How well does urinary lyso-Gb3 function as a biomarker in Fabry disease?

Journal Article (Journal Article)

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. CONCLUSION: Lyso-Gb(3) is a reliable independent biomarker for clinically important characteristics of Fabry disease.

Full Text

Duke Authors

Cited Authors

  • Auray-Blais, C; Ntwari, A; Clarke, JTR; Warnock, DG; Oliveira, JP; Young, SP; Millington, DS; Bichet, DG; Sirrs, S; West, ML; Casey, R; Hwu, W-L; Keutzer, JM; Zhang, XK; Gagnon, R

Published Date

  • December 14, 2010

Published In

Volume / Issue

  • 411 / 23-24

Start / End Page

  • 1906 - 1914

PubMed ID

  • 20716442

Electronic International Standard Serial Number (EISSN)

  • 1873-3492

Digital Object Identifier (DOI)

  • 10.1016/j.cca.2010.07.038


  • eng

Conference Location

  • Netherlands