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Disorders of Iron
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Search by Disorder
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| Iron Related Issues
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| Hemochromatosis
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Hemochromatosis (HHC) is an inherited condition of abnormal iron metabolism; it is not a blood disease. Individuals with hemochromatosis absorb too much iron from the diet. Iron cannot be excreted therefore the metal
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in tissues of major organs such as the liver, heart, pituitary, thyroid, pancreas,
and synovium (joints). These overburdened organs cease to function properly and eventually
become diseased. Therefore, undiagnosed and untreated HHC increases the risk for
diseases and conditions such as diabetes mellitus, irregular heart beat or heart attack,
arthritis (osteoarthritis, osteoporosis), cirrhosis of the liver or liver cancer, depression,
impotence, infertility, hypothyroidism, hypogonadism, and some cancers. Mismanaged iron in
the brain is seen in those patients with neurodegenerative diseases: Alzheimer's,
early onset Parkinson's, epilepsy, multiple sclerosis, and Huntington's disease.
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Types of Hemochromatosis:
Type I:
Type I Hemochromatosis is also called classic hemochromatosis is due to mutations of HFE, a gene located on chromosome 6. There are more than 20 known mutations of HFE, but the most important for iron loading to date are C282Y and H63D. When a person inherits any two mutations of HFE, the risk for iron overload is increased but inheriting 2 mutated copies of C282Y currently appears to present the greatest risk for iron loading. Type I hemochromatosis is seen mostly in whites (Caucasians), though cases of blacks who are homozygous for C282Y have been documented.
Type II:
Type II or juvenile form of hemochromatosis is not presently associated with HFE but due to other gene mutations. Type IIa is caused by a mutation (G320V) on a gene named Hemojuvelin found of chromosome 1. TypeIIb is associated with chromosome 19, due to a mutation of hepcidin, a protein produced by the liver that is believed to be significant in limiting intestinal iron absorption.
Type II hemochromatosis has an onset prior to age 30 but can be seen in patients as young as 6 years of age. Type Ia is thought to have its origin in the Carolinas.
Type III:
Type III Hemochromatosis is due to a mutation in the transferrin receptor 2 (tRf2)located on chromosome 7. This form can be seen in any ethnicity.
Type IV:
Type IV Hemochromatosis is due to a mutation in ferroportin, a protein that shuttles iron out of the cell and into the bloodstream. This form is different in that it is dominant, requiring only one mutated copy to inherit the disease. Type IV is seen mostly in Africans.
Genetics:
In classic hemochromatosis, the iron build up is slow, usually taking 25-30 years before observed damage can be detected. In clinical practice, HHC/iron overload is more often seen in male's in their mid to late fifties. For this reason HHC has acquired the mistaken identity of an older male's disease. HHC can be present in females, especially those who no longer menstruate.
HFE, the gene for classic hemochromatosis was discovered by a team of scientists in California in August 1996. Two major mutations of HFE attributable to iron loading are C282Y and H63D.
Numerous prevalence studies support that mutations of HFE are common among whites. In this population, one in 200-250 are homozygous (have two mutated copies) for C282Y. One in 50 are compound heterozygotes (have one C282Y mutation and one H63D mutation). One in 8-10 are heterozygotes or carriers.
Since the discovery of HFE, genetic testing has become a way to confirm the diagnosis of hemochromatosis. This test is also used to identify family members of a person with genetic hemochromatosis, which provides an opportunity to seek early treatment and prevent disease.
 Helpful Tip
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consider purchasing this copy of idInsight magazine from our
Iron Store.
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People At Risk:
- Scots-Irish
- British
- Dutch
- German
- French
- Spanish
- Italian
- Northern Western European descent
- Northern Western European males
- Females who no longer menstruate.
- Blood relatives of people diagnosed with Hemochromatosis
- People who have a family history of a premature death by heart attack
- People who have a family history of liver disease
- People who have a family history of diabetes mellitus (type II)
- Bronze colored skin
- Arthritis especially in the first two knuckles of the hands (iron fist)
Studies:
Evidence is sufficient to warrant regular monitoring iron levels in heterozygotes (carriers), especially when there is a family history of disease such as those mentioned in the previous paragraph.
