HYPERAMMONEMIC ENCEPHALOPATHY AFTER INITIATION OF VALPROATE THERAPY IN UNRECOGNIZED ORNITHINE TRANSCARBAMYLASE DEFICIENCY

Ornithine transcarbamylase deficiency is an X linked disorder and the most common inherited cause of hyperammonaemia. Fluctuating concentrat ions of ammonia, glutamine, and other excitotoxic amino acids result i n a chronic or episodically recurring encephalopathy. A heterozygous f emale patient first presented with protein intolerance, attacks of vom iting, and signs of mental retardation in early childhood. At the age of 16 complex partial seizures occurred which were treated with sodium valproate. Seven days after initiation of valproate therapy, she deve loped severe hyperammonaemic encephalopathy with deep somnolence. The maximum concentration of ammonia was 480 mu mol/l. After withdrawal of valproate, three cycles of plasma dialysis, and initiation of a speci fic therapy for the inborn metabolic disease, ammonia concentrations f ell to normal values. The patient remitted, returning to her premorbid state. Valproate can cause high concentrations of ammonia in serum in patients with normal urea cycle enzymes and may worsen a pre-existing hyperammonaemia caused by an enzymatic defect of the urea cycle. Suff icient diagnostic tests for the detection of metabolic disorders must be performed before prescribing valproate for patients with a history of encephalopathy.