Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917816 (mental retardation)
 15,867 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Routine screening for organic acids revealed increased and isolated urinary excretion of L-2-hydroxyglutaric acid in 8 mentally retarded patients from five unrelated families, including three pairs of siblings. L-2-Hydroxyglutaric acid concentration was also found to be increased in the cerebrospinal fluid (CSF) and to a lesser extent in plasma. The only other biochemical abnormality was an increased concentration of lysine, both in plasma and in CSF. No organic acid abnormality was found on screening of asymptomatic family members. Patients were of either sex, and became symptomatic during childhood, with moderate to severe mental deficiency in all and definite cerebellar dysfunction in 7. Magnetic resonance imaging revealed an identical abnormal pattern with subcortical leukoencephalopathy, cerebellar atrophy, and signal changes in the putamina and dentate nuclei, in all patients. No specific biochemical function or catabolic pathway involving L-2-hydroxyglutaric acid is known in mammals, including humans. Preliminary loading and dietary studies failed to reveal the origin of the compound. The elevated CSF/plasma ratio suggests that it is in part generated within the central nervous system. This report describes a novel inherited neurometabolic disease, probably autosomal recessive, with distinct clinical, biochemical, and neuroimaging features.
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PMID:L-2-hydroxyglutaric acidemia: a novel inherited neurometabolic disease. 164 74

L-2-Hydroxyglutaric acidaemia represents a newly defined inborn error of metabolism, with increased levels of L-2-hydroxyglutaric acid in urine, plasma and cerebrospinal fluid. The concentration in cerebrospinal fluid is higher than in plasma. The other consistent biochemical finding is an increase of lysine in blood and cerebrospinal fluid, but lysine loading does not increase L-2-hydroxyglutaric acid concentration in plasma. This autosomal recessively inherited disease is expressed as progressive ataxia, mental deficiency with subcortical leukoencephalopathy and cerebellar atrophy on magnetic resonance imaging. Since these features were described in 8 patients by Barth and co-workers in 1992, 4 more patients with similar findings have been diagnosed and added to the present series. L-2-Hydroxyglutaric acid is found in only trace amounts on routine gas chromatographic screening in normal persons, and its origin, its fate and even its relevance to normal metabolism are unknown. Therefore its catabolism was studied in normal liver. Incubation of rat liver with L-2-hydroxyglutaric acid did not produce H2O2, which excluded (peroxisomal) L-2-hydroxyacid oxidase as the main route of catabolism. However, L-2-hydroxyglutaric acid is rapidly dehydrogenated if NAD+ is added as a co-factor to the standard reaction medium. This could also be demonstrated in human liver. The preliminary evidence for this enzyme activity in rats and humans, L-2-hydroxyglutaric acid dehydrogenase, is given. Further investigations are required to clarify the possible relevance to the metabolic defect in L-2-hydroxyglutaric acidaemia.
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PMID:L-2-hydroxyglutaric acidaemia: clinical and biochemical findings in 12 patients and preliminary report on L-2-hydroxyacid dehydrogenase. 841 18