Tyrosinemia

Tyrosinemia is a genetic disorder characterized by elevated blood levels of the amino acid tyrosine, a building block of most proteins. Tyrosinemia is caused by the shortage (deficiency) of one of the enzymes required for the multistep process that breaks down tyrosine. If untreated, tyrosine and its byproducts build up in tissues and organs, which leads to serious medical problems.

There are three types of tyrosinemia. Each has distinctive symptoms and is caused by the deficiency of a different enzyme. Type I tyrosinemia, the most severe form of this disorder, is caused by a shortage of the enzyme fumarylacetoacetate hydrolase. Symptoms usually appear in the first few months of life and include failure to gain weight and grow at the expected rate (failure to thrive), diarrhea, vomiting, yellowing of the skin and whites of the eyes (jaundice), cabbage-like odor, and increased tendency to bleed (particularly nosebleeds). Type I tyrosinemia can lead to liver and kidney failure, problems affecting the nervous system, and an increased risk of liver cancer.

Type II tyrosinemia is caused by a deficiency of the enzyme tyrosine aminotransferase. This form of the disorder can affect the eyes, skin, and mental development. Symptoms often begin in early childhood and include excessive tearing, abnormal sensitivity to light (photophobia), eye pain and redness, and painful skin lesions on the palms and soles. About 50 percent of individuals with type II tyrosinemia have some degree of intellectual disability.

Type III tyrosinemia is a rare disorder caused by a deficiency of the enzyme 4-hydroxyphenylpyruvate dioxygenase. Characteristic features include intellectual disability, seizures, and periodic loss of balance and coordination (intermittent ataxia).

About 10 percent of newborns have temporarily elevated levels of tyrosine. In these cases, the cause is not genetic. The most likely causes are vitamin C deficiency or immature liver enzymes due to premature birth.

Worldwide, type I tyrosinemia affects about 1 person in 100,000. This type of tyrosinemia is much more common in Quebec, Canada. The overall incidence in Quebec is about 1 in 16,000 individuals. In the Saguenay-Lac St. Jean region of Quebec, type I tyrosinemia affects 1 person in 1,846.

Type II tyrosinemia occurs in fewer than 1 in 250,000 individuals. Type III tyrosinemia is very rare; only a few cases have been reported.

Mutations in the FAH, HPD, and TAT genes cause tyrosinemia.

In the liver, enzymes break down tyrosine in a five-step process into harmless molecules that are either excreted by the kidneys or used in reactions that produce energy. Mutations in the FAH, HPD, or TAT gene cause a shortage of one of the enzymes in this multistep process. The resulting enzyme deficiency leads to a toxic accumulation of tyrosine and its byproducts, which can damage the liver, kidneys, nervous system, and other organs and tissues.

Read more about the FAH, HPD, and TAT genes.

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.