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)

An 11-year old girl with spastic paraplegia and mental retardation has suffered from attacks of metabolic acidosis since the age of 18 months. "Ketotic hyperglycinemia" was diagnosed when she was 3 years old. Reinvestigation at 9 1/2 years included a two-day load with L-isoleucine, and propionyl-CoA carboxylase assay in cultured fibroblasts. The following compounds increased following the load: 3-hydroxypropionic acid, 2-methyl-3-hydroxybutyric acid, 2-ethylhydracrylic acid, 3-hydroxy-n-valeric acid, 3-oxo-n-valeric acid, 2-methyl-3-oxobutyric acid, 2-oxo-3-methylvaleric acid, 2-methyl-3-oxovaleric acid, N-tiglylglycine, methylcitric acid and butanone. Small amounts of alloisoleucine appeared in plasma. Propionyl-CoA carboxylase deficiency was suggested by this metabolite pattern and demonstrated in cultured fibroblasts.
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PMID:Propionyl-CoA carboxylase deficiency with overflow of metabolites of isoleucine catabolism at all levels. 75 79

Mental retardation associated with hypothyroidism may be caused by impairment of brain ketone body-metabolizing enzymes during the suckling period. However, much evidence suggests that, immediately after delivery, lactate, instead of ketone bodies or glucose, may be the best substrate for the brain. In this work, we have studied the effect of experimentally induced congenital hypothyroidism on the rate of lactate, glucose, and 3-hydroxybutyrate utilization in early neonatal brain slices. Methimazole (MMI) administration to the mothers caused a 5.4- and 1.7-fold decrease in neonatal plasma concentrations of L-thyroxine (T4) and 3,5,3'-triiodo-L-thyronine (T3), respectively. Propylthiouracil (PTU) administration to the mothers caused a 7.3- and > 2-fold decrease in plasma T4 and T3 concentrations, respectively. MMI-induced hypothyroidism did not significantly modify the rate of lactate, glucose, or 3-hydroxybutyrate oxidation to CO2 and their incorporation into lipids by the neonatal brain. However, PTU-induced hypothyroidism decreased the rate of lactate and glucose oxidation to CO2 and their incorporation into lipids by 17% (p < 0.05). 3-Hydroxybutyrate utilization was not modified by this treatment. Separation by HPLC of the lipids revealed that PTU-mediated inhibition of lipid synthesis from lactate and glucose may be accounted for by specific inhibition of the rate of sterol synthesis (15%, p < 0.05), whereas the rate of phospholipid synthesis was unaffected. These results suggest that the early newborn may develop mechanisms aimed at avoiding the possible brain damage caused by the inhibition of lipid synthesis brought about by mild neonatal hypothyroidism.
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PMID:Fuel utilization by early newborn brain is preserved under congenital hypothyroidism in the rat. 886 77