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Hereditary Hemochromatosis
  What Is Hemochromatosis?
what is hemochromatosis

By Amanda Ewart Toland, PhD

Reviewed by Chris Friedrich, MD, PhD





Although diabetes, impotence, and liver cancer may seem unrelated, they can all be consequences of a common inherited disorder called hemochromatosis, an iron overload disease. Few people have even heard of hemochromatosis, even though it is estimated to affect 1.5 million Americans, and probably accounts for 15 percent of the cases of adult onset diabetes.

 
 
 

What Is Hereditary Hemochromatosis?

what is hemochromatosis
Our bodies require a small amount of iron every day, but large amounts of iron can damage our organs
what is hemochromatosis

Hemochromatosis is a disorder that causes the body to absorb excess iron from food. Since there is no way for the body to get rid of iron (other than bleeding or shedding of skin and intestinal cells), people with hemochromatosis have to store the excess iron in cells of the liver, heart, pancreas, and other organs.

Our bodies require a small amount of iron every day, but large amounts of iron can damage our organs. If untreated, or not diagnosed early enough, hemochromatosis can lead to:

  • Diabetes
  • Joint pain
  • Abnormal heart rhythms
  • Heart failure
  • Cirrhosis of the liver, liver failure, or (rarely) liver cancer
  • Impotence or decreased sex drive in men; early menopause in women

Many individuals with advanced hemochromatosis also have color changes in their skin. This was one of the first clinical features recognized with this disorder, and is the origin of the name hemochromatosis.

what is hemochromatosis The Discovery and Naming of Hemochromatosis what is hemochromatosis

Over 100 years ago, doctors described a disorder in which individuals suffered from liver damage and diabetes. The skin of these patients often turned a bronze color, attributed to iron in the blood. For this reason, the disorder was named hemochromatosis, from the Greek heme meaning "of the blood" and from chroma meaning color.

what is hemochromatosistop
 

Who Gets Hemochromatosis?

The most common cause of hemochromatosis is genetics — hereditary hemochromatosis, in which the disease runs in families, is the most common inherited disorder. In fact, approximately 1 in 200 people in the United States is thought to have a mutation necessary for iron overload, but a far smaller number of people develop fully symptomatic hemochromatosis. Others who carry a mutation, but do not have symptoms of hemochromatosis, may be at increased risk for other disorders, such as cardiovascular problems.

 

What Are the Symptoms of Hereditary Hemochromatosis?

 With over 30 different symptoms associated with hemochromatosis, the disease can be extremely difficult to diagnose. Many of the early symptoms of hemochromatosis are nonspecific, including weakness and fatigue, loss of sex drive, and general muscle aches that can also be caused by a number of medical problems unrelated to hemochromatosis. Symptoms may begin anywhere from age 30 to age 60, although in some rare cases they occur as early as 20.

 

Early Symptoms of Hereditary Hemochromatosis

  • Weakness
  • Fatigue
  • Abdominal pain
  • General muscle aches
  • Loss of sex drive
  • Impotence
  • Cessation of monthly menstrual cycles
  • Joint pain in the fingers
  • Shortness of breath on exertion
  • Increased skin pigmentation (a bronze color)
  • Loss of body hair

During a physical examination, a doctor might note an enlarged liver (hepatomegaly) and increased skin pigmentation indicating that the patient is in the early stages of the disease. If the disease is diagnosed at this stage, treatment can begin that will reduce the chances of getting other, more serious complications.

 
More on Treatment and Prevention (Coming Soon)
what is hemochromatosis

If hemochromatosis remains undiagnosed and untreated, iron will continue to build up in the organs. Other, more serious health problems including diabetes mellitus (due to iron in the pancreas), cardiomyopathy (a stiff heart that doesn't function efficiently due to iron buildup in the heart), liver dysfunction, and cirrhosis of the liver can develop. Cirrhosis of the liver can lead to liver cancer, which occurs in about 30 percent of male subjects who have cirrhosis due to hemochromatosis. Unfortunately, if hemochromatosis is diagnosed at this late stage, it doesn't respond to treatment as well because organs have already been damaged. However, if the diagnosis is made before cirrhosis develops, life expectancy is normal, and, with treatment, almost all other complications of iron overload can be reversed or stopped from progressing.

what is hemochromatosistop

 

 

Natural History

Iron is essential for the body to conduct many necessary functions. In disorders like anemia for example, people don't have enough iron and need to take iron supplements. But too much iron can also be harmful. Excess iron is toxic, causing organ damage.

what is hemochromatosis
Although
uncommon, it is possible to be anemic and still have hemochromatosis.
what is hemochromatosis

