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Excess iron is stored in body tissues,
especially the liver, heart, and pancreas.
Hemochromatosis, the most common form of iron overload disease,
is an inherited disorder that causes the body to absorb and store
too much iron. The extra iron builds up in organs and damages them.
Without treatment, the disease can cause these organs to fail.
Iron is an essential nutrient found in many foods. The greatest
amount is found in red meat and iron-fortified bread and cereal. In
the body, iron becomes part of hemoglobin, a molecule in the blood
that transports oxygen from the lungs to all body tissues.
Healthy people usually absorb about 10 percent of the iron
contained in the food they eat to meet the body needs. People with
hemochromatosis absorb more than the body needs. The body has no
natural way to rid itself of excess iron, so extra iron is stored in
body tissues, especially the liver, heart, and pancreas.
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Genetic or hereditary hemochromatosis is mainly associated with a
defect in a gene called HFE, which helps regulate the amount
of iron absorbed from food. There are two known important mutations
in HFE, named C282Y and H63D. C282Y is the most important.
When C282Y is inherited from both parents, iron is overabsorbed from
the diet and hemochromatosis can result. H63D usually causes little
increase in iron absorption, but a person with H63D from one parent
and C282Y from the other may rarely develop hemochromatosis.
The genetic defect of hemochromatosis is present at birth, but
symptoms rarely appear before adulthood. A person who inherits the
defective gene from both parents may develop hemochromatosis. A
person who inherits the defective gene from only one parent is a
carrier for the disease but usually does not develop it. However,
carriers might have a slight increase in iron absorption.
Scientists hope that further study of HFE will reveal how
the body normally metabolizes iron. They also want to learn how iron
injures cells and whether it contributes to organ damage in other
diseases, such as alcoholic liver disease, hepatitis C, porphyria
cutanea tarda, heart disease, reproductive disorders, cancer,
autoimmune hepatitis, diabetes, and joint disease.
Juvenile hemochromatosis and neonatal hemochromatosis are two
forms of the disease that are not caused by an HFE defect.
Their cause is unknown. The juvenile form leads to severe iron
overload and liver and heart disease in adolescents and young adults
between the ages of 15 and 30, and the neonatal form causes the same
problems in newborn infants.
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Hereditary hemochromatosis is one of the most common genetic
disorders in the United States. It most often affects Caucasians of
Northern European descent, although other ethnic groups are also
affected. About 5 people in 1,000 (0.5 percent) of the U.S.
Caucasian population carry two copies of the hemochromatosis gene
and are susceptible to developing the disease. One person in 8 to 12
is a carrier of the abnormal gene. Hemochromatosis is less common in
African Americans, Asian Americans, Hispanic Americans, and American
Although both men and women can inherit the gene defect, men are
about five times more likely to be diagnosed with the effects of
hereditary hemochromatosis than women. Men also tend to develop
problems from the excess iron at a younger age.
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Joint pain is the most common complaint of people with
hemochromatosis. Other common symptoms include fatigue, lack of
energy, abdominal pain, loss of sex drive, and heart problems.
Symptoms tend to occur in men between the ages of 30 and 50 and in
women over age 50. However, many people have no symptoms when they
If the disease is not detected early and treated, iron may
accumulate in body tissues and may eventually lead to serious
problems such as
- liver disease, including an enlarged liver, cirrhosis, cancer,
and liver failure
- damage to the pancreas, possibly causing diabetes
- heart abnormalities, such as irregular heart rhythms or
congestive heart failure
- early menopause
- abnormal pigmentation of the skin, making it look gray or
- thyroid deficiency
- damage to the adrenal gland
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A thorough medical history, physical examination, and routine
blood tests help rule out other conditions that could be causing the
symptoms. This information often provides helpful clues, such as a
family history of arthritis or unexplained liver disease.
Blood tests can determine whether the amount of iron stored in
the body is too high. The transferrin saturation test determines how
much iron is bound to the protein that carries iron in the blood.
