$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 (203) 746-6518 The National Arthritis and Musculoskeletal and Skin Diseases Information Clearinghouse Box AMS Bethesda, MD 20892 (301) 495-4484 Bert N. La Du, M.D. Department of Pharmacology University of Michigan School of Medicine Ann Arbor, MI 48109-0626 (313) 763-6429 Research Trust for Metabolic Diseases in Children Golden Gates Lodge, Weston Road Crewe CW1 1XN, England Telephone: (0270) 250244 For Genetic Information and Genetic Counseling Referrals: 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 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.