RESUMO
OBJECTIVE: To evaluate the efficacy and safety of dietary lysine restriction as an adjunct to pyridoxine therapy on biochemical parameters, seizure control, and developmental/cognitive outcomes in children with pyridoxine-dependent epilepsy (PDE) caused by antiquitin (ATQ) deficiency. METHODS: In this observational study, seven children with confirmed ATQ deficiency were started on dietary lysine restriction with regular nutritional monitoring. Biochemical outcomes were evaluated using pipecolic acid and α-aminoadipic semialdehyde (AASA) levels in body fluids; developmental/cognitive outcomes were evaluated using age-appropriate tests and parental observations. RESULTS: Lysine restriction was well tolerated with good compliance; no adverse events were reported. Reduction in biomarker levels (measurement of the last value before and first value after initiation of dietary lysine restriction) ranged from 20 to 67% for plasma pipecolic acid, 13 to 72% for urinary AASA, 45% for plasma AASA and 42% for plasma P6C. For the 1 patient in whom data were available and who showed clinical deterioration upon interruption of diet, cerebrospinal fluid levels decreased by 87.2% for pipecolic acid and 81.7% for AASA. Improvement in age-appropriate skills was observed in 4 out of 5 patients showing pre-diet delays, and seizure control was maintained or improved in 6 out 7 children. CONCLUSIONS: This observational study provides Level 4 evidence that lysine restriction is well tolerated with significant decrease of potentially neurotoxic biomarkers in different body compartments, and with the potential to improve developmental outcomes in children with PDE caused by ATQ deficiency. To generate a strong level of evidence before this potentially burdensome dietary therapy becomes the mainstay treatment, we have established: an international PDE consortium to conduct future studies with an all-inclusive integrated study design; a website containing up-to-date information on PDE; a methodological toolbox; and an online registry to facilitate the participation of interested physicians, scientists, and families in PDE research.