$Unique_ID{BRK04299} $Pretitle{} $Title{Tyrosinemia, Hereditary} $Subject{Tyrosinemia, Hereditary Tyrosinemia, Hereditary, Hepatorenal Type Tyrosyluria Acute Form Hereditary Tyrosinemia Chronic Form Hereditary Tyrosinemia} $Volume{} $Log{} Copyright (C) 1987, 1988, 1990, 1992 National Organization for Rare Disorders, Inc. 446: Tyrosinemia, Hereditary ** IMPORTANT ** It is possible the main title of the article (Hereditary Tyrosinemia) is not the name you expected. Please check the SYNONYMS listing on the next page to find alternate names, disorder subdivisions, and related disorders covered by this article. Synonyms Tyrosinemia, Hereditary, Hepatorenal Type Tyrosyluria DISORDER SUBDIVISIONS Acute Form Hereditary Tyrosinemia Chronic Form Hereditary Tyrosinemia General Discussion ** REMINDER ** The information contained in the Rare Disease Database is provided for educational purposes only. It should not be used for diagnostic or treatment purposes. If you wish to obtain more information about the disorders, please contact your personal physician and/or the agencies listed in the "Resources" section of this report. Tyrosinemia is a rare inborn error of metabolism involving the amino acid tyrosine associated with a lack of the enzyme fumarylacetoacetase parahydroxyphenylpyruvic acid (p-HPPA) oxidase. The disorder is characterized by elevated levels of tyrosine and its metabolites (including succinylacetone) in the urine. It causes developmental delay and profound liver dysfunction, kidney problems, and liver cell cancer. There are often neurologic problems causing peripheral nerve palsy and paralysis. Symptoms The acute form of Tyrosinemia starts at birth, and is characterized by failure to thrive and liver enlargement with or without a distended abdomen. Vomiting, swelling (edema), fluid accumulation in the abdomen (dropsy or ascites), and moderate mental retardation may occur in at least half of the cases. Anemia, yellow tinted skin (jaundice), the passing of dark, bloody stools (melena), an enlarged spleen, blood in the urine (hematuria), diarrhea and spontaneous bruising (ecchymoses) occur in nearly one-third of patients with acute Tyrosinemia. The most serious complications involve neurologic crises. The chronic form of hereditary Tyrosinemia occurs in a relatively smaller number of patients. Symptoms develop as a complication of kidney malfunction and may include softened bones (rickets) and a mild liver disease (cirrhosis). Mental retardation and other neurologic abnormalities may also occur. Liver cell cancer also occurs. Causes Tyrosinemia is a hereditary disorder probably transmitted by autosomal recessive genes. The genetic abnormality causes insufficient levels of the enzyme parahydroxyphenylperuvic acid (p-HPPA) oxidase. (Human traits including the classic genetic diseases, are the product of the interaction of two genes for that condition, one received from the father and one from the mother. In recessive disorders, the condition does not appear unless a person inherits the same defective gene from each parent. If one receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will show no symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is twenty-five percent. Fifty percent of their children will be carriers, but healthy as described above. Twenty-five percent of their children will receive both normal genes, one from each parent and will be genetically normal.) Affected Population Tyrosinemia in the acute form affects approximately one in 100,000 newborns in the United States. Both sexes are affected in equal numbers. The chronic form of this disorder affects far fewer patients than the acute form. Therapies: Standard Prenatal diagnosis of children at risk for Tyrosinemia can be made from identification of amniotic cells in the uterus with a reduced activity of the enzyme fumarylacetoacetase or by detection of succinylacetone in amniotic fluid. The intake of the amino acids phenylalanine and tyrosine must be restricted in the diet of patients with Tyrosinemia. Since these amino acids occur in all foods, the diet must be severely restricted and medical foods or formulas substituted. However, some forms of Tyrosinemia do not respond to dietary restrictions. There are several disorders that mimic Tyrosinemia. Proper diagnosis is essential before long-term dietary treatment is initiated. Liver transplantation has proven to be helpful for severely affected patients. Genetic counseling is highly recommended. Other treatment is symptomatic and supportive. Therapies: Investigational A new drug is being studied for treatment of Hereditary Tyrosinemia. The drug called NTBC is manufactured by ICI and is being supplied by Professor Lindstedt of Gothenburg University in Sweden. For more information physicians may contact: Professor Lindstedt Dept. of Clinical Chemistry Gothenburg University Sahlgren's Hospital S-413 45 Gothenburg, Sweden This disease entry is based upon medical information available through November 1992. Since NORD's resources are limited, it is not possible to keep every entry in the Rare Disease Database completely current and accurate. Please check with the agencies listed in the Resources section for the most current information about this disorder. Resources For more information on Hereditary Tyrosinemia, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 Research Trust for Metabolic Diseases in Children Golden Gates Lodge, Weston Rd. Crewe CW1 1XN, England Telephone: (0270) 250244 National Digestive Diseases Information Clearinghouse Box NDDIC Bethesda, MD 20892 (301) 468-6344 Jess Thoene, M.D. Department of Pediatrics University of Michigan School of Medicine Ann Arbor, MI 48109 For information on genetics and genetic counseling referrals, please contact: March of Dimes Birth Defects Foundation 1275 Mamaroneck Avenue White Plains, NY 10605 (914) 428-7100 Alliance of Genetic Support Groups 35 Wisconsin Circle, Suite 440 Chevy Chase, MD 20815 (800) 336-GENE (301) 652-5553 References THE METABOLIC BASIS OF INHERITED DISEASE, 5th ed.: John B. Stanbury, et al., eds.: McGraw-Hill, 1983. Pp. 288-394. PRENATAL DIAGNOSIS OF HEREDITARY TYROSINEMIA BY DETERMINATION OF FUMARYLACETOACETASE IN CULTURED AMNIOTIC FLUID CELLS: E.A. Kvittingen, et al.; Pediatr Res (April 1985: issue 19,4). Pp. 334-337. Neurologic Crises in Hereditary Tyrosinemia: G. Mitchell, et al.; N Eng J Med (February 15, 1990: issue 322, (7)). Pp. 432-437.