Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report the clinical features, biochemical details, and treatment of the first detected cases of an inborn error of aromatic L-amino acid decarboxylase. Male monozygotic twins presented with extreme hypotonia and oculogyric crises. Concentrations of biogenic amines and their metabolites were reduced considerably both centrally and peripherally. Pterin and phenylalanine metabolism were normal. Activity of aromatic L-amino acid decarboxylase was virtually absent in a liver biopsy sample and greatly reduced in plasma. Concentrations of L-dopa, 3-methoxytyrosine, and 5-hydroxytryptophan were elevated in CSF, plasma, and urine. CSF S-adenosylmethionine concentrations were reduced. Pyridoxine treatment had no clinical effect but led to a fall in CSF L-dopa and 3-methoxytyrosine and a rise in S-adenosylmethionine. Treatment with either bromocriptine or tranylcypromine stopped the abnormal eye movements; tranylcypromine treatment also improved muscle tone and led to a rise in plasma norepinephrine and whole blood serotonin. Combined treatment with pyridoxine, bromocriptine, and tranylcypromine produced sustained improvement in tone and voluntary movements. The twins' parents were asymptomatic but had reduced plasma aromatic L-amino acid decarboxylase activity, consistent with heterozygosity. We monitored a subsequent pregnancy through biochemical analyses of a fetal liver biopsy sample and of amniotic fluid. We predicted an unaffected fetus, which was confirmed clinically and biochemically after birth.
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PMID:Aromatic L-amino acid decarboxylase deficiency: clinical features, diagnosis, and treatment of a new inborn error of neurotransmitter amine synthesis. 135 95

Aromatic L-amino acid decarboxylase deficiency is an inborn error of metabolism that leads to combined serotonin and catecholamine deficiency, first described by Hyland et al in 1990. The clinical features, biochemical findings, and treatment of the second family with this condition are reported. Our male patient presented with developmental delay, extreme hypotonia, oculogyric crises, and irritability. The diagnosis of this inborn error of biogenic amine metabolism was accomplished by determining low concentrations of homovanillic, 5-hydroxyindoleacetic acid, and 3-methoxy-4-hydroxyphenyl-ethyleneglycol in cerebrospinal fluid with normal biopterin metabolism and increased L-dopa, in plasma, cerebrospinal fluid, and urine. Greatly reduced activity of aromatic L-amino acid decarboxylase in plasma confirmed this diagnosis. Combined treatment with pyridoxine, tranylcypromine, and bromocriptine produced some clinical improvement.
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PMID:Aromatic L-amino acid decarboxylase deficiency: clinical features, diagnosis, and treatment of a second family. 930 16

A 15-year-old Chinese male with infantile-onset hypotonia, developmental delay, ptosis, and oculogyric episodes presented with a history of chronic diarrhoea since the age of 5 years. At presentation, he had an exacerbation of diarrhoeal symptoms resulting in dehydration and malnutrition with a concurrent severe chest infection. In view of his infantile-onset hypotonia, oculogyric crises, and protracted diarrhoea, an autonomic disturbance related to neurotransmitters was suspected. Urine organic acid profiling was compatible with aromatic L-amino acid decarboxylase deficiency. The diagnosis was confirmed based on cerebrospinal fluid analysis and genetic mutation analysis. The patient was treated with a combination of bromocriptine, selegiline, and pyridoxine; a satisfactory reduction in diarrhoea ensued. Our report highlights the importance of urine organic acid screening in infantile-onset hypotonia, especially when accompanied by oculogyric crises, and severe diarrhoea which could manifest as a result of autonomic disturbance.
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PMID:A rare cause of severe diarrhoea diagnosed by urine metabolic screening: aromatic L-amino acid decarboxylase deficiency. 2471 72