Rapid and sensitive screening for and chemical diagnosis of Canavan disease by gas chromatography-mass spectrometry.
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.
Inoue
Y
Y
Division of Human Genetics, Medical Research Institute, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 9200293, Japan.
Kuhara
T
T
D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000652:urine*; D017825:Canavan Disease / Q000175:diagnosis* / Q000652:urine; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015997:Neonatal Screening; D010865:Pilot Projects
D001224:Aspartic Acid; C000179:N-acetylaspartate