Silent tyrosinemia type I with normal succinylacetone presenting as hepatocellular carcinoma in a paediatric patient

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’ 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.