Tyrosinemia

Type I tyrosinemia is a severe, autosomal recessive, metabolic disorder, caused by a deficiency of the enzyme fumarylacetoacetate (FAH) resulting in central nervous system alterations, Fanconi’s syndrome with hypophosphatemic rickets and acute or chronic liver failure, if untreated. Hepatocellular carcinoma is a major complication of the disease. The disease was first described in Quebec in 1967, by Lorochelle and coworkers &. In this Canadian area incidence of disease is 1:800 births, while it ranges between 1:10,000 and 1:50,000, depending on population groups considered &.
Clinical manifestations of the disease mainly comprise liver, neurological, and renal symptoms. Diagnosis of tyrosenimia is made upon demonstration of reduced activity of FAH, and differential diagnosis comprises all the conditions that can cause isolated hypertyrosinemia.
Liver pathology of the acute fulminating form of the disease usually reveals micronodular cirrhosis, bile duct proliferation, hepatocyte steatosis with pseudoacinar or pseudoglandular formations &. In the chronic form of the disease, the liver shows a mixed micro- and macronodular cirrhosis, with fibrosis and steatosis &. In this form liver cell dysplasia and subsequent hepatic carcinoma may develop &.
Treatment of tyrosinemia type I, once based only on a specific diet, has considerably improved, with the recent introduction of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexenedione (NTBC) that prevents the production of toxic metabolites that induce the liver injury &. However, because it seems that NTBC does not prevent hepatocellular carcinoma formation, liver transplantation is indicated not only in all children with acute or chronic hepatic failure unresponsive to medical treatment, but recommended in all patients, with excellent reported results, except for the incomplete normalization of tubular dysfunction &.