Urinary Globotriaosylsphingosine-Related Biomarkers for Fabry Disease Targeted by Metabolomics

Fabry disease is a lysosomal storage disorder caused by deficiency of α-galactosidase A, resulting in glycosphingolipid accumulation in organs and tissues, including plasma and urine. Two disease-specific Fabry biomarkers have been identified and quantified in plasma and urine: globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3). The search continues for biomarkers that might be reliable indicators of disease severity and response to treatment. The main objective of this study was to target other urinary biomarkers using a time-of-flight mass spectrometry metabolomic approach. Urinary metabolites of 63 untreated Fabry patients and 59 controls were analyzed. A multivariate statistical analysis performed on a subset of male samples revealed seven novel Fabry biomarkers in urine, all lyso-Gb3 analogues having modified sphingosine moieties. The empirical formulas of the sphingosine modifications were determined by exact mass measurements (− C2H4, – C2H4 + O, – H2, – H2 + O, + O, + H2O2, + H2O3...