Research Article Increased Occurrence of Valproic Acid-Induced Hyperammonemia in Carriers of T1405N Polymorphism in

Copyright © 2013 Piotr K. Janicki et al.This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Numerous cases of severe and life-threatening hyperammonemia (HA) related to the treatment of epileptic seizures with valproic acid (VPA) have been previously reported in the medical literature. The aim of this prospective, multicenter study was to verify the putative association between T1405 polymorphism and occurrence of VPA-induced HA in the cohort of 142 adult Caucasian patients with epilepsy treated with VPA for at least 1 year and with normal liver functions. The nonsynonymous T1405N polymorphism genotyping was performed by real-time TaqMan PCR genotyping. In addition to plasma ammonia level, concentrations of liver enzymes and total VPA were measured in plasma with standard laboratory methods. HA (defined as ammonia plasma level>6