Hemochromatosis, the most common form of iron overload disease, is an inherited disorder that causes the body to absorb and store too much iron. The extra iron builds up in organs and damages them. Without treatment, the disease can cause these organs to fail.
Iron is an essential nutrient found in many foods. The greatest amount is found in red meat and iron-fortified bread and cereal. In the body, iron becomes part of hemoglobin, a molecule in the blood that transports oxygen from the lungs to all body tissues.
Healthy people usually absorb about 10 percent of the iron contained in the food they eat. People with hemochromatosis absorb about 20 percent. The body has no natural way to rid itself of excess iron, so extra iron is stored in body tissues, especially the liver, heart, and pancreas.
Genetic hemochromatosis is mainly associated with a defect in a gene called HFE, which regulates the amount of iron absorbed from food. Two mutations, named C282Y and H63D, can cause hemochromatosis. The genetic defect is present at birth, but symptoms rarely appear before adulthood. A person who inherits the defective gene from both parents develops hemochromatosis. A person who inherits the defective gene from only one parent is a carrier for the disease but usually does not develop it. However, carriers might have a slight increase in iron absorption.
Scientists hope that further study of HFE will reveal how the body normally metabolizes iron. They also want to learn how iron injures cells and whether it contributes to organ damage in other diseases, such as alcoholic liver disease, hepatitis C, porphyria cutanea tarda, heart disease, reproductive disorders, cancer, autoimmune hepatitis, diabetes, and joint disease.
Juvenile hemochromatosis and neonatal hemochromatosis are two forms of the disease that are not caused by an HFE defect. Their cause is unknown. The juvenile form leads to severe iron overload and liver and heart disease in adolescents and young adults between the ages of 15 and 30, and the neonatal form causes the same problems in infants.
Hemochromatosis is one of the most common genetic disorders in the United States. It most often affects Caucasians of Northern European descent, although other ethnic groups are also affected. About 5 people in 1,000 (0.5 percent) of the U.S. Caucasian population carry two copies of the hemochromatosis gene and are susceptible to developing the disease. One person in 8 to 12 is a carrier of the abnormal gene. Hemochromatosis is less common in African Americans, Asian Americans, Hispanic Americans, and American Indians.
Men are about five times more likely to be diagnosed with hemochromatosis than women. Men also tend to develop problems from the excess iron at a younger age.
Joint pain is the most common complaint of people with hemochromatosis. Other common symptoms include fatigue, lack of energy, abdominal pain, loss of sex drive, and heart problems. Symptoms tend to occur in men between the ages of 30 and 50 and in women over age 50. However, many people have no symptoms when they are diagnosed.
If the disease is not detected early and treated, iron will accumulate in body tissues and may eventually lead to serious problems such as
A thorough medical history, physical examination, and routine blood tests help rule out other conditions that could be causing the symptoms. This information often provides helpful clues, such as a family history of arthritis or unexplained liver disease.
Blood tests can determine whether the amount of iron stored in the body is too high. The transferrin saturation test determines how much iron is bound to the protein that carries iron in the blood. The serum ferritin test shows the level of iron in the liver. If either of these tests shows higher than normal levels of iron in the body, doctors can order a special blood test to detect the HFE mutation, which will help confirm the diagnosis. (If the mutation is not present, hemochromatosis is not the reason for the iron buildup, and the doctor will look for other causes.) A liver biopsy, in which a tiny piece of liver tissue is removed and examined under a microscope, will disclose how much iron has accumulated in the liver and whether it is damaged.
Hemochromatosis is often undiagnosed and untreated. It is considered rare and doctors may not think to test for it. The initial symptoms can be diverse and vague and can mimic the symptoms of many other diseases. Also, doctors may focus on the conditions caused by hemochromatosis--arthritis, liver disease, heart disease, or diabetes--rather than on the underlying iron overload. However, if hemochromatosis is diagnosed and treated before organ damage has occurred, a person can live a normal, healthy life.
Hemochromatosis is usually treated by a specialist in liver disorders and digestive disorders (gastroenterologist). Because of the other problems associated with hemochromatosis, several other specialists may be on the treatment team, such as an endocrinologist, hematologist, cardiologist, or rheumatologist. Internists or family practitioners can also treat the disease.
Treatment is simple, inexpensive, and safe. The first step is to rid the body of excess iron. The process is called phlebotomy, which means removing blood. Depending on how severe the iron overload is, a pint of blood will be taken once or twice a week for several months to a year, and occasionally longer. Blood ferritin levels will be tested after every 4 phlebotomies to monitor iron levels. The goal is to bring blood ferritin levels to the low end of normal and keep them there. Depending on the lab, that means less than 9 to 50 micrograms of blood ferritin per liter. Depending on the amount of overload at diagnosis, reaching normal levels can take up to 100 phlebotomies.
Once iron levels return to normal, maintenance therapy, which involves giving a pint of blood every 1 to 4 months for life, begins. Some people may need it more often. An annual blood ferritin test will help determine how often blood should be removed.
The earlier hemochromatosis is diagnosed and treated, the better. If treatment begins before any organs are damaged, associated conditions--such as liver disease, heart disease, arthritis, and diabetes--can be prevented. The outlook for people who already have these conditions at diagnosis depends on the degree of organ damage. For example, treating hemochromatosis can stop the progression of liver disease in its early stages, which means a normal life expectancy. However, if cirrhosis has developed, the person's risk of developing liver cancer is high, even if iron stores are reduced to normal levels.
People who have complications of hemochromatosis may want to consider getting treatment from a specialized hemochromatosis center. These centers are located throughout the country.
People with hemochromatosis should not take iron supplements. Those who have liver damage should not drink alcoholic beverages because they further damage the liver. Although treatment cannot cure the conditions associated with hemochromatosis, it will help most of them. The main exception is arthritis, which does not improve even after excess iron is removed.
Screening for hemochromatosis (testing people who have no symptoms) is not a routine part of medical care or checkups. However, researchers and public health officials do have some suggestions:
Since the genetic defect is common and early detection and treatment are so effective, some researchers and education and advocacy groups have suggested that widespread screening for hemochromatosis would be cost-effective and should be conducted. However, a simple, inexpensive, and accurate test for routine screening does not yet exist, and the available options have limitations. For example, the genetic test provides a definitive diagnosis, but it is expensive. The blood test for transferrin saturation is widely available and relatively inexpensive, but it may have to be done twice with careful handling to confirm a diagnosis.
Current research in hemochromatosis is concentrated in four areas:
Genetics. Scientists are working to understand more about how the HFE gene normally regulates iron levels.
Pathogenesis. Scientists are studying how iron injures body cells. Iron is an essential nutrient, but above a certain level it can damage or even kill the cell.
Epidemiology. Research is underway to explain why the amounts of iron people normally store in their bodies differ and why day-to-day fluctuations in an individual's own iron stores occur. Research is also being conducted to determine how many people with the defective HFE gene go on to develop symptoms, as well as why some people develop symptoms and others do not.
Screening and Testing. Scientists are working to determine at what age testing is most effective, which groups should be tested, and what the best tests for widespread screening are.