Fabry Disease Biomarkers: Analysis of Urinary Lyso‐Gb3 and Seven Related Analogs Using Tandem Mass Spectrometry. (1st July 2016)

• Record Type: Journal Article
• Authors: Lavoie, Pamela; Boutin, Michel; Abaoui, Mona; Auray‐Blais, Christiane
• Editors: Haines, Jonathan L.; Korf, Bruce R.; Morton, Cynthia C.; Seidman, Christine E.; Seidman, J.G.; Smith, Douglas R.
• Is Part Of: Current protocols in human genetics. Volume 90(2016)
• Page Start: 17.22.1
• Page End: 17.22.12
• Publication Date: 2016-07-01
• Subjects: analogs -- biomarkers -- Fabry disease -- lyso‐Gb3 -- mass spectrometry -- urine -- UPLC‐MS/MS; Human genetics -- Laboratory manuals; Genetic Techniques; Human genetics; Laboratory manuals; 599.935028
• DOI: 10.1002/cphg.1
• Languages: English
• ISSNs: 1934-8258

Abstract

Abstract: Fabry disease is an X‐linked lysosomal storage disorder caused by the absence or reduction of the enzyme α‐galactosidase A activity. Currently, globotriaosylsphingosine (lyso‐Gb3 ) and globotriaosylceramide (Gb3 ) are used as biomarkers to diagnose and monitor Fabry patients. However, recent metabolomic studies have shown that several glycosphingolipids are also elevated in biological fluids of affected patients and may be related to disease manifestations. This unit describes a multiplex methodology targeting the analysis of urinary lyso‐Gb3 and seven structurally related analogs. A solid‐phase extraction process is performed, then lyso‐Gb3 and its analogs are analyzed simultaneously with an internal standard by ultra‐performance liquid chromatography (UPLC) coupled to a tandem mass spectrometry (MS/MS) system. This methodology can be useful for the diagnosis of Fabry patients, including patients with cardiac variant mutations, but also to monitor the efficacy of therapeutic interventions, considering that lyso‐Gb3 analogs are more elevated than lyso‐Gb3 itself in urine. © 2016 by John Wiley & Sons, Inc.