Adolescent diagnosis of pyridoxine-dependent epilepsy

Pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive metabolic epilepsy classically presenting with refractory neonatal seizures that respond to pharmacological doses of pyridoxine (vitamin B6). Although traditionally regarded as a neonatal disorder, later presentations are increasingly recognised. We report an adolescent patient with long-standing treatment-resistant epilepsy and learning disability who was ultimately diagnosed with PDE. Whole genome sequencing identified compound-heterozygous pathogenic variants in ALDH7A1. The diagnosis was further supported by elevated urinary and plasma α-aminoadipic semialdehyde levels. Initiation of pyridoxine therapy combined with lysine-reduction treatment resulted in sustained seizure control and allowed gradual withdrawal of conventional antiseizure medications. This case highlights the importance of considering PDE in older children and adolescents with refractory epilepsy and neurodevelopmental impairment and demonstrates the value of integrating genomic and metabolic investigations to establish a definitive diagnosis.