{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:00:45Z","timestamp":1790748045596,"version":"4.1.0"},"reference-count":70,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T00:00:00Z","timestamp":1643846400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/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":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A broad spectrum of signs and symptoms has been attributed to primary carnitine deficiency (PCD) since its first description in 1973. Advances in diagnostic procedures have improved diagnostic accuracy and the introduction of PCD in newborn screening (NBS) programs has led to the identification of an increasing number of PCD patients, including mothers of screened newborns, who may show a different phenotype compared to clinically diagnosed patients. To elucidate the spectrum of signs and symptoms in PCD patients, we performed a structured literature review. Using a case\u2010by\u2010case approach, clinical characteristics, diagnostic data, and mode of patient identification were recorded. Signs and symptoms were categorized by organ involvement. In total, 166 articles were included, reporting data on 757 individual patients. In almost 20% (<jats:italic>N<\/jats:italic>\u00a0=\u2009136) of the cases, the diagnosis was based solely on low carnitine concentration which we considered an uncertain diagnosis of PCD. The remaining 621 cases had a diagnosis based on genetic and\/or functional (ie, carnitine transporter activity) test results. In these 621 cases, cardiac symptoms (predominantly cardiomyopathy) were the most prevalent (23.8%). Neurological (7.1%), hepatic (8.4%), and metabolic (9.2%) symptoms occurred mainly in early childhood. Adult onset of symptoms occurred in 16 of 194 adult patients, of whom 6 (3.1%) patients suffered a severe event without any preceding symptom (five cardiac events and one coma). In conclusion, symptoms in PCD predominantly develop in early childhood. Most newborns and mothers of newborns detected through NBS remain asymptomatic. However, though rarely, severe complications do occur in both groups.<\/jats:p>","DOI":"10.1002\/jimd.12475","type":"journal-article","created":{"date-parts":[[2022,1,8]],"date-time":"2022-01-08T10:59:30Z","timestamp":1641639570000},"page":"386-405","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Clinical characteristics of primary carnitine deficiency: A structured review using a case\u2010by\u2010case approach"],"prefix":"10.1002","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2057-5525","authenticated-orcid":false,"given":"Loek L.","family":"Crefcoeur","sequence":"first","affiliation":[{"name":"Department of Metabolic Diseases, Wilhelmina Children's Hospital University Medical Center Utrecht  Utrecht The Netherlands"},{"name":"Laboratory Genetic Metabolic Diseases, Amsterdam UMC location Academic Medical Center University of Amsterdam, Amsterdam Gastroenterology and Metabolism  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gepke","family":"Visser","sequence":"additional","affiliation":[{"name":"Department of Metabolic Diseases, Wilhelmina Children's Hospital University Medical Center Utrecht  Utrecht The Netherlands"},{"name":"Laboratory Genetic Metabolic Diseases, Amsterdam UMC location Academic Medical Center University of Amsterdam, Amsterdam Gastroenterology and Metabolism  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sacha","family":"Ferdinandusse","sequence":"additional","affiliation":[{"name":"Laboratory Genetic Metabolic Diseases, Amsterdam UMC location Academic Medical Center University of Amsterdam, Amsterdam Gastroenterology and Metabolism  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frits A.","family":"Wijburg","sequence":"additional","affiliation":[{"name":"Emma's Children's Hospital, Amsterdam UMC location Academic Medical Center University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirjam","family":"Langeveld","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Amsterdam UMC location Academic Medical Center University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Sjouke","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Amsterdam UMC location Academic Medical Center University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,2,3]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/5030"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.32.20378"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750\u20101172\u20107\u201068"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1159\/000448321"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e3181c5e6f7"},{"issue":"3","key":"e_1_2_9_7_1","first-page":"167","article-title":"Screening and diagnosis of children with primary carnitine deficiency in Zhejiang Province, China","volume":"18","author":"Yang LL","year":"2013","journal-title":"Hong Kong J Paediatr"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2019.00050"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.179.4076.899"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.25.1.16"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003\u20102697(81)90019\u20101"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02796479"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450\u2010199009000\u201000020"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.31.7.819"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1984.04050150079021"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(80)80571-3"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1985.04060110011003"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(84)80460-6"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/8904_2011_36"},{"key":"e_1_2_9_20_1","first-page":"155","volume-title":"Metabolic Diseases: foundations of Clinical Management, Genetics and Pathology","author":"Harding C","year":"2017"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.118.015578"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1067\/mpd.2001.111813"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2006.10.003"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n71"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545\u2010013\u20109640\u20100"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23315"},{"key":"e_1_2_9_27_1","unstructured":"MaoR.The SLC22A5 database2017. Accessed May 2 2021.http:\/\/arup.utah.edu\/database\/OCTN2\/OCTN2_welcome.php"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2020.11.005"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12887\u2010020\u201002372\u20107"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2020.04.039"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.901"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545\u2010010\u20109129\u2010z"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/8904_2012_198"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2009.12.015"},{"key":"e_1_2_9_35_1","doi-asserted-by":"crossref","unstructured":"TomlinsonS AthertonJ PrasadS.Primary carnitine deficiency: a rare reversible metabolic cardiomyopathy.2018;2018:3232105.","DOI":"10.1155\/2018\/3232105"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545\u2010007\u20100594\u2010y"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095\u2010006\u20109002\u20109"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.12112"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11154\u2010018\u20109448\u20101"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12291\u2010011\u20100134\u20102"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21607"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010020\u201001357\u20100"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436\u2010020\u201001070\u20100"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1243944"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12158"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201578"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/1098\u20101004(200011)16:5<401::AID\u2010HUMU4>3.0.CO;2\u2010J"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22286"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22285"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23839"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102431\u201012\u201018"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2018\u201000953"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2019.03.1622"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1159\/000333127"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1540\u20108159.2004.00507.x"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehu327"},{"issue":"7","key":"e_1_2_9_57_1","first-page":"499","article-title":"Systemic carnitine deficiency: its place in Reye's syndrome","volume":"10","author":"Chapoy P","year":"1981","journal-title":"Nouvelle Presse Med"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1023\/a:1005314910623"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004390051079"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2011.11.010"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30207"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2014.08.001"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010020\u201001371\u20102"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545\u2010012\u20109488\u20108"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20137"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjca.2019.05.014"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2015.07.027"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198012113032403"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.12.2247"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545\u2010007\u20100527\u20109"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.21167"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jimd.12475","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jimd.12475","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jimd.12475","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T08:03:50Z","timestamp":1692777830000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jimd.12475"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,3]]},"references-count":70,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2022,5]]}},"alternative-id":["10.1002\/jimd.12475"],"URL":"https:\/\/doi.org\/10.1002\/jimd.12475","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,3]]},"assertion":[{"value":"2021-08-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-01-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-02-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}