title: How well does urinary lyso-Gb3 function as a biomarker in Fabry disease?
abstract: BACKGROUND
  Fabry disease is characterized by accumulation of glycosphingolipids, such as globotriaosylceramide (Gb(3)), in many tissues and body fluids. A novel plasma biomarker, globotriaosylsphingosine (lyso-Gb(3)), is increased in patients with the disease. Until now, lyso-Gb(3) was not detectable in urine, possibly because of the presence of interfering compounds.
  
  
  METHODS
  We undertook to: 1) characterize lyso-Gb(3) in urine; 2) develop a method to quantitate urinary lyso-Gb(3) by mass spectrometry; 3) evaluate urinary lyso-Gb(3) as a potential biomarker for Fabry disease; and 4) determine whether lyso-Gb(3) is an inhibitor of α-galactosidase A activity. We analyzed urinary lyso-Gb(3) from 83 Fabry patients and 77 healthy age-matched controls.
  
  
  RESULTS
  The intraday and interday bias and precision of the method were <15%. Increases in lyso-Gb(3)/creatinine correlated with the concentrations of Gb(3) (r(2)=0.43), type of mutations (p=0.0006), gender (p<0.0001) and enzyme replacement therapy status (p=0.0012). Urine from healthy controls contained no detectable lyso-Gb(3). Lyso-Gb(3) did not inhibit GLA activity in dried blood spots. Increased urinary excretion of lyso-Gb(3) of Fabry patients correlated well with a number of indicators of disease severity.
  
  
  CONCLUSIONS
  Lyso-Gb(3) is a reliable independent biomarker for clinically important characteristics of Fabry disease.
authors: Service of Genetics, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada. Christiane.auray-blais@usherbrooke.ca
authors: Christiane
authors: C
authors: Auray-Blais
authors: Aimé
authors: A
authors: Ntwari
authors: Joe T R
authors: JT
authors: Clarke
authors: David G
authors: DG
authors: Warnock
authors: João Paulo
authors: JP
authors: Oliveira
authors: Sarah P
authors: SP
authors: Young
authors: David S
authors: DS
authors: Millington
authors: Daniel G
authors: DG
authors: Bichet
authors: Sandra
authors: S
authors: Sirrs
authors: Michael L
authors: ML
authors: West
authors: Robin
authors: R
authors: Casey
authors: Wuh-Liang
authors: WL
authors: Hwu
authors: Joan M
authors: JM
authors: Keutzer
authors: X Kate
authors: XK
authors: Zhang
authors: René
authors: R
authors: Gagnon
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000652:urine; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003401:Creatine / Q000652:urine; D000795:Fabry Disease / Q000201:enzymology / Q000503:physiopathology / Q000652:urine*; D005260:Female; D006017:Glycolipids / Q000494:pharmacology / Q000652:urine*; D006801:Humans; D007668:Kidney / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011609:Psychosine / Q000031:analogs & derivatives / Q000652:urine; D012015:Reference Standards; D015203:Reproducibility of Results; D012737:Sex Factors; D013107:Sphingolipids / Q000494:pharmacology / Q000652:urine*; D016482:Urinalysis / Q000379:methods* / Q000592:standards; D055815:Young Adult; D000519:alpha-Galactosidase / Q000037:antagonists & inhibitors
chemical_list: D015415:Biomarkers; D006017:Glycolipids; D013107:Sphingolipids; C063288:globotriaosyl lysosphingolipid; D011609:Psychosine; C035742:sphingosyl beta-glucoside; D000519:alpha-Galactosidase; D003401:Creatine