tyrosinemia type I
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, which is called fumarylacetoacetate hydrolase, leads to an accumulation of tyrosine and related substances in the body, which can damage tissues and organs.
There are several forms of tyrosinemia, but type I is the most severe. Symptoms will begin within the first few months of life. Early symptoms 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 a boiled cabbage or rotten mushroom-like odor. Tyrosine will 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.
If not recognized and promptly treated, tyrosinemia type I is usually fatal before the age of 10. Death is 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. With treatment, however, 90% of people with the disease will live to adulthood and experience fairly normal lives.
How common is Tyrosinemia Type I?
Tyrosinemia type I affects 1 in 100,000 to 120,000 people worldwide. In the U.S., an estimated 1 in 100 to 150 people are carriers of a genetic mutation that causes tyrosinemia type I. This disease is more common in Norway and Finland, where it affects 1 in 60,000 births. It is also common in Quebec, Canada, where it affects 1 in 16,000 people. In the Saguenay-Lac-Saint-Jean region of Quebec, the disease is especially common, affecting 1 in 1,846 people.
How is Tyrosinemia Type I treated?
The drug nitisinone (brand name: Orfadin) was FDA approved in 2002 to treat tyrosinemia type I. It prevents an accumulation of specific metabolic compounds in people 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 people 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.
In severe cases where the affected person cannot take nitisinone or already has cancerous cells in the liver, liver transplantation is an option. The procedure does carry serious risks, however. Prior to the development of nitisinone, liver transplantation was the only treatment for tyrosinemia type I.
What is the prognosis for a person with Tyrosinemia Type I?
Without treatment, tyrosinemia type I is usually fatal by the age of 10 due to liver or kidney failure, neurological crisis, or liver cancer. However if promptly diagnosed and treated with nitisinone and a managed diet, outcomes can be quite good with a survival rate greater than 90%. Children who receive this treatment can grow to normal size and show improved liver and kidney function as well as more normal bone structure.