{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:10:15Z","timestamp":1791850215521,"version":"4.3.4"},"reference-count":36,"publisher":"BMJ","issue":"12","license":[{"start":{"date-parts":[[2023,7,24]],"date-time":"2023-07-24T00:00:00Z","timestamp":1690156800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["543002003"],"award-info":[{"award-number":["543002003"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2023,6,17]]},"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Newborn screening (NBS) programmes identify a wide range of disease phenotypes, which raises the question whether early identification and treatment is beneficial for all. This study aims to answer this question for primary carnitine deficiency (PCD) taking into account that NBS for PCD identifies newborns with PCD and also until then undiagnosed mothers.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We investigated clinical, genetic (variants in <jats:italic>SLC22A5<\/jats:italic> gene) and functional (carnitine transport activity in fibroblasts) characteristics of all referred individuals through NBS (newborns and mothers) and clinically diagnosed patients with PCD (not through NBS). Disease phenotype in newborns was predicted using data from PCD mothers and cases published in literature with identical <jats:italic>SLC22A5<\/jats:italic> variants.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>PCD was confirmed in 19\/131 referred newborns, 37\/82 referred mothers and 5 clinically diagnosed patients. Severe symptoms were observed in all clinically diagnosed patients, 1 newborn and none of the mothers identified by NBS. PCD was classified as severe in all 5 clinically diagnosed patients, 3\/19 newborns and 1\/37 mothers; as benign in 8\/19 newborns and 36\/37 mothers and as unknown in 8\/19 newborns. Carnitine transport activity completely separated severe phenotype from benign phenotype (median (range): 4.0% (3.5\u20135.0)] vs 26% (9.5\u201342.5), respectively).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>The majority of mothers and a significant proportion of newborns with PCD identified through NBS are likely to remain asymptomatic without early treatment. Conversely, a small proportion of newborns with predicted severe PCD could greatly benefit from early treatment. Genetic variants and carnitine transport activity can be used to distinguish between these groups.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg-2023-109206","type":"journal-article","created":{"date-parts":[[2023,7,24]],"date-time":"2023-07-24T13:20:21Z","timestamp":1690204821000},"page":"1177-1185","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":16,"title":["Newborn screening for primary carnitine deficiency: who will benefit? \u2013 a retrospective cohort study"],"prefix":"10.1136","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2057-5525","authenticated-orcid":false,"given":"Loek","family":"Crefcoeur","sequence":"first","affiliation":[{"name":"Metabolic Diseases, Wilhelmina Children's Hospital, University Medical Centre, Utrecht, The Netherlands"},{"name":"Department of Pediatrics, Division of Metabolic Disorders, Amsterdam UMC Locatie AMC, Amsterdam, The Netherlands"},{"name":"Clinical 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The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine A","family":"Fuchs","sequence":"additional","affiliation":[{"name":"Metabolic Diseases, Wilhelmina Children's Hospital, University Medical Centre, Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidde","family":"Huidekoper","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Center for Lysosomal and Metabolic Diseases, Erasmus Medical Center, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4668-9977","authenticated-orcid":false,"given":"Mirian","family":"Janssen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janneke","family":"Langendonk","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Center for Lysosomal and Metabolic Diseases, Erasmus Medical Center, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rose","family":"Maase","sequence":"additional","affiliation":[{"name":"Department of Biologicals, Screening and Innovation, RIVM, Bilthoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique","family":"de Sain","sequence":"additional","affiliation":[{"name":"Section Metabolic Diagnostics, Department of Genetics, Wilhelmina Children's Hospital, University Medical Centre, Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estela","family":"Rubio","sequence":"additional","affiliation":[{"name":"Department of Pediatrics\/Laboratory of Clinical Genetics, Maastricht UMC+, Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3773-1929","authenticated-orcid":false,"given":"Francjan J","family":"van Spronsen","sequence":"additional","affiliation":[{"name":"Section of Metabolic Diseases, University Medical Centre Groningen, Beatrix Children's Hospital, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric Maxime","family":"Vaz","sequence":"additional","affiliation":[{"name":"Laboratory Genetic Metabolic Diseases, Amsterdam UMC, University of Amsterdam, Departments of Clinical Chemistry and Pediatrics, Core Facility Metabolomics, Emma Children\u2019s Hospital, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC Locatie Meibergdreef, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rendelien","family":"Verschoof","sequence":"additional","affiliation":[{"name":"Department for Vaccine Supply 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