Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013362 (dysarthria)
 3,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a 2-year-old boy with Leigh disease, spasticity, dysarthria, and optic atrophy gradually developed. Computed tomography and magnetic resonance imaging disclosed progressive, symmetric basal ganglia lesions. In muscle tissue, a defect of pyruvate dehydrogenase complex was found. Magnetic resonance volume selective proton spectroscopy (MRVS) of the basal ganglia demonstrated an abnormal lactate peak. A ketonemic diet coincided with clinical stabilization and arrest of progressive brain lesions. Lactate could no longer be demonstrated by MRVS. It reappeared with a new brain lesion coinciding with discontinuation of the diet. MRVS, therefore, appears to be a sensitive tool to evaluate pathologic lactate production in metabolic brain disease with disturbed energy metabolism and allows noninvasive therapy monitoring.
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PMID:Assessment and therapy monitoring of Leigh disease by MRI and proton spectroscopy. 155 78

Two half-brothers and their mother had symptomatic pyruvate dehydrogenase complex deficiency. The infants had severe congenital lactic acidosis, seizures, and apneic spells and died at the ages 3 and 4 months. The mother was less symptomatic with mental retardation, truncal ataxia, and dysarthria. The residual pyruvate dehydrogenase activities in cultured skin fibroblasts from the 2 infants and their mother were 7, 15, and 10% of control values. Immunoblot analysis showed negligible amounts of E1 alpha and E1 beta subunits of the complex. Northern blot analysis for the E1 alpha subunit showed normal results. In the 2 sons, complementary DNA sequence analysis revealed a cytosine to thymine mutation in exon 4, resulting in a change of arginine 127 to tryptophan in the E1 alpha subunit. Restriction enzyme analysis of the polymerase chain reaction product representing exon 4 of the E1 alpha gene revealed that the mother was a heterozygotes. Complementary DNA restriction analysis and methylation analysis of the X chromosome DXS255 loci revealed skewed activation of the mutant allele, consistent with the deficient pyruvate dehydrogenase activity in the mother's fibroblasts. The milder maternal phenotype is consistent with variable X-inactivation patterns in different organs of female heterozygotes.
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PMID:Pyruvate dehydrogenase deficiency: molecular basis for intrafamilial heterogeneity. 802 67

Two brothers presented in their mid-forties with movement disorders including atypical parkinsonism, choreiform movements, stereotypies, ataxia and dysarthria. Both brothers showed putaminal lucencies on imaging and, in the proband, a deficiency of the pyruvate dehydrogenase complex (PDHC) was found on skin fibroblast assay.
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PMID:Late-onset presentation of pyruvate dehydrogenase deficiency. 1519 21