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)

The primary defect in patients presenting with a history of protein intolerance, mental retardation, and epilepsy of variable degree, with the unique triad of hyperornithinemia, hyperammonemia, and homocitrullinuria (the HHH syndrome) has been postulated to be a defect in translocation of ornithine into the mitochondria. In a 12-year-old boy with the HHH syndrome, the hyperammonemia observed following a protein load was prevented when the same load was given orally with a 1 mmol/kg of ornithine-HCl. At a dosage level of 0.5 to 1.0 mmol/kg/day of ornithine HCl, administered in 3 divided doses with meals, the patient's protein tolerance improved. As pretreatment hyperammonemia reverted to normal levels, the patient was able to cope with increased dietary protein and his growth accelerated. During the 2-year interval of the study, the ornithine HCl supplements were withdrawn on 2 occasions, and within a week the hyperammonemia recurred. Whereas cultured fibroblasts from the HHH patient were capable of oxidizing U-14C-glutamate to 14CO2 as rapidly as normal cells. 1-14C-ornithine or 5-14C-ornithine were oxidized at only 1/28 or 1/49 of the normal rate. Ultrastructural studies of the HHH cultured fibroblast mitochondria revealed distinctive alterations in size and shape; unusually long, branching, and "curling," HHH mitochondria also showed accelerated regressive changes.
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PMID:The hyperornithinemia, hyperammonemia, homocitrullinuria syndrome: an ornithine transport defect remediable with ornithine supplements. 365 57

A new variant of glucosephosphate isomerase (GPI) associated with hemolytic anemia, mental retardation, and muscular hypotonia is described. The defective enzyme showed increased affinity for fructose-6-phosphate (F-6-P), decreased affinity for glucose-6-phosphate (G-6-P) altered electrophoretic and isoelectrofocusing patterns, and shift to the left of the precipitin curve. The enzyme was stable under all the conditions tested (heat, urea, guanidine-HCl, and storage). Optimum pH, Ki for 6-phosphogluconic acid (6-PGA) and for erythrose-4-phosphate (E-4-P), molecular weight, GPI-related antigen concentration, immunodiffusion pattern, and immunoinactivation were in the normal range. This is the first example of the association of a stable mutant GPI with severe hemolytic anemia. Enzyme instability has been present in all previously reported cases.
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PMID:The first stable variant of erythrocyte glucose-phosphate isomerase associated with severe hemolytic anemia. 743 96