Glycosphingolipid storage in Fabry mice extends beyond globotriaosylceramide and is affected by ABCB1 depletion.

Aim: Fabry disease is caused by α-galactosidase A deficiency leading to accumulation of globotriaosylceramide (Gb ₃ ) in tissues. Clinical manifestations do not appear to correlate with total Gb ₃ levels. Studies examining tissue distribution of specific acyl chain species of Gb ₃ and upstream glycosphingolipids are lacking.
Material & Methods/results: Thorough characterization of the Fabry mouse sphingolipid profile by LC-MS revealed unique Gb ₃ acyl chain storage profiles. Storage extended beyond Gb ₃ ; all Fabry tissues also accumulated monohexosylceramides. Depletion of ABCB1 had a complex effect on glycosphingolipid storage.
Conclusion: These data provide insights into how specific sphingolipid species correlate with one another and how these correlations change in the α-galactosidase A-deficient state, potentially leading to the identification of more specific biomarkers of Fabry disease.
Competing Interests: Financial & competing interests disclosure This study was supported by a Canadian Institutes of Health Research (CIHR) grant to JA Medin (Fabry Disease: Mechanisms and Next-Generation Therapeutics, MOP 123528). The authors are grateful to Waters Corporation for their continued scientific support and partnership. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.