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.
D000293:Adolescent; D000328:Adult; D000368:Aged; D000641:Ammonia / Q000097:blood*; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D014635:Valproic Acid / Q000009:adverse effects*
D014635:Valproic Acid; D000641:Ammonia