{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T04:47:00Z","timestamp":1791780420187,"version":"4.3.4"},"reference-count":34,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T00:00:00Z","timestamp":1791676800000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100013323","name":"Yancheng Science and Technology Bureau","doi-asserted-by":"publisher","award":["YCBE202465"],"award-info":[{"award-number":["YCBE202465"]}],"id":[{"id":"10.13039\/501100013323","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2026,10]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n \n Primary carnitine deficiency (PCD) is a treatable autosomal recessive disorder caused by\n SLC22A5<\/jats:italic>\n gene variants and included in newborn screening widely. However, its prevalence and variant spectrum vary greatly, and prenatal diagnosis for recurrence\u2010risk families remains rare. This study assessed tandem mass spectrometry (MS\/MS) combined with genetic testing in NBS and prenatal diagnosis of PCD in Yancheng, China, and described the local prevalence and variant characteristics.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n From 2015 to 2024, free carnitine (C0) levels were measured in neonatal dried blood spot (DBS) samples by MS\/MS for PCD screening. Newborns with persistently low C0 levels were recalled for diagnostic evaluation. At diagnosis, the C0 levels in both neonatal and maternal blood were measured, and next\u2010generation sequencing was performed for\n SLC22A5<\/jats:italic>\n variants in the newborns. For the recurrence\u2010risk family with a previous proband, Sanger sequencing was used to confirm the parental origin of the proband's variants, and prenatal diagnosis with amniotic fluid was performed in the subsequent pregnancy.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Combined MS\/MS and genetic testing led to the diagnosis of 17 newborns with PCD (15 molecularly confirmed with biochemical results, two clinically inferred) and three newborns with maternal carnitine deficiency among the 152 newborns with persistently low C0 levels on re\u2010screening. In these 17 PCD newborns, 10 distinct variant sites were detected, of which missense variants predominated, with c.1400C>G (p.S467C) being the most frequent (13\/32, 40.63%). For the proband in this recurrence\u2010risk family, the two pathogenic variants were inherited from each parent. The fetus carried only the maternal variant, without postnatal anomalies.<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n NBS using MS\/MS combined with genetic testing facilitates early diagnosis and classification of PCD. The screening\u2010detected prevalence of PCD in Yancheng was 1:25,852, with c.1400C>G (p.S467C) as the hotspot variant. Genetic testing of\n SLC22A5<\/jats:italic>\n provided effective prenatal diagnosis for the recurrence\u2010risk family.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/mgg3.70316","type":"journal-article","created":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T04:20:28Z","timestamp":1791778828000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Newborn Screening of Primary Carnitine Deficiency and Prenatal Genetic Diagnosis for a Recurrence\u2010Risk Family"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-7102-2073","authenticated-orcid":false,"given":"Huilin","family":"Sun","sequence":"first","affiliation":[{"name":"Center for Medical Genetics Yancheng Maternal and Child Health Care Hospital Affiliated to Yangzhou University Yancheng China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianli","family":"Zheng","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics Yancheng Maternal and Child Health Care Hospital Affiliated to Yangzhou University Yancheng China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Pediatric Genetic Metabolic Endocrine Clinic Yancheng Maternal and Child Health Care Hospital Affiliated to Yangzhou University Yancheng China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haihong","family":"Chen","sequence":"additional","affiliation":[{"name":"Office for Newborn Disease Screening Yancheng Maternal and Child Health Care Hospital Affiliated to Yangzhou University Yancheng China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics Yancheng Maternal and Child Health Care Hospital Affiliated to Yangzhou University Yancheng China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaorui","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics Yancheng Maternal and Child Health Care Hospital Affiliated to Yangzhou University Yancheng China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daocheng","family":"Bao","sequence":"additional","affiliation":[{"name":"Department