title: Valproate use associated with persistent hyperammonemia and mitochondrial injury in a child with Down's syndrome.
abstract: Valproate is a commonly prescribed anticonvulsant drug that may cause potentially fatal hepatotoxicity, bone-marrow toxicity, and pancreatitis. Toxicity usually resolves, though, after discontinuation of the medication. We report a 9-year-old boy who had Down's syndrome and who developed valproate-associated bone marrow toxicity, and hepatotoxicity that persisted greater than 2 years after discontinuation of valproate therapy. Three years after starting valproate, he developed erythrocyte aplasia with a severe, normochromic, macrocytic anemia requiring several blood transfusions. Several months later while still receiving valproate, he developed progressive hyperammonemia and decreased hepatic synthetic function. The macrocytic anemia resolved and hepatic synthetic function improved after discontinuation of valproate therapy. However, hyperammonemia, steatosis, mitochondrial injury, and marked hepatic iron accumulation persisted greater than 2 years after the valproate was discontinued. The persistent hyperammonemia was responsive to lactulose therapy. A decrease in hepatic iron content by serial phlebotomies did not result in any improvement in the hyperammonemia or hepatic synthetic function. This is the first report of persistent hyperammonemia and hepatic mitochondrial injury after valproic acid therapy.
authors.affiliation: Department of Pediatrics, St. Louis University School of Medicine, Missouri.
authors.forename: R E
authors.initials: RE
authors.lastname: Kane
authors.forename: S
authors.initials: S
authors.lastname: Kotagel
authors.forename: B R
authors.initials: BR
authors.lastname: Bacon
authors.forename: C A
authors.initials: CA
authors.lastname: Vogler
mesh_terms: D000641:Ammonia / Q000097:blood*; D001853:Bone Marrow / Q000187:drug effects; D002675:Child, Preschool; D004314:Down Syndrome / Q000150:complications; D005500:Follow-Up Studies; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D008928:Mitochondria / Q000187:drug effects*; D011517:Prothrombin Time; D012640:Seizures / Q000150:complications / Q000188:drug therapy; D012709:Serum Albumin; D014635:Valproic Acid / Q000009:adverse effects*
chemical_list: D012709:Serum Albumin; D014635:Valproic Acid; D000641:Ammonia