{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T20:25:39Z","timestamp":1792009539323,"version":"4.4.0"},"reference-count":26,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    A critical concern of newborn screening (NBS) for very\u2010long chain acyl\u2010CoA dehydrogenase deficiency (VLCADD) is the difficulty of predicting clinical outcomes. To address this, we investigated neonatal C18:2\u2010carnitine concentrations as a possible predictor of VLCADD phenotype. To investigate the impact of sex, gestational age (GA) at birth, sampling day and birth weight on C18:2\u2010carnitine, we analyzed NBS\u2010dried blood spots (DBS) from Dutch newborns born between 2018 and 2020 (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009209.785). After normalization for resulting confounders, C18:2\u2010carnitine concentrations were investigated in NBS\u2010DBS (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200915) and neonatal plasma (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200935) of Dutch VLCADD\u2010patients, and in German NBS\u2010DBS (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20096) and correlated with clinical severity and diagnostic assays. Results showed that C18:2\u2010carnitine concentrations were affected by GA, sampling day, birth weight and, to a lesser extent, by sex. High C18:2\u2010carnitine, normalized for GA, sampling day and birth weight, reliably identified all VLCADD\u2010patients with (expected) severe phenotypes. The differentiating C18:2\u2010carnitine was identified as linoleylcarnitine. In conclusion, this study shows that neonatal C18:2\u2010carnitine concentrations can serve to predict disease severity directly after positive NBS for VLCADD. Patients with high C18:2\u2010carnitine concentrations can be considered \u201csevere\u201d and require strict dietary treatment and close monitoring. Patients with low C18:2\u2010carnitine concentrations can be identified as \u201cmild\u201d and only need preventive dietary measures.\n                  <\/jats:p>","DOI":"10.1002\/jimd.70143","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:17:57Z","timestamp":1771373877000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Direct Prediction of\n                    <scp>VLCADD<\/scp>\n                    Severity Using Newborn Screening Analyte Data"],"prefix":"10.1002","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4775-1760","authenticated-orcid":false,"given":"Marit","family":"Schwantje","sequence":"first","affiliation":[{"name":"Department of Metabolic Diseases Wilhelmina Children's Hospital, University Medical Center Utrecht  Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rose E.","family":"Maase","sequence":"additional","affiliation":[{"name":"Reference Laboratory for Pre\u2010 and Neonatal Screening, Centre for Health Protection Bilthoven National Institute for Public Health and the Environment (RIVM)  Bilthoven the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenie","family":"Dekkers","sequence":"additional","affiliation":[{"name":"Center for Population Screening National Institute for Public Health and the Environment (RIVM)  Bilthoven the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7738-5709","authenticated-orcid":false,"given":"Sacha","family":"Ferdinandusse","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Pediatrics, Laboratory Genetic Metabolic Diseases Emma Children's Hospital, Amsterdam UMC Location University of Amsterdam  Amsterdam the Netherlands"},{"name":"Amsterdam Gastroenterology Endocrinology Metabolism, Inborn Errors of Metabolism  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric M.","family":"Vaz","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Pediatrics, Laboratory Genetic Metabolic Diseases Emma Children's Hospital, Amsterdam UMC Location University of Amsterdam  Amsterdam the Netherlands"},{"name":"Amsterdam Gastroenterology Endocrinology Metabolism, Inborn Errors of Metabolism  Amsterdam the Netherlands"},{"name":"Core Facility Metabolomics Amsterdam UMC Location University of Amsterdam  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friederieke","family":"H\u00f6rster","sequence":"additional","affiliation":[{"name":"Heidelberg University, Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine, Division of Pediatric Neurology and Metabolic Medicine and Dietmar Hopp Metabolic Center  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4251-7257","authenticated-orcid":false,"given":"Ulrike","family":"M\u00fctze","sequence":"additional","affiliation":[{"name":"Heidelberg University, Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine, Division of Pediatric Neurology and Metabolic Medicine and Dietmar Hopp Metabolic Center  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah C.","family":"Gr\u00fcnert","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Adolescent Medicine and Neonatology University Medical Centre, Faculty of Medicine  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gepke","family":"Visser","sequence":"additional","affiliation":[{"name":"Division of Metabolic Diseases, Amsterdam Gastroenterology and Metabolism Emma Children's Hospital, Amsterdam UMC Location University of Amsterdam  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique G. 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De Sain\u2010van der","family":"Velden","sequence":"additional","affiliation":[{"name":"Section Metabolic Diagnostics, Department of Genetics University Medical Centre Utrecht  Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9147-2406","authenticated-orcid":false,"given":"Sabine A.","family":"Fuchs","sequence":"additional","affiliation":[{"name":"Department of Metabolic Diseases Wilhelmina Children's Hospital, University Medical Center Utrecht  Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,17]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-013-9639-6"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-021115-105045"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.12997\/jla.2020.9.3.313"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12075"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.22"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-011-9391-8"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2020.165725"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M067470"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-010-9104-8"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01799333"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/0-306-46818-2_37"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1005358802096"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0258751"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2018.12.023"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-19-0922"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2020.09.001"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgmr.2020.100634"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2015.10.045"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0177812"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12037"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt521"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1006\/mgme.1999.2911"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-8981(97)00185-X"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41390-022-01979-z"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12519-014-0480-2"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/8904_2012_129"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jimd.70143","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jimd.70143","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jimd.70143","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T08:09:03Z","timestamp":1784880543000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jimd.70143"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,17]]},"references-count":26,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1002\/jimd.70143"],"URL":"https:\/\/doi.org\/10.1002\/jimd.70143","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,17]]},"assertion":[{"value":"2025-07-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70143"}}