A 20-month-old boy with developmental regression and myoclonic seizures is being considered for sodium valproate. Which underlying condition makes him at the highest risk for fatal idiosyncratic valproate-induced hepatotoxicity?
- A Febrile seizures with benign outcome
- B Suspected mitochondrial disease such as Alpers-Huttenlocher syndrome ✓
- C Childhood absence epilepsy
- D Benign rolandic epilepsy
Correct answer: B. Suspected mitochondrial disease such as Alpers-Huttenlocher syndrome
Explanation
Valproate hepatotoxicity risk is highest in children under 2 years receiving polytherapy, and it is especially concentrated in patients with inherited mitochondrial disorders such as Alpers-Huttenlocher syndrome, where POLG mutations impair mitochondrial DNA maintenance. Valproate inhibits mitochondrial beta-oxidation and complexes of the respiratory chain, precipitating fulminant hepatic failure. Genetic testing for POLG mutations before valproate exposure is advised in such children. Absence epilepsy responds to valproate without excess hepatic risk.
Reference: Nelson Textbook of Pediatrics, 21st ed.
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