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)

A girl suffering from marked muscular hypotonia, severe statomotor and mental retardation, bilateral optic atrophy with chorioretinal degeneration, convulsions and a moderate compensated metabolic acidosis is described. Screening for metabolic disorders revealed massive 3-methylglutaconic with 3-methylglutaric aciduria leading to the tentative diagnosis of 3-methylglutaconyl-CoA hydratase deficiency. Metabolite excretion was correlated with variation of leucine intake. 3-methyl-3-hydroxyglutaryl-CoA lyase activity in cultured fibroblasts was normal. The suspected metabolic defect was not demonstrable in cultured skin fibroblasts, however.
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PMID:3-Methylglutaconic and 3-methylglutaric aciduria in a patient with suspected 3-methylglutaconyl-CoA hydratase deficiency. 258 Jul 10

In a 4.5-month-old boy presenting with marked muscular hypotonia in the neonatal period, hepatomegaly, cardiac hypertrophy, recurrent hypoglycemia, metabolic acidosis, and secondary carnitine deficiency, there was a considerable urinary excretion of 3-methylglutaconic and 3-methylglutaric acid. Estimation of 3-methylglutaconyl-CoA hydratase, 3-hydroxy-3-methylglutaryl-CoA lyase and initial enzymatic steps of cholesterol biosynthesis in cultured fibroblasts and in different tissues postmortem revealed no enzyme deficiency. Analyses of the respiratory chain in postmortem tissues demonstrated severe impairment of complex I (NADH ubiquinone oxidoreductase) and complex IV (cytochrome c oxidase) activities in skeletal muscle and reduced complex IV activity in heart.
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PMID:Multiple respiratory chain abnormalities associated with hypertrophic cardiomyopathy and 3-methylglutaconic aciduria. 769 3

In this paper, we describe a distinct clinical subtype of 3-methylglutaconic aciduria. 3-Methylglutaconic aciduria is a group of different metabolic disorders biochemically characterized by increased urinary excretion of 3-methylglutaconic acid. We performed biochemical and genetic investigations, including urine organic acid analysis, NMR spectroscopy, measurement of 3-methylglutaconyl-CoA hydratase activity, cardiolipin levels, OPA3 gene analysis and measurement of the oxidative phosphorylation in four female patients with 3-methylglutaconic aciduria. 3-Methylglutaconic aciduria type I, Barth syndrome, and Costeff syndrome were excluded as the activity of 3-methylglutaconyl-CoA hydratase, the cardiolipin levels, and molecular analysis of the OPA3 gene, respectively, showed no abnormalities. The children presented with characteristic association of hearing loss and the neuro-radiological evidence of Leigh disease. They also had neonatal hypotonia, recurrent lactic acidemia, episodes with hypoglycemia and severe recurrent infections, feeding difficulties, failure to thrive, developmental delay, and progressive spasticity with extrapyramidal symptoms. Our patients were further biochemically characterized by a mitochondrial dysfunction and persistent urinary excretion of 3-methylglutaconic acid.
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PMID:Association of 3-methylglutaconic aciduria with sensori-neural deafness, encephalopathy, and Leigh-like syndrome (MEGDEL association) in four patients with a disorder of the oxidative phosphorylation. 1652 7

3-Methylglutaconic aciduria is the biochemical marker of several inherited metabolic diseases. Four types of 3-methylglutaconic aciduria can be distinguished. In the type I form, accumulation of 3-methylglutaconate is due to deficient activity of 3-methylglutaconyl-CoA hydratase, an enzyme of the leucine degradation pathway. In the other forms, 3-methylglutaconic acid is not derived from leucine but is of unidentified origin, possibly derived from other metabolic pathways, such as mevalonate metabolism. We report five patients, all presenting a severe early-onset phenotype characterized by 3-methylglutaconic aciduria, hypertrophic cardiomyopathy, cataract, hypotonia/developmental delay, lactic acidosis, and normal 3-methylglutaconyl-CoA hydratase activity. This peculiar phenotype, for which a primary mitochondrial disorder is hypothesized, identifies a novel subtype of 3-methylglutaconic aciduria.
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PMID:Hypertrophic cardiomyopathy, cataract, developmental delay, lactic acidosis: a novel subtype of 3-methylglutaconic aciduria. 1673 96