POLG – Valproate Fatal Risk — SCE Neurology MCQ

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HardEpilepsy & Seizure DisordersPOLG – Valproate Fatal RiskSCE Neurology

A 55-year-old woman with epilepsy has a POLG mutation. Why is valproate specifically contraindicated?

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Correct answer: B — Valproate can trigger fatal hepatotoxicity (Alpers syndrome) in POLG mutations — an MHRA contraindication

POLG mutations impair mitochondrial function. Valproate inhibits mitochondrial beta-oxidation, precipitating fatal hepatocerebral degeneration. MHRA lists POLG as a contraindication. Consider POLG testing before VPA in patients with epilepsy + features of mitochondrial disease. A: Potentially fatal risk. C: Not the mechanism. D: Not sedation. E: Multiple AEDs can be used.

Reference: MHRA; BNF; NICE NG217