{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T09:09:42Z","timestamp":1785143382254,"version":"3.55.0"},"reference-count":9,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"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":["JPGN rep."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Hyperornithinemia\u2010hyperammonemia\u2010homocitrullinuria (HHH) syndrome is a rare metabolic condition that can cause lethargy, ataxia, tachypnea, nausea, vomiting, seizures, coma, and acute liver failure. We present a 26\u2010month\u2010old female with acute liver failure who was diagnosed with HHH 1 week after admission. Histology revealed an acute hepatitic pattern of liver injury with numerous acidophils and glycogenated nuclei without zonal distribution, the former a rarely discussed feature. Acute management included intravenous dextrose and intralipids, with chronic management requiring a protein\u2010restricted diet, glycerol phenylbutyrate for nitrogen scavenging, and citrulline supplementation to support the urea cycle. This case contributes to our growing understanding of the phenotypic presentation of HHH, a rare genetic cause of liver failure not included on newborn screening but with specific treatment implications. We also highlight the importance of collecting biochemical genetics labs and liver biopsy early in the disease course and discuss how a patient's voluntary self\u2010restriction of protein can offer helpful clues in the diagnostic evaluation.<\/jats:p>","DOI":"10.1002\/jpr3.70206","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T08:33:21Z","timestamp":1785141201000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Biochemical testing and pathology reveal rare cause of pediatric acute liver failure: Hyperornithinemia\u2010hyperammonemia\u2010homocitrullinuria syndrome"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-8543-1363","authenticated-orcid":false,"given":"Tierra L.","family":"Mosher","sequence":"first","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics Stanford University School of Medicine Palo Alto California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn S.","family":"Czepiel","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics Stanford University School of Medicine Palo Alto California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew B.","family":"Neu","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics Stanford School of Medicine Palo Alto California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea Carolina Cortes","family":"Fernandez","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics Stanford School of Medicine Palo Alto California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. Walden","family":"Browne","sequence":"additional","affiliation":[{"name":"Department of Pathology Stanford School of Medicine Palo Alto California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie D.","family":"Niehaus","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics Stanford School of Medicine Palo Alto California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Gugig","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics Stanford University School of Medicine Palo Alto California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1097\/MPG.0000000000003268","article-title":"North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition position paper on the diagnosis and management of pediatric acute liver failure","volume":"74","author":"Squires JE","year":"2022","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"e_1_2_8_3_1","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s13023-015-0242-9","article-title":"The hyperornithinemia\u2010hyperammonemia\u2010homocitrullinuria syndrome","volume":"10","author":"Martinelli D","year":"2015","journal-title":"Orphanet J Rare Dis"},{"key":"e_1_2_8_4_1","first-page":"103","article-title":"Hyperornithinemia, hyperammonemia, and homocitrullinuria syndrome causing severe neonatal hyperammonemia","volume":"44","author":"Wild KT","year":"2019","journal-title":"JIMD Rep"},{"key":"e_1_2_8_5_1","volume-title":"GeneReviews\u00ae","author":"Simpson KL","year":"1993"},{"key":"e_1_2_8_6_1","volume-title":"GeneReviews\u00ae","author":"Camacho J","year":"1993"},{"key":"e_1_2_8_7_1","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1586\/17446651.2014.945908","article-title":"Glycerol phenylbutyrate for the chronic management of urea cycle disorders","volume":"9","author":"Oishi K","year":"2014","journal-title":"Expert Rev Endocrinol Metab"},{"key":"e_1_2_8_8_1","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.ymgme.2017.09.002","article-title":"Safety and efficacy of glycerol phenylbutyrate for management of urea cycle disorders in patients aged 2 months to 2 years","volume":"122","author":"Berry SA","year":"2017","journal-title":"Mol Gen Metab"},{"key":"e_1_2_8_9_1","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1097\/MPG.0b013e318145a8e5","article-title":"Hyperornithinemia\u2010hyperammonemia\u2010homocitrullinuria syndrome (HHH) presenting with acute fulminant hepatic failure","volume":"46","author":"Mhanni A","year":"2008","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"e_1_2_8_10_1","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1002\/j.1536-4801.1992.tb10776.x","article-title":"Hyperornithinemia, hyperammonemia, homocitrullinuria (HHH) syndrome: presentation as acute liver disease with coagulopathy","volume":"15","author":"Smith L","year":"1992","journal-title":"J Pediatr Gastroenterol Nutr"}],"container-title":["JPGN Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jpr3.70206","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jpr3.70206","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jpr3.70206","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T08:33:22Z","timestamp":1785141202000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jpr3.70206"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,27]]},"references-count":9,"alternative-id":["10.1002\/jpr3.70206"],"URL":"https:\/\/doi.org\/10.1002\/jpr3.70206","archive":["Portico"],"relation":{},"ISSN":["2691-171X","2691-171X"],"issn-type":[{"value":"2691-171X","type":"print"},{"value":"2691-171X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,27]]},"assertion":[{"value":"2025-09-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"jpr3.70206"}}