Abstract / Summary
Abstract Background Valproate is a broad-spectrum antiseizure medication widely used in pediatric epilepsy. Hyperammonemia and hyperammonemic encephalopathy are recognized adverse effects and may occur despite therapeutic valproate concentrations and normal liver function tests. Down syndrome is associated with mitochondrial dysfunction, but whether it confers additional susceptibility to valproate-induced hyperammonemic encephalopathy is unknown. Case Presentation: An 8-year-old boy with Down syndrome and epilepsy secondary to a remote left middle cerebral artery infarction presented with recurrent difficult-to-control seizures, including daily myoclonic seizures, drop attacks, and generalized tonic-clonic seizures. Valproate was initiated at 15 mg/kg/day. Four days later, he developed progressive encephalopathy requiring pediatric intensive care admission. Laboratory evaluation demonstrated severe hyperammonemia (750 µmol/L) despite therapeutic serum valproate concentration and normal liver function tests. Valproate was discontinued and intravenous sodium benzoate/sodium phenylacetate therapy was initiated. Ammonia levels normalized over approximately 48 hours with complete neurological recovery. Conclusion This case highlights the rapid onset of severe valproate-induced hyperammonemic encephalopathy despite a therapeutic serum valproate concentration and normal liver function tests. It raises, but does not establish, the possibility that underlying mitochondrial dysfunction in Down syndrome may modify susceptibility.