Early-Onset Polymorphic Seizures and Hydrocephalus: A Clue to an Underlying Pyridoxine-Dependent Epilepsy

Abstract Pyridoxine-dependent epilepsy (PDE) is a rare epileptic encephalopathy characterized by early-onset, drug-resistant seizures. It is predominantly caused by mutations in the ALDH7A1 gene, which leads to accumulation of α-aminoadipic semialdehyde (α-AASA) and piperidine-6-carboxylate (P6C) that inactivate pyridoxal 5′-phosphate, an essential cofactor in neurotransmitter metabolism. Seizures are typically unresponsive to standard antiseizure medications but show marked reduction with pyridoxine therapy. We report a 6-month-old boy, born to parents with third-degree consanguinity, who developed drug-resistant seizures of varying semiology from day 2 of life, which showed complete cessation after addition of pyridoxine. Magnetic resonance imaging revealed hydrocephalus. Genetic testing confirmed a pathogenic ALDH7A1 variant. He remains seizure-free on pyridoxine, arginine, and a lysine-restricted diet. This case highlights the importance of early trial of pyridoxine in neonates with resistant seizures. Hydrocephalus is an important clue toward the diagnosis. Genetic confirmation and lifelong pyridoxine therapy, along with a lysine-restricted diet and parental counselling, can prevent recurrent seizures and neurological deterioration. Prompt recognition of PDE, especially in high-risk settings like consanguinity or atypical imaging, enables targeted treatment and improved neurodevelopmental outcomes.