Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content +++ Key Features ++ Consider in a child who has liver disease with or without accompanying renal disease or bone disease Elevated urinary succinylacetone is diagnostic of type 1 tyrosinemia Type I tyrosinemia is an autosomal recessive condition caused by deficiency of fumarylacetoacetase +++ Clinical Findings ++ Presents with acute or progressive hepatic parenchymal damage with elevated α-fetoprotein, renal tubular dysfunction with generalized aminoaciduria, hypophosphatemic rickets, or neuronopathic crises Tyrosine and methionine are increased in blood and tyrosine metabolites and δ-aminolevulinic acid in urine Liver failure may be rapidly fatal in infancy or somewhat more chronic, with a high incidence of liver cell carcinoma in long-term survivors Tyrosinemia type II presents with corneal ulcers and keratotic lesions on palms and soles and very high plasma tyrosine levels (> 600 μM) Patients with tyrosinemia type III can also have developmental delays and ataxia +++ Diagnosis ++ Increased succinylacetone occurs only in fumarylacetoacetase deficiency and is diagnostic, and is increasingly used in newborn screening Diagnosis is confirmed by mutation analysis or by enzyme assay in liver tissue Prenatal diagnosis is possible Types II and type III are diagnosed by molecular methods +++ Treatment ++ A diet low in phenylalanine and tyrosine ameliorates liver disease, but it does not prevent carcinoma development Pharmacologic therapy to inhibit the upstream enzyme 4-hydroxyphenylpyruvate dehydrogenase using 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) Decreases the production of toxic metabolites, maleylacetoacetate and fumarylacetoacetate Improves the liver disease and renal disease Prevents acute neuronopathic attacks Greatly reduces the risk of hepatocellular carcinoma Liver transplantation is effective therapy Types II and III respond well to dietary tyrosine restriction Your MyAccess profile is currently affiliated with '[InstitutionA]' and is in the process of switching affiliations to '[InstitutionB]'. Please click ‘Continue’ to continue the affiliation switch, otherwise click ‘Cancel’ to cancel signing in. Get Free Access Through Your Institution Learn how to see if your library subscribes to McGraw Hill Medical products. Subscribe: Institutional or Individual Sign In Username Error: Please enter User Name Password Error: Please enter Password Forgot Username? Forgot Password? Sign in via OpenAthens Sign in via Shibboleth