LysoGb3 quantification facilitates phenotypic categorization of Fabry disease patients: Insights gained by a novel MS/MS method
Author
Růžička, Petr
Reichmannová, Stella
Publication date
2024Published in
Clinica Chimica ActaVolume / Issue
561 (July)ISBN / ISSN
ISSN: 0009-8981ISBN / ISSN
eISSN: 1873-3492Metadata
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This publication has a published version with DOI 10.1016/j.cca.2024.119824
Abstract
Background: Fabry disease (FD) is an X-linked lysosomal storage disease resulting from pathogenic variants in the GLA gene coding alpha-galactosidase A (AGAL) and cleaving terminal alpha-linked galactose. Globotriaosylceramide (Gb3) is the predominantly accumulated sphingolipid. Gb3, deacylated-Gb3 (lysoGb3), and methylated-Gb3 (metGb3) have been suggested as FD biomarkers. Materials and Methods: We developed a novel LC-MS/MS method for assessing lysoGb3 levels in plasma and Gb3 and metGb3 in urine and tested 62 FD patients, 34 patients with GLA variants of unknown significance (VUS) and 59 healthy controls. AGAL activity in white blood cells (WBCs) and plasma was evaluated in parallel. Results: In males, lysoGb3 concentrations in plasma separated classic and late-onset FD patients from each other and from individuals carrying GLA VUS and healthy controls. Calculating AGAL activity/plasmatic lysoGb3 ratio allowed to correctly categorize all females with classic and majority of patients with late-onset FD phenotypes. Correlation of AGAL activity in WBCS with lipid biomarkers identified threshold activity values under which the biomarkers' concentrations increase. Conclusion: We developed a novel simplified LC-MS/MS method for quantitation of plasma lysoGb3. AGAL activity/plasma lysoGb3 ratio was identified as the best predictor for FD. AGAL activity correlated with plasma lysoGb3 and corresponded to individual FD phenotypes.
Keywords
Fabry disease, Mass spectrometry, Globotriaosylsphingosine, Diagnostics, Phenotype, Lysosomal storage,
Permanent link
https://hdl.handle.net/20.500.14178/2635License
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