Hemochromatosis National Digestive Diseases Information Clearinghouse What is hemochromatosis? gene with the C282Y defect will have higher- than-average iron absorption. However, Hemochromatosis is the most common form not all of these people will develop health of iron overload disease. Too much iron in problems associated with hemochromatosis. the body causes hemochromatosis. Iron is One recent study found that 31 percent of important because it is part of hemoglobin, people with two copies of the C282Y defect a molecule in the blood that transports developed health problems by their early oxygen from the lungs to all body tissues. fifties.2 Men who develop health problems However, too much iron in the body leads to from HFE defects typically develop them iron overload—a buildup of extra iron that, after age 40.1 Women who develop health without treatment, can damage organs such problems from HFE defects typically develop as the liver, heart, and pancreas; endocrine them after menopause.1 glands; and joints. People who inherit two H63D defects or The three types of hemochromatosis one C282Y and one H63D defect may have are primary hemochromatosis, also higher-than-average iron absorption.3 called hereditary hemochromatosis; However, they are unlikely to develop iron secondary hemochromatosis; and neonatal overload and organ damage. hemochromatosis. Rare defects in other genes may also cause What causes primary hemochromatosis. Mutations in the hemojuvelin or hepcidin genes cause hemochromatosis? juvenile hemochromatosis, a type of primary Primary Hemochromatosis hemochromatosis. People with juvenile hemochromatosis typically develop severe Inherited genetic defects cause primary iron overload and liver and heart damage hemochromatosis, and mutations in the HFE between ages 15 and 30. gene are associated with up to 90 percent of cases.1 The HFE gene helps regulate the Secondary Hemochromatosis amount of iron absorbed from food. The two known mutations of HFE are C282Y and Hemochromatosis that is not inherited H63D. C282Y defects are the most common is called secondary hemochromatosis. cause of primary hemochromatosis. The most common cause of secondary hemochromatosis is frequent blood People inherit two copies of the HFE transfusions in people with severe anemia. gene—one copy from each parent. Most Anemia is a condition in which red blood people who inherit two copies of the HFE cells are fewer or smaller than normal, which means they carry less oxygen to the body’s Researchers supported by the National cells. Types of anemia that may require Institute of Diabetes and Digestive and frequent blood transfusions include Kidney Diseases (NIDDK) recently found that a combination of exchange • congenital, or inherited, anemias such transfusion—removing blood and replacing it as sickle cell disease, thalassemia, and with donor blood—and IV immunoglobulin Fanconi’s syndrome is an effective treatment for babies born with • severe acquired anemias, which are not neonatal hemochromatosis.5 inherited, such as aplastic anemia and autoimmune hemolytic anemia Who is more likely to Liver diseases—such as alcoholic liver develop hemochromatosis? disease, nonalcoholic steatohepatitis, and Primary hemochromatosis mainly affects chronic hepatitis C infection—may cause Caucasians of Northern European mild iron overload. However, this iron descent. This disease is one of the most overload causes much less liver damage than common genetic disorders in the United the underlying liver disease causes. States. About four to five out of every Neonatal Hemochromatosis 1,000 Caucasians carry two copies of the C282Y mutation of the HFE gene and are Neonatal hemochromatosis is a rare disease susceptible to developing hemochromatosis.1 characterized by liver failure and death About one out of every 10 Caucasians carries in fetuses and newborns. Researchers one copy of C282Y.1 are studying the causes of neonatal hemochromatosis and believe more than one Hemochromatosis is extremely rare in factor may lead to the disease. African Americans, Asian Americans, Hispanics/Latinos, and American Indians. Experts previously considered neonatal HFE mutations are usually not the cause of hemochromatosis a type of primary hemochromatosis in these populations. hemochromatosis. However, recent studies suggest genetic defects that increase iron Both men and women can inherit the gene absorption do not cause this disease. defects for hemochromatosis; however, Instead, the mother’s immune system may not all will develop the symptoms of produce antibodies—proteins made by hemochromatosis. Men usually develop the immune system to protect the body symptoms at a younger age than women. from foreign substances such as bacteria Women lose blood—which contains iron— or viruses—that damage the liver of the regularly during menstruation; therefore, fetus. Women who have had one child with women with the gene defects that cause neonatal hemochromatosis are at risk for hemochromatosis may not develop iron having more children with the disease.4 overload and related symptoms and Treating these women