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: Eduard Alexander Struys, Benjamin Nota, Abdellatif Bakkali, Saad Al Shahwan, Gajja Sophi Salomons, Brahim Tabarki
• Journal: Pediatrics (Pediatrics) Vol. 130 Issue 6 Pg. e1716-9 (Dec 2012) ISSN: 1098-4275 [Electronic] United States
• PMID: 23147983 (Publication Type: Case Reports, Journal Article)

Chemical References

• Molybdoferredoxin
• 2-Aminoadipic Acid
• allysine
• Pyridoxal Phosphate
• ALDH7A1 protein, human
• Aldehyde Dehydrogenase
• Sulfurtransferases
• molybdopterin synthase
• Pyridoxine
• Leucovorin

Topics

• 2-Aminoadipic Acid (analogs & derivatives, urine)
• Aldehyde Dehydrogenase (genetics)
• Brain (metabolism, pathology)
• Child, Preschool
• Consanguinity
• DNA Mutational Analysis
• Developmental Disabilities (diagnosis, drug therapy, genetics, urine)
• Diagnosis, Differential
• Diffusion Magnetic Resonance Imaging
• Electroencephalography (drug effects)
• Epilepsy (diagnosis, drug therapy, genetics, urine)
• Exons (genetics)
• Female
• Genetic Carrier Screening
• Homozygote
• Humans
• Infant
• Infant, Newborn
• Leucovorin (therapeutic use)
• Male
• Metal Metabolism, Inborn Errors (diagnosis, drug therapy, genetics, urine)
• Molybdoferredoxin (genetics, urine)
• Neurologic Examination (drug effects)
• Pyridoxal Phosphate (deficiency, metabolism)
• Pyridoxine (therapeutic use)
• Sequence Analysis, DNA
• Sulfurtransferases (genetics)