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$Unique_ID{BRK03441}
$Pretitle{}
$Title{Alkaptonuria}
$Subject{Alkaptonuria Alkaptonuric Ochronosis Alcaptonuria (alternate spelling
for Alkaptonuria) Hereditary Alkaptonuria Homogentisic Acid Oxidase Deficiency
Homogentisic Aciduria Ochronosis Ochronotic Arthritis}
$Volume{}
$Log{}

Copyright (C) 1984, 1985, 1987, 1989, 1992 National Organization for Rare
Disorders, Inc.

23:
Alkaptonuria

** IMPORTANT **
It is possible that the main title of the article (Alkaptonuria) is not
the name you expected.  Please check the SYNONYMS listing to find the
alternate name and disorder subdivisions covered by this article.

Synonyms

     Alkaptonuric Ochronosis
     Alcaptonuria (alternate spelling for Alkaptonuria)
     Hereditary Alkaptonuria
     Homogentisic Acid Oxidase Deficiency
     Homogentisic Aciduria
     Ochronosis
     Ochronotic Arthritis

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 this disorder, please
contact your personal physician and/or the agencies listed in the "Resources"
section of this report.


Alkaptonuria is a very rare hereditary disorder that is characterized by
the excretion of large volumes of dark colored urine.  The darkened urine is
the result of the exposure to the air (spontaneous oxidation) of homogentisic
acid that accumulates in the urine.  Homogentisic acid also accumulates in
the body tissues.  In normal functioning, the amino acid tyrosine is
metabolized into homogentisic acid, and further into maleylacetoacetic acid.
In alkaptonuria, this metabolic pathway is not completed because of a
deficiency of the enzyme homogentisic acid oxidase; therefore, the further
metabolism of homogentisic acid is prevented.   Excess accumulation of this
acid leads to the severe degeneration of the cartilage of the spine and other
major joints, and ultimately to osteoarthritis.

Symptoms

Patients with Alkaptonuria develop dark discolorations (ochronosis) of the
nose, outer ears, and outer membrane covering the eyes (sclera).  These
discolorations usually begin to appear at the age of 20 to 30.  The urine may
be dark in color, or may darken upon exposure to air.   Later patients
generally develop stiffness, pain, and restricted motion in the hips, knees
and shoulders.   As the disease progresses, freedom of movement is more
severely restricted because of lack of mobility of the spine.  The earlobe
thickens as the cartilage becomes harder and the middle and inner ear
structures become darkened.  Patients with Alkaptonuria who also have kidney
disease, tend to get symptoms earlier and their symptoms tend to be more
severe.  This is due to an impaired excretion of homogentisic acid.

Causes

Alkaptonuria is inherited as an autosomal recessive trait.   This genetic
defect causes a deficiency of the enzyme homogentisic acid oxidase.  Human
traits, including the classic genetic diseases, are the product of the
interaction of two genes, 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 for the same trait 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 not show 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

Alkaptonuria affects males and females in equal numbers, although symptoms

tend to be more severe in males and most severe in those patients with
impaired kidney function.  Alkaptonuria occurs in an unusually high number of
people in Czechoslovakia and the Dominican Republic.

Therapies:  Standard

Patients with Alkaptonuria are counseled to avoid occupations in which the
large joints and spine are subjected to stress.   There have been attempts to
prevent symptoms by consuming a diet low in tyrosine or high in ascorbic
acid.  These regimens have had no effect on the disorder.  Other treatment is
symptomatic and supportive.

Genetic counseling may be of benefit for patients and their families.

Therapies:  Investigational

Research on birth defects and their causes is ongoing.  The National
Institutes of Health (NIH) is sponsoring the Human Genome Project which is
aimed at mapping every gene in the human body and learning why they sometimes
malfunction.  It is hoped that this new knowledge will lead to prevention and
treatment of genetic disorders in the future.

Research on inborn errors of metabolism is ongoing.  Scientists are
studying the causes of these disorders and trying to design enzyme
replacement therapies that will return a missing enzyme to the body.

This disease entry is based upon medical information available through
September 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 Alkaptonuria, please contact:

     National Organization for Rare Disorders (NORD)
     P.O. Box 8923
     New Fairfield, CT  06812-1783
     [phone]

     The National Arthritis and Musculoskeletal and Skin Diseases Information
     Clearinghouse
     Box AMS
     Bethesda, MD 20892
     [phone]

     Bert N. La Du, M.D.
     Department of Pharmacology
     University of Michigan School of Medicine
     Ann Arbor, MI  48109-0626
     [phone]

     Research Trust for Metabolic Diseases in Children
     Golden Gates Lodge, Weston Road
     Crewe CW1 1XN, England
     Telephone:  [phone]

For Genetic Information and Genetic Counseling Referrals:

     March of Dimes Birth Defects Foundation
     1275 Mamaroneck Avenue
     White Plains, NY 10605
     [phone]

     Alliance of Genetic Support Groups
     35 Wisconsin Circle, Suite 440
     Chevy Chase, MD  20815
     (800) 336-GENE
     [phone]

References

INTERNAL MEDICINE, 2nd Ed.:  Jay H. Stein, ed.-in-chief; Little, Brown and
Co., 1987.  Pp. 1352, 2065.

MENDELIAN INHERITANCE IN MAN, 10th Ed.:  Victor A. McKusick, Editor:
Johns Hopkins University Press, 1992.  Pp. 1208.

THE METABOLIC BASIS OF INHERITED DISEASE, 6th Ed.:  Charles R. Scriver, et
al., Editors; McGraw Hill, 1989.  Pp. 775-787.

INTERNAL MEDICINE, 2nd Ed.:  Jay H. Stein, Editor-In-Chief; Little, Brown
and Co., 1987.  Pp. 1352, 2065.

CECIL TEXTBOOK OF MEDICINE, 19th Ed.:  James B. Wyngaarden, and Lloyd H.
Smith, Jr., Editors; W.B. Saunders Co., 1990.  Pp. 1103-1104.

BIRTH DEFECTS ENCYCLOPEDIA, Mary Louise Buyse, M.D., Editor-In-Chief;
Blackwell Scientific Publications, 1990.  Pp. 84-85.