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 Δ1-piperideine-6-carboxylate (P6C)–α-aminoadipic semialdehyde (α-AASA) dehydrogenase. The accumulating P6C inactivates pyridoxal 5′-phosphate (PLP) by forming a Knoevenagel condensation product. Measurement of urinary α-AASA provides a simple way of confirming the diagnosis of PDS and ALDH7A1 gene analysis provides a means for prenatal diagnosis