An improved functional assay in blood spot to diagnose Barth syndrome using the monolysocardiolipin/cardiolipin ratio
| Autor: | Femke S. Stet, Frédéric M. Vaz, Johanne H. Klinkspoor, Susan M. I. Goorden, Riekelt H. Houtkooper, Martin A. T. Vervaart, Hilary J. Vernon, Ronald J.A. Wanders, Henk van Lenthe, Willem Kulik |
|---|---|
| Přispěvatelé: | Laboratory Genetic Metabolic Diseases, Amsterdam Gastroenterology Endocrinology Metabolism, ACS - Diabetes & metabolism, ACS - Heart failure & arrhythmias, APH - Aging & Later Life, Laboratory for General Clinical Chemistry, APH - Methodology, Amsterdam Reproduction & Development (AR&D), APH - Personalized Medicine |
| Rok vydání: | 2021 |
| Předmět: |
Adult
Male Functional assay Adolescent Phospholipid Cardiomyopathy Tafazzin inborn errors of metabolism Neutropenia Young Adult chemistry.chemical_compound Genetics medicine Cardiolipin Humans Lymphocytes Child Genetics (clinical) mass spectrometry dried blood spot testing biology Chemistry Monolysocardiolipin Reproducibility of Results biomarkers cardiolipins Barth syndrome medicine.disease Molecular biology Child Preschool Linear Models biology.protein Female Lysophospholipids |
| Zdroj: | Journal of inherited metabolic disease, 45(1), 29-37. Springer Netherlands |
| ISSN: | 1573-2665 0141-8955 |
| DOI: | 10.1002/jimd.12425 |
| Popis: | Barth syndrome is an X-linked disorder characterized by cardiomyopathy, skeletal myopathy and neutropenia, caused by deleterious variants in TAFAZZIN. This gene encodes a phospholipid-lysophospholipid transacylase that is required for the remodeling of the mitochondrial phospholipid cardiolipin (CL). Biochemically, individuals with Barth syndrome have a deficiency of mature CL and accumulation of the remodeling intermediate monolysocardiolipin (MLCL). Diagnosis typically relies on mass spectrometric measurement of CL and MLCL in cells or tissues, and we previously described a method in blood spot that uses a specific MLCL/CL ratio as diagnostic biomarker. Here, we describe the evolution of our blood spot assay that is based on the implementation of reversed phase-UHPLC separation followed by full scan high resolution mass spectrometry. In addition to the MLCL/CL ratio, our improved method also generates a complete CL spectrum allowing the interrogation of the CL fatty acid composition, which considerably enhances the diagnostic reliability. This addition negates the need for a confirmatory test in lymphocytes thereby providing a shorter turn-around-time while achieving a more certain test result. As one of the few laboratories that offer this assay we also evaluated the diagnostic yield and performance from 2006-2021 encompassing the use of both the original and improved assay. In this period we performed 796 diagnostic analyses of which 117 (15%) were characteristic of Barth syndrome. In total we diagnosed 93 unique individuals with Barth syndrome, including three females, which together amounts to about 40% of all reported individuals with Barth syndrome in the world. This article is protected by copyright. All rights reserved. |
| Databáze: | OpenAIRE |
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