Fabry Disease: Enzyme Deficiency in the Human Body

Fabry disease is an inherit (genetic or DNA) metabolic fat storage disorder, certain fats (globotriaosylceramide or GL-3) accumulate in the blood vessels over many years, leading to the involvement (or damage) of various tissues and organs of the body, including the heart and kidney. In 1898, two European dermatologists, Johann Fabry of Dortmund, Germany and William Anderson of London, reported independently the first description of Fabry disease. In the mid 1960s, the connection of the disease was linked to an enzyme defect. The deficiency of human body to produce the enzyme (alpha-galactosidase A or ceramidetrihexosidase), involved in the breakdown of fats, and found in a defective 'X' chromosome. Fabry disease affects approximately 5,000 people worldwide, and the average life - span of patients is fifty years.

Genetically Fabry disease affects men and women differently. If a man has Fabry Disease: Each daughter will be a carrier, since all daughters inherit their father's 'X' chromosome. Each son will be unaffected, since sons do not inherit the 'X' chromosome from their fathers. If a woman is carrier of Fabry Disease: Each daughter will have a fifty percent chance of being a carrier. Each son will have a fifty percent chance of inheriting the gene for Fabry Disease. Statistically, the disease in males is one in 40,000. A blood test will determine if the disease is present, and recommended taking the test, if there is a family history of Fabry Disease, preventing any permanent damage to the organs. Also, a skin biopsy examines for an increase fat in the skin cells, which may suggest Fabry Disease. During prenatal period (Nine weeks into the pregnancy) enzyme activity of alpha-galactosidase 'A' is measured to determine if a male fetus will have the affected gene. Eventually, the metabolic disorder causes pain, disability, and typically a shortened life - span.

During adolescence or childhood, symptoms of Fabry disease include pain and burning sensations in the hands or feet, which is intensified during exercise and hot weather. Also, other symptoms include: Decrease ability to perspire, cloudiness of the cornea, kidney and heart health problems because of a decrease of blood supply (Could increase the risk of a heart attack), small and raised reddish purple blemishes on the skin, back pain, and abdominal discomfort. Furthermore, known to cause psychological and social issues.

Enzyme replacement is an effective treatment for Fabry disease. A modified form of the Alpha - galactosidase A is intravenously administered, usually for two weeks. Replacing the deficiency of the enzyme can stop the progression of the disease and treat the symptoms. Pain associated to Fabry disease can be treated with various types of medications.

In April 2003, the Food and Drug Administration granted approval to Genzyme Corporation market and sell Fabrazyme (agalsidase beta), the first enzyme replacement treatment approval in the United States, for the treatment of Fabry disease. The drug helps keep the kidneys and heart healthy. Also, Fabrazyme received Orphan Drug designation, which provides seven years of market exclusivity for the product under the federal program, designed to treat rare disorders. Robert J. Desnick, M.D, Ph. D, professor and chairman of human genetics at Mount Sinai School of Medicine said: "FDA approval of Fabrazyme is a culmination of more than 30 years of research on enzyme replacement therapy for Fabrey disease." David Meeker M.D., Genzyme's senior vice president for the therapeutics in Europe said: "The European approval of this product was based on a through clinical development program, which included a multi - center Phase 3 trial (The trial enrolled 58 patients at eight medical centers, including five in Europe)."

Fabrazyme most common reported adverse reactions: Increase or decrease heart rate, increased blood pressure, chest pain, throat tightness, shortness of breath, itching hives, chills/rigors, nausea, vomiting, lip or ear swelling, and rash. These symptoms declined during continued use of Fabrazyme. Patients that have previous heart disease, allergic to certain medications (or currently taking prescription or nonprescription medication), foods, dyes or preservatives, and women trying to get pregnant or who are pregnant and breast feeding should notify their physician or health care provider, before taking this medication. Prior to administering the medication, during clinical phase study, subjects were pretreated with acetaminophen and an antihistamine to decrease or prevent infusion associated reactions. The safety and efficacy of Fabrazyme in pediatric patients has not been evaluated.