Hepatocellular carcinoma despite long-term survival in chronic tyrosinaemia I

Tyrosinaemia I (fumarylacetoacetate hydrolase deficiency) is an autosomal r ecessive inborn error of tyrosine metabolism that produces liver failure in infancy or a more chronic course of liver disease with cirrhosis, often co mplicated by hepatocellular carcinoma, in childhood or early adolescence. W e studied a 37-year-old woman with tyrosinaemia I whose severe liver diseas e in infancy and rickets during childhood resolved with dietary therapy. Fr om 14 years of age she resumed an unrestricted diet with the continued pres ence of the biochemical features of tyrosinaemia, yet maintained normal liv er function. In adult years she accumulated only small amounts of succinyla cetone. Despite this evolution to a mild biochemical and clinical phenotype , she eventually developed hepatocellular carcinoma. Her fumarylacetoacetat e hydrolase genotype consists of a splice mutation, IVS6-1g >t, and a novel missense mutation, Q279R. Studies of resected liver demonstrated the absen ce of hydrolytic activity and of immunological expression of fumarylacetoac etate hydrolase in liver tumour. In nontumoral areas, however, 53% of norma l hydrolytic activity and immunologically present fumarylacetoacetate hydro lase was found. This case demonstrates the high risk of liver cancer in tyr osinaemia I even in a seemingly favourable biological environment.