{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T02:16:49Z","timestamp":1758161809091,"version":"3.44.0"},"reference-count":11,"publisher":"Mathematical Modelling and Numerical Simulation with Applications","issue":"03","license":[{"start":{"date-parts":[[2022,2,10]],"date-time":"2022-02-10T00:00:00Z","timestamp":1644451200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Pediatr Genet"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hyperornithinemia\u2013hyperammonemia\u2013homocitrullinuria (HHH) syndrome, an inborn error of metabolism, is an inherited syndrome caused by loss-of-function mutations in the SLC25A15, resulting in ornithine translocase1 (ORNT1) deficiency. Disrupted ornithine transportation in an affected individual usually manifests with the accumulation of intermediate metabolites, leading to neurological impairment, hepatitis, and\/or protein intolerance at various ages of onset. In this paper, we report a compound heterozygous mutation in SLC25A15 from a 2-year-old girl who presented with neurological alterations and hepatic failure. Before developing neurological sequelae, she had signs of globally delayed development. The accumulation of toxic metabolites may explain these neurological consequences. After biochemical confirmation of HHH, whole-exome sequencing (WES) was performed, which identified mutations at codons 21 and 179 of SLC25A15 that are predicted to result in the loss of function of ORNT1. Each of the mutations was found to be inherited from one of her parents. After therapy, her toxic metabolites decreased significantly. In conclusion, HHH syndrome frequently manifests with nonspecific symptoms and unapparent biochemical profiles, which may lead to delayed diagnosis. Correction of the accumulating metabolites is necessary to prevent irreversible neurological impairment. Furthermore, performing a WES provides a shortcut for accurate diagnosis.<\/jats:p>","DOI":"10.1055\/s-0041-1742247","type":"journal-article","created":{"date-parts":[[2022,2,10]],"date-time":"2022-02-10T18:55:25Z","timestamp":1644519325000},"page":"205-210","source":"Crossref","is-referenced-by-count":0,"title":["A Novel Mutation of ORNT1 Detected in a Hyperornithinemia\u2013Hyperammonemia\u2013Homocitrullinuria Syndrome Child by Clinical Whole-Exome Sequencing"],"prefix":"10.53391","volume":"13","author":[{"given":"Wison","family":"Laochareonsuk","sequence":"additional","affiliation":[{"name":"Division of Biomedical Science and Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seksit","family":"Osatakul","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology Unit, Division of Pediatrics, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Utcharee","family":"Intusoma","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Unit, Division of Pediatrics, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanwisa","family":"Maneechay","sequence":"additional","affiliation":[{"name":"Translational Medicine Research Center, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Surasak","family":"Sangkhathat","sequence":"additional","affiliation":[{"name":"Translational Medicine Research Center, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand"},{"name":"Division of Surgery, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"31409","published-online":{"date-parts":[[2022,2,10]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.ymgme.2013.07.008","article-title":"The incidence of urea cycle disorders","volume":"110","author":"M L Summar","year":"2013","journal-title":"Mol Genet Metab"},{"issue":"02","key":"ref2","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/9658","article-title":"Hyperornithinaemia-hyperammonaemia-homocitrullinuria syndrome is caused by mutations in a gene encoding a mitochondrial ornithine transporter","volume":"22","author":"J A Camacho","year":"1999","journal-title":"Nat Genet"},{"issue":"01","key":"ref3","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s13023-015-0242-9","article-title":"The hyperornithinemia-hyperammonemia-homocitrullinuria syndrome","volume":"10","author":"D Martinelli","year":"2015","journal-title":"Orphanet J Rare 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