Pyridoxine-dependent epilepsy with elevated urinary α-amino adipic semialdehyde in molybdenum cofactor deficiency

• Published in: Pediatrics (Evanston) 2012-12, Vol.130 (6), p.e1716-e1719
• Main Authors: Struys, Eduard Alexander, Nota, Benjamin, Bakkali, Abdellatif, Al Shahwan, Saad, Salomons, Gajja Sophi, Tabarki, Brahim
• Format: Article
• Language: English
• Subjects: 2-Aminoadipic Acid - analogs & derivatives; 2-Aminoadipic Acid - urine; Aldehyde Dehydrogenase - genetics; Brain - metabolism; Brain - pathology; Child, Preschool; Consanguinity; Developmental Disabilities - diagnosis; Developmental Disabilities - drug therapy; Developmental Disabilities - genetics; Developmental Disabilities - urine; Diagnosis, Differential; Diffusion Magnetic Resonance Imaging; DNA Mutational Analysis; Electroencephalography - drug effects; Epilepsy - diagnosis; Epilepsy - drug therapy; Epilepsy - genetics; Epilepsy - urine; Exons - genetics; Female; Genetic Carrier Screening; Homozygote; Humans; Infant; Infant, Newborn; Leucovorin - therapeutic use; Male; Metal Metabolism, Inborn Errors - diagnosis; Metal Metabolism, Inborn Errors - drug therapy; Metal Metabolism, Inborn Errors - genetics; Metal Metabolism, Inborn Errors - urine; Molybdoferredoxin - genetics; Molybdoferredoxin - urine; Neurologic Examination - drug effects; Pyridoxal Phosphate - deficiency; Pyridoxal Phosphate - metabolism; Pyridoxine - therapeutic use; Sequence Analysis, DNA; Sulfurtransferases - genetics
• ISSN: 0031-4005; 1098-4275
• DOI: 10.1542/peds.2012-1094

α-Amino adipic semialdehyde (α-AASA) accumulates in body fluids from patients with pyridoxine-dependent epilepsy because of mutations in antiquitin (ALDH7A1) and serves as the biomarker for this condition. We have recently found that the urinary excretion of α-AASA was also increased in molybdenum cofactor and sulfite oxidase deficiencies. The seizures in pyridoxine-dependent epilepsy are caused by lowered cerebral levels of pyridoxal-5-phosphate (PLP), the bioactive form of pyridoxine (vitamin B(6)), which can be corrected by the supplementation of pyridoxine. The nonenzymatic trapping of PLP by the cyclic form of α-AASA is causative for the lowered cerebral PLP levels. We describe 2 siblings with clinically evident pyridoxine-responsive seizures associated with increased urinary excretion of α-AASA. Subsequent metabolic investigations revealed several metabolic abnormities, all indicative for molybdenum cofactor deficiency. Molecular investigations indeed revealed a known homozygous mutation in the MOCS2 gene. Based upon the clinically evident pyridoxine-responsive seizures in these 2 siblings, we recommend considering pyridoxine supplementation to patients affected with molybdenum cofactor or sulfite oxidase deficiencies.