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

Autor: Hoda Safari Yazd, Sina Feizbakhsh Bazargani, Christine A. Vanbeek, Kelli King-Morris, Coy Heldermon, Mark S. Segal, Richard Yost, William L. Clapp, Timothy J. Garrett
Rok vydání: 2021
Předmět:
medicine.medical_specialty
Pathology
CAN
Acetonitrile
MS/MS
Tandem Mass Spectrometry
OCT
Optimal Cutting Temperature
CDH
Cerebrodihexoside
LC/MS
Liquid Chromatography-Mass Spectrometry
UHPLC-HRMS
Ultra-High Pressure Liquid Chromatography-High-Resolution Mass Spectrometry
Clinical Biochemistry
Globotriaosylceramide
Cnvs
Copy Number Variants
Microbiology
Special issue on Lipidomics
chemistry.chemical_compound
ERT
Enzyme Replacement Therapy
Liquid chromatography–mass spectrometry
Ga2
Galabiosylceramide
Biopsy
Lipidomics
Medical technology
medicine
R855-855.5
GLA
Glactosidase Alpha
SRM
Selected Reaction Monitoring
Spectroscopy
EIC
Extracted Ion Chromatogram
ND
Not Detected
Kidney
Clinical pathology
medicine.diagnostic_test
business.industry
Gb3
Globotriaosylceramide
SECIM
Southeast Center for Integrated Metabolomics
medicine.disease
Fabry disease
Chcl3
Chloroform
α-GAL A
α-Galactosidase A
Lyso-Gb3
Globotriaosylsphingosine
Medical Laboratory Technology
medicine.anatomical_structure
chemistry
IPA
2-Propanol
Renal biopsy
Meoh
Methanol
business
LSD
Lysosomal Storage Disorder
Zdroj: Journal of Mass Spectrometry and Advances in the Clinical Lab, Vol 22, Iss, Pp 71-78 (2021)
Journal of Mass Spectrometry and Advances in the Clinical Lab
ISSN: 2667-145X
DOI: 10.1016/j.jmsacl.2021.11.004
Popis: Highlights • Fabry is an X-linked lysosomal storage disease with deficiency in α-galactosidase. • This deficiency results in the accumulation of glycosphinogolipids. • Diagnosis is often made by analysis of globotriaosylceramide in fluids and tissues. • Fabry is often misdiagnosed in female patients due to residual enzyme activity. • Lipidomics by LC-HRMS enables identification of new biomarkers in Fabry.
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.
Databáze: OpenAIRE
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