{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T09:09:05Z","timestamp":1792660145031,"version":"4.5.0"},"reference-count":16,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T00:00:00Z","timestamp":1629763200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Barth syndrome is an X\u2010linked disorder characterized by cardiomyopathy, skeletal myopathy, and neutropenia, caused by deleterious variants in <jats:italic>TAFAZZIN<\/jats:italic>. This gene encodes a phospholipid\u2010lysophospholipid 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\u2010UHPLC 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\u2010around\u2010time 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 to 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.<\/jats:p>","DOI":"10.1002\/jimd.12425","type":"journal-article","created":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T03:11:06Z","timestamp":1628737866000},"page":"29-37","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["An improved functional assay in blood spot to diagnose Barth syndrome using the monolysocardiolipin\/cardiolipin ratio"],"prefix":"10.1002","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9048-1041","authenticated-orcid":false,"given":"Fr\u00e9d\u00e9ric M.","family":"Vaz","sequence":"first","affiliation":[{"name":"Laboratory Genetic Metabolic Diseases, Amsterdam UMC, University of Amsterdam, Departments of Clinical Chemistry and Pediatrics Amsterdam Gastroenterology Endocrinology Metabolism  Amsterdam The Netherlands"},{"name":"Department of Pediatrics Emma Children's Hospital, Amsterdam UMC, University of Amsterdam  Amsterdam The Netherlands"},{"name":"Core Facility Metabolomics, Amsterdam UMC University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henk","family":"van Lenthe","sequence":"additional","affiliation":[{"name":"Laboratory Genetic Metabolic Diseases, Amsterdam UMC, University of Amsterdam, Departments of Clinical Chemistry and Pediatrics Amsterdam Gastroenterology Endocrinology Metabolism  Amsterdam The Netherlands"},{"name":"Core Facility Metabolomics, Amsterdam UMC University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2116-7697","authenticated-orcid":false,"given":"Martin A. T.","family":"Vervaart","sequence":"additional","affiliation":[{"name":"Laboratory Genetic Metabolic Diseases, Amsterdam UMC, University of Amsterdam, Departments of Clinical Chemistry and Pediatrics Amsterdam Gastroenterology Endocrinology Metabolism  Amsterdam The Netherlands"},{"name":"Core Facility Metabolomics, Amsterdam UMC University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Femke S.","family":"Stet","sequence":"additional","affiliation":[{"name":"Laboratory Genetic Metabolic Diseases, Amsterdam UMC, University of Amsterdam, Departments of Clinical Chemistry and Pediatrics Amsterdam Gastroenterology Endocrinology Metabolism  Amsterdam The Netherlands"},{"name":"Core Facility Metabolomics, Amsterdam UMC University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanne H.","family":"Klinkspoor","sequence":"additional","affiliation":[{"name":"Central Diagnostic Laboratory, Amsterdam UMC University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9940-9866","authenticated-orcid":false,"given":"Hilary J.","family":"Vernon","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan M. I.","family":"Goorden","sequence":"additional","affiliation":[{"name":"Laboratory Genetic Metabolic Diseases, Amsterdam UMC, University of Amsterdam, Departments of Clinical Chemistry and Pediatrics Amsterdam Gastroenterology Endocrinology Metabolism  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9961-0842","authenticated-orcid":false,"given":"Riekelt H.","family":"Houtkooper","sequence":"additional","affiliation":[{"name":"Laboratory Genetic Metabolic Diseases, Amsterdam UMC, University of Amsterdam, Departments of Clinical Chemistry and Pediatrics Amsterdam Gastroenterology Endocrinology Metabolism  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willem","family":"Kulik","sequence":"additional","affiliation":[{"name":"Laboratory Genetic Metabolic Diseases, Amsterdam UMC, University of Amsterdam, Departments of Clinical Chemistry and Pediatrics Amsterdam Gastroenterology Endocrinology Metabolism  Amsterdam The Netherlands"},{"name":"Core Facility Metabolomics, Amsterdam UMC University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7818-1452","authenticated-orcid":false,"given":"Ronald J. A.","family":"Wanders","sequence":"additional","affiliation":[{"name":"Laboratory Genetic Metabolic Diseases, Amsterdam UMC, University of Amsterdam, Departments of Clinical Chemistry and Pediatrics Amsterdam Gastroenterology Endocrinology Metabolism  Amsterdam The Netherlands"},{"name":"Department of Pediatrics Emma Children's Hospital, Amsterdam UMC, University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,8,24]]},"reference":[{"key":"e_1_2_8_2_1","article-title":"Clinical presentation and natural history of Barth Syndrome: An Overview","author":"Vernon HJ","year":"2021","journal-title":"J Inherit Metab Dis"},{"key":"e_1_2_8_3_1","volume-title":"Barth Syndrome","author":"Ferreira C","year":"1993"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.3952"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2006.04.054"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2007.095711"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2009.01.032"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2009.07.009"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2019.09.074"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2012.01.015"},{"issue":"4","key":"e_1_2_8_11_1","first-page":"495","article-title":"Barth syndrome in male and femal siblings caused by a novel mutation in the TAZ gene","volume":"27","author":"Avdjieva\u2010Tzavella DM","year":"2016","journal-title":"Genet Couns"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.d059824"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-014-9747-y"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-012-9552-4"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2016.00437"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi7023282"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12008"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jimd.12425","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jimd.12425","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jimd.12425","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T23:05:50Z","timestamp":1692831950000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jimd.12425"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,24]]},"references-count":16,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,1]]}},"alternative-id":["10.1002\/jimd.12425"],"URL":"https:\/\/doi.org\/10.1002\/jimd.12425","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,24]]},"assertion":[{"value":"2021-06-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-08-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-08-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}