Iron Overload and Hemochromatosis

Hereditary hemochromatosis is one of the most common genetic diseases in humans, but many people have never heard of it. In the United States, as many as one million people have evidence of the disorder, and up to one in every ten people may carry the gene for it.

In people who have hemochromatosis, the body accumulates excess amounts of iron. This can result in serious and sometimes fatal health problems. Some diseases associated with hemochromatosis are arthritis, cirrhosis of the liver, diabetes, heart failure and liver cancer.

Signs and Symptoms
Early symptoms of hemochromatosis are nonspecific and might include fatigue, heart palpitations, joint pain, non-specific stomach pain, impotence and loss of menstrual periods. Even without other symptoms, people with hemochromatosis may have abnormal liver function test results. Symptoms – which reflect the tissue and organ damage that result from the disease – usually appear in middle age, although some people may develop problems earlier.

Later disease symptoms include gray or bronze coloration to the skin, liver cirrhosis, liver cancer, diabetes, hypopituitarism, decreased pituitary or gonadal function, heart disease or heart failure, joint disease, chronic abdominal pain, severe fatigue and certain infections.

Excess iron in the diet, alcohol use, infections, iron lost through blood donations and menstruation, and other environmental factors may affect the clinical course of hemochromatosis. For example, alcohol use may worsen the disease, whereas iron lost through blood donations or menstruation may lessen its severity.

Diagnosis
Early detection of hemochromatosis is essential because the disease's potentially serious complications can be prevented by early therapy. Although a sensitive and relatively inexpensive screening test for iron overload is available, routine medical care or checkups usually do not include hemochromatosis testing. As a result many cases may remain undetected. People who have a close blood relative with hemochromatosis, as well as those who have the signs and symptoms described above, should talk with their health care provider about the possibility of being evaluated for hemochromatosis.

Treatment
Periodically removing blood (also called phlebotomy) to remove excess iron is a necessary component in treating hemochromatosis. In the initial phase of treatment, one unit of whole blood, which contains about 250 milligrams of iron, is removed, usually once or twice weekly. This "de-ironing" phase continues until all excess stored iron is removed, as indicated by monitoring hemoglobin and serum ferritin concentrations. The frequency and duration of this process can vary among patients by age, gender, reason for diagnosis, and severity of symptoms.

The second phase of treatment is long-term maintenance of normal iron stores. The frequency of blood removal in this phase is determined individually for each patient, according to symptoms and levels of hemoglobin and serum ferritin.

Blood Donation
Frequently patients and their care providers ask whether it is safe for individuals with hemochromatosis to donate blood to community organizations. The Food and Drug Administration (FDA) recently announced that blood from therapeutic phlebotomies for persons with hemochromatosis could be used for transfusion if the blood donation facility met certain criteria: 1) the blood collection center may not charge for the therapeutic phlebotomy and 2) the blood center must apply to FDA for exemption from existing regulations. As part of that exemption, the blood center must collect and submit specified data to the FDA. The FDA will consider exemption applications on a case-by-case basis. (Additional questions about blood donation from patients with hemochromatosis should be referred to the FDA, online at http://www.fda.gov/cber/blood.htm or by phone at 1-888-889-7274.)

Prognosis
The long-term health outcome for people with hemochromatosis depends on the degree of organ damage that has already taken place by the time the patient is diagnosed with the disease. For a person who has no evident tissue or organ damage, proper management of the disease can result in a normal long-term outcome and life expectancy. For a person who has evident tissue or organ damage, further damage can be halted, but damage already incurred may not be reversible.

Public Health Issues
In the United States, it is estimated that as many one in every 200 to 500 people, or approximately one million people, have evidence of hemochromatosis, and as many as one in every 10 people may carry the gene for this hereditary disease.

The prevention and control of hemochromatosis is an achievable goal and is important to the overall prevention of chronic disease. Current research priorities include 1) determining the proportion of people with hemochromatosis who will become symptomatic and 2) evaluating the risks, benefits, and effectiveness of different methods of case detection and follow-up.

Educating health care providers and patients about hemochromatosis is central to the public health plan of action in the US. The 1996 identification of the gene associated with hemochromatosis provides us with an important opportunity to prevent the progression and complications of hemochromatosis. It remains to be determined how best to use genetic testing to assist clinicians and patients.

Each year, Medical College of Wisconsin physicians care for more than 180,000 patients, representing nearly 500,000 patient visits. Medical College physicians practice at Children's Hospital of Wisconsin, Froedtert Memorial Lutheran Hospital, the Milwaukee VA Medical Center, and many other hospitals and clinics in Milwaukee and southeastern Wisconsin.