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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Valproic acid-induced hyperammonemia in mentally retarded adults.

All individuals receiving valproic acid therapy in an institution for the mentally retarded were evaluated for hyperammonemia. Of these 19 adults, 6 had persistent and 5 others had intermittent hyperammonemia. The hyperammonemic patients were asymptomatic, except that 2 had occasional lethargy. Hyperammonemia was detected more often in younger adults and in those treated with multiple anticonvulsants, especially phenytoin. Valproate-induced hyperammonemia is probably the result of depletion of mitochondrial acetyl CoA and decreased production of N-acetylglutamate, the obligatory activator of the first enzyme of the urea cycle, carbamyl phosphate synthetase I. Anticonvulsant-mediated microsomal enzyme induction may also contribute.[1]


  1. Valproic acid-induced hyperammonemia in mentally retarded adults. Williams, C.A., Tiefenbach, S., McReynolds, J.W. Neurology (1984) [Pubmed]
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