levoleucovorin and Metal-Metabolism--Inborn-Errors

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.

Topics: 2-Aminoadipic Acid; Aldehyde Dehydrogenase; Brain; Child, Preschool; Consanguinity; Developmental Disabilities; Diagnosis, Differential; Diffusion Magnetic Resonance Imaging; DNA Mutational Analysis; Electroencephalography; Epilepsy; Exons; Female; Genetic Carrier Screening; Homozygote; Humans; Infant; Infant, Newborn; Leucovorin; Male; Metal Metabolism, Inborn Errors; Molybdoferredoxin; Neurologic Examination; Pyridoxal Phosphate; Pyridoxine; Sequence Analysis, DNA; Sulfurtransferases