Hereditary hemochromatosis is the most common single-gene disease in Western populations, affecting 1 out of every 200-300 people. Yet it is almost unheard of by the general public, and many health professionals are insufficiently aware of it. Because the disorder can cause diabetes via damage to the pancreas, it is something that deserves greater recognition in the American Diabetes Association community.
Hereditary hemochromatosis is the most common of several "iron overload" diseases, which are characterized by an excess accumulation of iron in the body. In the case of hemochromatosis, a single gene mutation causes extra iron to be absorbed from food in the intestine, and the body lacks an efficient means of excreting the excess iron it takes in. Over time, this iron accumulates in the tissues of the body, most notably the pancreas, the liver, and the heart. The extra iron builds up in the organs and damages them.
Without treatment, the disease can cause these organs to fail, leading to diabetes, cirrhosis, and heart disease. In many patients, the buildup of iron eventually becomes so excessive that it visibly shows up in the skin, turning it a dark gray or bronze color. In fact, hemochromatosis is sometimes referred to as "bronze diabetes" because of the appearance of some patients when they are diagnosed.
How Common is It?
As many as 1 in 200 Americans are believed to carry both copies of the gene for hemochromatosis, and it is estimated that about half of them will eventually develop complications. That puts it roughly on a par with type 1 diabetes for prevalence. Like type 2 diabetes, it is severely underdiagnosed.
What are the Symptoms?
Symptoms include the following and tend to occur in men between the ages of 30 and 50 and in women over age 50 with joint pain being the most common:
- Joint pain
- Lack of energy
- Abdominal pain
- Loss of sex drive
- Symptoms typically seen with diabetes and heart disease
How is it Diagnosed?
Blood tests (a transferrin saturation test or a serum ferritin test) can determine whether the amount of iron stored in the body is too high. It is also possible to test directly for the defective gene. Despite its prevalence and the availability of simple tests for it, hemochromatosis is often undiagnosed and untreated. 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.
What Causes It?
Hemochromatosis is caused by a defect in a gene called HFE, which helps regulate the amount of iron absorbed from food. A person who inherits the defective gene from both parents (someone who is homozygous) may develop hemochromatosis. Studies indicate that virtually everyone who is homozygous for the HFE defect develops increased iron levels, with about half of them developing complications as a result. People who inherit the defective gene from only one parent (someone who is heterozygous) are carriers for the disease but usually do not develop it, although they may have slightly increased iron levels.
The Founder Effect: An Interesting Genetic Story
Hereditary hemochromatosis represents a striking example of the "founder effect," which describes a genetic disease that arises from a mutation in just one or a few individuals. In the case of hemochromatosis, it is believed that a single individual in Europe, 60 to 70 generations ago, was the sole origin of most of the hemochromatosis seen in the world today. A chance mutation in the HFE gene in this individual was passed on, and because the defective gene didn't cause any problems in people through child-bearing age (and may have conferred some benefit in times of nutritional deficit), there was no negative selection to stop it from being passed on. Because of its origin, hemochromatosis today most often affects Caucasians of Northern European descent, although other ethnic groups can be affected by other iron overload diseases.
Men Versus Women
Although both men and women can inherit the hemochromatosis gene, men are much more likely to be diagnosed with the effects of hemochromatosis than women, and men also tend to develop problems from the excess iron at a younger age. The most likely explanation for the difference: menstruation and childbirth. Because women regularly lose a significant amount of blood every month until menopause, as well as during childbirth, they consequently lose a significant amount of iron associated with that blood. For women who are homozygous for hemochromatosis, the blood loss appears to be just enough to keep the hemochromatosis asymptomatic until well after menopause.
How is it Treated?
Once it is diagnosed, it is managed extremely effectively via frequent phlebotomy (blood letting)
That difference between men and women in the progression of hemochromatosis is a clue to the simple, straightforward treatment for hemochromatosis: phlebotomy, or blood-letting. When first diagnosed, people with hemochromatosis are put on an intensive schedule of phlebotomy to bring their iron levels down. They must give a pint of blood once or twice a week, often for many months. Measures of blood iron levels are monitored, and when they are finally in the normal range, the patient is put on a maintenance schedule of giving a pint of blood at greater intervals, usually every 2 or 3 months. Unlike diabetes, hemochromatosis is virtually cured through its treatment, with patients remaining completely asymptomatic as long as iron levels are monitored and maintained in the normal range.
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 increases, even if iron stores are reduced to normal levels. People with diabetes resulting from pancreatic damage usually see an improvement if not a reversal of their diabetes, depending on how much damage has occurred.
Where Does the Blood Go?
The American Red Cross, which controls about 45% of the nation's blood supply, does not currently accept donations from people with known hemochromatosis. Everyone agrees that the blood is safe and of high quality. There is no risk of passing on a genetic disease through blood transfusions. But the Red Cross has a long-standing policy that potential donors are not allowed to receive direct compensation for their donation (beyond the usual orange juice and cookie). Because people with hemochromatosis would otherwise have to pay for their therapeutic phlebotomies, they would in effect be getting something of value for being able to donate for free. Thus the Red Cross has ruled that such donations violate their policy.
FDA regulations do permit hemochromotosis patients to donate blood, but with some special restrictions on how the blood is marked and how the blood banks operate. As a consequence, few blood blanks in the US currently accept blood from people with hemochromatosis, and most of the blood given as a result of therapeutic phlebotomy is discarded. (People with hemochromatosis who wish to donate blood should check to see if any blood banks in their area will accept their donations.) This is not true in other countries, which have generally removed any restrictions on this blood. The American Medical Association and many other groups have advocated for removal of restrictions for the acceptance of blood donations from people with hemochromatosis.