{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T20:15:33Z","timestamp":1790972133966,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T00:00:00Z","timestamp":1753228800000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"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":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Cerebrotendinous xanthomatosis (CTX) is a treatable neurometabolic disorder. Chenodeoxycholic acid (CDCA) is the first\u2010line treatment and can potentially halt disease progression if initiated before neurologic symptoms appear. This nationwide, multicenter study evaluates the long\u2010term effects of treatment in 86 genetically confirmed patients with CTX receiving CDCA for \u2265\u20096\u2009months, focusing on neurologic and extraneurologic outcomes, prognostic factors, and biochemical response. Clinical and biochemical parameters were recorded at baseline and follow\u2010up, and neurological outcomes were assessed using neurological disability scores. Our results indicate a critical age of 28\u2009years for the start of treatment. Patients diagnosed before 28\u2009years showed 100% neurological stabilization or improvement, whereas patients diagnosed later had a higher rate of disease progression (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). CDCA effectively stabilized or improved pyramidal and cerebellar symptoms, although myoclonus and parkinsonism remained less responsive. Psychiatric symptoms showed a lower treatment response, with psychosis being the most refractory finding. CDCA resulted in a strong and sustained reduction in cholestanol levels, although biochemical response did not always correlate with clinical improvement. Longer diagnostic delay and presence of anxiety and pyramidal\/cerebellar symptoms were associated with poorer outcomes. Notably, a cholestatic child, for whom liver transplantation had initially been considered, recovered completely under CDCA therapy. Our results show that early diagnosis and initiation of CDCA therapy significantly improve neurological outcomes in CTX. However, even in late\u2010diagnosed patients, treatment continues to be beneficial, demonstrating that it is never too late to start therapy. Biochemical response does not always predict clinical improvement; multidisciplinary follow\u2010up is essential.\n                  <\/jats:p>","DOI":"10.1002\/jimd.70069","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T05:28:52Z","timestamp":1753334932000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Long\u2010Term Outcomes of Chenodeoxycholic Acid Therapy for Cerebrotendinous Xanthomatosis: A Nationwide Study on Prognostic Factors and Treatment Response"],"prefix":"10.1002","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7159-4008","authenticated-orcid":false,"given":"Tanyel","family":"Zubarioglu","sequence":"first","affiliation":[{"name":"Division of Pediatric Nutrition and Metabolism \u0130stanbul University\u2010Cerrahpa\u015fa, Cerrahpa\u015fa Medical Faculty  \u0130stanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Banu","family":"Kad\u0131o\u011flu\u2010Y\u0131lmaz","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nutrition and Metabolism Konya Sel\u00e7uk University Medical Faculty  Konya Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Engin","family":"K\u00f6se","sequence":"additional","affiliation":[{"name":"Department of Pediatric Metabolism Ankara University Faculty of Medicine  Ankara Turkey"},{"name":"Ankara University Rare Diseases Application and Research Center  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pelin","family":"Teke\u2010K\u0131sa","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nutrition and Metabolism Dokuz Eylul University Medical Faculty  \u0130zmir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2167-8139","authenticated-orcid":false,"given":"Mehmet Cihan","family":"Balc\u0131","sequence":"additional","affiliation":[{"name":"Division of Nutrition and Metabolism Istanbul University, Istanbul Faculty of Medicine  \u0130stanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Havva","family":"Yaz\u0131c\u0131","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nutrition and Metabolism Ege University Medical Faculty  \u0130zmir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burcu","family":"\u00d6zturk\u2010Hi\u015fmi","sequence":"additional","affiliation":[{"name":"Division of Pediatric Metabolic Disorders Marmara University School of Medicine  \u0130stanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdurrahman","family":"Akg\u00fcn","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Metabolic Diseases Firat University School of Medicine  Elaz\u0131\u011f Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deniz","family":"Kor","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nutrition and Metabolism Cukurova University Medical Faculty  Adana Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6947-2573","authenticated-orcid":false,"given":"Sevil","family":"Y\u0131ld\u0131z","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nutrition and Metabolism Health Sciences University, Bursa Yuksek Ihtisas Training and Research Hospital  Bursa Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gonca","family":"K\u0131l\u0131\u00e7\u2010Y\u0131ld\u0131r\u0131m","sequence":"additional","affiliation":[{"name":"Pediatric Nutrition and Metabolism Unit Eskisehir Osmangazi University, Faculty of Medicine  Eski\u015fehir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erdo\u011fan","family":"Soyu\u00e7en","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Inherited Pediatric Metabolic Diseases Akdeniz University Faculty of Medicine  Antalya Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aylin","family":"Ak\u00e7al\u0131","sequence":"additional","affiliation":[{"name":"Department of Neurology Gaziantep University Faculty of Medicine  Gaziantep Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9076-1388","authenticated-orcid":false,"given":"Y\u0131lmaz","family":"Y\u0131ld\u0131z","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Metabolism Hacettepe University, Faculty of Medicine  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asl\u0131","family":"Durmu\u015f","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nutrition and Metabolism Health Sciences University, Trabzon Kanuni Training and Research Hospital  Trabzon Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dilek","family":"G\u00fcne\u015f","sequence":"additional","affiliation":[{"name":"Division of Inborn Metabolic Disease Ba\u011fc\u0131lar Training and Research Hospital  \u0130stanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pembe","family":"Soylu\u2010\u00dcstkoyuncu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Pediatric Metabolic Diseases Unit Health Sciences