Disorder Profile: Hemochromatosis
For more about
the gene that causes hereditary hemochromatosis, see the HFE
Gene Profile. The following disease information was adapted from
Publication No. 00-4621.
- Hemochromatosis is first described by Tousseau, who cared for
a diabetic patient with cirrhosis of the liver and bronzed skin
pigmentation, classic symptoms of HH.
- Von Recklinghausen names the disease "hemochromatosis"
and identifies an iron-containing pigment in the liver cells of
- Sheldon describes the hereditary nature of the disease in his
- Stevens reported that a gene for HH may be located on chromosome
6 near the HLA-A locus. Simon concluded that HH demonstrates recessive
- Feder identifies the hemochromatosis gene and the missense
mutations (Cys282Tyr and His63Asp) that cause HH. The hemochromatosis
gene was originally HLA-H, but was later changed to HFE.
- CDC and the National Human Genome Research Institute sponsor a
meeting to examine issues related to the discovery of HFE. A panel
of experts conclude that large-scale population screening is not
- Research by Roldan links acute liver failure to iron supplementation
in a 29-yea- old woman whose HH went undiagnosed. To increase physician
awareness of HH, a special December issue of the Annals of Internal
Medicine features 11 articles on the disease.
Online Mendelian Inheritance in Man, OMIM (TM). Johns Hopkins
University, Baltimore, MD. MIM No. 235200 (September 10, 2001) <http://www.ncbi.nlm.nih.gov/omim/>
Jennifer Farmer . "Hereditary Hemochromatosis." MARHGNews.
Mid-Atlantic Regional Human Genetics Network. Summer 1999.
(HH), the most common form of iron overload disease, is an inherited disorder
that causes the body to absorb and store too much iron. Excess iron is
stored throughout the body in organs and tissues including the pancreas,
liver, and skin. Without treatment, the iron deposits can damage these
organs and tissues.
HH is an autosomal recessive disorder caused by mutations
in the HFE gene, which regulates the amount of iron absorbed from food.
A person who inherits a defective gene from each parent will develop hemochromatosis.
A person who inherits a defective gene from one parent is a carrier but
usually does not develop the disease. Carriers, however, might have a
slight increase in iron absorption.
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 also are affected. About 5 people in 1000 (0.5%) 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. Hemochromatosis is less common in African Americans, Asian
Americans, Hispanic Americans, and American Indians.
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 are diagnosed.
the disease is not detected early and treated, iron will accumulate in
body tissues and may eventually lead to serious problems such as the following.
Liver disease, including enlarged liver, hepatitis,
cirrhosis, cancer, and liver failure
Heart abnormalities, such as irregular heart rhythms
or congestive heart failure
pigmentation of the skin, making it look gray or bronze
Damage to the pancreas, possibly causing diabetes
Damage to the adrenal gland
Diagnosis and Genetic Testing
A thorough medical history, physical examination,
and routine blood tests help rule out other conditions that could be causing
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.
Transferrin Saturation Test: Determines how much iron is bound
to the protein that carries iron in the blood. 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.
Serum Ferritin Test: Shows the level of iron in the liver.
Liver Biopsy: Procedure in which a needle is inserted through the
rib cage and abdominal cavity to obtain a sample of liver tissue for testing
Molecular Genetic Testing: Direct DNA testing for two HFE gene
mutations (C282Y and H63D) associated with hemochromatosis is available
at a number of laboratories. These genetic tests offer a detection rate
of about 87% for HH; therefore, a person who has the mutant gene could
test negative. Genetic testing is the only way to determine whether or
not someone is a carrier of the disease .
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 is taken once or twice a week for several
months to a year, occasionally longer. Blood ferritin levels are tested
after every four phlebotomies to monitor iron levels. The goal is to bring
blood ferritin levels to the low end of normal and keep them there (that
means less than 9 to 50 micrograms of blood ferritin per liter). Depending
on the amount of overload at diagnosis, reaching normal levels can take
up to 100 phlebotomies.
