$Unique_ID{BRK03806} $Pretitle{} $Title{Hemochromatosis, Hereditary} $Subject{Hemochromatosis, Hereditary Bronze Diabetes Cirrhosis, congenital pigmentary Familial Hemochromatosis Hemochromatosis Syndrome Hemosiderosis Iron Overload Disease Sideroblastic Anemia Troisier-Hanot-Chauffard Syndrome} $Volume{} $Log{} Copyright (C) 1984, 1985, 1987, 1988, 1990, 1991, 1992, 1993 National Organization for Rare Disorders, Inc. 13: Hemochromatosis, Hereditary ** IMPORTANT ** It and is possible that the main title of the article (Hemochromatosis) Hereditary is not the name you expected. Please check the SYNONYMS listing to find the alternate name and disorder subdivisions covered by this article. Synonyms Bronze Diabetes Cirrhosis, congenital pigmentary Familial Hemochromatosis Hemochromatosis Syndrome Hemosiderosis Iron Overload Disease Iron Retention Primary Hemochromatosis Information on the following diseases can be found in the Related Disorders section of this report: Sideroblastic Anemia Troisier-Hanot-Chauffard Syndrome 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. Hereditary Hemochromatosis is a metabolic disorder characterized by excessive absorption of iron. The high accumulation of iron eventually damages numerous organs. Involvement of the liver, pancreas or heart may lead to serious complications, particularly in older patients. Joints and skin may also become diseased. Symptoms The symptoms of Hereditary Hemochromatosis usually develops in men between the ages of 40 and 60 years and later in women although the disorder can be diagnosed much earlier. The symptoms vary according to the organs involved. There may be no symptoms in the early years except for a healthy skin coloring that resembles a suntan. Early symptoms may include weakness, weight loss, apathy, loss of sexual drive (libido), and pain in the arms and legs. Muscle tenderness and cramps in the legs may also develop. Symptoms may occur earlier in men than in women because women lose blood during menstruation and childbirth. When blood is lost, iron levels in the body are reduced. Later stages of the disease are characterized by cirrhosis of the liver. Cirrhosis is a progressive illness in which the liver becomes covered with fiberlike tissue and eventually this causes a marked decrease in liver function. Enlargement of the liver may begin years before it becomes impaired. Eventually this organ becomes firm and smooth, with excess iron deposits within the liver cells. Untreated Hereditary Hemochromatosis may also cause diabetes, gradual darkening of the skin and congestive heart failure. Cancer of the liver is more common than in the general population. When the heart muscle is involved, the heart may become enlarged and have an irregular beat (arrhythmias). An accumulation of fluid around the heart may result in congestive heart failure. Involvement of the pituitary gland can cause the malfunction of a variety of other endocrine glands (secondary dysfunction) that the pituitary normally controls. These may include the thyroid gland whose malfunctioning may cause an increased sensitivity to cold. There may be an insufficient amount of adrenocorticoids causing weakness and a lack of resistance to stress. A malfunction of the sex glands (the testes in men and the ovaries in women) may also cause a wasting away of the testicles (testicular atrophy), loss of sexual drive (libido) or missed menstruation (amenorrhea). Causes Hemochromatosis is inherited as an autosomal 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. 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. Hereditary Hemochromatosis is expressed fully in individuals who are homozygous for the defective gene since they have two identical disease genes at the same location on matched chromosomes. People who are heterozygous (have only one defective gene) may develop Hemochromatosis only if they have diabetes, are alcoholic or have some other precipitating factor. Heterozygous means a condition in which a person has two different genes at the same place on matched chromosomes. An individual who is heterozygous for a particular trait has inherited a gene for that trait from one parent and the normal gene from the other parent. An individual heterozygous for a hereditary disorder produced by a recessive gene will not show the disease or will have a milder