Early-onset pyridoxine-dependent epilepsy due to ALDH7A1 deficiency: the first genetically confirmed case from...

Pyridoxine-dependent epilepsy (PDE) caused by aldehyde dehydrogenase 7 family member A1 (ALDH7A1) deficiency is a rare autosomal recessive epileptic encephalopathy. It typically presents in the neonatal period with intractable seizures responsive to high-dose vitamin B6. Atypical later-onset presentations expand the clinical spectrum. Early recognition is crucial to prevent irreversible neurodevelopmental impairment.

We report a 2-year-old Palestinian girl, born to consanguineous parents, who developed neonatal metabolic acidosis and encephalopathy, recurrent seizures from early infancy, and global developmental delay. EEG revealed epileptiform discharges, and brain MRI demonstrated partial agenesis of the corpus callosum and mild dilation of the lateral ventricle. Conventional antiepileptic therapy provided no improvement.

Whole-exome sequencing at 1 year and 8 months identified a homozygous 9.9 kb deletion in ALDH7A1, confirming PDE. High-dose pyridoxine (150 mg/day) achieved seizure control, allowing tapering of other antiepileptics. Supportive management included electrolyte monitoring and treatment of dehydration.

This case highlights the clinical heterogeneity of PDE-ALDH7A1, underscores the importance of early genetic testing, and demonstrates the efficacy of timely pyridoxine therapy.