{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T10:29:38Z","timestamp":1788172178576,"version":"build-2803163510"},"reference-count":40,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,4,18]],"date-time":"2021-04-18T00:00:00Z","timestamp":1618704000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Urea cycle disorders (UCDs) are inherited metabolic disorders with impaired nitrogen detoxification caused by defects in urea cycle enzymes. They often manifest with hyperammonemic attacks resulting in significant morbidity or death. We performed a nationwide questionnaire\u2010based study between January 2000 and March 2018 to document all UCDs in Japan, including diagnoses, treatments, and outcomes. A total of 229 patients with UCDs were enrolled in this study: 73 males and 53 females with ornithine transcarbamylase deficiency (OTCD), 33 patients with carbamoylphosphate synthetase 1 deficiency, 48 with argininosuccinate synthetase deficiency, 14 with argininosuccinate lyase deficiency, and 8 with arginase deficiency. Survival rates at 20\u2009years of age of male and female patients with late\u2010onset OTCD were 100% and 97.7%, respectively. Blood ammonia levels and time of onset had a significant impact on the neurodevelopmental outcome (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u2009.001 and\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0=\u00a0.028, respectively). Hemodialysis and liver transplantation did not prevent poor neurodevelopmental outcomes. While treatment including medication, hemodialysis, and liver transplantation may aid in decreasing blood ammonia and\/or preventing severe hyperammonemia, a blood ammonia level \u2265\u2009360 \u03bcmol\/L was found to be a significant indicator for a poor neurodevelopmental outcome. In conclusion, although current therapy for UCDs has advanced and helped saving lives, patients with blood ammonia levels \u2265\u2009360 \u03bcmol\/L at onset often have impaired neurodevelopmental outcomes. Novel neuroprotective measures should therefore be developed to achieve better neurodevelopmental outcomes in these patients.\n                  <\/jats:p>","DOI":"10.1002\/jimd.12384","type":"journal-article","created":{"date-parts":[[2021,4,11]],"date-time":"2021-04-11T04:32:10Z","timestamp":1618115530000},"page":"826-837","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Long\u2010term outcome of urea cycle disorders: Report from a nationwide study in Japan"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1328-6696","authenticated-orcid":false,"given":"Jun","family":"Kido","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medical Sciences, Faculty of Life Sciences Kumamoto University  Kumamoto 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