How well does urinary lyso-Gb(3) function as a biomarker in Fabry disease?

• Type: Article in International Scientific Journal
• Date: 2010

Authors

Auray Blais, C (Author) Other; Ntwari, A (Author) Other; Clarke, JTR (Author) Other; Warnock, DG (Author) Other; João Paulo Oliveira (Author) FMUP; Young, SP (Author) Other; Millington, DS (Author) Other; Bichet, DG (Author) Other; Sirrs, S (Author) Other; West, ML (Author) Other; Casey, R (Author) Other; Hwu, WL (Author) Other; Keutzer, JM (Author) Other; Zhang, XK (Author) Other; Gagnon, R (Author) Other

Journal

Title: Clinica Chimica Acta

Vol. 411 No. 23-24

Pages: 1906-1914

ISSN: 0009-8981

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 87 Citations

Scopus - 93 Citations

Scientific classification

FOS: Medical and Health sciences > Other medical sciences

Other information

Authenticus ID: P-003-03F

DOI: 10.1016/j.cca.2010.07.038

Abstract (EN): 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-Gb3 is an inhibitor of a-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 CIA 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9