Mutations in antiquitin in individuals with pyridoxine-dependent seizures.
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.
Mills
Philippa B
PB
Institute of Child Health, University College London with Great Ormond Street Hospital for Children National Health Service Trust, 30 Guilford Street, London, UK.
Struys
Eduard
E
Jakobs
Cornelis
C
Plecko
Barbara
B
Baxter
Peter
P
Baumgartner
Matthias
M
Willemsen
Michèl A A P
MA
Omran
Heymut
H
Tacke
Uta
U
Uhlenberg
Birgit
B
Weschke
Bernhard
B
Clayton
Peter T
PT
D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D016466:CHO Cells; D002648:Child; D002675:Child, Preschool; D006224:Cricetinae; D003412:Cricetulus; D005091:Exons / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D009154:Mutation / Q000235:genetics*; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000378:metabolism; D010875:Pipecolic Acids / Q000378:metabolism; D011392:Proline / Q000378:metabolism; D011732:Pyridoxal Phosphate / Q000378:metabolism; D011736:Pyridoxine / Q000378:metabolism*; D012640:Seizures / Q000235:genetics*
D001426:Bacterial Proteins; D010875:Pipecolic Acids; D011732:Pyridoxal Phosphate; D011392:Proline; C089507:ALDH7A1 protein, human; D000444:Aldehyde Dehydrogenase; D000587:Oxidoreductases Acting on CH-NH Group Donors; C109029:delta-1-piperideine-6-carboxylate dehydrogenase; D011736:Pyridoxine