Fabry disease is an X-linked lysosomal storage disorder with marked variability in the phenotype and genotype. Glycosphingolipids such as globotriaosylceramide (Gb) isoforms/analogs, globotriaosylsphingosine (lyso-Gb) and analogs, and galabiosylceramide (Ga) isoforms/analogs may accumulate in biological fluids and different organs. The aims of this study were to: 1) develop/validate a novel UHPLC-MS/MS method for relative quantitation of Gb in leukocytes (unfractionated white blood cells), B lymphocytes and monocytes; 2) evaluate these biomarkers in a cohort of Fabry patients and healthy controls; and 3) assess correlations between these biomarkers, treatment and genotype. Whole blood, plasma and urine samples from 21 Fabry patients and 20 healthy controls were analyzed. Samples were purified by liquid-liquid extraction and analyzed by UHPLC-MS/MS in positive electrospray ionization. Methylated Gb isoforms were detected, showing that a methylation process occurs at the cellular level. Our results show that there were no significant differences in the distribution of the different Gb isoforms/analogs in blood cells between Fabry patients and healthy controls. In leukocyte, Gb[(d18:1)(C14:0)], Gb[(d18:1)(C16:0)], Gb [(d18:1)(C16:0)]Me, Gb [(d18:1)(C16:1)], Gb [(d18:1)(C18:0)], Gb [(d18:1)(C18:1)], Gb [(d18:1)(C20:1)], Gb [(d18:1)(C24:2)], Gb [(d18:1)(C26:1)] and total Gb allowed good discrimination between male Fabry patients and male controls, patients having higher biomarker levels than controls. Regarding B lymphocytes and monocytes, the same tendency was observed without reaching statistical significance. A positive concordance between mutation types and biomarker levels in white blood cells was established. Our results might provide a deeper mechanistic comprehension of the underlying biochemical processes of Gb biomarkers in white blood cells of Fabry patients.
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