title: Urinary biomarker investigation in children with Fabry disease using tandem mass spectrometry.
abstract: BACKGROUND
  Fabry disease is an X-linked lysosomal storage disorder affecting both males and females with tremendous genotypic/phenotypic variability. Concentrations of globotriaosylceramide (Gb3), globotriaosylsphingosine (lyso-Gb3)/related analogues were investigated in pediatric and adult Fabry cohorts. The aims of this study were to transfer and validate an HPLC-MS/MS methodology on a UPLC-MS/MS new generation platform, using an HPLC column, for urine analysis of treated and untreated pediatric and adult Fabry patients, to establish correlations between the excretion of Fabry biomarkers with gender, treatment, types of mutations, and to evaluate the biomarker reliability for early detection of pediatric Fabry patients.
  
  
  METHODS
  A UPLC-MS/MS was used for biomarker analysis.
  
  
  RESULTS
  Reference values are presented for all biomarkers. Results show that gender strongly influences the excretion of each biomarker in the pediatric Fabry cohort, with females having lower urinary levels of all biomarkers. Urinary distribution of lyso-Gb3/related analogues in treated Fabry males was similar to the untreated and treated Fabry female groups in both children and adult cohorts. Children with the late-onset p.N215S mutation had normal urinary levels of Gb3, and lyso-Gb3 but abnormal levels of related analogues.
  
  
  CONCLUSIONS
  In this study, Fabry males and most Fabry females would have been diagnosed using the urinary lyso-Gb3/related analogue profile.
authors.affiliation: Service of Genetics, Department of Pediatrics, Faculty of Medicine and Health Sciences, Centre hospitalier universitaire de Sherbrooke, 3001, 12(th) Avenue North, Sherbrooke, QCJ1H 5N4, Canada. Electronic address: christiane.auray-blais@usherbrooke.ca.
authors.forename: Christiane
authors.initials: C
authors.lastname: Auray-Blais
authors.affiliation: Service of Genetics, Department of Pediatrics, Faculty of Medicine and Health Sciences, Centre hospitalier universitaire de Sherbrooke, 3001, 12(th) Avenue North, Sherbrooke, QCJ1H 5N4, Canada.
authors.forename: Catherine-Marie
authors.initials: CM
authors.lastname: Blais
authors.affiliation: Lysosomal Disorders Unit, Royal Free Hospital, Pond Street, London NW3 2QG, United Kingdom.
authors.forename: Uma
authors.initials: U
authors.lastname: Ramaswami
authors.affiliation: Service of Genetics, Department of Pediatrics, Faculty of Medicine and Health Sciences, Centre hospitalier universitaire de Sherbrooke, 3001, 12(th) Avenue North, Sherbrooke, QCJ1H 5N4, Canada.
authors.forename: Michel
authors.initials: M
authors.lastname: Boutin
authors.affiliation: University of Versailles-St Quentin en Yvelines, UFR des Sciences de la Santé Simone Veil, EA 2493, 2 Allée de la source de la Bièvre, 78180 Montigny, France.
authors.forename: Dominique P
authors.initials: DP
authors.lastname: Germain
authors.affiliation: IWK Health Centre, Dalhousie University, 5850/5980 University Avenue, PO Box 9700, Halifax, NS B3K 6R8, Canada.
authors.forename: Sarah
authors.initials: S
authors.lastname: Dyack
authors.affiliation: Division of Clinical and Translational Genetics, Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, United States.
authors.forename: Olaf
authors.initials: O
authors.lastname: Bodamer
authors.affiliation: Department of Pediatrics, Section of Pediatric Nephrology, Genetics and Metabolism, Unit of Rare Diseases, University Hospital "Germans Trias i Pujol", Universitat Autònoma de Barcelona, 08916 Badalona, Catalonia, Spain.
authors.forename: Guillem
authors.initials: G
authors.lastname: Pintos-Morell
authors.affiliation: University of Toronto, 555, University Avenue, Toronto, ON M5G 1X8, Canada.
authors.forename: Joe T R
authors.initials: JT
authors.lastname: Clarke
authors.affiliation: Université de Montréal, Centre de recherche, Hôpital du Sacré-Cœur de Montréal, 5400, Boulevard Gouin Ouest, Montréal, QC H4J 1C5, Canada.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Bichet
authors.affiliation: Division of Nephrology, University of Alabama at Birmingham, Richard Arrington Jr Boulevard South, Birmingham, AL 35218, United States.
authors.forename: David G
authors.initials: DG
authors.lastname: Warnock
authors.affiliation: University of Versailles-St Quentin en Yvelines, UFR des Sciences de la Santé Simone Veil, EA 2493, 2 Allée de la source de la Bièvre, 78180 Montigny, France.
authors.forename: Lucia
authors.initials: L
authors.lastname: Echevarria
authors.affiliation: IWK Health Centre, Dalhousie University, 5850/5980 University Avenue, PO Box 9700, Halifax, NS B3K 6R8, Canada.
authors.forename: Michael L
authors.initials: ML
authors.lastname: West
authors.affiliation: Service of Genetics, Department of Pediatrics, Faculty of Medicine and Health Sciences, Centre hospitalier universitaire de Sherbrooke, 3001, 12(th) Avenue North, Sherbrooke, QCJ1H 5N4, Canada.
authors.forename: Pamela
authors.initials: P
authors.lastname: Lavoie
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000652:urine*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D015331:Cohort Studies; D000795:Fabry Disease / Q000175:diagnosis* / Q000235:genetics / Q000652:urine*; D005260:Female; D005838:Genotype; D006017:Glycolipids / Q000652:urine*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D013107:Sphingolipids / Q000652:urine*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014281:Trihexosylceramides / Q000652:urine*; D055815:Young Adult; D000519:alpha-Galactosidase / Q000235:genetics
chemical_list: D015415:Biomarkers; D006017:Glycolipids; D013107:Sphingolipids; D014281:Trihexosylceramides; C063288:globotriaosyl lysosphingolipid; C018549:globotriaosylceramide; C576330:GLA protein, human; D000519:alpha-Galactosidase
keywords: Biomarkers; Children; Fabry disease; Globotriaosylceramide; Globotriaosylsphingosine and analogues; Mass spectrometry