Challenges and potential of an early lysine-restricted diet for pyridoxine-dependent epilepsy: A case report

Pyridoxine-dependent epilepsy (PDE) is caused by biallelic disease-associated variants in the ALDH7A1 gene, leading to the accumulation of neurotoxic intermediates such as α-aminoadipic semialdehyde (α-AASA), despite adequate seizure control with pyridoxine. This accumulation is thought to contribute to intellectual and developmental impairments. We report a case of PDE in a Japanese patient for whom a lysine-restricted diet involving a lysine- and tryptophan-free amino acid formula was introduced from early infancy. In this case, maternal pyridoxine treatment was also initiated prenatally. After birth, the patient was started on this formula together with oral arginine supplementation. The patient's serum α-AASA and pipecolic acid levels initially decreased following dietary intervention but gradually increased with age. Despite early diagnosis and treatment, the patient exhibited a significant delay in expressive language and a moderate delay in motor development, whereas other developmental domains remained within the normal to borderline range. Importantly, no clinical seizures have occurred since birth. This is the first report of a Japanese patient with PDE who was treated with a lysine-restricted diet from infancy and whose clinical outcome was followed until 4 years of age. Although such dietary management may contribute to metabolic control, it requires sustained commitment and substantial effort from the family. Early diagnosis and timely initiation of treatment are critical for optimizing developmental outcomes. More case-based data and practical guidance on dietary adaptation are needed to improve long-term care strategies for PDE.