Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026838 (spasticity)
 6,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

3-Methylglutaconic aciduria has been found in two distinct syndromes. In one there is deficient activity of 3-methylglutaconyl coenzyme A hydratase, and the only clinical manifestation observed has been retardation of speech development. In the other, which includes a majority of the patients studied, we document that the activity of this enzyme in fibroblast extracts is normal. The phenotype of this disorder is one of profound neurological impairment with retarded psychomotor development, hypotonicity and/or spasticity, convulsions or EEG abnormalities, and sensorineural changes in the eye and ear.
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PMID:3-Methylglutaconic aciduria: a phenotype in which activity of 3-methylglutaconyl-coenzyme A hydratase is normal. 319 37

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 (MGA) encompasses a heterogeneous group of disorders, often coinciding with elevated levels of urinary 3-methylglutaric acid. Type I MGA is a disorder of leucine metabolism, while the biological basis for the MGA is unclear for the other types (MGA types II-V). MGA type III (Costeff optic atrophy syndrome, autosomal recessive optic atrophy-3 or optic atrophy plus syndrome, OMIM 258501) is distinguished by early bilateral optic atrophy, later-onset spasticity, extrapyramidal dysfunction, ataxia, and occasional cognitive deficits. It is caused by homozygous mutations in the optic atrophy 3 gene (OPA3). We present a case of a patient with MGA who has infantile-onset optic atrophy, ataxia, extrapyramidal movements and spasticity, but with normal intellect. Sequencing of the patient's DNA revealed a homozygous nonsense mutation c.415C>T (p.Q139X) in exon 2 of transcript 2 of the OPA3 gene, as well as a common silent polymorphism c.231T>C in the same exon. This is the first nonsense mutation found in OPA3. The molecular findings in OPA3 are also reviewed, including mutations in OPA3 that result in autosomal dominant optic atrophy and cataract (ADOAC). The recessive mode of inheritance of MGA type III as a result of the p.Q139X mutation is supported by the carrier status of the unaffected father.
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PMID:Costeff optic atrophy syndrome: new clinical case and novel molecular findings. 1898 35