FABRYS DISEASE Hi Muriel, One inherited disease of particular interest is Fabry's disease, which has a focus on Tancook Island, Lunenburg County, Nova Scotia, and should be included. The island is a perfect place for familial research due to the constant residency pattern. Fabrys disease is a disorder with an enzyme missing for processing a particular kind of fat that is on the membranes of cells. I used to talk about this in lectures to medical and graduate students (before I knew that I had ancestors from Tancook Island!). Let me know if you need more information. Lloyd Lloyd A. Horrocks, Ph.D., Professor Emeritus Dept. of Molecular & Cellular Biochemistry, The Ohio State University 1645 Neil Avenue, Columbus, OH 43210 phone: 614-292-2339, fax: 614-292-4118 email: <Horrocks.2@osu.edu * * * * * * (Following is from internet research type in FABRY on your search engine) Introduction The purpose of this text is to provide patients and their families with information about the symptoms, diagnosis, management, and experimental treatment of Fabry disease. In 1898, two dermatologists, Johann Fabry in Dortmund, Germany and William Anderson in London, England, independently described the first patients with the disorder now known as Fabry disease. Forty years later, it was recognized that the disease resulted from abnormal deposits of a particular fatty substance (known as lobotriaosylceramide) in blood vessel walls throughout the body. In the 1960's, the primary defect was identified as the inherited deficiency of the enzyme, -galactosidase A, which is normally responsible for the breakdown of globotriaosylceramide. The gene for this enzyme was isolated and characterized in 1986 at Mount Sinai, permitting improved diagnosis, especially of female carriers, and the capability to produce large amounts of the normal enzyme for trials of enzyme replacement therapy. What Is the Nature of the Metabolic Defect in Fabry Disease? The body performs thousands of metabolic processes which are necessary for the production of vital compounds and the recycling or removal of others. One such compound called globotriaosylceramide is formed of three sugars and a fatty substance called ceramide, and is found in most cells of the body. Normally globotriaosylceramide is broken down (metabolized) to lactosylceramide by the enzyme -galactosidase A. In patients with Fabry disease, this enzyme does not function properly or is absent, and globotriaosylceramide cannot be broken down in cells, leading to its progressive accumulation. Thus, Fabry disease is often referred to as a "storage disorder" because of the abnormal accumulation of globotriaosylceramide. In patients with Fabry disease, globotriaosylceramide accumulates preferentially in the walls of blood vessels. As the abnormal storage of this fatty compound increases with time, the channels of these vessels become narrowed, leading to decreased blood flow and decreased nourishment of the tissues normally fed by these vessels. This process occurs in all blood vessels throughout the body, but particularly affects small vessels in the skin, kidneys, heart, and nervous system. How Is Fabry Disease Inherited? Fabry disease is an inherited disorder. The defective gene is on the X-chromosome, which is one of the two chromosomes that determine an individual's sex. Females have two X chromosomes, one inherited from each of their parents. Males have one X chromosome inherited from their mothers and one Y chromosome inherited from their fathers. A female Fabry carrier has one X chromosome with a defective Fabry gene and one X chromosome with the normal gene, and thus is protected from the major manifestations of the disease. Males with Fabry disease have one X-chromosome that contains the abnormal gene and thus, show symptoms of the disease. The inheritance pattern of Fabry disease is termed "X-linked recessive inheritance." A female carrier of Fabry disease has a 50% chance of transmitting the defective Fabry gene to her sons who will develop Fabry disease. In addition, she has a 50% chance of transmitting the Fabry gene to her daughters who will be carriers like their mother. It must be emphasized that these risk figures apply to each pregnancy individually, that is, for each male child there is a 50% chance to have the disease, and for each female child there is a 50% risk to be a carrier. If a male with Fabry disease and an unaffected (non-carrier) female have children, all of their daughters will be Fabry carriers and none of their sons will be affected with Fabry disease. Fabry disease occurs in all ethnic groups. It is estimated that one person in 40,000 has the disease. How does Fabry disease affect males? Typically, the disease begins in childhood with episodes of pain and discomfort in the hands and feet (known as acroparesthesias). The painful episodes may be brought on by exercise, fever, fatigue, stress, or change in weather conditions. In addition, young patients develop a spotted, dark red skin rash (known as angiokeratoma) seen most densely from the umbilicus to the knees, a decreased ability to perspire, and a characteristic change on the cornea of the eye that does not affect vision. The disease progresses very slowly and symptoms of kidney, heart and/or neurologic involvement occur between the ages of 30 to 45. In fact, many patients are first diagnosed when the accumulated storage material begins to affect kidney or heart function. Therefore, it is important to annually monitor kidney function by blood and urine tests because kidney disease is a major complication that can occur in affected males. A common heart symptom in Fabry patients is mitral valve prolapse, which is a benign condition that is present in approximately 10% of the normal population. More serious, but rarer, complications of Fabry disease include heart disease and strokes. ======================================= I apologize for the appearance of the above -- it does look better on the researched pages. Of interest was the fact the research study was conducted on Tancook Island. Muriel M. Davidson <davidson3542@home.com>