{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:35:59Z","timestamp":1776126959638,"version":"3.50.1"},"reference-count":14,"publisher":"BMJ","issue":"10","license":[{"start":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:00:00Z","timestamp":1760313600000},"content-version":"unspecified","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Case Rep"],"accepted":{"date-parts":[[2025,9,28]]},"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:p>Hepatocellular carcinoma (HCC) has a low incidence in paediatric patients; Tyrosinemia type I (TYR1) is a known cause of HCC. Early detection through newborn screening is vital, yet not universally adopted. Moreover, some genotypes might be false-negative results despite timely testing. This case reports a mid-adolescent male immigrant with a history of unspecified hepatitis and familial a TYR1 variant of uncertain significance (VUS). He exhibited right upper quadrant pain, weight loss, diarrhoea and elevated liver enzymes, with imaging revealing a liver mass diagnosed as well-differentiated Evans\u2019 stage III HCC. Although his blood tyrosine levels were elevated, urine succinylacetone was normal, and genetic testing identified a homozygous fumarylacetoacetate hydrolase mutation classified as a VUS. The diagnosis was complicated by the absence of TYR1 within the newborn screening at the time of his birth, highlighting the need for early detection and the importance of family history.<\/jats:p>","DOI":"10.1136\/bcr-2025-267282","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T08:00:27Z","timestamp":1760428827000},"page":"e267282","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Silent tyrosinemia type I with normal succinylacetone presenting as hepatocellular carcinoma in a paediatric patient"],"prefix":"10.1136","volume":"18","author":[{"given":"Jean-Marco","family":"Verdi","sequence":"first","affiliation":[{"name":"Department of Paediatrics, Icahn School of Medicine at Mount Sinai, New York, New York, USA"},{"name":"Paediatrics, NYC Health + Hospitals\/Elmhurst, Elmhurst, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola Carolina","family":"Espin","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Icahn School of Medicine at Mount Sinai, New York, New York, USA"},{"name":"Paediatrics, NYC Health + Hospitals\/Elmhurst, Elmhurst, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle","family":"Bao","sequence":"additional","affiliation":[{"name":"Department of Paediatric Gastroenterology, Hepatology and Nutrition, Icahn School of Medicine at Mount Sinai, New York, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Swati","family":"Antala","sequence":"additional","affiliation":[{"name":"Division of Paediatric Hepatology, Icahn School of Medicine at Mount Sinai, New York, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2025,10,13]]},"reference":[{"key":"2025101401002277000_18.10.e267282.1","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1007\/s11605-017-3420-3","article-title":"Hepatocellular Carcinoma in Children and Adolescents: Clinical Characteristics and Treatment","volume":"21","author":"Wang","year":"2017","journal-title":"J Gastrointest Surg"},{"key":"2025101401002277000_18.10.e267282.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2014.07.010"},{"key":"2025101401002277000_18.10.e267282.3","unstructured":"Orphanet . Pediatric hepatocellular carcinoma. 2019. Available: https:\/\/www.orpha.net\/en\/disease\/detail\/33402"},{"key":"2025101401002277000_18.10.e267282.4","unstructured":"Adnan M , Puranik S . Hypertyrosinemia. In: Statpearls. Treasure Island (FL): StatPearls Publishing, 2025. Available: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK578205\/"},{"key":"2025101401002277000_18.10.e267282.5","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2016-104289"},{"key":"2025101401002277000_18.10.e267282.6","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1007\/s40272-019-00364-4","article-title":"Long-Term Outcomes and Practical Considerations in the Pharmacological Management of Tyrosinemia Type 1","volume":"21","author":"van Ginkel","year":"2019","journal-title":"Paediatr Drugs"},{"key":"2025101401002277000_18.10.e267282.7","doi-asserted-by":"crossref","unstructured":"Das AM , Ballhausen D , Haas D , et al . Diagnosis, treatment, management and monitoring of patients with tyrosinaemia type 1: Consensus group recommendations from the German\u2010speaking countries. J of Inher Metab Disea 2025;48. doi:10.1002\/jimd.12824","DOI":"10.1002\/jimd.12824"},{"key":"2025101401002277000_18.10.e267282.8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.clinms.2019.01.005","article-title":"Diagnosis and the importance of early treatment of tyrosinemia type 1: A case report","volume":"12","author":"\u0160kari\u010di\u0107","year":"2019","journal-title":"Clin Mass Spectrom"},{"key":"2025101401002277000_18.10.e267282.9","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1002\/bdr2.1653","article-title":"Mandatory newborn screening in the United States: History, current status, and existential challenges","volume":"112","author":"McCandless","year":"2020","journal-title":"Birth Defects Res"},{"key":"2025101401002277000_18.10.e267282.10","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1002\/humu.23047","article-title":"Silent Tyrosinemia Type I Without Elevated Tyrosine or Succinylacetone Associated with Liver Cirrhosis and Hepatocellular Carcinoma","volume":"37","author":"Blackburn","year":"2016","journal-title":"Hum Mutat"},{"key":"2025101401002277000_18.10.e267282.11","first-page":"255","article-title":"Hereditary tyrosinaemia type 1 in the absence of succinylacetone: 4-oxo 6-hydroxyhepanoate (4OHHA), a putative diagnostic biomarker","volume":"65","author":"Rehsi","year":"2024","journal-title":"JIMD Rep"},{"key":"2025101401002277000_18.10.e267282.12","doi-asserted-by":"crossref","DOI":"10.3390\/ijns9040066","article-title":"A False-Negative Newborn Screen for Tyrosinemia Type 1-Need for Re-Evaluation of Newborn Screening with Succinylacetone","volume":"9","author":"Dijkstra","year":"2023","journal-title":"Int J Neonatal Screen"},{"key":"2025101401002277000_18.10.e267282.13","unstructured":"National Center for Biotechnology Information . ClinVar; [VCV003610779.1]. Available: https:\/\/www.ncbi.nlm.nih.gov\/clinvar\/variation\/VCV003610779.1 [Accessed 7 May 2025]."},{"key":"2025101401002277000_18.10.e267282.14","unstructured":"VarSome. FAH (NM_000137.4):c.257A>C, p.(Gln86pro). 2023. 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