{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T03:57:47Z","timestamp":1790913467474,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T00:00:00Z","timestamp":1759708800000},"content-version":"vor","delay-in-days":278,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"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":["Pediatrics International"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Primary systemic carnitine deficiency (CDSP) is a rare inherited metabolic disorder characterized by impaired carnitine transport due to mutations in the\n                      <jats:italic>SLC22A5<\/jats:italic>\n                      gene, leading to impaired mitochondrial fatty acid oxidation. The aim of this retrospective, descriptive study was to investigate the clinical, biochemical, and molecular features of CDSP in Turkey, where the lack of a national expanded metabolic screening program contributes to delayed diagnosis and severe complications.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The clinical, biochemical, and molecular profiles of 12 patients from eight families diagnosed between 2003 and 2025 were retrospectively analyzed. Data on family history, consanguinity, clinical manifestations\u2014including cardiomyopathy, muscle weakness, neurological symptoms, and liver dysfunction\u2014plasma free carnitine levels, and echocardiographic measurements were collected and analyzed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The majority of patients (92%) were from consanguineous families. Cardiomyopathy was the most common clinical feature (75%), followed by muscle weakness (50%), neurological symptoms (42%), and liver dysfunction (33%). A novel\n                      <jats:italic>SLC22A5<\/jats:italic>\n                      variant (c.125T&gt;C; p.Leu42Pro) was identified that expands the known genetic spectrum of CDSP. Oral carnitine supplementation significantly increased plasma free carnitine levels (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.01) and improved long\u2010term interventricular septal thickness Z\u2010scores (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.045). In addition, cholestasis was observed in two patients, suggesting an expanded disease phenotype.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These results emphasize the crucial role of early detection and family screening in the prevention of life\u2010threatening complications associated with CDSP. Long\u2010term carnitine therapy improves metabolic and cardiac outcomes, underscoring the need for early intervention and inclusion of CDSP in national newborn screening programs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ped.70211","type":"journal-article","created":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T23:26:58Z","timestamp":1759793218000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Primary systemic carnitine deficiency: Phenotypic variability, diagnostic challenges, and long\u2010term outcomes"],"prefix":"10.1111","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5466-0915","authenticated-orcid":false,"given":"Eymen","family":"P\u0131nar","sequence":"first","affiliation":[{"name":"Department of Pediatrics \u0130stanbul University\u2010Cerrahpa\u015fa, Cerrahpa\u015fa Faculty of Medicine  \u0130stanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7159-4008","authenticated-orcid":false,"given":"Tanyel","family":"Zubarioglu","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nutrition and Metabolism \u0130stanbul University\u2010Cerrahpa\u015fa, Cerrahpa\u015fa Faculty of Medicine  \u0130stanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0734-4415","authenticated-orcid":false,"given":"Han\u0131m","family":"Babazade","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nutrition and Metabolism \u0130stanbul University\u2010Cerrahpa\u015fa, Cerrahpa\u015fa Faculty of Medicine  \u0130stanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8645-5975","authenticated-orcid":false,"given":"Ka\u011fan","family":"\u00c7al\u0131\u015fgan","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nutrition and Metabolism \u0130stanbul University\u2010Cerrahpa\u015fa, Cerrahpa\u015fa Faculty of Medicine  \u0130stanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3315-5124","authenticated-orcid":false,"given":"Mehmet \u015eerif","family":"Cansever","sequence":"additional","affiliation":[{"name":"Research Laboratory of Metabolism \u0130stanbul University\u2010Cerrahpa\u015fa, Cerrahpa\u015fa Faculty of Medicine  \u0130stanbul Turkey"},{"name":"Department of Medical Documentation and Techniques, Division of Medical Laboratory Techniques \u0130stanbul University\u2010Cerrahpa\u015fa, The Vocational School of Health Services  \u0130stanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5170-5594","authenticated-orcid":false,"given":"Ertu\u011frul","family":"K\u0131yk\u0131m","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nutrition and Metabolism \u0130stanbul University\u2010Cerrahpa\u015fa, Cerrahpa\u015fa Faculty of Medicine  \u0130stanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7256-0750","authenticated-orcid":false,"given":"\u00c7i\u011fdem","family":"Aktu\u011flu Zeybek","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nutrition and Metabolism \u0130stanbul University\u2010Cerrahpa\u015fa, Cerrahpa\u015fa Faculty of Medicine  \u0130stanbul Turkey"},{"name":"Research Laboratory of Metabolism \u0130stanbul University\u2010Cerrahpa\u015fa, Cerrahpa\u015fa Faculty of Medicine  \u0130stanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,6]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23315"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12475"},{"key":"e_1_2_13_4_1","first-page":"1993","volume-title":"GeneReviews\u00ae [Internet]","author":"El\u2010Hattab AW","year":"2012"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545\u2010013\u20109606\u20102"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12158"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/heart.83.6.667"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrdd.20124"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijns4010001"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1067\/mpd.2001.111813"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.111.6.1399"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545\u2010007\u20100666\u2010z"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545\u2010007\u20100527\u20109"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2021.648939"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijns7010015"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2021.635353"},{"key":"e_1_2_13_18_1","unstructured":"Australian Government Department of Health.List of conditions screened by jurisdiction\u2014September 2022 [Internet]. Available from:https:\/\/www.health.gov.au\/resources\/publications\/list\u2010of\u2010conditions\u2010screened\u2010by\u2010jurisdiction\u2010september\u20102022?language=en"},{"key":"e_1_2_13_19_1","first-page":"23","article-title":"20\u2009years after discovery of the causative gene of primary carnitine deficiency","volume":"25","author":"Tang N","year":"2020","journal-title":"HK J Paediatr"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.21037\/atm.2017.s133"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgmr.2018.05.003"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.12.2247"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.15537\/smj.2020.7.25147"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545\u2010007\u20100553\u20107"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijns9010006"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21607"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545\u2010013\u20109640\u20100"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545\u2010012\u20109488\u20108"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmd2.12319"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmd2.12334"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmd2.12383"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/8904_2016_30"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1023\/a:1005506024055"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1055\/s\u20100042\u20101747933"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.3345\/kjp.2012.55.2.58"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439\u2010020\u201002199\u20103"}],"container-title":["Pediatrics International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ped.70211","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/ped.70211","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ped.70211","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T03:43:57Z","timestamp":1790912637000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ped.70211"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1]]},"references-count":35,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1111\/ped.70211"],"URL":"https:\/\/doi.org\/10.1111\/ped.70211","archive":["Portico"],"relation":{},"ISSN":["1328-8067","1442-200X"],"issn-type":[{"value":"1328-8067","type":"print"},{"value":"1442-200X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1]]},"assertion":[{"value":"2025-04-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-31","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70211"}}