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)

The son of Kurdish, consanguineous parents (cousin marriage) presented from the first day of life with initially focal and later generalized attacks of epileptic seizures and a severe generalized muscular hypotonia. Urinary excretion of 3-hydroxyisovalerate and of 3-methylcrotonylglycine was persistently increased. Diagnosis of isolated biotin-resistant 3-methylcrotonyl-CoA carboxylase deficiency was confirmed in cultured fibroblasts. Psychomotor retardation was progressive, seizures and marked EEG abnormalities persisted. Treatment with leucine and protein-resistricted diet under hospital control did not significantly improve these conditions. The patient died from a cardiac and circulatory failure after a prolonged epileptic attack, with bronchial aspiration. The non-responsiveness of our patient to therapy and the fatal outcome indicate the existence of a severe neonatal variant of this otherwise rather benign genetic enzyme deficiency.
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PMID:Isolated biotin-resistant deficiency of 3-methylcrotonyl-CoA carboxylase presenting as a clinically severe form in a newborn with fatal outcome. 129 82

We report the first case of isolated biotin resistant 3-methylcrotonyl-CoA carboxylase (MCC) deficiency in Argentina. The diagnosis was established at 14 months of age by urinary organic-acid analysis and confirmed by enzyme assay in fibroblasts. The patient suffered from severe psychomotor retardation, hypotonia, areflexia, and failure to thrive, and died unexpectedly at 3 years 4 months of life. Brain MRI at 14 months showed signals of the white matter on cerebral T2-weighted, which were indicative of confluent and multiple foci of leukodystrophy, a pattern not previously described in this entity. In addition, high levels of oxypurines were detected in cerebrospinal fluid. This might be related to energetic consequences of the enzyme deficiency in the brain. This case extends the phenotype of isolated MCC deficiency in infancy and suggests this entity should be considered to be one of the possible causes of "metabolic leukodystrophies."
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PMID:Leukodystrophy and CSF purine abnormalities associated with isolated 3-methylcrotonyl-CoA carboxylase deficiency. 1189 4

A patient with a severe neonatal variant of 3-methylcrotonyl-CoA carboxylase (MCC) deficiency is reported. The first child of healthy consanguineous Turkish parents presented on the second day of life with dehydration, cyanosis, no sucking, generalized muscular hypotonia, encephalopathy, respiratory depression requiring mechanic ventilation, macrocephaly, severe acidosis and hypoglycaemia. Elevated C5-OH-carnitine in dried blood spot by tandem MS and elevated urinary excretion of 3-hydroxyisovaleric acid and 3-methylcrotonylglycine suggested MCC deficiency, confirmed by enzyme analysis in cultured fibroblasts. Cerebral ultrasonography and cranial CT findings revealed progressive changes such as disseminated encephalomalacia, cystic changes, ventricular dilatation and cerebral atrophy. Treatment with high-dose biotin and protein-restricted diet was ineffective and the patient died at the age of 33 days with progressive neurological deterioration. Mutation analysis revealed a homozygous mutation in the splice acceptor site of intron 15 in the MCC beta-subunit. Early-onset severe necrotizing encephalopathy should be included in the differential diagnosis of isolated MCC deficiency.
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PMID:Consanguineous 3-methylcrotonyl-CoA carboxylase deficiency: early-onset necrotizing encephalopathy with lethal outcome. 1587 10