Pyridoxine-dependent seizures in Dutch patients: diagnosis by elevated urinary alpha-aminoadipic semialdehyde levels

Arch Dis Child. 2007 Aug;92(8):687-9. doi: 10.1136/adc.2006.103192. Epub 2006 Nov 6.


Background: Pyridoxine-dependent seizures (PDS) is a rare, autosomal recessively inherited disorder. Recently alpha-aminoadipic semialdehyde (alpha-AASA) dehydrogenase deficiency was identified as a major cause of PDS, which causes accumulation of both alpha-AASA and pipecolic acid (PA) in body fluids.

Methods: We studied urinary and plasma alpha-AASA and PA levels in 12 Dutch clinically diagnosed patients with PDS.

Results: Alpha-AASA was elevated in both urine and plasma in 10 patients. In these patients plasma PA levels were also elevated but urinary PA levels were normal.

Discussion: In all patients with clinically definite PDS, and in most patients with probable or possible PDS, the clinical diagnosis of PDS could be confirmed at the metabolite level. Non-invasive urinary screening for alpha-AASA accumulation provides a reliable tool to diagnose PDS and can save these patients from the classical and potentially dangerous pyridoxine withdrawal test to prove PDS.

MeSH terms

  • Aldehyde Dehydrogenase / blood
  • Aldehyde Dehydrogenase / urine
  • Biomarkers / blood
  • Biomarkers / urine
  • Female
  • Humans
  • Hyperlysinemias / diagnosis*
  • Netherlands
  • Pipecolic Acids* / blood
  • Pipecolic Acids* / urine
  • Pyridoxine / therapeutic use
  • Seizures / blood
  • Seizures / diagnosis*
  • Seizures / urine
  • Vitamin B Complex / therapeutic use


  • Biomarkers
  • Pipecolic Acids
  • Vitamin B Complex
  • ALDH7A1 protein, human
  • Aldehyde Dehydrogenase
  • Pyridoxine