title: Heparan sulfate levels in mucopolysaccharidoses and mucolipidoses.
abstract: Glycosaminoglycans are accumulated in both mucopolysaccharidoses (MPS) and mucolipidoses (ML). MPS I, II, III and VII and ML II and ML III patients cannot properly degrade heparan sulphate (HS). In spite of the importance of HS storage in the metabolic pathway in these diseases, blood and urine HS levels have not been determined systematically using a simple and economical method. Using a new ELISA method using anti-HS antibodies, HS concentrations in blood and urine were determined in MPS and ML II and ML III patients. HS concentrations were determined in 156 plasma samples from MPS I (n = 23), MPS II (n = 26), MPS III (n = 24), MPS IV (n = 62), MPS VI (n = 5), MPS VII (n = 5), ML II (n = 8) and ML III (n = 3), and 205 urine samples from MPS I (n = 33), MPS II (n = 33), MPS III (n = 30), MPS IV (n = 82), MPS VI (n = 7), MPS VII (n = 9), ML II (n = 8) and ML III (n = 3). The ELISA method used monoclonal antibodies against HS. MPS I, II, III and VII and ML II and III patients had significant elevation in plasma HS, compared to the age-matched controls (p < 0.0001). Eighty-three out of 89 (93.3%) of individual values in the above MPS types and ML were above the mean +2SD of the controls. In urine samples, 75% of individual values in patients with those types were above the mean +2SD of the controls. In contrast to the previous understanding of the HS metabolic pathway, plasma HS levels in all five MPS VI and 15% of MPS IV patients were elevated above the mean +2SD of the controls. These findings suggest that HS concentration determined by ELISA, especially in plasma, could be a helpful marker for detection of the most severe MPS I, II, III, VI and VII and ML II, distinguishing them from normal populations.
authors.affiliation: Department of Pediatrics, Cardinal Glennon Children's Hospital, Saint Louis University, MO 63110-2586, USA. tomatsus@slu.edu
authors.forename: S
authors.initials: S
authors.lastname: Tomatsu
authors.forename: M A
authors.initials: MA
authors.lastname: Gutierrez
authors.forename: T
authors.initials: T
authors.lastname: Ishimaru
authors.forename: O M
authors.initials: OM
authors.lastname: Peña
authors.forename: A M
authors.initials: AM
authors.lastname: Montaño
authors.forename: H
authors.initials: H
authors.lastname: Maeda
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authors.initials: S
authors.lastname: Velez-Castrillon
authors.forename: T
authors.initials: T
authors.lastname: Nishioka
authors.forename: A A
authors.initials: AA
authors.lastname: Fachel
authors.forename: A
authors.initials: A
authors.lastname: Cooper
authors.forename: M
authors.initials: M
authors.lastname: Thornley
authors.forename: E
authors.initials: E
authors.lastname: Wraith
authors.forename: L A
authors.initials: LA
authors.lastname: Barrera
authors.forename: L S
authors.initials: LS
authors.lastname: Laybauer
authors.forename: R
authors.initials: R
authors.lastname: Giugliani
authors.forename: I V
authors.initials: IV
authors.lastname: Schwartz
authors.forename: G Schulze
authors.initials: GS
authors.lastname: Frenking
authors.forename: M
authors.initials: M
authors.lastname: Beck
authors.forename: S G
authors.initials: SG
authors.lastname: Kircher
authors.forename: E
authors.initials: E
authors.lastname: Paschke
authors.forename: S
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: K
authors.initials: K
authors.lastname: Ullrich
authors.forename: K
authors.initials: K
authors.lastname: Isogai
authors.forename: Y
authors.initials: Y
authors.lastname: Suzuki
authors.forename: T
authors.initials: T
authors.lastname: Orii
authors.forename: A
authors.initials: A
authors.lastname: Noguchi
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000378:metabolism; D002624:Chemistry, Clinical / Q000379:methods; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D006025:Glycosaminoglycans / Q000737:chemistry; D006493:Heparin / Q000737:chemistry; D006497:Heparan Sulfate / Q000097:blood / Q000737:chemistry* / Q000652:urine; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D009081:Mucolipidoses / Q000097:blood / Q000175:diagnosis* / Q000652:urine; D009083:Mucopolysaccharidoses / Q000097:blood / Q000175:diagnosis* / Q000652:urine
chemical_list: D015415:Biomarkers; D006025:Glycosaminoglycans; D006493:Heparin; D006497:Heparan Sulfate