form of it. The exact enzyme that is lacking in Hereditary Hemochromatosis is not known. Relatives of an individual who has this disease can be diagnosed using tissue typing. This test is very expensive and generally not practical for the general population. Doctors can measure the level of transferrin in the blood to screen for this disease before damage is done to the organs. Transferrin is a protein in the blood that carries iron. This test is inexpensive. The defective gene that causes Hereditary Hemochromatosis has been located on the short arm of chromosome 6 close to HLA-A (6p21.3). Genetic testing can be performed to identify carriers of the gene. Affected Population It has been estimated that Hereditary Hemochromatosis may affect as many as 600,000 to 1.6 million Americans. Statistics indicate that as many as five in 1000 white persons in the United States are affected by the disorder. There may be as many as 24 to 32 million carriers. However, the disorder is rarely diagnosed. Fewer than 250,000 cases have been identified in the United States. Many patients are diagnosed on autopsy because they appear to be healthy adults who die suddenly. Identification of affected individuals signals that their relatives should be tested. Related Disorders Symptoms of the following disorder can be similar to those of Hereditary Hemochromatosis. Comparisons may be useful for a differential diagnosis. Sideroblastic Anemia is a rare disorder of the blood that is characterized by the abnormal production of hemoglobin. Hemoglobin production is low due to insufficient or ineffective use of iron, which may be in abundant supply. The major symptoms include general weakness, fatigue and difficulty breathing. Exertion may cause chest pains resembling angina. The mucous membranes and the skin on the hands and arms may be pale, often with a lemon-yellow cast. On occasion, bleeding that occurs under the skin produces a brownish-red coloration of the skin. The spleen and liver may become enlarged. (For more information on this disorder, choose "Sideroblastic Anemia" as your search term in the Rare Disease Database.) Therapies: Standard Once the diagnosis of Hereditary Hemochromatosis is made, organ damage can be prevented by removal of iron through repeated removal of blood from a vein (phlebotomy). This is the standard means of removing excess iron from the body. The earlier in the course of the disease this is instituted, the better the prognosis. In cases where repeated phlebotomy causes anemia, injections of deferroxamine (Desferroxamine) may allow reduction of iron levels without producing anemia. Secondary disorders are treated symptomatically. Therapies: Investigational In 1990 Dr. Gary M. Brittenham was given a grant from the FDA Office of Orphan Products Development for his work on the pharmokinetics of Oral PIH Chelation in Iron Overload Disease (Hemochromatosis). Dr. Brittenham is with the Cleveland Metropolitan General Hospital in Cleveland, OH. This disease entry is based upon medical information available through June 1993. 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 Hereditary Hemochromatosis, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 Hereditary Hemochromatosis Research Foundation P.O. Box 8569 Albany, NY 12208 (518) 489-0972 Iron Overload Diseases Association 224 Datura Street, Suite 911 West Palm Beach, FL 33401 (407) 659-5616 National Digestive Diseases Information Clearinghouse Box NDDIC Bethesda, MD 20892 (301) 468-6344 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 THE MERCK MANUAL 15th ed: R. Berkow, et al: eds; Merck, Sharp & Dohme Research Laboratories, 1987. Pp. 942-4. MENDELIAN INHERITANCE IN MAN, 9th Ed.: Victor A. McKusick, Editor: Johns Hopkins University Press, 1990. Pp. 1235-1238. CECIL TEXTBOOK OF MEDICINE, 19th Ed.: James B. Wyngaarden, and Lloyd H. Smith, Jr., Editors; W.B. Saunders Co., 1990. Pp. 1133-1136. BIRTH DEFECTS ENCYCLOPEDIA, Mary Louise Buyse, M.D., Editor-In-Chief; Blackwell Scientific Publications, 1990. Pp. 856-858. OVERVIEW OF HEMOCHROMATOSIS, L.H. Smith, Jr.; West J Medicine (Sept. 1990; 153(3)): Pp. 296-308. IDIOPATHIC HEMOCHROMATOSIS, T.B. Kinney and S.A. DeLuca; Am Fam Physician (Sept. 1991 44(3)): Pp. 873-875. IMMUNOGENETICS OF HEREDITARY HEMOCHROMATOSIS, C.F. Bryan; Am Journal of Medical Science (Jan 1991 301(1)): Pp. 47-49.