Tyrosinaemia

What is tyrosinaemia?

Tyrosinaemia is a genetic disorder characterised by elevated blood levels of the amino acid tyrosine, a building block of most proteins. Tyrosinaemia 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 tyrosinaemia, each with distinctive symptoms and caused by the deficiency of a different enzyme. Type I tyrosinaemia is the most severe form of this disorder and 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), diarrhoea, vomiting, yellowing of the skin and whites of the eyes (jaundice), cabbagelike odour, and increased tendency to bleed (particularly nosebleeds). Type I tyrosinaemia can lead to liver and kidney failure, problems affecting the nervous system, and an increased risk of liver cancer.

Type II tyrosinaemia 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 half of individuals with type II tyrosinaemia are also mentally retarded.

Type III tyrosinaemia is a rare disorder caused by a deficiency of the enzyme 4-hydroxyphenylpyruvate dioxygenase. Characteristic features include mild mental retardation, 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.

How common is tyrosinaemia?

Worldwide, type I tyrosinaemia affects about 1 person in 100,000. This type of tyrosinaemia 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 1 tyrosinaemia affects 1 person in 1,846.

Type 2 tyrosinaemia occurs in fewer than 1 in 250,000 individuals. Type 3 tyrosinaemia is very rare; only a few cases have been reported.

What genes are related to tyrosinaemia?

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

In the liver, tyrosine is broken down in a five-step process to 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, or other tissues.

How do people inherit tyrosinaemia?

This condition is inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder are carriers of one copy of the altered gene but do not show signs and symptoms of the disorder.

What other names do people use for tyrosinaemia?

• Hereditary Tyrosinaemias
• Hypertyrosinaemia