Mutations in antiquitin in individuals with pyridoxine-dependent seizures

Nat Med. 2006 Mar;12(3):307-9. doi: 10.1038/nm1366. Epub 2006 Feb 19.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehyde Dehydrogenase / genetics*
  • Animals
  • Bacterial Proteins / metabolism
  • CHO Cells
  • Child
  • Child, Preschool
  • Cricetinae
  • Cricetulus
  • Exons / genetics
  • Heterozygote
  • Homozygote
  • Humans
  • Mutation / genetics*
  • Oxidoreductases Acting on CH-NH Group Donors / metabolism
  • Pipecolic Acids / metabolism
  • Proline / metabolism
  • Pyridoxal Phosphate / metabolism
  • Pyridoxine / metabolism*
  • Seizures / genetics*

Substances

  • Bacterial Proteins
  • Pipecolic Acids
  • Pyridoxal Phosphate
  • Proline
  • ALDH7A1 protein, human
  • Aldehyde Dehydrogenase
  • Oxidoreductases Acting on CH-NH Group Donors
  • delta-1-piperideine-6-carboxylate dehydrogenase
  • Pyridoxine