{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T06:10:53Z","timestamp":1793945453771,"version":"4.8.0"},"reference-count":28,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,11,16]],"date-time":"2024-11-16T00:00:00Z","timestamp":1731715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Vietnam Ministry of Science and Technology","award":["\u0110T\u0110L.CN-133\/21"],"award-info":[{"award-number":["\u0110T\u0110L.CN-133\/21"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Hyperornithinemia\u2013hyperammonemia\u2013homocitrullinuria syndrome (HHH; OMIM 238970) is one of the rare urea cycle disorders. Ornithine carrier 1 deficiency causes HHH syndrome, characterized by failure of mitochondrial ornithine uptake, hyperammonemia, and accumulation of ornithine and lysine in the cytoplasm. The initial presentation and time of diagnosis in HHH highly varies. Genetic analysis is critical for diagnosis. Materials and Methods: This study encompassed retrospective and prospective analyses of four unrelated Vietnamese children diagnosed with HHH syndrome. Results: The age of diagnosis ranged from 10 days to 46 months. All four cases demonstrated hyperornithinemia and prolonged prothrombin time. Three out of four cases presented with hyperammonemia, elevated transaminases, and uraciluria. No homocitrulline was detected in the urine. Only one case depicted oroticaciduria. Genetic analyses revealed three pathogenic variants in the SLC25A15 gene, with the c.535C&gt;T (p.Arg179*) variant common in Vietnamese patients. The c.562_564del (p.Phe188del) and c.408del (p.Met137Cysfs*10) variants were detected in one case. The latter variant has yet to be reported in the literature on HHH patients. After intervention with a protein-restricted diet, ammonia-reducing therapy, and L-carnitine supplementation, hyperammonemia was not observed, and liver enzyme levels returned to normal. Conclusions: Our results highlighted the clinical and biochemical heterogeneity of HHH syndrome and posed that HHH syndrome should be considered when individuals have hyperammonemia, elevated transaminase, and decreased prothrombin time.<\/jats:p>","DOI":"10.3390\/medicina60111877","type":"journal-article","created":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T05:36:45Z","timestamp":1731908205000},"page":"1877","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Hyperornithinemia\u2013Hyperammonemia\u2013Homocitrullinuria Syndrome in Vietnamese Patients"],"prefix":"10.3390","volume":"60","author":[{"given":"Khanh Ngoc","family":"Nguyen","sequence":"first","affiliation":[{"name":"Center of Endocrinology, Metabolism, Genetic\/Genomics and Molecular Therapy, Vietnam National Children\u2019s Hospital, 18\/879 La Thanh, Dong Da, Hanoi 11512, Vietnam"},{"name":"Department of Paediatrics, Hanoi Medical University, 1st Ton That Tung Street, Hanoi 11521, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Van Khanh","family":"Tran","sequence":"additional","affiliation":[{"name":"Center for Gene and Protein Research, Hanoi Medical University, 1st Ton That Tung Street, Hanoi 11521, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ngoc Lan","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Center for Gene and Protein Research, Hanoi Medical University, 1st Ton That Tung Street, Hanoi 11521, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thi Bich Ngoc","family":"Can","sequence":"additional","affiliation":[{"name":"Center of Endocrinology, Metabolism, Genetic\/Genomics and Molecular Therapy, Vietnam National Children\u2019s Hospital, 18\/879 La Thanh, Dong Da, Hanoi 11512, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thi Kim Giang","family":"Dang","sequence":"additional","affiliation":[{"name":"Center of Endocrinology, Metabolism, Genetic\/Genomics and Molecular Therapy, Vietnam National Children\u2019s Hospital, 18\/879 La Thanh, Dong Da, Hanoi 11512, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thu Ha","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Center of Endocrinology, Metabolism, Genetic\/Genomics and Molecular Therapy, Vietnam National Children\u2019s Hospital, 18\/879 La Thanh, Dong Da, Hanoi 11512, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thi Thanh Mai","family":"Do","sequence":"additional","affiliation":[{"name":"Center of Endocrinology, Metabolism, Genetic\/Genomics and Molecular Therapy, Vietnam National Children\u2019s Hospital, 18\/879 La Thanh, Dong Da, Hanoi 11512, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9557-9868","authenticated-orcid":false,"given":"Le Thi","family":"Phuong","sequence":"additional","affiliation":[{"name":"Center for Gene and Protein Research, Hanoi Medical University, 1st Ton That Tung Street, Hanoi 11521, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thinh Huy","family":"Tran","sequence":"additional","affiliation":[{"name":"Biochemistry Department, Hanoi Medical University, 1st Ton That Tung Street, Hanoi 11521, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2776-4911","authenticated-orcid":false,"given":"Thanh Van","family":"Ta","sequence":"additional","affiliation":[{"name":"Biochemistry Department, Hanoi Medical University, 1st Ton That Tung Street, Hanoi 11521, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen Huu","family":"Tu","sequence":"additional","affiliation":[{"name":"Hanoi Medical Univerity Hospital, Hanoi Medical University, 1st Ton That Tung Street, Hanoi 11521, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0418-2613","authenticated-orcid":false,"given":"Chi Dung","family":"Vu","sequence":"additional","affiliation":[{"name":"Center of Endocrinology, Metabolism, Genetic\/Genomics and Molecular Therapy, Vietnam National Children\u2019s Hospital, 18\/879 La Thanh, Dong Da, Hanoi 11512, Vietnam"},{"name":"Department of Paediatrics, Hanoi Medical University, 1st Ton That Tung Street, Hanoi 11521, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/8904_2018_132","article-title":"Hyperornithinemia, hyperammonemia, and homocitrullinuria syndrome causing severe 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