Mutations in antiquitin in individuals with pyridoxine-dependent seizures.

Institute of Child Health, University College London with Great Ormond Street Hospital for Children National Health Service Trust, 30 Guilford Street, London, UK.
Nature Medicine (Impact Factor: 28.05). 04/2006; 12(3):307-9. DOI: 10.1038/nm1366
Source: PubMed

ABSTRACT We show here that children with pyridoxine-dependent seizures (PDS) have mutations in the ALDH7A1 gene, which encodes antiquitin; these mutations abolish the activity of antiquitin as a delta1-piperideine-6-carboxylate (P6C)-alpha-aminoadipic semialdehyde (alpha-AASA) dehydrogenase. The accumulating P6C inactivates pyridoxal 5'-phosphate (PLP) by forming a Knoevenagel condensation product. Measurement of urinary alpha-AASA provides a simple way of confirming the diagnosis of PDS and ALDH7A1 gene analysis provides a means for prenatal diagnosis.

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