Classical and Emerging Biomarkers in Pyridoxine-Dependent Epilepsy (PDE-ALDH7A1): Implications for Early Diagnosis and Therapy

ALDH7A1 (biallelic LOF variants)

ALDH7A1 deficiency → blocked lysine catabolism → α-AASA and P6C accumulation → secondary PLP (pyridoxal-5'-phosphate) depletion → severe cofactor deficiency for GABA and serotonin decarboxylases

Comprehensive review of classical and emerging biomarkers in PDE-ALDH7A1, a pyridoxine-treatable recessive epileptic encephalopathy. Classical biomarkers (α-AASA and P6C in plasma/urine/CSF) have transformed the biological diagnosis of this disease, with new markers emerging: lysine, pipecolic acid, 2-oxoadipic acid, and derived ratios. The article discusses implications for early neonatal diagnosis and monitoring of treatment efficacy (pyridoxine + lysine-restricted diet).

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

PDE-ALDH7A1 is the archetype of treatable epileptic encephalopathy with late diagnosis. The combination of α-AASA + ALDH7A1 genotyping should be systematic in any pyridoxine-sensitive neonatal/infantile epilepsy. Emerging biomarkers open the way to biological monitoring beyond simple clinical seizure control.

clinically actionable biomarkers (therapeutic monitoring) +2; treatable disease (pyridoxine) +2; emerging new biomarkers +2; Biomolecules +1