title: Simultaneous determination of alpha-aminoadipic semialdehyde, piperideine-6-carboxylate and pipecolic acid by LC-MS/MS for pyridoxine-dependent seizures and folinic acid-responsive seizures.
abstract: Pyridoxine-dependent seizures (PDS) is an autosomal recessive disorder characterized by seizures presenting in neonates or infants up to 3 years of age which respond to pharmacological doses of pyridoxine. Alpha-aminoadipic semialdehyde dehydrogenase (antiquitin) deficiency was identified as an underlying defect in PDS characterized by accumulation of alpha-aminoadipic semialdehyde (alpha-AASA) as a specific marker and recently folinic acid-responsive seizures (FRS) were found to be allelic to PDS as the putative mutations were identified in the antiquitin gene (ALDH7A1). alpha-AASA is known to be in reversible equilibrium with its cyclic Shiff base, delta(1)-piperideine-6-carboxylate (P6C). Pipecolic acid (PA) is another biomarker often elevated but is not specific to PDS. Here, we developed the liquid chromatography-mass spectrometry (LC-MS/MS) method to determine the analytes of alpha-AASA, P6C and PA simultaneously in plasma and validated the assay using samples from confirmed cases. This approach eliminates the extra time and expense of running multiple assays and provides valuable information for the rapid diagnosis and treatment of patients with PDS and FRS which potentially could lead to a better outcome with improved quality of life. The stability study showed that alpha-AASA and P6C were unstable even at -20 degrees C. A careful sample handling with immediate freezing and testing is required for reliable result.
authors.affiliation: Seattle Children's Research Institute, Seattle, WA 98101, United States. katerina.sadilkova@seattlechildrens.org
authors.forename: Katerina
authors.initials: K
authors.lastname: Sadilkova
authors.forename: Sidney M
authors.initials: SM
authors.lastname: Gospe
authors.forename: Si Houn
authors.initials: SH
authors.lastname: Hahn
mesh_terms: D015074:2-Aminoadipic Acid / Q000031:analogs & derivatives* / Q000097:blood; D000444:Aldehyde Dehydrogenase / Q000235:genetics; D000818:Animals; D002138:Calibration; D002417:Cattle; D002648:Child; D002675:Child, Preschool; D002853:Chromatography, Liquid / Q000379:methods*; D006801:Humans; D002955:Leucovorin / Q000627:therapeutic use; D013058:Mass Spectrometry / Q000379:methods*; D010848:Picolinic Acids / Q000097:blood*; D010875:Pipecolic Acids / Q000097:blood*; D055550:Protein Stability; D012640:Seizures / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D013696:Temperature; D013997:Time Factors
chemical_list: D010848:Picolinic Acids; D010875:Pipecolic Acids; D015074:2-Aminoadipic Acid; C008919:delta-1-piperidine-6-carboxylic acid; C000061:allysine; C089507:ALDH7A1 protein, human; D000444:Aldehyde Dehydrogenase; C031345:pipecolic acid; D002955:Leucovorin