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Hereditary Tyrosinemia
Monday, 13 October 2003
Monday, 29 November 2004
Tyrosinemia Type I

What

Tyrosinemia Type I is a rare genetic disorder that occurs in the body’s metabolism (the chemical and physical processes that occur in tissues) when there is a deficiency in a specific enzyme named fumarylacetoacetate hydrolase. This enzyme is needed to completely break down the amino acid called tyrosine, which is a building block of protein. When tyrosine cannot be broken down, toxic byproducts accumulate in the body and primarily leads to destruction of the liver. These toxic byproducts can also damage the kidneys and the nervous system. Tyrosine is found in meats, dairy products, and other protein rich foods, hence a diet low in these foods is essential.

Who

The disease is inherited in an autosomal recessive fashion. Therefore, two parents who carry the gene have a one out of four chance of having a child with this disease. Carriers generally do not have any symptoms of the disease and frequently do not know that they are genetic carriers. The world-wide incidence of hereditary tyrosinemia is 1 in every 100,000 live births. In French Canadians, the estimated incidence of carriers of a specific mutation is 1 in 14 people. Sex distribution is equal.

Signs and Symptoms

Most children born with Tyrosinemia will have symptoms within the first 2-3 months of life which can be any or all of the following:

  • poor feeding and poor weight gain
  • enlarged liver and/or spleen
  • tendency to bleed (nosebleeds, bruising)
  • jaundice (yellow skin tone)
  • vomiting and diarrhea
  • decreased activity level
  • delayed walking
  • seizures
  • body odor resembling boiled cabbage

Possible Causes

In the liver, the amino acid tyrosine is broken down into an intermediate molecule called fumarylacetoacetate. Normally, this molecule is then further broken down into other harmless molecules that are excreted by the liver and kidneys. In children with tyrosinemia, the enzyme needed to further break down or metabolize fumarylacetoacetate properly is missing. Instead, a poisonous byproduct, succinylacetone, is produced. This toxic succinylacetone molecule prevents proper cell function in the liver and kidneys, resulting in progressive liver and kidney failure. The toxins can also affect the nervous system, causing seizures.

Diagnosis

Blood and urine tests are the most definitive way to diagnose tyrosinemia. The results of certain laboratory tests can be used to interpret the degree of liver damage at the time of testing. The test values for liver enzymes will generally be high, indicating liver damage. Testing for amino acid levels in the blood and urine will show an elevation of tyrosine and its Blood and urine tests are the most definitive way to diagnose tyrosinemia. The results of certain laboratory tests can be used to interpret the degree of liver damage at the time of testing. The test values for liver enzymes will generally be high, indicating liver damage. Testing for amino acid levels in the blood and urine will show an elevation of tyrosine and its by-products. Protein may also be present in the urine. Imaging studies are usually of no help unless an alternate diagnosis is being considered. Liver biopsy usually shows evidence of inflammation and cirrhosis.

Treatment

Since tyrosine is found in certain foods, nutritional treatment should be designed to minimize the tyrosine intake as well as another amino acid, phenylalanine which is related to tyrosine. Such a nutritional regimen must be taken under the care of a trained nutritionist working with a geneticist. This does not cure tyrosinemia, but controls metabolic abnormalities and allows for normal growth and development in the child. Currently, liver transplantation is the only effective way of treating advanced disease. A new product, NTBC, was FDA-approved in January 2002, which prevents the formation of fumarylacetoacetate. Again, this drug is not a cure and only manages the disease. Strict diet adherence is still necessary.

Prognosis

Without treatment, death secondary to liver failure usually occurs by 2 years of age. With proper dietary management, normal childhood activity does not need to be restricted. Many children have gone off to attend universities and have normal lives. Long-term effectiveness of NTBC in preventing liver and kidney disease is still unknown. Liver transplantation has many risks that should be discussed with your physician, but is frequently necessary and helpful. Affected patients and their families should seek genetic counseling; prenatal diagnosis of future pregnancies is available for parents of an affected child.

Connect with other parents

In the spirit of community and support, Madisons Foundation offers the unique service of connecting parents of children with rare diseases. If you would like to be connected to other parents of children with this disease, please fill out this brief form.

Weblinks

National Coalition for PKU and allied disorders
A comprehensive website designed for patients and their families. The website includes information on HT, links to ongoing research, support groups and other resources, as well as low protein food sources and recipes.

MSN Support Group
A support group on the Microsoft network. This site allows you to connect to others affected by HT. It also has information about the disease as well as links to other good sites.

Liver Kids
A nice website with information about the disease as well as links to other informative sites. There is also information about liver donations on this site.

Google Search for Hereditary Tyrosinemia

References and Sources

Emedicine Nelson’s