Valproic acid and secondary hyperammonemia

An 11-year-old girl with complex seizures was started on valproic acid (VPA) in addition to clonazepam and ethosuximide. Shortly thereafter, she developed marked hyperammonemia that was worsened by a protein load. The hyperammonemia improved somewhat when protein was not given, and it resolved on discontinuation of the valproic acid. No associated changes in serum transaminases or bilirubin were observed. Isolated hyperammonemia may occur soon after VPA ingestion and appears to be a relatively infrequent, reversible side effect. The mechanism of hyperammonemia probably differs from other manifestations of hepatotoxicity, such as elevated transaminases or frank hepatic failure.