Rapid and sensitive screening for and chemical diagnosis of Canavan disease by gas chromatography-mass spectrometry

J Chromatogr B Analyt Technol Biomed Life Sci. 2004 Jun 25;806(1):33-9. doi: 10.1016/j.jchromb.2004.03.018.


The use of a rapid and sensitive assay for N-acetylaspartate (NAA) in urine or eluates from dried urine on filter paper to make a chemical diagnosis of Canavan disease (CD) is described. It involves a simplified urease pretreatment for sample preparation and gas chromatography-mass spectrometry (EI, scanning mode) with or without stable isotope dilution. Significant improvements in the recovery of NAA and the GC-MS data-handling device made the assay without stable isotope dilution sensitive and quantitative enough to diagnose CD: Its coefficient of variation (CV) was below 12%. The CV obtained with stable isotope dilution was below 9%. One patient with CD had an abnormal NAA level that was more than 6 S.D. above the mean of the age-matched controls. This diagnostic procedure is accurate for screening and for the chemical diagnosis of CD, with a good cost:benefit ratio. The urinary NAA levels of the healthy controls decreased significantly with age. This change should be considered in making a chemical diagnosis of this disease.

MeSH terms

  • Aspartic Acid / analogs & derivatives*
  • Aspartic Acid / urine*
  • Canavan Disease / diagnosis*
  • Canavan Disease / urine
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Female
  • Gas Chromatography-Mass Spectrometry / methods*
  • Humans
  • Infant
  • Infant, Newborn
  • Neonatal Screening
  • Pilot Projects


  • Aspartic Acid
  • N-acetylaspartate