$Unique_ID{BRK03728} $Pretitle{} $Title{Fabry Disease} $Subject{Fabry Disease Anderson-Fabry Disease GLA Deficiency Ceramide Trihexosidase Deficiency Angiokeratoma Diffuse Angiokeratoma Corporis Diffusum Hereditary Dystopic Lipidosis Alpha-Galactosidase Deficiency Glycolipid Lipidosis Angiokeratoma of Fordyce Angiokeratome of Mibelli Lysosomal Storage Diseases} $Volume{} $Log{} Copyright (C) 1986, 1988, 1989, 1990, 1991 National Organization for Rare Disorders, Inc. 200: Fabry Disease ** IMPORTANT ** It is possible that the main title of the article (Fabry Disease) is not the name you expected. Please check the SYNONYM listing to find the alternate names and disorder subdivisions covered by this article. Synonyms Anderson-Fabry Disease GLA Deficiency Ceramide Trihexosidase Deficiency Angiokeratoma Diffuse Angiokeratoma Corporis Diffusum Hereditary Dystopic Lipidosis Alpha-Galactosidase Deficiency Glycolipid Lipidosis Information on the following diseases can be found in the Related Disorders section of this report: Angiokeratoma of Fordyce Angiokeratome of Mibelli Lysosomal Storage Diseases 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. Fabry disease is a rare inherited disorder which results from a deficiency of an enzyme known as alpha-galactosidase A. This enzyme is responsible for the breakdown of compounds called glycolipids (fats containing carbohydrates like glucose). When the enzyme is missing or non-functional, these glycolipids accumulate, particularly in the walls of blood vessels throughout the body. This sex-linked hereditary disorder primarily affects males, but carrier females occasionally may have mild manifestations. Symptoms In males with Fabry disease, the first symptoms usually noted in childhood include the development of small, red skin lesions (known as angiokeratoma) on the abdomen, groin and upper thighs and episodes of burning/tingling pain in the hands and feet. The painful episodes are triggered by fever, fatigue, stress and rapid changes in the weather. With advancing age, males experience problems associated with the slowly progressive narrowing and blockage of blood vessels through the body. Most patients develop kidney disease and require chronic dialysis or kidney transplantation. Patients may also have heart disease or strokes due to blood vessel involvement. Males with milder symptoms have been described who have not experienced the pain and who do not develop kidney failure. Carrier females, who carry one disease-causing gene and one normal gene, may experience occasional episodes of pain, particularly in childhood. About 80% of carrier females have a subtle change in their corneas which does not affect vision. Most carrier females live a normal life-span. Causes Fabry disease is a hereditary, sex-linked disease which results from the deficiency of an enzyme called alpha-galactosidase A. The missing enzyme causes accumulation of glycolipid products (fats containing carbohydrates like glucose) in various tissues of the body and in particular in the walls of blood vessels. The disorder is inherited as an x-linked recessive trait. 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. X-linked recessive disorders are conditions which are coded on the X chromosome. Females have two X chromosomes, but males have one X chromosome and one Y chromosome. Therefore, in females, disease traits on the X chromosome can be masked by the normal gene on the other X chromosome. Since males only have one X chromosome, if they inherit a gene for a disease present on the X, it will be expressed. Men with X-linked disorders transmit the gene to all their daughters, who are carriers, but never to their sons. Women who are carriers of an X-linked disorder have a fifty percent risk of transmitting the carrier condition to their daughters, and a fifty percent risk of transmitting the disease to their sons. Affected Population Fabry disease strikes predominantly males. Females with this disorder have a milder form of the disease than males. There are an estimated 1 in 40,000 persons with Fabry disease in the US. Related Disorders Symptoms of the following disorders can be similar to those of Fabry disease. Comparisons may be useful for a differential diagnosis: The Angiokeratomas of Fordyce are similar in appearance to the small red lesions in Fabry disease but are limited to the scrotum and usually appear after age thirty. The Angiokeratomas of Mibelli are wart-like lesions on the extensor surfaces of the extremities of young adults and are associated with chilblains (skin lesions resulting from exposure to extreme cold). Lysosomal Storage Diseases such as Fucosidosis, Sialidasis, Adult-Type B Galactosidase Deficiency and Aspartylglucosominuria have angiokeratoma which are similar or indistinguishable from the lesions of Fabry disease. Therapies: Standard Relief from the chronic episodes of pain in the extremities can be achieved with daily oral medication (dilantin). Kidney failure can be treated by chronic hemodialysis or kidney transplantation. Other problems should be treated symptomatically after consultation with a physician experienced in the care of Fabry patients. Genetic counseling may be of benefit for patients and their families. Therapies: Investigational Recently, research efforts have resulted in the manufacture of the orphan drug alpha-galactosidase A as a treatment for Fabry Disease. The FDA is testing the biologic Alpha-Galactosidase A (CC Galactosidase), developed by Dr. David Calhoun, as a treatment for Fabry's Disease. More research is needed to determine the long-term safety and effectiveness of this treatments. For more information, physicians may contact the International Center for Fabry Disease listed in the Resources section. This disease entry is based upon medical information available through October 1991. 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 National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 203-746-6518 R.J. Desnick, Ph.D., M.D. International Center for Fabry Disease Mt. Sinai School of Medicine 5th Ave at 100th St. New York, NY 10029 212-241-6944 Dr. Roscoe O. Brady NIH/National Institute of Neurological Disorders & Stroke (NINDS) 9000 Rockville Pike Bethesda, MD 20892 (301) 496-3285 National Tay-Sachs and Allied Diseases Association, Inc. 2001 Beacon St. Rm. 304 Brookline, MA 02164 617-277-4463 0r 277-3965 NIH/National Institute of Neurological Disorders & Stroke (NINDS) 9000 Rockville Pike Bethesda, MD 20892 (301) 496-5751 (800) 352-9424 Research Trust for Metabolic Diseases in Children Golden Gates Lodge, Weston Rd. 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 MENDELIAN INHERITANCE IN MAN, 9th Ed.: Victor A. McKusick, Editor: Johns Hopkins University Press, 1990. Pp. 1564-1567. THE METABOLIC BASIS OF INHERITED DISEASE, 6th Ed.: Charles R. Scriver, et al., Editors; McGraw Hill, 1989. Pp. 1754-1774. CECIL TEXTBOOK OF MEDICINE, 19th Ed.: James B. Wyngaarden, and Lloyd H. Smith, Jr., Editors; W.B. Saunders Co., 1990. Pp. 1144-1145. THE MERCK MANUAL 15th ed: R. Berkow, et al: eds; Merck, Sharp & Dohme Research Laboratories, 1987, Pp. 522, 1012.