Title: Pyridoxine dependent epilepsy: beyond ALDH7A1 gene mutation

Objectives: Profile of pyridoxine dependent (PDE) epilepsy in Oman.

Introduction: PDE are group of metabolic seizures, which respond to pyridoxine and no antiepileptic drugs. The most common mutation known is ALDH7A1. ¹ PROSC mutation was recognized recently. ²

Methods: The children with refractory neonatal and early infancy onset seizures who responded to pyridoxine were analyzed. The diagnosis was based on control of seizures on pyridoxine. The children were divided into four groups depending on the clinical response and genetic mutations.

Results: Thirty-five children with PDE were seen. Four patterns were observed. PDE with ALDH7A1 gene mutation-4children, PDE with PROSC mutation-4, PDE with neither ALDH7A1 nor PROSC mutation-20 and pyridoxine responsive seizures (response to combination of pyridoxine and antiepileptic drugs combination). Discussion: PDE should be considered always in childhood refractory seizures particularly less than three years of age. Any type of seizure can be seen in PDE. ALDH7A1 mutation was the only gene known to be associated with PDE. ¹ Recently PROSC gene mutation was found to be associated with PDE. ² A larger group of our children who responded to pyridoxine had no known genetic defect.

Conclusion: Non ALDH7A1 and non PROSC PDE were common in this country. Future genetic work may find a new novel gene or another disorder responding to pyridoxine.

Reference:

1. Mills BS, Struys K, Jakobs C et al. Mutation in antiquitin in individuals with pyridoxine dependent seizures. Nat Med 2006; 12:307-9.
2. Plecko B P, Zweier M, Begemann A et al. Confirmation of mutations in PROSC as a novel cause of vitamin B6 dependent epilepsy. J Med Genet 2017;0: 1-6, doi: 10.11.1136/jmedgenet-2017-104521.