Once iron levels
return to normal, maintenance therapy, which involves removing a pint
of blood every 1 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, the better. If treatment
begins before any organs are damaged, associated conditions such as liver
disease, heart disease, arthritis, and diabetes can be prevented. Individuals
who have already developed complications from hemochromatosis may not
be cured but usually can be helped. The main exception is arthritis, which
does not improve even after excess iron is removed.
hemochromatosis should not take iron supplements. Those who have liver
damage should not drink alcoholic beverages because they further damage
Since effective treatment is available for a genetic disorder as
common as HH, why isn't population screening recommended?
A lot of uncertainties still surround the initiation of population
screening for this and other genetic disorders. One uncertainty
is that different genetic mutations can result in varying degrees
of disease severity. For example, people who have two copies of
the H63D mutation generally develop a very mild form of the disease
or may never develop any symptoms at all. Diagnosing a genetic disease
in an asymptomatic individual could have negative psychological
effects. Another uncertainty is that current genetic-testing methods
are unable to detect about 10% of mutations, so many people at risk
for developing iron overload later in life may be undiagnosed .
with any attempt at population screening for disease, the possibility
of discrimination is always present. In the United Kingdom, where
hemochromatosis is the most common genetic disease, the private
health insurance company for a man diagnosed with the disorder refused
to cover treatment because the insurer considered hemochromatosis
to be a preexisting condition . Other instances of discrimination
have been reported by individuals applying for life insurance.
some states have policies addressing genetic discrimination, the
coverage, protections afforded, and enforcement schemes vary from
state to state. Currently, no federal legislation has been passed
relating to genetic discrimination in individual insurance coverage
or to genetic discrimination in the workplace.
a better understanding of the complex genotype-phenotype relationship
associated with hereditary hemochromatosis is achieved and more
of the many uncertainties associated with disease screening are
resolved, the need for large-scale population screening will continue
to be debated.
and Support Groups
Canadian Hemochromatosis Society
Trials for Hemochromatosis at ClinicalTrials.gov
Overload and Hemochromatosis
- A collection of hereditary hemochromatosis resources maintained by
the Centers for Disease Control and Prevention (CDC)
Hemochromatosis - Links to resources from the National Institutes
of Health and other hemochromatosis organizations
Tests - Overview of some laboratory tests
involved in diagnosing hereditary hemochromatosis, provided by Lab
Tests Online, a peer-reviewed, noncommercial resource on clinical
Testing for Hereditary Hemochromatosis" - Article featured
in the Spring 1997 issue of the Genetic Drift Newsletter by the
Mountain States Genetic
Network (MoSt GeNe).
Other Hemochromatosis Resources
Genes, Your Health: Hemochromatosis - A multimedia guide, funded
by the Josiah Macy, Jr. Foundation, that visually depicts what causes
hemochromatosis, how it is inherited, how it is diagnosed, how it is
treated, and what it is like to have the disease.
Education and Research - Information about hemochromatosis targeted
to both health care providers and patients. This resource is provided
by the University of Washington Division of Gastroenterology.
1. Kris V. Kowdley
et al. "Hereditary Hemochromatosis." <http://www.geneclinics.org>
In GeneReviews at GeneTest-GeneClinics. and < http://www.genetests.org>
(Updated March 31, 2000, accessed December 21, 2001)
2. Michele Reyes
and Muin J. Khoury. "Screening for Hereditary Hemochromatosis: Still Premature."
GeneLetter 2 (17), August 2001.
3. Wylie Burke et
al. "Hereditary Hemochromatosis. Gene Discovery and its Implications for
Population-Based Screening." JAMA 280 (2): 172-8.
Farmer. "Hereditary Hemochromatosis." MARHGNews. Mid-Atlantic Regional
Human Genetics Network. Summer 1999.
5. "MPs Call for
Tough Controls on Human Genetics." GenEthics News. July/August