title: UPLC-MS/MS detection of disaccharides derived from glycosaminoglycans as biomarkers of mucopolysaccharidoses.
abstract: Mucopolysaccharidoses (MPSs) are a group of disorders resulting from primary defects in lysosomal enzymes involved in the degradation of glycosaminoglycans (GAGs). Depending on the specific enzyme defect, the catabolism of one or more GAGs is blocked leading to accumulation in tissues and biological fluids. GAG measurements are important for high-risk screening, diagnosis, monitoring treatment efficacy, and patient follow up. The dimethylmethylene blue (DMB) spectrophotometric method commonly used in most biochemical genetics laboratories relies on a non-specific total GAG analysis which has led to false positive results, and even false negative results (mainly for MPS III and IV patients). The main objective of our project was to devise and validate a reliable tandem mass spectrometry multiplex analysis for the urine quantitation of four GAGs (dermatan sulfate (DS), heparan sulfate (HS), keratan sulfate (KS), and chondroitin sulfate (CS)) for an eventual technological transfer to the clinic. The developed methodology is rapid (7 min) and our results showed good intraday and interday precision (RSDs ≤ 8.7%) and accuracy (Biases range: -12.0%-18.4%). Linearity was good (r(2) > 0.995) for DS, HS, CS, and KS calibration curves. In comparison with the DMB spectrophotometric method, this multiplex tandem mass spectrometry method allows GAG fractionation, thus a differentiation of MPS types, except for MPS I and II which are characterized by the same GAG profile. The devised method is a useful and reliable tool for diagnosis of MPS patients, as well as their monitoring and follow up, as shown by longitudinal studies.
authors: Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, CR-CHUS, Hospital Fleurimont, 3 001, 12th Avenue North, Sherbrooke, QC, J1H 5N4, Canada. Electronic address: christiane.auray-blais@usherbrooke.ca.
authors: Christiane
authors: C
authors: Auray-Blais
authors: Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, CR-CHUS, Hospital Fleurimont, 3 001, 12th Avenue North, Sherbrooke, QC, J1H 5N4, Canada.
authors: Pamela
authors: P
authors: Lavoie
authors: Nemours/Alfred I DuPont Hospital for Children, 1600 Rockland Road, Wilmington, DE, 19803, United States.
authors: Shunji
authors: S
authors: Tomatsu
authors: Centre de Référence Maladies Métaboliques, Hôpital Universitaire Necker-Enfants Malades et Institut IMAGINE, 149 Rue de Sèvres, 75015, Paris, France.
authors: Vassili
authors: V
authors: Valayannopoulos
authors: McGill University Health Center, 1001 Boulevard Décarie, Montreal, QC H4A 3J1, Canada.
authors: John J
authors: JJ
authors: Mitchell
authors: Division of Clinical and Metabolic Genetics, Department of Pediatrics, Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada.
authors: Julian
authors: J
authors: Raiman
authors: Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, CR-CHUS, Hospital Fleurimont, 3 001, 12th Avenue North, Sherbrooke, QC, J1H 5N4, Canada.
authors: Maxime
authors: M
authors: Beaudoin
authors: Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, CR-CHUS, Hospital Fleurimont, 3 001, 12th Avenue North, Sherbrooke, QC, J1H 5N4, Canada.
authors: Bruno
authors: B
authors: Maranda
authors: Division of Clinical and Metabolic Genetics, Department of Pediatrics, Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada.
authors: Joe T R
authors: JT
authors: Clarke
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D004187:Disaccharides / Q000032:analysis*; D005260:Female; D006025:Glycosaminoglycans / Q000737:chemistry*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009083:Mucopolysaccharidoses / Q000175:diagnosis* / Q000652:urine; D053719:Tandem Mass Spectrometry; D055815:Young Adult
chemical_list: D015415:Biomarkers; D004187:Disaccharides; D006025:Glycosaminoglycans
keywords: Chondroitin sulfate; Dermatan sulfate; Glycosaminoglycans; Heparan sulfate; Keratan sulfate; Mucopolysaccharidoses; Tandem mass spectrometry