title: Novel gb(3) isoforms detected in urine of fabry disease patients: a metabolomic study.
abstract: Fabry disease is characterized by the accumulation of globotriaosylsphingosine (lyso-Gb(3)) and globotriaosylceramide (Gb(3)) in biological fluids and tissues. Metabolomic studies recently undertaken by our group, showed the presence of novel plasma and urine lyso-Gb(3)-related analogs in male and female Fabry patients. These analogs are distinguished by differences in structure of the sphingosine moiety. The principal aim of this study was to evaluate the possibility of detecting other Fabry disease biomarkers structurally related to Gb(3). A time-of-flight mass spectrometry metabolomic approach, focusing on mass-to-charge (m/z) ratios from 1000 to 1200 Da, was devised. This m/z window corresponds to the isoforms and potential analogs of Gb(3). Five different categories of Gb(3)- related isoforms/analogs were detected: Gb(3)-related isoforms with saturated fatty acids, methylated Gb(3)-related isoforms, Gb(3)-related isoforms/analogs with one double bond, Gb(3) analogs with hydrated sphingosine, and Gb(3)-related isoforms/analogs with two double bonds. A secondary objective was to elucidate the relationship between Gb(3) and lyso-Gb(3). The methylation observed on Gb(3)-related analogs was not detected on lyso-Gb(3). We speculate that the methylated Gb(3) may be an intermediate compound in the deacylation of Gb(3) to generate the lyso-Gb(3) molecule. We are in the process of devising a quantification methodology for these methylated Gb(3)-related analogs in Fabry patients to try to understand the underlying biochemical mechanisms involved in this complex disease.
authors.affiliation: Service of Genetics, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, 3001, 12th Avenue North, Sherbrooke (Québec), J1H 5N4, Canada. christiane.auray-blais@usherbrooke.ca
authors.forename: C
authors.initials: C
authors.lastname: Auray-Blais
authors.forename: M
authors.initials: M
authors.lastname: Boutin
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000652:urine; D002648:Child; D002675:Child, Preschool; D000795:Fabry Disease / Q000652:urine*; D006801:Humans; D008297:Male; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D020033:Protein Isoforms; D055815:Young Adult
chemical_list: D015415:Biomarkers; D020033:Protein Isoforms