of Neonatology Yancheng Maternal and Child Health Care Hospital Affiliated to Yangzhou University Yancheng China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangfang","family":"Yang","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics Yancheng Maternal and Child Health Care Hospital Affiliated to Yangzhou University Yancheng China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianbing","family":"Liu","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics Yancheng Maternal and Child Health Care Hospital Affiliated to Yangzhou University Yancheng China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,11]]},"reference":[{"issue":"6","key":"e_1_2_14_2_1","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1002\/jmd2.12383","article-title":"Patients With Primary Carnitine Deficiency Treated With L\u2010Carnitine Are Alive and Doing Well\u2014A 10\u2010Year Follow\u2010Up in The Faroe Islands","volume":"64","author":"Abrahamsen R. K.","year":"2023","journal-title":"JIMD Reports"},{"issue":"4","key":"e_1_2_14_3_1","doi-asserted-by":"crossref","first-page":"72","DOI":"10.3390\/ijns10040072","article-title":"Incidence of Inborn Errors of Metabolism and Endocrine Disorders Among 40965 Newborn Infants at Riyadh Second Health Cluster of the Ministry of Health Saudi Arabia","volume":"10","author":"Alshehri A. S.","year":"2024","journal-title":"International Journal of Neonatal Screening"},{"issue":"1","key":"e_1_2_14_4_1","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1186\/s13023-022-02512-5","article-title":"Outcomes of Mitochondrial Long Chain Fatty Acid Oxidation and Carnitine Defects From a Single Center Metabolic Genetics Clinic","volume":"17","author":"Ambrose A.","year":"2022","journal-title":"Orphanet Journal of Rare Diseases"},{"issue":"1","key":"e_1_2_14_5_1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.3390\/ijns10010019","article-title":"Harnessing Next\u2010Generation Sequencing as a Timely and Accurate Second\u2010Tier Screening Test for Newborn Screening of Inborn Errors of Metabolism","volume":"10","author":"Chan T. C. H.","year":"2024","journal-title":"International Journal of Neonatal Screening"},{"key":"e_1_2_14_6_1","doi-asserted-by":"crossref","first-page":"1062715","DOI":"10.3389\/fgene.2022.1062715","article-title":"Clinical, Biochemical, and Molecular Genetic Characteristics of Patients With Primary Carnitine Deficiency Identified by Newborn Screening in Shanghai, China","volume":"13","author":"Chang S.","year":"2022","journal-title":"Frontiers in Genetics"},{"issue":"12","key":"e_1_2_14_7_1","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1136\/jmg-2023-109206","article-title":"Newborn Screening for Primary Carnitine Deficiency: Who Will Benefit? \u2013a Retrospective Cohort Study","volume":"60","author":"Crefcoeur L.","year":"2023","journal-title":"Journal of Medical Genetics"},{"key":"e_1_2_14_8_1","volume-title":"StatPearls","author":"Dahash B. A.","year":"2023"},{"issue":"1","key":"e_1_2_14_9_1","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s13023-025-03546-1","article-title":"Combined Biochemical Profiling and DNA Sequencing in the Expanded Newborn Screening for Inherited Metabolic Diseases: The Experience in an Italian Reference Center","volume":"20","author":"Fecarotta S.","year":"2025","journal-title":"Orphanet Journal of Rare Diseases"},{"issue":"10","key":"e_1_2_14_10_1","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1002\/humu.23839","article-title":"A Mutation Creating an Upstream Translation Initiation Codon in SLC22A5 5'UTR Is a Frequent Cause of Primary Carnitine Deficiency","volume":"40","author":"Ferdinandusse S.","year":"2019","journal-title":"Human Mutation"},{"issue":"12","key":"e_1_2_14_11_1","doi-asserted-by":"crossref","first-page":"1684","DOI":"10.1002\/humu.23315","article-title":"Functional and Molecular Studies in Primary Carnitine Deficiency","volume":"38","author":"Frigeni M.","year":"2017","journal-title":"Human Mutation"},{"issue":"3","key":"e_1_2_14_12_1","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.ymgme.2017.06.015","article-title":"Biochemical Characteristics of Newborns With Carnitine Transporter Defect Identified by Newborn Screening in California","volume":"122","author":"Gallant N. 