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.
MeSH terms
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2-Aminoadipic Acid / analogs & derivatives*
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2-Aminoadipic Acid / urine
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Aldehyde Dehydrogenase / genetics*
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Brain / metabolism
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Brain / pathology
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Child, Preschool
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Consanguinity*
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DNA Mutational Analysis
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Developmental Disabilities / diagnosis
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Developmental Disabilities / drug therapy
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Developmental Disabilities / genetics
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Developmental Disabilities / urine
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Diagnosis, Differential
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Diffusion Magnetic Resonance Imaging
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Electroencephalography / drug effects
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Epilepsy / diagnosis*
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Epilepsy / drug therapy
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Epilepsy / genetics*
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Epilepsy / urine
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Exons / genetics
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Female
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Genetic Carrier Screening
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Homozygote
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Humans
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Infant
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Infant, Newborn
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Leucovorin / therapeutic use
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Male
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Metal Metabolism, Inborn Errors / diagnosis*
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Metal Metabolism, Inborn Errors / drug therapy
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Metal Metabolism, Inborn Errors / genetics*
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Metal Metabolism, Inborn Errors / urine
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Molybdoferredoxin / genetics
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Molybdoferredoxin / urine
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Neurologic Examination / drug effects
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Pyridoxal Phosphate / deficiency
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Pyridoxal Phosphate / metabolism
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Pyridoxine / therapeutic use
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Sequence Analysis, DNA
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Sulfurtransferases / genetics
Substances
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Molybdoferredoxin
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2-Aminoadipic Acid
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allysine
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Pyridoxal Phosphate
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ALDH7A1 protein, human
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Aldehyde Dehydrogenase
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Sulfurtransferases
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molybdopterin synthase
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Pyridoxine
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Leucovorin
Supplementary concepts
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Molybdenum cofactor deficiency
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Pyridoxine-dependent epilepsy