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)

We are reporting a girl aged eight years with ketotic hypoglycemia, mental deficiency and retarded motor and somatic development. Investigation of plasma amino acid concentrations during a spontaneous hypoglycemia revealed an increase in the branched-chain amino acids valine (4.1), leucine (7.8) and isoleucine (1.7 mg/100 ml), while alanine was decreased (1.2 mg/100 ml) and ketonuria was present. The determination of the branched-chain ketoacid decarboxylase in leukocytes showed a decrease of approximately 50% of normal for alpha-ketoisocaproic acid (KIC) as substrate, whereas values for alpha-ketoisovaleric acid (KIVA) and alpha-keto-beta-methylvaleric acid (MEVA) were normal. In fibroblasts activities for all three substrates were in the normal range. Intermittend maple-syrup-urine disease was excluded by oral loading tests with the branched-chain amino acids and with an isocaloric, high-protein diet. Impairment of oxydative decarboxylation of leucine, valine, and isoleucine secondary to increased ketogenesis may play an etiologic role in ketotic hypoglycemia, since we observed, by gaschromatographic analysis, an increase in the urinary excretion of KIVA (5.5 mumol/h), KIC (29.4), and MEVA (47.9) after a provocative test with an isocaloric ketogenic diet for 36 hrs. The significance of branched-chain hyperaminoacidemia and branched chain alpha-ketoaciduria is discussed in this context.
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PMID:[Intermittent branched--chain ketoacidurie in ketotic hypoglycemia: investigations to localize the biochemical defect (author's transl)]. 125 52

Learning disability is a common feature of patients affected by maple syrup urine disease (MSUD). However, the pathomechanisms underlying learning deficit in this disorder are poorly known. In the present study, we investigated the effect of acute administration of the alpha-keto acids accumulating in MSUD into the hippocampus on the behavior of rats in the open field and in the inhibitory avoidance tasks. Adult male Wistar rats received intrahippocampal injections of alpha-ketoisocaproic acid (KIC, 8 micromol), alpha-ketoisovaleric acid (KIV, 5 micromol), alpha-keto-beta-methylvaleric acid (KMV, 5 micromol), or NaCl (8 micromol) (controls) immediately after or 10 min before training. Testing session was performed 24 h later. Posttraining administration of the keto acids had no effect on learning in the open-field task. In contrast, pretraining administration of KIV and KMV impaired habituation in the open field. Similarly, pretraining administration of KIC, KIV, and KMV affected rat performance in the inhibitory avoidance task, suggesting disruption of acquisition. The results indicate that the alpha-keto acids accumulating in MSUD induce learning deficits in aversive and nonaversive tasks. We therefore suggest that these findings may be related to the psychomotor delay/mental retardation observed in MSUD, and may indicate the contribution of increased brain concentrations of these organic acids to the pathophysiology of the neurological dysfunction of MSUD patients.
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PMID:Intrahippocampal administration of the alpha-keto acids accumulating in maple syrup urine disease provokes learning deficits in rats. 1472 56