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$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.