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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aldehyde Dehydrogenase / genetics*
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Animals
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Bacterial Proteins / metabolism
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CHO Cells
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Child
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Child, Preschool
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Cricetinae
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Cricetulus
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Exons / genetics
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Heterozygote
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Homozygote
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Humans
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Mutation / genetics*
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Oxidoreductases Acting on CH-NH Group Donors / metabolism
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Pipecolic Acids / metabolism
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Proline / metabolism
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Pyridoxal Phosphate / metabolism
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Pyridoxine / metabolism*
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Seizures / genetics*
Substances
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Bacterial Proteins
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Pipecolic Acids
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Pyridoxal Phosphate
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Proline
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ALDH7A1 protein, human
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Aldehyde Dehydrogenase
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Oxidoreductases Acting on CH-NH Group Donors
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delta-1-piperideine-6-carboxylate dehydrogenase
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Pyridoxine