What Is Tyrosinemia Type I? Tyrosinemia type I is an inherited metabolic disorder in which the body lacks an enzyme needed to break down the amino acid tyrosine, an important building block of proteins. The deficiency in this enzyme, called fumarylacetoacetate hydrolase, leads to an accumulation of tyrosine and related substances in the body which can result in damage to tissues and organs. Tyrosinemia type I is caused by mutations in the FAH gene. Symptoms of the condition begin within the first few months of life and can include diarrhea, vomiting, an enlarged liver, failure to grow at a normal rate, yellowing of the skin and whites of the eyes (jaundice), a softening of the bones, irritability, and an odor like boiled cabbage or rotten mushrooms. Tyrosine can also build up in the cornea, causing itchy, irritated eyes. The liver is progressively damaged, as are the kidneys and central nervous system. If left untreated, children with tyrosinemia type I may have episodes of abdominal pain, an altered mental state, pain or numbness in the extremities, and/or respiratory failure. A mechanical ventilator may be necessary for episodes of respiratory failure, which often last between one and seven days. How Common Is Tyrosinemia Type I? Tyrosinemia type I affects 1 in 100,000 to 120,000 individuals worldwide. It is more common in Norway and Finland, where it affects 1 in 60,000 births and in Quebec, Canada, where it affects 1 in 16,000 individuals. In the Saguenay-Lac-Saint-Jean region of Quebec, the disease has a much higher frequency, affecting 1 in every 1,846 individuals. How Is Tyrosinemia Type I Treated? The drug nitisinone was FDA approved in 2002 to treat tyrosinemia type I. It prevents an accumulation of specific metabolic compounds in individuals with the disease and is typically taken as soon as the disease is diagnosed. The earlier the disease is recognized and treated, the less damage is done to the body and the better the prognosis. It is important that individuals with tyrosinemia type I manage their diets closely in a prescribed manner to control intakes of tyrosine and another amino acid, phenylalanine. Daily nitisinone intake and careful diet monitoring will be necessary throughout the life of someone with tyrosinemia type I. Failure to comply with recommended treatments may result in the return of severe, potentially fatal symptoms and damage to the body. Liver transplantation is an option in severe cases where an individual cannot take nitisinone or already has cancerous cells in the liver. This procedure does carry serious risks. Prior to the development of nitisinone, liver transplantation was the only treatment for tyrosinemia type I. What Is the Prognosis for an Individual with Tyrosinemia Type I? If not recognized and promptly treated, tyrosinemia type I is usually fatal before the age of 10 often due to liver or kidney failure, a neurological crisis, or hepatocellular carcinoma, a type of liver cancer. Some children may die within weeks of experiencing the first symptoms. However, with treatment and a managed diet, 90% of individuals with the disease will live to adulthood and experience fairly normal lives. Other names fortyrosinemia type I FAH deficiency Fumarylacetoacetase deficiency Fumarylacetoacetate hydrolase deficiency Hepatorenal tyrosinemia Hereditary tyrosinemia type I Tyrosinemia type 1 Tyrosinemia type I References Bergman et al., 1998, Hum Mutat, 12(1):19-26, PMID: 9633815 King et al., 2017, https://www.ncbi.nlm.nih.gov/books/NBK1515/ McKiernan et al., 2015, Arch Dis Child, 100(8):738-41, PMID: 25564536 Morrow et al., 2017, Adv Exp Med Biol, 959:9-21, PMID: 28755181 OMIM: Online Mendelian Inheritance in Man, OMIM [276700], 2016, http://www.omim.org/276700 Rootwelt et al., 1996, Hum Mutat, 7(3):239-43, PMID: 8829657