University, Kayseri City Education and Research Hospital  Kayseri Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c7i\u011fdem Seher","family":"Kasapkara","sequence":"additional","affiliation":[{"name":"Department of Pediatric Metabolism Ankara Y\u0131ld\u0131r\u0131m Beyaz\u0131t University, Ankara Bilkent City Hospital  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u015eahin","family":"Erd\u00f6l","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Metabolism Uludag University Faculty of Medicine  Bursa Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emine","family":"G\u00f6ksoy","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nutrition and Metabolism Adnan Menderes University Medical Faculty  Ayd\u0131n Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1982-8046","authenticated-orcid":false,"given":"Halil Tuna","family":"Akar","sequence":"additional","affiliation":[{"name":"Pediatric Metabolic Diseases Unit Ankara Etlik City Hospital  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haluk","family":"G\u00fcm\u00fc\u015f","sequence":"additional","affiliation":[{"name":"Department of Neurology Konya Sel\u00e7uk University Medical Faculty  Konya Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmet Hakan","family":"Ekmek\u00e7i","sequence":"additional","affiliation":[{"name":"Department of Neurology Konya Sel\u00e7uk University Medical Faculty  Konya Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatma Tuba","family":"Emino\u011flu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Metabolism Ankara University Faculty of Medicine  Ankara Turkey"},{"name":"Ankara University Rare Diseases Application and Research Center  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3151-3741","authenticated-orcid":false,"given":"Nur","family":"Arslan","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nutrition and Metabolism Dokuz Eylul University Medical Faculty  \u0130zmir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ha\u015fmet Ayhan","family":"Hana\u011fas\u0131","sequence":"additional","affiliation":[{"name":"Department of Neurology Istanbul University, Istanbul Faculty of Medicine  \u0130stanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ebru","family":"Canda","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nutrition and Metabolism Ege University Medical Faculty  \u0130zmir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emine","family":"Gen\u00e7","sequence":"additional","affiliation":[{"name":"Division of Pediatric Metabolic Disorders Marmara University School of Medicine  \u0130stanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I\u015f\u0131l","family":"\u00d6zer","sequence":"additional","affiliation":[{"name":"Department of Pediatric Metabolism Ondokuz May\u0131s University, Faculty of Medicine  Samsun Turkey"},{"name":"Division of Pediatric Nutrition and Metabolism Kafkas University Medical Faculty  Kars Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2365-0850","authenticated-orcid":false,"given":"Ay\u015feg\u00fcl","family":"G\u00fcnd\u00fcz","sequence":"additional","affiliation":[{"name":"Department of Neurology \u0130stanbul University\u2010Cerrahpa\u015fa, Cerrahpa\u015fa Medical Faculty  \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 Medical Faculty  \u0130stanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c7i\u011fdem","family":"Aktu\u011flu\u2010Zeybek","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nutrition and Metabolism \u0130stanbul University\u2010Cerrahpa\u015fa, Cerrahpa\u015fa Medical Faculty  \u0130stanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,23]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/08830738030180091001"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010014\u20100179\u20104"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jlr.2021.100078"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgmr.2021.100719"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/joim.13277"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2024.108493"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2003.50394"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010021\u201001980\u20105"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545\u2010013\u20109674\u20103"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468\u20101331.2011.03439.x"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacl.2018.06.008"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1177\/1747493019840933"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198301273080401"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000006731"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10072\u2010019\u201004169\u20108"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/WNF.0b013e318288076a"},{"issue":"5","key":"e_1_2_11_18_1","first-page":"907","article-title":"Cerebrotendinous Xanthomatosis in the Israeli Druze: Molecular Genetics and Phenotypic Characteristics","volume":"55","author":"Leitersdorf E.","year":"1994","journal-title":"American Journal of Human Genetics"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003\u20104819\u201075\u20106\u2010843"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacl.2024.02.009"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11011\u2010021\u201000714\u20107"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1159\/000506770"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13760\u2010017\u20100851\u20102"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545\u2010018\u20100162\u20107"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545\u2010015\u20109873\u20101"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2013.76"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2022.12.011"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.P075051"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacl.2024.03.004"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/oby.22130"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0700899104"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u20102009\u20100944"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00431\u2010015\u20102584\u20107"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jimd.70069","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jimd.70069","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jimd.70069","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:06:47Z","timestamp":1784678807000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jimd.70069"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7]]},"references-count":32,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["10.1002\/jimd.70069"],"URL":"https:\/\/doi.org\/10.1002\/jimd.70069","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7]]},"assertion":[{"value":"2025-04-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70069"}}