title: Pyridoxine-dependent epilepsy with elevated urinary α-amino adipic semialdehyde in molybdenum cofactor deficiency.
abstract: 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.
authors.affiliation: Metabolic Unit, Department of Clinical Chemistry, VU Medical Center, Amsterdam, Netherlands. e.struys@vumc.nl
authors.forename: Eduard Alexander
authors.initials: EA
authors.lastname: Struys
authors.forename: Benjamin
authors.initials: B
authors.lastname: Nota
authors.forename: Abdellatif
authors.initials: A
authors.lastname: Bakkali
authors.forename: Saad
authors.initials: S
authors.lastname: Al Shahwan
authors.forename: Gajja Sophi
authors.initials: GS
authors.lastname: Salomons
authors.forename: Brahim
authors.initials: B
authors.lastname: Tabarki
mesh_terms: D015074:2-Aminoadipic Acid / Q000031:analogs & derivatives* / Q000652:urine; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002675:Child, Preschool; D003241:Consanguinity; D004252:DNA Mutational Analysis; D002658:Developmental Disabilities / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics / Q000652:urine; D003937:Diagnosis, Differential; D038524:Diffusion Magnetic Resonance Imaging; D004569:Electroencephalography / Q000187:drug effects; D004827:Epilepsy / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics* / Q000652:urine; D005091:Exons / Q000235:genetics; D005260:Female; D006580:Genetic Carrier Screening; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D002955:Leucovorin / Q000627:therapeutic use; D008297:Male; D008664:Metal Metabolism, Inborn Errors / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics* / Q000652:urine; D008983:Molybdoferredoxin / Q000235:genetics / Q000652:urine; D009460:Neurologic Examination / Q000187:drug effects; D011732:Pyridoxal Phosphate / Q000172:deficiency / Q000378:metabolism; D011736:Pyridoxine / Q000627:therapeutic use; D017422:Sequence Analysis, DNA; D013466:Sulfurtransferases / Q000235:genetics
chemical_list: D008983:Molybdoferredoxin; D015074:2-Aminoadipic Acid; C000061:allysine; D011732:Pyridoxal Phosphate; C089507:ALDH7A1 protein, human; D000444:Aldehyde Dehydrogenase; D013466:Sulfurtransferases; C085585:molybdopterin synthase; D011736:Pyridoxine; D002955:Leucovorin