Quantitative analysis of ethanolamine plasmalogen species in red blood cells using liquid chromatography tandem mass spectrometry for diagnosing peroxisome biogenesis disorders.

Autor: De Biase I; Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT, USA; ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT, USA. Electronic address: irene.de-biase@aruplab.com., Yuzyuk T; Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT, USA; ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT, USA., Cui W; Child Health and Human Development Program, Research Institute of the McGill University, Montreal, Quebec, Canada., Zuromski LM; Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT, USA., Moser AB; Hugo W Moser Research Institute, Kennedy Krieger Institute, Baltimore, MD, USA., Braverman NE; Child Health and Human Development Program, Research Institute of the McGill University, Montreal, Quebec, Canada; Department of Human Genetics and Pediatrics, McGill University, Montreal, Quebec, Canada.
Jazyk: angličtina
Zdroj: Clinica chimica acta; international journal of clinical chemistry [Clin Chim Acta] 2023 Mar 01; Vol. 542, pp. 117295. Date of Electronic Publication: 2023 Mar 11.
DOI: 10.1016/j.cca.2023.117295
Abstrakt: Plasmalogens are glycerophospholipids characterized by a vinyl-ether bond with a fatty alcohol at the sn-1 position, a polyunsaturated fatty acid at the sn-2 position, and a polar head at the sn-3 position, commonly phosphoethanolamine. Plasmalogens play crucial roles in several cellular processes. Reduced levels have been associated with Alzheimer's and Parkinson's disease progression. Markedly reduced plasmalogens are a classic feature of peroxisome biogenesis disorders (PBD) because plasmalogen synthesis requires functional peroxisomes. Particularly, severe plasmalogen deficiency is the biochemical hallmark of rhizomelic chondrodysplasia punctata (RCDP). Traditionally, plasmalogens are evaluated in red blood cells (RBCs) by gas-chromatography/mass-spectrometry (GC-MS), which cannot distinguish individual species. We developed a liquid-chromatography/tandem mass-spectrometry (LC-MS/MS) method to quantify eighteen phosphoethanolamine plasmalogens in RBCs to diagnose PBD patients, especially RCDP. Validation results showed a specific, robust, and precise method with broad analytical range. Age-specific reference intervals were established; control medians were used to assess plasmalogen deficiency in patients' RBCs. Clinical utility was also confirmed in Pex7 deficient mouse models recapitulating severe and milder RCDP clinical phenotypes. To our knowledge, this is the first attempt to replace the GC-MS method in the clinical laboratory. In addition to diagnosing PBDs, structure-specific plasmalogen quantitation could help understand disease pathogenesis and monitor therapy.
Competing Interests: Declaration of Competing Interest 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.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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