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LC-MS lipidomics of renal biopsies for the diagnosis of Fabry disease.

Authors :: Yazd HS
Bazargani SF
Vanbeek CA
King-Morris K
Heldermon C
Segal MS
Clapp WL
Garrett TJ
Source :: Journal of mass spectrometry and advances in the clinical lab [J Mass Spectrom Adv Clin Lab] 2021 Nov 26; Vol. 22, pp. 71-78. Date of Electronic Publication: 2021 Nov 26 (Print Publication: 2021).
Publication Year :: 2021
Abstract: Introduction: Lipidomics analysis or lipid profiling is a system-based analysis of all lipids in a sample to provide a comprehensive understanding of lipids within a biological system. In the last few years, lipidomics has made it possible to better understand the metabolic processes associated with several rare disorders and proved to be a powerful tool for their clinical investigation. Fabry disease is a rare X-linked lysosomal storage disorder (LSD) caused by a deficiency in α-galactosidase A (α-GAL A). This deficiency results in the progressive accumulation of glycosphingolipids, mostly globotriaosylceramide (Gb <subscript>3</subscript> ), globotriaosylsphingosine (lyso-Gb <subscript>3</subscript> ), as well as galabiosylceramide (Ga <subscript>2</subscript> ) and their isoforms/analogs in the vascular endothelium, nerves, cardiomyocytes, renal glomerular podocytes, and biological fluids. Objectives: The primary objective of this study was to evaluate lipidomic signatures in renal biopsies to help understand variations in Fabry disease markers that could be used in future diagnostic tests. Methods: Lipidomic analysis was performed by ultra-high pressure liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) on kidney biopsies that were left over after clinical pathology analysis to diagnose Fabry disease. Results: We employed UHPLC-HRMS lipidomics analysis on the renal biopsy of a patient suspicious for Fabry disease. Our result confirmed α-GAL A enzyme activity declined in this patient since a Ga2-related lipid biomarker was substantially higher in the patient's renal tissue biopsy compared with two controls. This suggests this patient has a type of LSD that could be non-classical Fabry disease. Conclusion: This study shows that lipidomics analysis is a valuable tool for rare disorder diagnosis, which can be conducted on leftover tissue samples without disrupting normal patient care. Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2021 THE AUTHORS. Publishing services by ELSEVIER B.V. on behalf of MSACL.)