Tandem mass spectrometry multiplex analysis of methylated and non-methylated urinary Gb3 isoforms in Fabry disease patients

Fabry disease is a lysosomal storage disorder leading to the accumulation of glycosphingolipids in biological fluids and tissues. Globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3) are currently used for Fabry screening and diagnosis. However, these biomarkers are not always increas...

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Bibliographic Details
Published in:Clinica chimica acta 2016-01, Vol.452, p.191-198
Main Authors: Abaoui, Mona, Boutin, Michel, Lavoie, Pamela, Auray-Blais, Christiane
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Calibration
Child
Child, Preschool
Fabry disease
Fabry Disease - metabolism
Fabry Disease - urine
Female
Globotriaosylceramide
Glycolipids - chemistry
Glycolipids - metabolism
Glycolipids - urine
Humans
Infant
Male
Methylated Gb3 isoforms
Methylation
Middle Aged
Molecular Structure
Non-methylated Gb3 isoforms
Protein Isoforms - chemistry
Protein Isoforms - metabolism
Protein Isoforms - urine
Sphingolipids - chemistry
Sphingolipids - metabolism
Sphingolipids - urine
Tandem Mass Spectrometry
Trihexosylceramides - chemistry
Trihexosylceramides - metabolism
Trihexosylceramides - urine
UPLC–MS/MS
Young Adult
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Summary:Fabry disease is a lysosomal storage disorder leading to the accumulation of glycosphingolipids in biological fluids and tissues. Globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3) are currently used for Fabry screening and diagnosis. However, these biomarkers are not always increased in Fabry patients with residual enzyme activity. We recently identified 7 urinary methylated Gb3-related isoforms. The aims of this study were (1) to develop and validate a novel LC–MS/MS method for the relative quantification of methylated and non-methylated Gb3 isoforms normalized to creatinine, (2) to evaluate these biomarkers in Fabry patients and healthy controls, and (3) to assess correlations between biomarker urinary excretion with age, gender, treatment and genotype of patients. Urine samples from 150 Fabry patients and 95 healthy controls were analyzed. Samples were purified and injected in the tandem mass spectrometer working in positive electrospray ionization. Relative quantification was performed for 15 methylated and non-methylated Gb3 isoforms. Significant correlations (p
ISSN:0009-8981
1873-3492
DOI:10.1016/j.cca.2015.11.018