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

Christiane Auray-Blais, Aimé Ntwari, Joe T R Clarke, David G Warnock, João Paulo Oliveira, Sarah P Young, David S Millington, Daniel G Bichet, Sandra Sirrs, Michael L West, Robin Casey, Wuh-Liang Hwu, Joan M Keutzer, X Kate Zhang, René Gagnon

Index: Clin. Chim. Acta 411(23-24) , 1906-14, (2010)

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Abstract

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.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.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.Lyso-Gb(3) is a reliable independent biomarker for clinically important characteristics of Fabry disease.Copyright © 2010 Elsevier B.V. All rights reserved.