Asymptomatic hyperammonemia in children treated with valproic acid

It is known that valproic acid changes the ammonia metabolism. It has been suggested that blood ammonia levels do not correlate with valproate-induced encephalopathy.(1,2) In addition, the hyperammonemia together with encephalopathy was reported both with hepatic dysfunction and without it.(3-5). It was also reported that therapy with valproic acid led to the decreased plasma free carnitine concentration associated with hyperammonemia.(6,7) Ohtani et al(8) reported that there was a negative correlation between plasma ammonia and carnitine levels in patients taking valproic acid, and after giving L-carnitine (50 mg/kg/day) for 4 weeks, both hyperammonemia and carnitine deficiency were improved. We planned this study in patients without hepatic dysfunction and taking valproic acid to evaluate: (1) whether or not hyperammonemia rises; (2) if it is symptomatic; (3) if it rises, to what extent; (4) which variables affect it; and (5) if it is responsive to oral L-carnitine, and if so, how long carnitine therapy should be given to these patients.