Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

D-2-Hydroxyglutaric aciduria has been observed in patients with extremely variable clinical symptoms, creating doubt about the existence of a disease entity related to the biochemical finding. An international survey of patients with D-2-hydroxyglutaric aciduria was initiated to solve this issue. The clinical history, neuroimaging, and biochemical findings of 17 patients were studied. Ten of the patients had a severe early-infantile-onset encephalopathy characterized by epilepsy, hypotonia, cerebral visual failure, and little development. Five of these patients had a cardiomyopathy. In neuroimaging, all patients had a mild ventriculomegaly, often enlarged frontal subarachnoid spaces and subdural effusions, and always signs of delayed cerebral maturation. In all patients who underwent neuroimaging before 6 months, subependymal cysts over the head or corpus of the caudate nucleus were noted. Seven patients had a much milder and variable clinical picture, most often characterized by mental retardation, hypotonia, and macrocephaly, but sometimes no related clinical problems. Neuroimaging findings in 3 patients variably showed delayed cerebral maturation, ventriculomegaly, or subependymal cysts. Biochemical findings included elevations of D-2-hydroxyglutaric acid in urine, plasma, and cerebrospinal fluid in both groups. Cerebrospinal fluid gamma-aminobutyric acid was elevated in almost all patients investigated. Urinary citric acid cycle intermediates were variably elevated. The conclusion of the study is that D-2-hydroxyglutaric aciduria is a distinct neurometabolic disorder with at least two phenotypes.
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PMID:D-2-Hydroxyglutaric aciduria: biochemical marker or clinical disease entity? 989 84

Guanidinoacetate methyltransferase (GAMT) deficiency is an inherited neurometabolic disorder biochemically characterized by tissue accumulation of guanidinoacetate (GAA) and depletion of creatine. Affected patients present epilepsy and mental retardation whose etiopathogeny is unclear. In a previous study we showed that instrastriatal administration of GAA caused a reduction of Na(+),K(+)-ATPase and creatine kinase (CK) activities, as well as an increase in TBARS (an index of lipid peroxidation). In the present study we investigated the in vitro and in vivo effects of GAA on glucose uptake from [U-(14)C] acetate (citric acid cycle activity) and on the activities of complexes II, II-III, III and IV of the respiratory chain in striatum of rats. Results showed that 50 and 100 microM GAA (in vitro studies) and GAA administration (in vivo studies) significantly inhibited complexes II and II-III, respectively, but did not alter complexes III and IV, as well as CO(2) production. We also studied the influence of taurine or vitamins E and C on the inhibitory effects caused by intrastriatal administration of GAA on complexes II and II-III, Na(+),K(+)-ATPase and CK activities, and on TBARS in rat striatum. Pre-treatment with taurine and vitamins E and C revealed that taurine prevents the effects of intrastriatal administration of GAA on the inhibition of complex II, complex II-III, and Na(+),K(+)-ATPase activities. Vitamins E and C prevent the effects of intrastriatal administration of GAA on the inhibition of CK and Na(+),K(+)-ATPase activities, and on the increase of TBARS. The data suggest that GAA in vivo and in vitro treatment disturbs important parameters of striatum energy metabolism and that oxidative damage may be mediating these effects. It is presumed that defects in striatum bioenergetics might be involved in the pathophysiology of striatum damage characteristic of patients with GAMT-deficiency.
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PMID:Evidence that the inhibitory effects of guanidinoacetate on the activities of the respiratory chain, Na+,K+-ATPase and creatine kinase can be differentially prevented by taurine and vitamins E and C administration in rat striatum in vivo. 1740 7