Current management options for tyrosinemia

Abstract

Hypertyrosinemia is observed in three inherited disorders of tyrosine metabolism. Hereditary Tyrosinemia Type I (HTT-I), or hepatorenal tyrosinemia, is an autosomal reces-sive disorder caused by mutation in the fumarylacetoacetate hydrolase (FAH) gene. HTT-I is associated with severe involvement of the liver, kidneys, and central nervous system, and is due to toxic accumulation of metabolites of tyrosine, such as succinylacetone. HTT-I is the inborn error with the highest incidence of progression to hepatocellular carcinoma. Elevated succinylacetone, in dried filter paper blood samples, or in plasma or urine, is pathogno-monic and diagnostic for HTT-I and is the most reliable neonatal screening method. Liver transplantation is the definitive management, but the need for this is markedly decreased by the combined dietary and drug management. A diet low in tyrosine and phenylalanine, plus nitisinone (2-[2-nitro-4-trifluoromethylbenzoyl]-1,3-cyclohexanedione) (NCTB) are consid-ered the gold standard management options. Carnitine and 1,25-OH-vitamin D are adjuvant therapy. Strict follow up with succinylacetone level for monitoring of treatment should be done. Abdominal ultrasonography and abdominal computerized tomography scan or mag-netic resonance imaging should also be done for surveillance of the possible development of hepatocellular carcinoma.