LC-MS lipidomics of renal biopsies for the diagnosis of Fabry disease.
J Mass Spectrom Adv Clin Lab
; 22: 71-78, 2021 Nov.
Article
em En
| MEDLINE
| ID: mdl-34918004
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 (Gb3), globotriaosylsphingosine (lyso-Gb3), as well as galabiosylceramide (Ga2) 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.
CAN, Acetonitrile; CDH, Cerebrodihexoside; Chcl3, Chloroform; Cnvs, Copy Number Variants; EIC, Extracted Ion Chromatogram; ERT, Enzyme Replacement Therapy; GLA, Glactosidase Alpha; Ga2, Galabiosylceramide; Gb3, Globotriaosylceramide; IPA, 2-Propanol; LC/MS, Liquid Chromatography-Mass Spectrometry; LSD, Lysosomal Storage Disorder; Lyso-Gb3, Globotriaosylsphingosine; MS/MS, Tandem Mass Spectrometry; Meoh, Methanol; ND, Not Detected; OCT, Optimal Cutting Temperature; SECIM, Southeast Center for Integrated Metabolomics; SRM, Selected Reaction Monitoring; UHPLC-HRMS, Ultra-High Pressure Liquid Chromatography-High-Resolution Mass Spectrometry; α-GAL A, α-Galactosidase A
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Diagnostic_studies
Idioma:
En
Revista:
J Mass Spectrom Adv Clin Lab
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos