Valproic Acid Induced Hyperammonemia: A Case Report

Valproic acid (VPA) is a widely used antiepileptic and mood-stabilizing drug, but its administration is associated with various adverse effects, including hyperammonaemia. Valproic acid-induced hyperammonaemia (VPA-IH) is a potentially serious metabolic disturbance that can lead to encephalopathy, cognitive dysfunction, lethargy, vomiting, and, in severe cases, coma. The underlying mechanisms of VPA-IH are multifactorial and may include inhibition of carbamoyl phosphate synthetase I (CPSI) in the urea cycle, increased mitochondrial toxicity, and disruption of glutamine metabolism. Risk factors for VPA-IH include polypharmacy, especially with other antiepileptic drugs, underlying urea cycle disorders, liver dysfunction, and genetic predisposition. While some patients with VPA-IH remain asymptomatic, others develop valproate-induced encephalopathy (VIE), necessitating prompt recognition and management. Diagnosis involves measuring plasma ammonia levels, especially in patients with unexplained neurological symptoms while on VPA therapy. Management strategies include discontinuation or dose reduction of VPA, administration of alternative anticonvulsants, and use of ammonia-lowering agents such as L-carnitine, sodium benzoate, or lactulose in severe cases. Monitoring of ammonia levels and liver function tests is crucial in patients on long-term VPA therapy. Awareness of VPA-IH among clinicians can facilitate early diagnosis and prevent serious complications. Future research should focus on identifying genetic markers for susceptibility and optimizing treatment strategies for affected individuals.