Tyrosinemia type 1, 2, 3 (Tyrosinemia types 1, 2, 3) - Genes FAH, TAT, HPD.  

Tyrosinemia is a genetic disorder characterized by elevated concentrations of amino acid tyrosine, present in most proteins. Tyrosinemia is caused by deficiency of one of the enzymes required for the process decomposes tyrosine. If left untreated, tyrosine and its derivatives they accumulate in tissues and organs, leading to health problems.

There are three types of tyrosinemia. Each has characteristic symptoms and is caused by deficiency of a different enzyme.

Tyrosinemia type 1, the most severe form of this condition, is caused by a deficiency of the enzyme fumarylacetoacetate hydrolase. Symptoms usually appear in the first months of life and include lack of weight gain and growth retardation, diarrhea, vomiting, yellowing of the skin and jaundice, as well as an increased tendency to bleed, especially nosebleeds. Additionally, it can lead to liver and kidney failure, problems affecting the nervous system, and increased risk of liver cancer.

Tyrosinemia type 2, is caused by a deficiency of the enzyme tyrosine aminotransferasa-. This form of the disorder can affect the eyes, skin, and mental development. Often, symptoms begin in early childhood and include excessive tearing, photophobia, eye pain and redness, and painful skin lesions on the palms and soles. About 50 percent of people with type 2 tyrosinemia have some degree of intellectual disability.

Tyrosinemia type 3, is a little alteration cofrecuente caused by a deficiency of hydroxyphenylpyruvate dioxygenase-4-enzyme. Characteristic features include mental retardation, seizures and intermittent ataxia.

This process is due to mutations in the FAH, HPD, and TAT genes. These mutations, causing a shortage of one of the enzymes that decompose tyrosine in five step process harmless molecules which either are excreted by the kidneys or used in energy - producing reactions. The resulting enzyme deficiency causes a toxic buildup of tyrosine and their derivatives, which can damage the liver, kidneys, nervous system and other organs and tissues.

The FAH gene, located on the long arm of chromosome 15 (15q25.1), encodes an enzyme called fumarylacetoacetate hydrolase-. This enzyme is abundant in the liver and kidneys, being smaller amounts in many tissues. Fumarylacetoacetate hydrolase-is the last of a series of five enzymes required to break down the amino acid tyrosine. More specifically, fumarylacetoacetate hydrolase becomes a byproduct called tyrosine fumarylacetoacetate into smaller molecules which either are excreted by the kidneys or used in energy - producing reactions. There are more than 40 mutations in the FAH gene causing tyrosinemia type I. The altered gene produces an unstable or inactive enzyme, causing a reduction or absence of the activity of fumarylacetoacetate hydrolase. Without sufficient activity fumarylacetoacetate hydrolase, tyrosine is not processed completely. Instead of being converted to harmless molecules, the fumarylacetoacetate, accumulates in the liver and kidneys. High concentrations of fumarylacetoacetate be toxic and cause liver and kidney problems characteristic of this disorder.

HPD gene, located on the long arm of chromosome 12 (12q24.31), el-hydroxyphenylpyruvate 4 encoding, necessary to decompose the amino acid tyrosine dioxygenase enzyme. This enzyme is abundant in the liver and found in smaller amounts in the kidneys. More specifically, the dioxygenase enzyme 4-hydroxyphenylpyruvate becomes a byproduct called tyrosine 4-hydroxyphenylpyruvate to homogentisic acid. Have identified several mutations in the gene causing the HPD type 3. As a result of these mutations tyrosinemia, activity hydroxyphenylpyruvate dioxygenase-4 enzyme is unusually low or absent. With inadequate activity of the enzyme, 4-hydroxyphenylpyruvate becomes a toxic compound instead of homogentisic acid, and may impair cellular functions, particularly in the nervous system.

TAT gene, located on the long arm of chromosome 16 (16q22.1), encodes a liver enzyme called tyrosine aminotransferase which converts tyrosine into smaller molecules, which are excreted by the kidneys or used in energy - producing reactions . There are more than 10 mutations in the gene that cause TAT tyrosinemia type 2. The altered gene produces an enzyme tyrosine aminotransferase very reduced activity. As a result of these mutations, tyrosine is not processed efficiently, and increase the concentration of tyrosine in the blood and urine.

This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.

Tests in IVAMI: in IVAMI perform detection of mutations associated with tyrosinemia type I, II and III, by the complete PCR amplification of the exons of the FAH, HPD genes, and TAT, respectively, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).