The serum ferritin test shows the level of iron in the liver. If
either of these tests shows higher than normal levels of iron in the
body, doctors can order a special blood test to detect the
HFE mutation, which will help confirm the diagnosis. (If the
mutation is not present, hereditary hemochromatosis is not the
reason for the iron buildup, and the doctor will look for other
causes.) A liver biopsy, in which a tiny piece of liver tissue is
removed and examined under a microscope, may be needed. It will show
how much iron has accumulated in the liver and whether the liver is
Hemochromatosis is often undiagnosed and untreated. It is
considered rare and doctors may not think to test for it. 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. However,
if the iron overload caused by hemochromatosis is diagnosed and
treated before organ damage has occurred, a person can live a
normal, healthy life.
Hemochromatosis is usually treated by a specialist in liver
disorders (hepatologist), digestive disorders (gastroenterologist),
or blood disorders (hematologist). Because of the other problems
associated with hemochromatosis, several other specialists may be on
the treatment team, such as an endocrinologist, cardiologist, or
rheumatologist. Internists or family practitioners can also treat
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Treatment is simple, inexpensive, and safe. The first step is to
rid the body of excess iron. The process is called phlebotomy, which
means removing blood. Depending on how severe the iron overload is,
a pint of blood will be taken once or twice a week for several
months to a year, and occasionally longer. Blood ferritin levels
will be tested periodically to monitor iron levels. The goal is to
bring blood ferritin levels to the low end of normal and keep them
there. Depending on the lab, that means 25 to 50 micrograms of
ferritin per liter of serum. Depending on the amount of iron
overload at diagnosis, reaching normal levels can take many
Once iron levels return to normal, maintenance therapy, which
involves giving a pint of blood every 2 to 4 months for life,
begins. Some people may need it more often. An annual blood ferritin
test will help determine how often blood should be removed.
The earlier hemochromatosis is diagnosed and treated in
appropriate cases, the better. 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. Appropriate regular follow-up
with a specialist is necessary.
People who have complications of hemochromatosis may want to
consider getting treatment from a specialized hemochromatosis
center. These centers are located throughout the country.
People with hemochromatosis should not take iron supplements.
Those who have liver damage should not drink alcoholic beverages
because they may further damage the liver.
Although treatment cannot cure the conditions associated with
established hemochromatosis, it will help most of them. The main
exception is arthritis, which does not improve even after excess
iron is removed.
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Screening for hemochromatosis (testing people who have no
symptoms) is not a routine part of medical care or checkups.
However, researchers and public health officials do have some
- Brothers and sisters of people who have hemochromatosis should
have their blood tested to see if they have the disease or are
- Parents, children, and other close relatives of people who
have the disease should consider testing.
- Doctors should consider testing people who have joint disease,
severe and continuing fatigue, heart disease, elevated liver
enzymes, impotence, and diabetes, because these conditions may
result from hemochromatosis.
Since the genetic defect is common and early detection and
treatment are so effective, some researchers and education and
advocacy groups have suggested that widespread screening for
hemochromatosis would be cost-effective and should be conducted.
However, a simple, inexpensive, and accurate test for routine
screening does not yet exist, and the available options have
limitations. For example, the genetic test provides a definitive
diagnosis, but it is expensive. The blood test for transferrin
saturation is widely available and relatively inexpensive, but it
may have to be done twice with careful handling to confirm a
diagnosis and to show that it is the consequence of iron
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Current research in hemochromatosis is concentrated in four
Genetics. Scientists are working to understand more about
how the HFE gene normally regulates iron levels and why not
everyone with an abnormal pair of genes develops the disease.
Pathogenesis. Scientists are studying how iron injures
body cells. Iron is an essential nutrient, but above a certain level
it can damage or even kill the cell.
Epidemiology. Research is under way to explain why the
amounts of iron people normally store in their bodies differ.
Research is also being conducted to determine how many people with
the defective HFE gene go on to develop symptoms, as well as
why some people develop symptoms and others do not.
Screening and testing. Scientists are working to determine
at what age testing is most effective, which groups should be
tested, and what the best tests for widespread screening are.
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Iron Disorders Institute,
National Organization for Rare Disorders, Inc.
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