Question: What causes Hemochromatosis ?
Answer: Primary Hemochromatosis Inherited genetic defects cause primary hemochromatosis, and mutations in the HFE gene are associated with up to 90 percent of cases.1 The HFE gene helps regulate the amount of iron absorbed from food. The two known mutations of HFE are C282Y and H63D. C282Y defects are the most common cause of primary hemochromatosis. People inherit two copies of the HFE geneone copy from each parent. Most people who inherit two copies of the HFE gene with the C282Y defect will have higher-than-average iron absorption. However, not all of these people will develop health problems associated with hemochromatosis. One recent study found that 31 percent of people with two copies of the C282Y defect developed health problems by their early fifties.2 Men who develop health problems from HFE defects typically develop them after age 40.1 Women who develop health problems from HFE defects typically develop them after menopause.1 People who inherit two H63D defects or one C282Y and one H63D defect may have higher-than-average iron absorption.3 However, they are unlikely to develop iron overload and organ damage. Rare defects in other genes may also cause primary hemochromatosis. Mutations in the hemojuvelin or hepcidin genes cause juvenile hemochromatosis, a type of primary hemochromatosis. People with juvenile hemochromatosis typically develop severe iron overload and liver and heart damage between ages 15 and 30. Secondary Hemochromatosis Hemochromatosis that is not inherited is called secondary hemochromatosis. The most common cause of secondary hemochromatosis is frequent blood transfusions in people with severe anemia. Anemia is a condition in which red blood cells are fewer or smaller than normal, which means they carry less oxygen to the bodys cells. Types of anemia that may require frequent blood transfusions include - congenital, or inherited, anemias such as sickle cell disease, thalassemia, and Fanconis syndrome - severe acquired anemias, which are not inherited, such as aplastic anemia and autoimmune hemolytic anemia Liver diseasessuch as alcoholic liver disease, nonalcoholic steatohepatitis, and chronic hepatitis C infectionmay cause mild iron overload. However, this iron overload causes much less liver damage than the underlying liver disease causes. Neonatal Hemochromatosis Neonatal hemochromatosis is a rare disease characterized by liver failure and death in fetuses and newborns. Researchers are studying the causes of neonatal hemochromatosis and believe more than one factor may lead to the disease. Experts previously considered neonatal hemochromatosis a type of primary hemochromatosis. However, recent studies suggest genetic defects that increase iron absorption do not cause this disease. Instead, the mothers immune system may produce antibodiesproteins made by the immune system to protect the body from foreign substances such as bacteria or virusesthat damage the liver of the fetus. Women who have had one child with neonatal hemochromatosis are at risk for having more children with the disease.4 Treating these women during pregnancy with intravenous (IV) immunoglobulina solution of antibodies from healthy peoplecan prevent fetal liver damage.4 Researchers supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) recently found that a combination of exchange transfusionremoving blood and replacing it with donor bloodand IV immunoglobulin is an effective treatment for babies born with neonatal hemochromatosis.5
Source: NIDDK

Question: How to diagnose Hemochromatosis ?
Answer: Health care providers use medical and family history, a physical exam, and routine blood tests to diagnose hemochromatosis or other conditions that could cause the same symptoms or complications. - Medical and family history. Taking a medical and family history is one of the first things a health care provider may do to help diagnose hemochromatosis. The health care provider will look for clues that may indicate hemochromatosis, such as a family history of arthritis or unexplained liver disease. - Physical exam. After taking a medical history, a health care provider will perform a physical exam, which may help diagnose hemochromatosis. During a physical exam, a health care provider usually - examines a patients body - uses a stethoscope to listen to bodily sounds - taps on specific areas of the patients body - Blood tests. A blood test involves drawing blood at a health care providers office or a commercial facility and sending the sample to a lab for analysis. Blood tests can determine whether the amount of iron stored in the body is higher than normal:1 - The transferrin saturation test shows how much iron is bound to the protein that carries iron in the blood. Transferrin saturation values above or equal to 45 percent are considered abnormal. - The serum ferritin test detects the amount of ferritina protein that stores ironin the blood. Levels above 300 g/L in men and 200 g/L in women are considered abnormal. Levels above 1,000 g/L in men or women indicate a high chance of iron overload and organ damage. If either test shows higher-than-average levels of iron in the body, health care providers can order a special blood test that can detect two copies of the C282Y mutation to confirm the diagnosis. If the mutation is not present, health care providers will look for other causes. - Liver biopsy. Health care providers may perform a liver biopsy, a procedure that involves taking a piece of liver tissue for examination with a microscope for signs of damage or disease. The health care provider may ask the patient to temporarily stop taking certain medications before the liver biopsy. The health care provider may ask the patient to fast for 8 hours before the procedure. During the procedure, the patient lies on a table, right hand resting above the head. The health care provider applies a local anesthetic to the area where he or she will insert the biopsy needle. If needed, a health care provider will also give sedatives and pain medication. The health care provider uses a needle to take a small piece of liver tissue. He or she may use ultrasound, computerized tomography scans, or other imaging techniques to guide the needle. After the biopsy, the patient must lie on the right side for up to 2 hours and is monitored an additional 2 to 4 hours before being sent home. A health care provider performs a liver biopsy at a hospital or an outpatient center. The health care provider sends the liver sample to a pathology lab where the pathologista doctor who specializes in diagnosing diseaselooks at the tissue with a microscope and sends a report to the patients health care provider. The biopsy shows how much iron has accumulated in the liver and whether the patient has liver damage. Hemochromatosis is rare, and health care providers may not think to test for this disease. Thus, the disease is often not diagnosed or treated. The initial symptoms can be diverse, vague, and similar to the symptoms of many other diseases. Health care providers may focus on the symptoms and complications caused by hemochromatosis rather than on the underlying iron overload. However, if a health care provider diagnoses and treats the iron overload caused by hemochromatosis before organ damage has occurred, a person can live a normal, healthy life. Who should be tested for hemochromatosis? Experts recommend testing for hemochromatosis in people who have symptoms, complications, or a family history of the disease. Some researchers have suggested widespread screening for the C282Y mutation in the general population. However, screening is not cost-effective. Although the C282Y mutation occurs quite frequently, the disease caused by the mutation is rare, and many people with two copies of the mutation never develop iron overload or organ damage. Researchers and public health officials suggest the following: - Siblings of people who have hemochromatosis should have their blood tested to see if they have the C282Y mutation. - Parents, children, and other close relatives of people who have hemochromatosis should consider being tested. - Health care providers should consider testing people who have severe and continuing fatigue, unexplained cirrhosis, joint pain or arthritis, heart problems, erectile dysfunction, or diabetes because these health issues may result from hemochromatosis.
Source: NIDDK