A fatal hepatic failure in a 3 year-old girl with myoclonic epilepsy after 3 months of treatment with valproate (VPA) is reported from Hopital d’Enfants, Marseilles, and Hopital des Enfants-Malades, Paris, France. Elevated plasma lactate and lactate/pyruvate molar ratios in plasma suggested a defect in oxidative phosphorylation and prompted investigation of respiratory chain activity. Circulating lymphocytes revealed a cytochrome c oxidase (COX) deficiency, later confirmed by post-mortem analysis in liver and cultured skin fibroblasts. Skeletal muscle analysis was normal. 
COMMENT. Lactate/pyruvate plasma levels are recommended in children with possible mitochondrial disorders and epilepsy when VPA treatment is employed. Valproate associated hepatotoxicity is discussed in previous issues of Ped Neur Briefs Jan, May, and Aug 1993, and June 1987.