICU admission indicated severe hypoxemia and respiratory acidosis (pH: 7.153, PO 2 : 66 mmHg, PCO 2 : 50.2 mmHg, and PO 2 /FiO 2 : 110 mmHg); tracheal intubation was then performed. On day 2 of ICU admission, the patient’s awareness gradually recovered and her abdominal pain spontaneously disappeared. Further examination revealed stubborn respiratory failure, meaning that the patient was unable to be removed from the ventilator. Muscle power of the limbs was 0/5 proximally and 2/5 distally. Furthermore, sensation and cranial nerve examinations were normal. Cranial computed tomography (CT) and abdominal CT did not indicate any abnormalities ( Figure 1b ), although the chest CT showed patchy exudation of the lower lungs, which did not explain the patient’s respiratory failure. Bedside ultrasound revealed that diaphragm displacement during spontaneous breathing mode was 5.4 mm, whereas normal displacement is considered to be greater than 10 mm. Blood tests showed that serum creatinine was elevated at 350.5 µmol/L (normal range: 44–133 µmol/L), and urea nitrogen was elevated at 22.23 mmol/L (normal range: 2.9–7.5 mmol/L), although these levels returned to normal soon after hemodialysis. The initial cerebrospinal fluid (CSF) examination was within the normal range, and anti-ganglioside antibodies, such as GM1 and GD1a, were negative. Furthermore, electromyography findings showed unspecific peripheral nerve damage ( Figure 2 ). The patient was treated with a course of intravenous immunoglobulin for a probable diagnosis of Guillain–Barré syndrome (GBS), but no relief was achieved. The patient’s condition continued to worsen, and on day 14 after ICU admission, her abdominal pain and constipation returned, along with changes in her neurological examination. Her overall weakness worsened, with muscle power of 0/5 (absolutely no movement) in all four limbs. Furthermore, a cranial nerve examination showed new nasal and labial asymmetry, and her eyelids were unable to close. Abdominal CT at this time showed extensive colonic expansion ( Figure 1c ). Another CSF examination was performed, but the results remained normal, with no cytoalbuminologic dissociation. It was also noted that the color of the patient’s urine turned visibly reddish on exposure to sunlight ( Figure 3 ). A diagnosis of AIP was finally confirmed by genetic analysis, which identified a missense mutation: c.541C>T, encoding p. Gln181 in the HMBS gene ( Figure 4 ). Targeted mutation analysis was then performed in her two children, but neither of them carried the disease-causing gene. Because heme arginate is not available in mainland China, the patient was treated with intravenous glucose infusion (50%). Twenty-four hours after glucose medication, her abdominal pain was alleviated and her urine returned to a normal color; however, her peripheral neuropathy did not markedly improve. After 2 weeks of treatment, the tracheal tube was removed. The patient was then transferred back to her local hospital for rehabilitation training because of the poor muscle strength in her limbs. At the 1-year follow-up, her overall muscle power had gradually improved to grade 3/5, and she was able to walk with the aid of a rehabilitation walking assistance vehicle. To date, the patient has not experienced any other AIP attacks, but she still has severe neurological sequelae.'}
|
IEM-Treatment
|
IEM_Treatment
|
[
"Because heme arginate is not available in mainland China , the patient was treated with intravenous glucose infusion ( 50 % ) ."
] |
test-2089
|
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.'}
|
Vitals-and-Hematology
|
Vitals_Hema
|
[
"Increased leukocyte count, neutrophil ratio",
"T ≤ 38.2 ° C )"
] |
test-2090
|
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.'}
|
Gastrointestinal-System
|
GI
|
[
"eating difficulty",
"Chronic diarrhea was absent"
] |
test-2091
|
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.'}
|
Patient-History
|
History
|
[
"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",
"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",
"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."
] |
test-2092
|
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.'}
|
Neurology
|
Neuro
|
[
"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",
"psychiatric signs",
"Cerebral MRI suggested white matter ( WM ) demyelination and slight cerebral atrophy",
"poor mental state",
"Neurological examination indicated cervical rigidity and Kernig sign. Deep tendon reflexes and limb muscle strength were normal. Babinski sign was negative",
"psychiatric and behavioral disturbances, cognitive decline",
"peripheral neuropathy, high signal intensity in the WM and mild cerebral atrophy on brain MRI.",
"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",
"Cerebrospinal fluid protein was mildly elevated : 680.4 mg / L ( normal range : 150 - 400 mg / L",
"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,"
] |
test-2093
|
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.'}
|
Laboratory-and-Imaging
|
Lab_Image
|
[
"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 )",
"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",
"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.",
"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.",
"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",
"Cerebral MRI suggested white matter ( WM ) demyelination and slight cerebral atrophy ( Figure 2 G 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 ).",
"Targeted sequencing revealed that the proband had compound heterozygous mutations in the CYP27A1 gene"
] |
test-2094
|
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.'}
|
Cardiovascular-System
|
CVS
|
[] |
test-2095
|
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.'}
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Endocrinology
|
ENDO
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[] |
test-2096
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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.'}
|
Genitourinary-System
|
GU
|
[
"multiple left kidney stones, a right kidney cyst, and a hypoechoic area in the bladder, which could move with body position",
"Sediments in the bladder",
"history of renal calculus",
"Sediments in the bladder",
"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",
"renal calculus",
"incontinence"
] |
test-2097
|
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.'}
|
Respiratory-System
|
RESP
|
[] |
test-2098
|
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.'}
|
Musculoskeletal-System
|
MSK
|
[
"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",
"Enlarged Achilles tendons and nodules on the bilateral tibial tubercles were observed",
"enlargement of the Achilles tendon, which showed up as low signal intensity on both T1- and T2 - weighted images",
"bilateral xanthomas of the Achilles tendon and tibial tubercles",
"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"
] |
test-2099
|
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.'}
|
Eyes-Ears-Nose-Throat
|
EENT
|
[
"no evidence of cataract"
] |
test-2100
|
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.'}
|
Dermatology
|
DERM
|
[
"dark skin",
"no evidence of cataract or xanthomas at other sites such as the eyelids"
] |
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