Normally we get 10 to 20 milligrams of iron a day in our diet. However, of that amount the body typically only absorbs 1 to 2 milligrams. The rest of the iron is not absorbed, and some is lost in any skin cells that are shed. Individuals with hereditary hemochromatosis absorb 3 to 4 milligrams of iron through the intestine (about twice the normal amount), and the body does not have any way to get rid of it. Over decades, this iron accumulates in organs including the heart, liver, and pancreas. Iron accumulation results in organ damage and other conditions like diabetes and abnormal heart rhythms that are signs that the organs are sick.

what is hemochromatosis
Excess iron accumulation in the organs begins
in childhood, but the symptoms of this disorder do not usually appear
until adulthood.
what is hemochromatosis

It takes a long time for organs to sustain enough damage due to excess iron before they begin to malfunction. Excess iron accumulation in the organs begins in childhood, but the symptoms of this disorder do not usually appear until adulthood. Symptoms of hemochromatosis begin to occur when the body has stored 20 grams or more of iron, which can take 4 to 6 decades.

what is hemochromatosistop

 

 

When Will Symptoms of Hemochromatosis Appear?

Many factors effect when symptoms of hemochromatosis may appear.

  • Alcohol. Because alcohol is an independent toxin to the liver, liver disease may be present earlier due to the combined effects of alcohol and iron.
  • Diet. People who take vitamin supplements that contain iron, or take vitamin C, which increases the body's effectiveness at absorbing iron, may have symptoms at a younger-than-average age.
  • Gender. Men are twice as likely to go to their doctor with symptoms of hereditary hemochromatosis than women. In untreated men, symptoms usually begin between age 40 and 60. For women, the symptoms usually start later, between age 50 and 65. One reason is that women have regular episodes of blood loss through menstruation or childbirth.
  • Blood loss. Individuals who lose iron through blood donation may also delay the onset of symptoms.
  • Mutation type. There are two common mutations in a gene called HFE, which is known to cause hereditary hemochromatosis. One of these two mutations, H63D, is associated with a less severe and later onset form of hemochromatosis. People who have one or two copies of this mutation have a milder form of the disease compared to people who have two copies of the other common mutation (called C282Y).

 

The good news is that the earlier hemochromatosis is diagnosed, the easier the treatment process is, and the less likely that organ damage will have occurred. If someone has a predisposition towards abnormal iron storage, regular loss of iron (through blood draws), avoiding iron supplements, and high doses of vitamin C can prevent buildup of excess iron and the damage it causes. The treatment for a person with hemochromatosis includes getting iron levels back to normal, as well as specific treatment for any organ damage.

Hemochromatosis Is Underdiagnosed

Although hemochromatosis is common, the disease is often underdiagnosed. This may be in part because symptoms occur in mid-adult life, mimicking many other adult onset disorders such as diabetes and heart disease. Another reason may be that the textbook symptoms that doctors learn (liver disease, diabetes, and bronzed skin) may not be the first symptoms that appear in people with hemochromatosis.

For recent news about how hemochromotosis is underdiagnosed, see Related News below.

what is hemochromatosistop

 

 

How Is Hemochromatosis Diagnosed

Because this disorder is easily detected through tests for blood iron levels and by looking for mutations in the hemochromatosis gene (HFE), more doctors are diagnosing individuals with the disease before they have symptoms. Before moving on to genetic testing or liver biopsy, doctors usually perform screening tests.

Screening Tests for Hemochromatosis What the Test Measures
Tranferrin saturation (related to the total iron binding capacity, or TIBC) The percentage of iron transport proteins in the blood currently carrying iron atoms.
Serum ferritin The amount of the long-term storage protein for iron. (An indirect measure of the amount of iron stored in your liver.)

 

Tranferrin Saturation Test

The transferrin saturation test determines how much iron is held by the protein that carries iron in the blood. A fasting transferrin saturation of 60 percent or higher in men, or 50 percent or higher in women, on at least two occasions, is considered a sign of iron overload. However, factors in addition to hemochromatosis can cause iron overload. Values of greater than 45 percent are considered suggestive of hemochromatosis and deserve further evaluation.

Serum Ferritin Level Test

The serum ferritin test acts as an indirect measure of iron storage in the liver. Serum ferritin levels are considered in the normal range for males and postmenopausal females if they are between 20 and 300 ug/L, or between 20 and 200ug/L for premenopausal females. People with advanced hemochromatosis may have serum ferritin levels as high as 15,000 ug/L. However, other factors besides hemochromatosis can cause high serum ferritin levels, including liver disease, infection, cancer, heart disease, AIDS, metabolic disorders, and inflammatory conditions such as arthritis.

