This information just came in a newsletter that I subscribe to. I thought
that since at least one line of Cagles are affected with this problem that
it was appropriate to post to this list. It is a long post.
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Gene Mutation Behind Hemochromatosis
Study finds link to iron-absorption disease
FRIDAY, May 23 (HealthDayNews) -- German and American researchers have
linked a gene mutation in the liver to hemochromatosis, a disease that
causes a person's intestine to absorb too much iron.
If left untreated, the condition can lead to an overload of iron in the
body, which can result in heart disease, liver cancer or other fatal
conditions.
This study offers new information about how hemochromatosis develops.
"The mutation that causes the disease was thought to have its major effects
in the intestine, where cells absorb iron from food. Our current study has
changed that picture," researcher Martina Muckenthaler, of the European
Molecular Biology Laboratory in Heidelberg, says in a news release.
People with hemochromatosis have inherited a defective copy of a gene called
Hfe from each parent. This gene mutation can be traced back several
centuries in Celtic history, where it originated in a single person who
passed it down to descendents.
The disease has now spread to become the most common inherited disease in
the Western world, affecting about one in every 250 people.
The study appears in a recent issue of Nature Genetics.
More about Hemochomatosis:
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.
Causes
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.
Risk Factors
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 Indians.
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.
Symptoms
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 are diagnosed.
If the disease is not detected early and treated, iron may accumulate in
body tissues and may eventually lead to serious problems such as
? arthritis
? 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
? impotence
? early menopause
? abnormal pigmentation of the skin, making it look gray or bronze
? thyroid deficiency
? damage to the adrenal gland
Diagnosis
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 damaged.
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 the disease.
Treatment
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 phlebotomies.
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. Information is available from the
organizations listed under For More Information.
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.
Tests for Hemochromatosis
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 suggestions:
? Brothers and sisters of people who have hemochromatosis should have their
blood tested to see if they have the disease or are carriers.
? 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 overload.
Research
Current research in hemochromatosis is concentrated in four areas:
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.
For More Information
Information about hemochromatosis is available from these organizations:
American Hemochromatosis Society, Inc.
777 East Atlantic Avenue
Suite Z-363
Delray Beach, FL 33483-5352
Phone: 1-888-655-IRON (4766) or (561) 266-9037
Fax: (561) 278-0171
Email: ahs(a)emi.net
Internet:
www.americanhs.org
American Liver Foundation
75 Maiden Lane
Suite 603
New York, NY 10038-4810
Phone: 1-800-465-4837 or 1-888-443-7222
Fax: (973) 256-3214
Email: info(a)liverfoundation.org
Internet:
www.liverfoundation.org
The Hemochromatosis Foundation, Inc.
P.O. Box 8569
Albany, NY 12208
(Please send a self-addressed, stamped
envelope to receive materials.)
Phone: (518) 489-0972
Fax: (518) 489-0227
Internet:
www.hemochromatosis.org
National Organization for Rare Disorders, Inc. (NORD)
55 Kenosia Avenue
P.O. Box 1968
Danbury, CT 06813-1968
Phone: 1-800-999-6673 or (203) 744-0100
Fax: (203) 798-2291
Email: orphan(a)rarediseases.org
Internet:
www.rarediseases.org