Hyperammonaemic encephalopathy after initiation of valproatetherapy in unrecognised ornithine transcarbamylase deficiency

Ornithine transcarbamylase deficiency is an X linked disorderand the most common inherited cause of hyperammonaemia. Fluctuating concentrations of ammonia, glutamine, and otherexcitotoxic amino acids result in a chronic or episodically recurringencephalopathy. A heterozygous female patient first presented withprotein intolerance, attacks of vomiting, and signs of mentalretardation in early childhood. At the age of 16 complex partialseizures occurred which were treated with sodium valproate. Seven daysafter initiation of valproate therapy, she developed severehyperammonaemic encephalopathy with deep somnolence. The maximumconcentration of ammonia was 480 µmol/l. After withdrawal ofvalproate, three cycles of plasma dialysis, and initiation of aspecific therapy for the inborn metabolic disease, ammoniaconcentrations fell to normal values. The patient remitted, returningto her premorbid state. Valproate can cause high concentrations ofammonia in serum in patients with normal urea cycle enzymes and mayworsen a pre-existing hyperammonaemia caused by an enzymatic defect ofthe urea cycle. Sufficient diagnostic tests for the detection ofmetabolic disorders must be performed before prescribing valproate forpatients with a history of encephalopathy.