{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T01:01:55Z","timestamp":1784682115843,"version":"3.55.0"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:00:00Z","timestamp":1760054400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:00:00Z","timestamp":1760054400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labour and Welfare","doi-asserted-by":"publisher","award":["23FC1033"],"award-info":[{"award-number":["23FC1033"]}],"id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23K07294"],"award-info":[{"award-number":["23K07294"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23K07316"],"award-info":[{"award-number":["23K07316"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020026","name":"Citrin Foundation","doi-asserted-by":"publisher","award":["RG22003"],"award-info":[{"award-number":["RG22003"]}],"id":[{"id":"10.13039\/501100020026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020026","name":"Citrin Foundation","doi-asserted-by":"publisher","award":["RG22005"],"award-info":[{"award-number":["RG22005"]}],"id":[{"id":"10.13039\/501100020026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["320030_207965"],"award-info":[{"award-number":["320030_207965"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["CRSII\u2010222794"],"award-info":[{"award-number":["CRSII\u2010222794"]}],"id":[{"id":"10.13039\/501100001711","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":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Urea cycle disorders (UCDs) are rare inherited metabolic diseases characterized by defective detoxification of nitrogen, leading to hyperammonemia and neurological complications. While pediatric UCDs have been extensively studied in Japan, data on adult patients remain limited. This study aims to evaluate the current status of Japanese adult UCD patients, hereby comparing long\u2010term outcomes after neonatal\/infantile or late onset in a new nationwide study investigating clinical manifestations and management. In total, we collected data of 116 adult UCD patients diagnosed and\/or treated at various institutions, combining this new cohort (34 UCD patients between January 2010 and December 2022) with data from a previous nationwide study (82 UCD patients between January 2000 and March 2018). Among 116 adult UCD patients, ornithine transcarbamylase deficiency was the most common subtype (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u200969). Hyperammonemia occurred in 91.4% of patients, and intellectual disability was present in 50.0%. Patients generally showed reduced final height and BMI compared to Japanese controls, particularly among females and those with infantile\u2010onset UCDs. Peak ammonia levels \u2265\u2009360\u2009\u03bcmol\/L were significantly associated with intellectual disability. Liver transplantation (LT) was performed in 20 patients, and although it helped to avoid hyperammonemia, it did not statistically improve neurocognitive outcomes in patients with peak ammonia &lt;\u2009360\u2009\u03bcmol\/L. This study provides the first comprehensive overview of adult UCD patients in Japan, highlighting frequent growth impairment and variable cognitive outcomes. LT improves metabolic control but cannot prevent intellectual disability in all patients. These findings underscore the need for early diagnosis, individualized treatment strategies, and long\u2010term follow\u2010up into adulthood.\n                  <\/jats:p>","DOI":"10.1002\/jimd.70099","type":"journal-article","created":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:53:52Z","timestamp":1760165632000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Current Status of Adult Patients With Urea Cycle Disorders in Japan: From the Nation\u2010Wide Study"],"prefix":"10.1002","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1328-6696","authenticated-orcid":false,"given":"Jun","family":"Kido","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Faculty of Life Sciences Kumamoto University  Kumamoto Japan"},{"name":"Department of Pediatrics Kumamoto University Hospital  Kumamoto Japan"},{"name":"University Children's Hospital Zurich and Children's Research Centre University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0635-091X","authenticated-orcid":false,"given":"Johannes","family":"H\u00e4berle","sequence":"additional","affiliation":[{"name":"University Children's Hospital Zurich and Children's Research Centre University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keishin","family":"Sugawara","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Life Sciences Kumamoto University  Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiichi","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Organ Transplantation Center, National Center for Child Health and Development  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4684-0446","authenticated-orcid":false,"given":"Akinari","family":"Fukuda","sequence":"additional","affiliation":[{"name":"Organ Transplantation Center, National Center for Child Health and Development  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Mizuta","sequence":"additional","affiliation":[{"name":"Department of Transplant Surgery Saitama Children's Medical Center  Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Kikuchi","sequence":"additional","affiliation":[{"name":"Physical Medicine and Rehabilitation Sakata Medical Center  Yamagata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Togashi","sequence":"additional","affiliation":[{"name":"Department of Neurology Municipal Kofu Hospital  Yamanashi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5892-8317","authenticated-orcid":false,"given":"Takashi","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Surgery, Graduate School of Medicine Kyoto University  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9731-8290","authenticated-orcid":false,"given":"Kenyu","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Department of Clinical Investigation Kumamoto University Hospital  Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimitoshi","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Life Sciences Kumamoto University  Kumamoto Japan"},{"name":"Department of Pediatrics Kumamoto University Hospital  Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,10]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12100"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.18.5060"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1067\/mpd.2002.122394"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2013.07.008"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320390226"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0022\u20103476(99)70448\u20108"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00431\u2010003\u20101188\u20109"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545\u2010005\u20100303\u20107"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010016\u20100493\u20100"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11011\u2010018\u20100259\u20106"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.86.1.54"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/ped.70121"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgmr.2021.100805"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(79)91503\u20104"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa066596"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00431\u2010006\u20100143\u2010y"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/ped.13163"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004670100702"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semnephrol.2008.05.007"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/petr.12196"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/lt.21297"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545\u2010006\u20100145\u2010y"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.21037\/tp\u201021\u2010576"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/petr.12987"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12415"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2012.06.065"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545\u2010013\u20109624\u20100"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010014\u20100187\u20104"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545\u2010015\u20109839\u20103"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545\u2010015\u20109840\u2010x"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545\u2010017\u20100132\u20105"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1023\/a:1005374027693"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545\u2010011\u20109427\u20100"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12384"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgmr.2021.100724"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2016.17"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010020\u201067496\u20103"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41390\u2010023\u201002722\u2010y"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12403"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12843"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jimd.70099","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jimd.70099","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jimd.70099","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:11:42Z","timestamp":1784679102000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jimd.70099"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,10]]},"references-count":40,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1002\/jimd.70099"],"URL":"https:\/\/doi.org\/10.1002\/jimd.70099","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,10]]},"assertion":[{"value":"2025-06-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70099"}}