title: Validation of disaccharide compositions derived from dermatan sulfate and heparan sulfate in mucopolysaccharidoses and mucolipidoses II and III by tandem mass spectrometry.
abstract: Glycosaminoglycans (GAGs) are accumulated in various organs in both mucopolysaccharidoses (MPS) and mucolipidoses II and III (ML II and III). MPS and ML II and III patients can not properly degrade dermatan sulfate (DS) and/or heparan sulfate (HS). HS storage occurs in the brain leading to neurological signs while DS storage involves mainly visceral and skeletal manifestations. Excessive DS and HS released into circulation and thus blood levels of both are elevated, therefore, DS and HS in blood could be critical biomarkers for MPS and ML. Such measurement can provide a potential early screening, assessment of the clinical course and efficacy of therapies. We here assay DS and HS levels in MPS and ML patients using liquid chromatography tandem mass spectrometry (LC/MS/MS). Plasma samples were digested by heparitinase and chondroitinase B to obtain disaccharides of DS and HS, followed by LC/MS/MS analysis. One hundred-twenty samples from patients and 112 control samples were analyzed. We found that all MPS I, II, III and VI patients had a significant elevation of all DS+HS compositions analyzed in plasma, compared with the controls (P<0.0001). Specificity and sensitivity was 100% if the cut off value is 800 ng/ml between control and these types of MPS group. All MPS I, II and III patients also had a significant elevation of plasma HS, compared with the controls (P<0.0001). All MPS VI patients had a significant elevation of plasma DS, compared with the controls (P<0.0001). These findings suggest measurement of DS and/or HS levels by LC/MS/MS is applicable to the screening for MPS I, II, III and VI patients.
authors.affiliation: Department of Pediatrics, Saint Louis University, St Louis, MO, United States. tomatsus@slu.edu
authors.forename: Shunji
authors.initials: S
authors.lastname: Tomatsu
authors.forename: Adriana M
authors.initials: AM
authors.lastname: Montaño
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Oguma
authors.forename: Vu Chi
authors.initials: VC
authors.lastname: Dung
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Oikawa
authors.forename: María L
authors.initials: ML
authors.lastname: Gutiérrez
authors.forename: Seiji
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Masaru
authors.initials: M
authors.lastname: Fukushi
authors.forename: Luis A
authors.initials: LA
authors.lastname: Barrera
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kida
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Kubota
authors.forename: Tadao
authors.initials: T
authors.lastname: Orii
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003871:Dermatan Sulfate / Q000097:blood* / Q000652:urine; D004187:Disaccharides / Q000097:blood*; D006025:Glycosaminoglycans / Q000652:urine; D006497:Heparan Sulfate / Q000097:blood* / Q000652:urine; D006801:Humans; D007223:Infant; D008875:Middle Aged; D009081:Mucolipidoses / Q000097:blood* / Q000652:urine; D009083:Mucopolysaccharidoses / Q000097:blood* / Q000652:urine; D053719:Tandem Mass Spectrometry / Q000379:methods*; D055815:Young Adult
chemical_list: D003871:Dermatan Sulfate; D004187:Disaccharides; D006025:Glycosaminoglycans; D006497:Heparan Sulfate