Tyrosinaemia.
Three different Types of tyrosinaemia
Tyrosinaemia is a rare genetic disorder exhibiting high blood levels of tyrosine, an amino acid and component of most proteins. There is a deficiency of one of the enzymes necessary for the complex process of breaking down tyrosine. When tyrosine and it’s byproducts build up in tissues and organs it can lead to serious medical problems if left untreated.
There are three different types of tyrosinaemia, each having specific symptoms and caused by the lack of a different enzyme in each case.
Type I tyrosinaemia
This is the most serious form of the disorder and is characterised by a shortage of the enzyme fumarylacetoacetate hydrolase. Symptoms are usually apparent in the first few months of a newborn’s life. They include the failure of the infant to gain weight and grow at the usual rate, the whites of the eyes and the skin take on a yellow appearance, there is vomiting and diarrhea. There can be an increased tendency of bleeding, and nosebleeds. An odour similar to cabbage can be detected. Type I tyrosinaemia can lead to liver and kidney failure, nervous system problems, and the risk of liver cancer is increased.
The incidence of Type I tyrosinaemia varies across the world from a typical 1: 100,000 – but as high as 1: 1,900 in certain communities, a high incidence occurring, for example, in Quebec, Canada.
Type II tyrosinaemia
In this case the deficient enzyme is tyrosine aminotransferase. Type II can affect the skin, eyes, and mental development, approximately fifty percent of individuals with Type II have mental retardation. Symptoms typically start in early childhood and include painful skin lesions on the digits, palms and soles, light sensitivity (photophobia), eye pain, redness and excessive tearing.
The incidence of Type II is less than 1 : 250,000.
Type III tyrosinaemia
This is a particularly rare disorder and the mildest of the three types. The deficient enzyme in this case is enzyme 4-hydroxyphenylpyruvate dioxygenase. Symptoms that may present include intermittent occurrences of loss of balance and coordination, mild mental retardation, seizures.
Type III tyrosinaemia is extremely rare, only a few cases have ever been reported.
Note that temporarily elevated levels of tyrosine are present in approximately ten percent of newborns. However the cause in this case is not genetic. The most probable cause is a deficiency of vitamin C or undeveloped liver enzymes due to a premature birth.
Treatment
Dietry management by restricting the intake of tyrosine and phenylalanine to the minimum.
Progress has been made under a nine year study administering NTBC - The therapy appears to be effective in preventing progressive liver and renal disease, although the long-term outcome of NTBC therapy is not yet known.
How is tyrosinaemia inherited?
Many genetic conditions and traits are inherited in an autosomal recessive pattern when two copies of the gene in each cell are altered. Usually, the parents of an individual with an autosomal recessive disorder do not show any signs, or symptoms of the disorder, but are carriers of one copy of the altered gene.
Genes involved with tyrosinaemia
Tyrosinaemia is caused by mutations in the FAH, HPD, and TAT genes.
Tyrosine is broken down in the liver to form harmless molecules during a complex process. The molecules are then either excreted by the kidneys or used in bodily processes that produce energy. Mutations in the FAH, HPD, or TAT gene cause a shortage of one of the enzymes in this complex process. This enzyme deficiency results in a toxic accumulation of tyrosine and its byproducts. This can lead to the damage of the liver, kidneys, nervous system, or other tissues.
Prevention
Pre-natal screening is available.