during pregnancy complications until after menopause. with intravenous (IV) immunoglobulin—a solution of antibodies from healthy people— can prevent fetal liver damage.4 2 Hemochromatosis What are the symptoms How is hemochromatosis of hemochromatosis? diagnosed? A person with hemochromatosis may notice Health care providers use medical and one or more of the following symptoms: family history, a physical exam, and routine blood tests to diagnose hemochromatosis or • joint pain other conditions that could cause the same • fatigue, or feeling tired symptoms or complications. • unexplained weight loss • Medical and family history. Taking • abnormal bronze or gray skin color a medical and family history is one of the first things a health care • abdominal pain provider may do to help diagnose • loss of sex drive hemochromatosis. The health care provider will look for clues that may Not everyone with hemochromatosis will indicate hemochromatosis, such as a develop these symptoms. family history of arthritis or unexplained liver disease. What are the complications • Physical exam. After taking a medical of hemochromatosis? history, a health care provider will Without treatment, iron may build up in the perform a physical exam, which may organs and cause complications, including help diagnose hemochromatosis. During a physical exam, a health care • cirrhosis, or scarring of liver tissue provider usually • diabetes – examines a patient’s body • irregular heart rhythms or weakening of – uses a stethoscope to listen to bodily the heart muscle sounds – taps on specific areas of the patient’s • arthritis body • erectile dysfunction • Blood tests. A blood test involves The complication most often associated drawing blood at a health care with hemochromatosis is liver damage. Iron provider’s office or a commercial facility buildup in the liver causes cirrhosis, which and sending the sample to a lab for increases the chance of developing liver analysis. Blood tests can determine cancer. whether the amount of iron stored in the body is higher than normal:1 For some people, complications may be the first sign of hemochromatosis. However, not – The transferrin saturation test everyone with hemochromatosis will develop shows how much iron is bound to the complications. protein that carries iron in the blood. Transferrin saturation values above or equal to 45 percent are considered abnormal. 3 Hemochromatosis – The serum ferritin test detects the she may use ultrasound, computerized amount of ferritin—a protein that tomography scans, or other imaging stores iron—in the blood. Levels techniques to guide the needle. After above 300 µg/L in men and 200 µg/L the biopsy, the patient must lie on in women are considered abnormal. the right side for up to 2 hours and is Levels above 1,000 µg/L in men or monitored an additional 2 to 4 hours women indicate a high chance of iron before being sent home. overload and organ damage. A health care provider performs a liver If either test shows higher-than-average biopsy at a hospital or an outpatient levels of iron in the body, health care center. The health care provider sends providers can order a special blood test the liver sample to a pathology lab that can detect two copies of the C282Y where the pathologist—a doctor who mutation to confirm the diagnosis. If specializes in diagnosing disease—looks the mutation is not present, health care at the tissue with a microscope and providers will look for other causes. sends a report to the patient’s health care provider. The biopsy shows how • Liver biopsy. Health care providers may much iron has accumulated in the perform a liver biopsy, a procedure that liver and whether the patient has liver involves taking a piece of liver tissue damage. for examination with a microscope for signs of damage or disease. The Hemochromatosis is rare, and health health care provider may ask the patient care providers may not think to test for to temporarily stop taking certain this disease. Thus, the disease is often medications before the liver biopsy. not diagnosed or treated. The initial The health care provider may ask the symptoms can be diverse, vague, and patient to fast for 8 hours before the similar to the symptoms of many other procedure. diseases. Health care providers may focus on the symptoms and complications caused During the procedure, the patient lies by hemochromatosis rather than on the on a table, right hand resting above the underlying iron overload. However, if a head. The health care provider applies health care provider diagnoses and treats the a local anesthetic to the area where he iron overload caused by hemochromatosis or she will insert the biopsy needle. If before organ damage has occurred, a person needed, a health care provider will also can live a normal, healthy life. give sedatives and pain medication. The health care provider uses a needle to take a small piece of liver tissue. He or 4 Hemochromatosis How is hemochromatosis Who should be tested treated? for hemochromatosis? Health care providers treat hemochromatosis Experts recommend testing for by drawing blood.