If individuals have elevated serum ferritin levels, or fasting transferrin saturation levels, genetic testing for hemochromatosis may help to identify the reason for the increase in iron storage.

Liver Biopsy

Doctors often perform a liver biopsy in people who have high serum ferritin levels (e.g., over 1000ug/L) in order to determine the extent of liver damage and to distinguish between hemochromatosis and other liver diseases. A liver biopsy can also provide a clearer picture of the amount of iron that is being stored in the liver, which is known as hepatic iron concentration.

Before the availability of genetic testing for hemochromatosis, a liver biopsy with measurements of hepatic iron was considered the "gold standard" for diagnosing hemochromatosis. A liver biopsy is now rarely needed to make the diagnosis, and is usually only used in cases of apparent iron overload with a negative genetic test result and no other family history of hemochromatosis.

However, a liver biopsy is the only test that can tell whether cirrhosis is present, which is the only complication that affects the lifespan of someone with hemochromatosis, since it increases the risk for liver cancer. A liver biopsy should be recommended for anyone with hemochromatosis who is also:

  • Over 40 years old
  • Has a ferritin level over 1000 ug/L, or
  • Has abnormal liver function test results.

Outside of those three conditions the likelihood of cirrhosis is so low it does not usually justify the risk of the procedure.

what is hemochromatosis HLA Antigen Testing what is hemochromatosis

Testing of HLA antigens was also once used to help make the diagnosis. This was because the gene for hemochromatosis was very close to the highly polymorphic HLA genes on chromosome six, and certain HLA gene alleles were often found in patients with hemochromatosis. This test had many false positive and false negative results, and is now obsolete (although still offered by some laboratories).

what is hemochromatosistop

 

Preventing the Symptoms of Hemochromatosis

Like other genetic disorders, symptoms of hemochromatosis are preventable if treatment is started early. Prevention includes removing iron through weekly phlebotomy (blood removal) treatments until iron levels reach normal; preventing further accumulation through blood removal three to four times a year, and avoiding supplemental iron and high doses of vitamin C.

what is hemochromatosistop

 

When Is Iron Overload Not Hereditary Hemochromatosis?

Although the most common reason for abnormal iron storage in the body is hereditary hemochromatosis, there are other medical reasons for excess iron accumulation:

  • Dietary iron overload. The body can only release a certain amount of excess iron a day. If individuals take excessive amounts of iron through vitamins, medicine, or a diet rich in red meat, they may have temporary hemochromatosis.
  • Chronic liver disease. Individuals with liver disease due to alcoholism, hepatitis C or other disorders may have higher than usual amounts of iron stored in the liver or other organs. This is termed hemosiderosis, and the appearance of the liver on biopsy is different than hemochromatosis.
  • Other rare hereditary conditions. Other hereditary conditions can cause a build-up of excess iron. These include thalassemia and other anemias requiring multiple transfusions; juvenile onset hereditary hemochromatosis and porphyria cutaneous tarda.

what is hemochromatosistop

Related News
In order to view these articles you will need to have a MyGeneticHealth account. If you are not already a member, selecting the article will automatically take you to a page where you can sign up.
Relatives of hemochromatosis patients may have undetected related conditions

References

Website of the Iron Disorders Insitute. (2000). http://www.irondisorders.org

Salonen, JT, Tuomainen, T-P, and Kontula, K. (2000). Role of C282Y mutation in haemochromatosis gnee in development of type 2 diabetes in healthy men: prospective cohort study. BMJ. 320: 1706-7.

Edwards, CQ, et al. (1988). Prevalence of hemochromatosis among 11,065 presumably healthy blood donors. New Engl. J. Med. 318: 1355-1362.

Burke, W, et al. (1998). Hemochromatosis: genetics helps to define a multifactorial disease. Clin. Genet. 54: 1-9.

Hereditary Hemochromatosis from GeneClinics Web Site. (2000). http://www.geneclinics.org.

McDonnell, S, et al. (1999). A survey of 2,851 patients with hemochromatosis: symptoms and response to treatment. Am. J. Med. 106: 619-624.

Voelkerding, K. (1998). Clinical and Diagnostic Update on hereditary Hemochromatosis. American Society of Clinical Patholgists Fall Meeting. Program #9476.

Powell, LW, et al. (1998). Diagnosis of hemochromatosis. Ann. Int. Med. 129: 925-931.

Witte, DL, et al. (1996). Practice guideline development task force of the College of American Pathologists. Hereditary Hemochromatosis. 245: 139-200.

Edwards, C and Barton, J. (2000) Hemochromatosis: Genetics, Pathology, Diagnosis and Treatment. Cambridge University Press. Cambridge, United Kingdom.

 

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