The risk of asymptomatic hyperammonemia in children with idiopathic epilepsy treated with valproate: Relationship to blood carnitine status

Abstract

Valproate (VPA) administration may be associated with adverse metabolic effects, among is hyperammonemia, which could suggest metabolic abnormalities as carnitine deficiency. This study aimed to evaluate the risk frequency of hyperammonemia and abnormal carnitine levels in children receiving VPA who were otherwise free of neurological or obvious nutritional problems. Ammonia levels were prospectively evaluated in 60 epileptic children with primary epilepsy free of neurological or nutritional problems and were treated with VPA for at least 1 year. Forty healthy children were included as controls. Ammonia levels were correlated with total carnitine (TC), free carnitine (FC), acylcarnitine (AC) and AC/FC ratio. The abnormal ammonia and carnitine levels were also re-checked after 3 months treatment with L-carnitine. Compared to pre-treatment and control levels, the mean TC and FC were lower (p<0.001) while ammonia (p<0.01), AC (p<0.05) and AC/FC ratio (p<0.01) were higher. In the treated group of epileptics, TC and FC were negatively associated with ammonia (r=-0.896, p<0.0001; r=-0.935, p<0.0001). Significant associations were found between FC and AC/FC levels and patient's age (FC; r=0.457, p<0.05, AC/FC; r=-0.435, p<0.05) and dose of VPA (FC; r=-0.753, p<0.001, AC/FC; r=0.591, p<0.01). Ammonia was correlated with patients' age (r=-0.532, p<0.01) and dose of VPA (r=0.673, p<0.01). The abnormal ammonia and carnitine levels were returned to normal after L-carnitine supplementation. Epileptic children treated with VPA and free of neurological disabilities are at risk for hyperammonemia that may be associated with hypocarnitinemia. Patients will benefit from early recognition and preventive measures as carnitine supplementation.