{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T08:54:55Z","timestamp":1781772895017,"version":"3.54.5"},"reference-count":14,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"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":["JIMD Reports"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Hyperammonemic crisis (HAC) remains a major risk factor for urea cycle disorders (UCD), and practical outpatient predictors are limited. We tested whether short\u2010term changes in plasma glutamine (\u0394Gln) and ammonia (\u0394NH\n                    <jats:sub>3<\/jats:sub>\n                    ) predict HAC and whether effects differ by onset type. In a retrospective cohort (2014\u20132024) of 18 patients with UCD (neonatal\u2010onset [NO] nine; late\u2010onset [LO] nine), HAC was defined as ammonia (NH\n                    <jats:sub>3<\/jats:sub>\n                    ) &gt;\u2009150 \u03bcg\/dL (88.1 \u03bcmol\/L). For each patient, \u0394Gln and \u0394NH\n                    <jats:sub>3<\/jats:sub>\n                    were calculated between sequential outpatient samples. Investigation 1 compared the changes observed between 31\u201360\u2009days and 8\u201330\u2009days before HAC, with stable period changes. Investigation 2 compared changes at 61\u201390 and 31\u201360\u2009days before HAC with stable period changes. Associations were evaluated using generalized linear mixed\u2010effects models with onset\u2010specific effects. In NO, larger \u0394Gln during Investigation 1 was associated with higher HAC risk (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001) whereas \u0394NH\n                    <jats:sub>3<\/jats:sub>\n                    was not associated with HAC (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.361). The probability of HAC in NO was estimated to reach 67.1% at \u0394Gln +500 \u03bcmol\/L. In LO, neither \u0394Gln nor \u0394NH\n                    <jats:sub>3<\/jats:sub>\n                    during Investigation 1 showed a significant association with HAC, and the estimated probabilities remained low across the observed ranges. During Investigation 2, no significant associations between biomarkers and HAC were observed in either group. Progressive increases in plasma glutamine levels within the 31\u201360 and 8\u201330\u2009days pre\u2010HAC window may serve as early markers of HAC risk in NO\u2010UCD, supporting the utility of longitudinal monitoring. These trends were not associated with LO\u2010UCD, suggesting the need for alternative surveillance strategies tailored to the onset phenotype.\n                  <\/jats:p>","DOI":"10.1002\/jmd2.70105","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T08:25:20Z","timestamp":1781771120000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Longitudinal Changes in Glutamine and Ammonia in Relation to Hyperammonemic Crisis in Urea Cycle Disorders"],"prefix":"10.1002","volume":"67","author":[{"given":"Yasuaki","family":"Yasuda","sequence":"first","affiliation":[{"name":"Department of Pediatrics Fujita Health University School of Medicine  Toyoake Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6944-4131","authenticated-orcid":false,"given":"Yoko","family":"Nakajima","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Fujita Health University School of Medicine  Toyoake Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuta","family":"Sudo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Fujita Health University School of Medicine  Toyoake Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuma","family":"Ishihara","sequence":"additional","affiliation":[{"name":"Innovative and Clinical Research Promotion Center Gifu University Hospital  Gifu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuya","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Fujita Health University School of Medicine  Toyoake Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,18]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12100"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12031"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12384"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010020\u201067496\u20103"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.34763\/jmotherandchild.20202402si.2015.000006"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0022\u20103476(05)81200\u20104"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1012995701589"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2014.148"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2015.11.005"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51668"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010016\u20100493\u20100"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545\u2010013\u20109624\u20100"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1373\/49.4.681"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/chemosensors13060206"}],"container-title":["JIMD Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmd2.70105","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jmd2.70105","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmd2.70105","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T08:25:20Z","timestamp":1781771120000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jmd2.70105"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,18]]},"references-count":14,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1002\/jmd2.70105"],"URL":"https:\/\/doi.org\/10.1002\/jmd2.70105","archive":["Portico"],"relation":{},"ISSN":["2192-8312","2192-8312"],"issn-type":[{"value":"2192-8312","type":"print"},{"value":"2192-8312","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,18]]},"assertion":[{"value":"2025-12-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70105"}}