Is oxidative stress an overlooked player in pyridoxine-dependent epilepsy? A focused review

Abstract

Pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive developmental and epileptic encephalopathy that is responsive to pharmacologic doses of vitamin B₆. The deficiency of antiquitin, an enzyme involved in the catabolism of lysine, is believed to be its key molecular basis. Research to date has tended to focus on two known catabolic pathways of lysine, namely, saccharopine and pipecolic acid. However, the occurrence of oxidative stress and the presence of its metabolites have been only briefly highlighted in the literature. Owing to the importance of the topic and its potential for future diagnosis, prognosis and therapy, this paper reviews the suggested mechanisms of oxidative stress in antiquitin deficiency along with the proposed reactions and intermediates, and finally, discusses the challenges and opportunities.

Keywords: Oxidative stress; PDE-ALDH7A1/Antiquitin deficiency; Pyridoxine-dependent epilepsy; Vitamin B(6)-dependent seizures.