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Valproate-induced coma with ketosis and carnitine insufficiency
W J Triggs1, T P Bohan, S N Lin
1Department of Neurology, University of Texas Medical School Health Science Center, Houston.
Archives of Neurology
|October 1, 1990
Summary
Valproate can cause coma in patients with low carnitine levels, even within therapeutic ranges. This suggests a potential metabolic predisposition to valproate-induced encephalopathy.
Area of Science:
- Neurology
- Metabolic Disorders
- Pharmacology
Background:
- Valproate is a widely used antiepileptic and mood-stabilizing drug.
- Encephalopathy is a known, though rare, complication of valproate therapy.
- The exact mechanisms underlying valproate-induced encephalopathy remain incompletely understood.
Observation:
- Two patients developed coma while receiving valproate (32-40 mg/kg/day).
- Both patients exhibited ketosis and adipic aciduria.
- Plasma free carnitine levels were reduced during coma and post-recovery.
Findings:
- Normal valproate levels and liver function tests were noted.
- One patient showed ethylmalonic acid, butyrylcarnitine, and glutarylcarnitine excretion.
- These findings suggest a possible multiple acyl-CoA dehydrogenation defect.
Implications:
- Low serum carnitine levels may increase susceptibility to valproate-induced altered consciousness.
- Carnitine deficiency could be a risk factor for valproate-associated encephalopathy.
- Further investigation into carnitine status in patients treated with valproate is warranted.