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)

Congenital deficiencies of the urea cycle enzyme ornithine transcarbamylase (OTC) result in chronic hyperammonemia and severe neurological dysfunction including seizures and mental retardation. As part of a series of studies to elucidate the pathophysiologic mechanisms responsible for the CNS consequences of OTC deficiency, concentrations of ammonia-related and neurotransmitter amino acids were measured as their o-phthalaldehyde derivatives using high performance liquid chromatography with fluorescence detection in regions of the brains of sparse-fur (spf) mice, a mutant with an X-linked inherited defect of OTC. Compared to CD-1/Y controls, the brains of spf/Y mutant mice contained significant alterations of several amino acids. A generalized, up to 2-fold, increase of brain glutamine was observed, consistent with the exposure of these brains to increased concentrations of ammonia. Significant increases of brain alanine were also observed and, together with previous reports of increased concentrations of alpha-ketoglutarate, are consistent with ammonia-induced inhibition of alpha-ketoglutarate dehydrogenase in the brains of spf/Y mice. Increased brain content of the excitatory amino acid aspartate could be responsible for the seizures frequently encountered in congenital OTC deficiency.
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PMID:Regional amino acid neurotransmitter changes in brains of spf/Y mice with congenital ornithine transcarbamylase deficiency. 791 68

Canavan disease (CD) is an autosomal recessive disorder caused by aspartoacylase deficiency leading to accumulation of N-acetylaspartic acid and spongy degeneration of the brain. The mouse model for CD showed low levels of glutamate and gamma-aminobutyric acid (GABA) in the brain. Whether the low levels of glutamate and GABA observed in the CD mouse brain lead to abnormal production of glutamate-GABA associated enzymes and resulting succinate production is not obvious. While glutamate dehydrogenase and alpha-ketoglutarate dehydrogenase complex activities are lower in the cerebellum and brain stem of the CD mouse, alanine aminotransferase and succinate semialdehyde dehydrogenase (SSADH) activities and succinate level are similar to the levels observed in the wild type. Deficiency of SSADH has been suggested to be associated with mental retardation and hypotonia, similar to the clinical features of CD. The normal SSADH activity in the CD mouse brain suggests that mental retardation and hypotonia seen in the CD mouse is not due to SSADH activity and if documented also in patients with CD.
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PMID:Mental retardation and hypotonia seen in the knock out mouse for Canavan disease is not due to succinate semialdehyde dehydrogenase deficiency. 1501 27