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P.","year":"2023","journal-title":"Annals of Noninvasive Electrocardiology"},{"issue":"1","key":"e_1_2_14_15_1","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1186\/s13052-025-01911-1","article-title":"Newborn Screening of Primary Carnitine Deficiency: Clinical and Molecular Genetic Characteristics","volume":"51","author":"Hu H.","year":"2025","journal-title":"Italian Journal of Pediatrics"},{"issue":"7","key":"e_1_2_14_16_1","doi-asserted-by":"crossref","first-page":"e247225","DOI":"10.1136\/bcr-2021-247225","article-title":"Rare Case of Primary Carnitine Deficiency Presenting as Acute Liver Failure","volume":"15","author":"Jain S.","year":"2022","journal-title":"BMJ Case Reports"},{"key":"e_1_2_14_17_1","doi-asserted-by":"crossref","first-page":"1304458","DOI":"10.3389\/fgene.2023.1304458","article-title":"Primary Carnitine Deficiency: Estimation of Prevalence in Chinese Population and Insights Into Newborn Screening","volume":"14","author":"Ji X.","year":"2023","journal-title":"Frontiers in Genetics"},{"issue":"3","key":"e_1_2_14_18_1","first-page":"309","article-title":"Analysis of Screening Results of Tandem Mass Spectrometry for Neonates With Primary Carnitine Deficiency in Shijiazhuang Area","volume":"42","author":"Jia L.","year":"2021","journal-title":"Chinese Journal of Pediatrics"},{"issue":"1","key":"e_1_2_14_19_1","doi-asserted-by":"crossref","first-page":"e202400002","DOI":"10.1002\/minf.202400002","article-title":"Structural and Dynamic Assessment of Disease\u2010Causing Mutations for the Carnitine Transporter OCTN2","volume":"44","author":"Jokiel J.","year":"2025","journal-title":"Molecular Informatics"},{"issue":"1","key":"e_1_2_14_20_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12872-023-03676-z","article-title":"A Novel Pathogenic Variant in the Carnitine Transporter Gene, SLC22A5, in Association With Metabolic Carnitine Deficiency and Cardiomyopathy Features","volume":"24","author":"Jolfayi A. 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A.","year":"2021","journal-title":"Molecular Genetics and Metabolism Reports"},{"key":"e_1_2_14_29_1","doi-asserted-by":"crossref","first-page":"631688","DOI":"10.3389\/fgene.2021.631688","article-title":"Tandem Mass Spectrometry Screening for Inborn Errors of Metabolism in Newborns and High\u2010Risk Infants in Southern China: Disease Spectrum and Genetic Characteristics in a Chinese Population","volume":"12","author":"Tan J.","year":"2021","journal-title":"Frontiers in Genetics"},{"key":"e_1_2_14_30_1","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1186\/s13023-025-04133-0","article-title":"Benefits and Pitfalls in Newborn Screening for Carnitine Uptake Deficiency: A 4\u2010Year Single\u2010Center Experience","volume":"21","author":"Turturo M.","year":"2026","journal-title":"Orphanet Journal of Rare Diseases"},{"issue":"1","key":"e_1_2_14_31_1","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1186\/s13023-023-02735-0","article-title":"A Qualitative Study on the Perspectives of Mothers Who Had Been Diagnosed With Primary Carnitine Deficiency Through Newborn Screening of Their Child","volume":"18","author":"Heuvel L. M.","year":"2023","journal-title":"Orphanet Journal of Rare Diseases"},{"key":"e_1_2_14_32_1","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.issn.0376\u20102491.2019.02.003"},{"key":"e_1_2_14_33_1","doi-asserted-by":"crossref","first-page":"686137","DOI":"10.3389\/fgene.2021.686137","article-title":"Newborn Screening and Genetic Analysis Identify Six Novel Genetic Variants for Primary Carnitine Deficiency in Ningbo Area, China","volume":"12","author":"Yang X.","year":"2021","journal-title":"Frontiers in Genetics"},{"issue":"2","key":"e_1_2_14_34_1","first-page":"47","article-title":"Assessment and Application of Acylcarnitines Summations as Auxiliary Quantization Indicator for Primary Carnitine Deficiency","volume":"11","author":"Zhi H.","year":"2025","journal-title":"Journal of Clinical Medicine Research"},{"issue":"1","key":"e_1_2_14_35_1","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1186\/s13023-024-03267-x","article-title":"Screening Primary Carnitine Deficiency in 10 Million Chinese Newborns: A Systematic Review and Meta\u2010Analysis","volume":"19","author":"Zhou J.","year":"2024","journal-title":"Orphanet Journal of Rare Diseases"}],"container-title":["Molecular Genetics & Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.70316","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mgg3.70316","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.70316","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T04:20:35Z","timestamp":1791778835000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.70316"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":34,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1002\/mgg3.70316"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.70316","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"2026-02-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70316"}}