title: Validation of an LC-MS/MS assay for detecting relevant disaccharides from keratan sulfate as a biomarker for Morquio A syndrome.
abstract: BACKGROUND
  Mucopolysaccharidosis IVA (MPS IVA, Morquio A syndrome) is an inherited lysosomal storage disease caused by deficiency of N-acetylgalactosamine-6-sulfatase (GALNS), an enzyme required for stepwise degradation of keratan sulfate (KS). We have developed a selective, sensitive, accurate and precise LC-MS/MS assay for the KS-derived disaccharides Galβ1-4GlcNAc(6S) and Gal(6S)β1-4GlcNAc(6S) in human urine and plasma using keratanase II digestion.
  
  
  RESULTS
  Mean accuracy was 96-106% in urine and 97-108% in plasma. Precision was high, with relative standard deviations of 1-2% (intra-day) and 2-5% (inter-day) in urine and 1-2% (intra-day) and 4-7% (inter-day) in plasma. The lower limit of quantitation was 0.026 µg/ml (plasma) and 0.104 µg/ml (urine), with a quantitation range of 0.026-5 µg/ml (plasma) and 0.104-20 µg/ml (urine).
  
  
  CONCLUSIONS
  Clinical sample analysis in 168 MPS IVA patients and 225 healthy controls demonstrates the clinical utility of this method.
authors: BioMarin Pharmaceutical Inc., Novato, CA 94949, USA.
authors: Lisa Argento
authors: LA
authors: Martell
authors: Robert L
authors: RL
authors: Cunico
authors: Jayoung
authors: J
authors: Ohh
authors: Wendy
authors: W
authors: Fulkerson
authors: Richard
authors: R
authors: Furneaux
authors: Erik D
authors: ED
authors: Foehr
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002648:Child; D002675:Child, Preschool; D002853:Chromatography, Liquid / Q000379:methods*; D004187:Disaccharides / Q000097:blood* / Q000652:urine*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007632:Keratan Sulfate / Q000097:blood* / Q000652:urine*; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D008875:Middle Aged; D009085:Mucopolysaccharidosis IV / Q000097:blood / Q000175:diagnosis* / Q000652:urine
chemical_list: D015415:Biomarkers; D004187:Disaccharides; D007632:Keratan Sulfate