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

doi:10.1016/j.cca.2010.07.038

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

Medicine

Research output: Contribution to journal › Article › peer-review

97 Citations (Scopus)

Abstract

Background: Fabry disease is characterized by accumulation of glycosphingolipids, such as globotriaosylceramide (Gb₃), in many tissues and body fluids. A novel plasma biomarker, globotriaosylsphingosine (lyso-Gb₃), is increased in patients with the disease. Until now, lyso-Gb₃ was not detectable in urine, possibly because of the presence of interfering compounds. Methods: We undertook to: 1) characterize lyso-Gb₃ in urine; 2) develop a method to quantitate urinary lyso-Gb₃ by mass spectrometry; 3) evaluate urinary lyso-Gb₃ as a potential biomarker for Fabry disease; and 4) determine whether lyso-Gb₃ is an inhibitor of α-galactosidase A activity. We analyzed urinary lyso-Gb₃ 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-Gb₃/creatinine correlated with the concentrations of Gb₃ (r²=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-Gb₃. Lyso-Gb₃ did not inhibit GLA activity in dried blood spots. Increased urinary excretion of lyso-Gb₃ of Fabry patients correlated well with a number of indicators of disease severity. Conclusion: Lyso-Gb₃ is a reliable independent biomarker for clinically important characteristics of Fabry disease.

Original language	English
Pages (from-to)	1906-1914
Number of pages	9
Journal	Clinica Chimica Acta
Volume	411
Issue number	23-24
DOIs	https://doi.org/10.1016/j.cca.2010.07.038
Publication status	Published - Dec 14 2010

Bibliographical note

Funding Information:
This research was funded by a grant-in-aid of research from Genzyme , the Canadian Institutes of Health Research and La Fondation des Étoiles . We are grateful to Waters Corporation for their continued scientific support and partnership. We would like to thank Marie-Françoise Arthus, Tommy Gagnon, Leslie Jackson, RN and Marsha Browning for their collaboration. We are thankful to the patients with Fabry disease for their cooperation. The funding organizations played no role in the design of study, choice of enrolled patients, review and interpretation of data, and preparation or approval of manuscript.

ASJC Scopus Subject Areas

Biochemistry
Clinical Biochemistry
Biochemistry, medical

Access to Document

10.1016/j.cca.2010.07.038

Cite this

Auray-Blais, C., Ntwari, A., Clarke, J. T. R., Warnock, D. G., Oliveira, J. P., Young, S. P., Millington, D. S., Bichet, D. G., Sirrs, S., West, M. L., Casey, R., Hwu, W. L., Keutzer, J. M., Zhang, X. K., & Gagnon, R. (2010). How well does urinary lyso-Gb₃ function as a biomarker in Fabry disease? Clinica Chimica Acta, 411(23-24), 1906-1914. https://doi.org/10.1016/j.cca.2010.07.038

@article{86d67727c12f4b3ea495906f5b15c619,

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 (Gb3), in many tissues and body fluids. A novel plasma biomarker, globotriaosylsphingosine (lyso-Gb3), is increased in patients with the disease. Until now, lyso-Gb3 was not detectable in urine, possibly because of the presence of interfering compounds. Methods: We undertook to: 1) characterize lyso-Gb3 in urine; 2) develop a method to quantitate urinary lyso-Gb3 by mass spectrometry; 3) evaluate urinary lyso-Gb3 as a potential biomarker for Fabry disease; and 4) determine whether lyso-Gb3 is an inhibitor of α-galactosidase A activity. We analyzed urinary lyso-Gb3 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-Gb3/creatinine correlated with the concentrations of Gb3 (r2=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-Gb3. Lyso-Gb3 did not inhibit GLA activity in dried blood spots. Increased urinary excretion of lyso-Gb3 of Fabry patients correlated well with a number of indicators of disease severity. Conclusion: Lyso-Gb3 is a reliable independent biomarker for clinically important characteristics of Fabry disease.",

author = "Christiane Auray-Blais and Aim{\'e} Ntwari and Clarke, {Joe T.R.} and Warnock, {David G.} and Oliveira, {Jo{\~a}o Paulo} and Young, {Sarah P.} and Millington, {David S.} and Bichet, {Daniel G.} and Sandra Sirrs and West, {Michael L.} and Robin Casey and Hwu, {Wuh Liang} and Keutzer, {Joan M.} and Zhang, {X. Kate} and Ren{\'e} Gagnon",

note = "Funding Information: This research was funded by a grant-in-aid of research from Genzyme , the Canadian Institutes of Health Research and La Fondation des {\'E}toiles . We are grateful to Waters Corporation for their continued scientific support and partnership. We would like to thank Marie-Fran{\c c}oise Arthus, Tommy Gagnon, Leslie Jackson, RN and Marsha Browning for their collaboration. We are thankful to the patients with Fabry disease for their cooperation. The funding organizations played no role in the design of study, choice of enrolled patients, review and interpretation of data, and preparation or approval of manuscript.",

year = "2010",

month = dec,

day = "14",

doi = "10.1016/j.cca.2010.07.038",

language = "English",

volume = "411",

pages = "1906--1914",

journal = "Clinica Chimica Acta",

issn = "0009-8981",