HFE-associated hereditary hemochromatosis (HFE-HHC) is a common and treatable inherited disease in which the body absorbs and stores too much iron, potentially damaging organs such as the liver, heart, and pancreas. If the disease is diagnosed and treated before symptoms develop, people with HFE-HHC typically have a normal lifespan. If the disease is untreated, however, it can lead to fatal liver and heart failure.
For reasons not well understood, the majority of people with the genetic mutations that cause HFE-HHC do not develop symptoms of the disease at any point in their lives. For these people, simple blood tests can determine whether or not the body is storing too much iron. If it is, beginning treatment early can leave a person virtually symptom-free for life.
Depending on the specific mutation(s) a person has, he or she can be more or less likely to develop the iron overload symptoms of HFE-HHC.
People who have two copies of the C282Y mutation are most likely to have dangerously elevated levels of iron in their blood. Studies have found that among those with the C282Y/C282Y combination, men are more likely to develop symptoms of iron overload than women, perhaps because women's menstrual cycles lower their iron levels on a regular basis. Do keep in mind, however, that the majority of people with two copies of the C282Y mutation do not develop any symptoms of HFE-HHC.
Those who have C282Y in combination with another HFE-HHC mutation are much less likely to develop symptoms of the disease. Only 0.5% to 2% of people with C282Y in combination with another mutation are thought to have clinical signs of the disease. People with this genetic combination who have another disease of the liver may be more likely to develop HFE-HHC symptoms.
Among people who have two copies of any other HFE-HHC mutation, including a very common mutation known as H63D, the likelihood of developing symptoms is extremely low. In the absence of another liver disease, two copies of any HFE-HHC mutation other than C282Y is unlikely to cause any health problems.
In men who have not been treated for HFE-HHC, the first symptoms of the disease typically begin between the ages of 30 to 50; for untreated women, symptoms usually begin later, after menopause.
Early symptoms often include weakness, abdominal pain, joint pain, weight loss, loss of interest in sex, chest pain, and a progressive gray or bronze pigmentation to the skin. Liver disease (either fibrosis or the more serious cirrhosis) is a common problem associated with HFE-HHC. Cirrhosis can lead to fatal liver failure and/or an increased likelihood of developing cancer of the liver.
The heart can also be affected by HFE-HHC, seen as an irregular heartbeat and/or congestive heart failure. Other problems caused by HFE-HHC can include diabetes, arthritis, impotence (in men), early menopause (in women), thyroid problems, and adrenal gland problems.
HFE-HHC mutations are extremely common, particularly among Caucasians. Roughly one-third (33%) of Caucasians are carriers of the condition, most commonly the H63D mutation. The H63D mutation is almost always associated with asymptomatic cases unless paired with the C282Y mutation. In the general population, 1 in 200 to 400 has two copies of the C282Y genetic mutation, the combination of mutations which is most likely to cause symptoms of HFE-HHC.
Please bear in mind that most people who have these genetic mutations do not develop the disease.
The disease is less common among Hispanics, African Americans, Asians, and Native Americans. Roughly 13% of Hispanics, 8.5% of Asians, and 6% of African Americans is a carrier for the mild mutation, H63D. An additional 3% of Hispanics, 2.3% of African Americans are carriers of the potentially disease-causing C282Y mutation.
Ideally HFE-HHC is treated before the organs of the body are damaged. However, not everyone who has the mutations that cause HFE-HHC develops symptoms or requires treatment. A simple blood test of iron levels in the blood—physicians specifically look at serum ferritin concentration and transferrin-iron saturation levels—can determine whether the body is absorbing too much. When iron reaches a certain threshold, treatment is recommended. If iron levels have not reached that threshold, no treatment is necessary. Blood tests must be repeated periodically to check these iron levels.
If a person has a high level of iron, treatment involves removing a certain quantity of blood at regular intervals. This is known as phlebotomy. Typically phlebotomy is performed frequently—perhaps weekly or twice weekly—until certain iron levels are reached, and then performed less frequently—often 2 to 4 times a year—on an indefinite basis. This treatment is simple, inexpensive, and safe.
If a person is already suffering from symptoms of HFE-HHC, treatment can lessen or relieve some of the symptoms. Cirrhosis is unlikely to improve with treatment, although treatment may slow its progression. If liver disease has reached severe levels, liver transplantation may be an option. Those who have any amount of liver damage are advised to avoid alcohol.
All people with symptoms of HFE-HHC are advised to eat only moderate amounts of iron-rich foods, avoid taking iron supplements or excess vitamin C, and refrain from eating uncooked seafood, as they are highly susceptible to a particular kind of bacterial infection.
The prognosis for a person with the genetic mutations that cause HFE-HHC is generally good, as the majority of people in that situation do not develop symptoms of the disease. Most will not have dangerously elevated levels of iron in their blood, and therefore will not have any iron-overload problems.
For those that do have dangerously high iron levels in their blood, beginning treatment before symptoms appear is a critical part of ensuring a long, healthy life. Nearly all symptoms of the disease can be prevented with early and ongoing treatment. If a person with HFE-HHC is treated before he or she develops cirrhosis of the liver, he or she can expect a normal lifespan. Among people who already have cirrhosis associated with HFE-HHC, 72% will survive at least 5 more years and 62% will survive at least 10 more years. People who already have cirrhosis are at an increased risk for developing a type of liver cancer.
A non-profit aiming to educate and support people with HFE-HHC and their families, it also works to educate the medical community on the latest research on the disease. It was founded by the daughter of a woman who died from HFE-HHC.
4044 W. Lake Mary Blvd., Unit #104
Lake Mary, FL 32746-2012 (Note: For information by mail, send a self-addressed envelope with three first class stamps.)
Phone: (888) 655-4766
Secondary Phone: (407) 829-4488
A medical database of genetic disorders funded by the National Institutes of Health and developed at the University of Washington, Seattle. Much of the language in GeneReviews is meant for physicians and other scientists.
A volunteer non-profit organization aiming to help people with iron disorders receive an early and accurate diagnosis, get appropriate treatment and live in good health.
2722 Wade Hampton Blvd, Suite A
Greenville, SC, 29615
Secondary Phone: (864) 292-1175