According to Finnish studies, the mean age of death by heart attack for females is at the same rate as men but death may occur twenty years after menopause or cessation of menstrual cycle. For women, monthly blood loss due to period appears to serve as a preventive means of excess iron accumulation.
For this reason, men might realize the same benefit by donating blood. According to University of Kansas Medical Center cardiologist David Meyers, MD, Iron Disorders Institute Scientific Advisory Board member "males can reduce risk of heart attack by 50% with one blood donation a year."
Signs and Symptoms:
Symptoms are non-specific. Chronic fatigue and joint pain are among the first and most common symptoms
reported by patients with hemochromatosis.
Later symptoms and findings can include:
Abdominal Pain
Irregular Heart Rhythm
Loss of Period Loss of Interest In Sex
Hair Loss
Skin Color Changes
Detection:
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It is easy to see why an incomplete diagnosis can occur when the focus is on one disease |
| or combination of diseases consequential to hemochromatosis. The
underlying cause of iron overload is frequently missed.
Hemochromatosis can be detected in several ways:
Tests are available to determine whether or not you have an iron loading condition. These include specific blood tests, genetic analysis, and possibly liver biopsy, if the serum ferritin is above 1,000ng/mL.
Specific tests include: fasting serum iron, total iron binding capacity (TIBC),
hemoglobin/hematocrit, and serum ferritin. Other tests that are less commonly used but that
can be helpful are UIBC or the serum transferrin receptor. The TIBC and serum iron
are used to calculate the transferrin-iron saturation percentage (Tsat%). This number is
derived by dividing serum iron by TIBC and multiplying the answer by 100%. Normally Tsat% is 25-35%;
values greater than 45% are indicative of iron overload and should be investigated.
The serum iron test needs to be done fasting: nothing by mouth past midnight or prior to blood work. Also, the patient should avoid vitamin C supplements three days prior to tests and reduce consumption of Vitamin C rich juices during this same three-day period of time. The best time for blood work is in the morning.
Both ferritin and TSat% will be elevated if tissue iron levels are excessive. See normal ranges for ferritin by age and gender using the chart above.
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Hemochromatosis is Often Misdiagnosed:
According to the Centers for Disease Control and Prevention, people with HHC are misdiagnosed 67% of the time and usually see an average of three doctors before obtaining a successful diagnosis. This remains a critical health concern, because hemochromatosis is common and early detection with treatment can save lives and improve quality of life. Also, if a person with hemochromatosis is diagnosed prior to serum ferritin greater than 1,000ng/mL, the chance of cirrhosis is less than 1%!
Genetic testing also called molecular analysis or DNA analysis, is available through any health care provider or can be ordered online from companies such as DNA Direct. Before getting genetically tested it is important to be fully informed of the potential for discrimination such as employment or insurance denial or cancellation. Genetic testing used in the right way can be helpful and even prevent unnecessary suffering or death.
Who Should Be Genetically Tested:
- Parents who are planning a family to determine if they are carriers and have the potential to pass mutated copies to their children.
- Parents where one spouse has been diagnosed with hemochromatosis to determine if the children are at risk.
Two carriers who may never manifest symptoms can have a child who is homozygous and who develops disease. In cases of carrier parents, where the child inherits both mutations, genetic testing can help to know if a child is at risk. Iron levels can be monitored periodically thereafter. As older children are eligible, regular blood donation can begin and possibly prevent disease.
Genetic testing can be done by two methods: cheek brush or whole blood.
Cheek brush collection involves scraping cells from inside the mouth using a mascara-like wand with tiny bristles on the end. Whole blood collection requires a needle to be inserted into the arm (same place where blood is removed during donation or phlebotomy) and a vial of blood removed. According to John Longshore, Ph.D, Iron Disorders Institute Scientific Advisory Board member and expert in Laboratory Diagnostics, both methods are reliable. One should take care to protect sample which might include using an overnight mailing service, as extreme cold or heat may destroy tissue sample.
Liver biopsy: This is an invasive procedure and is no longer used to diagnose hemochromatosis, although it is used to diagnose other conditions such as NASH (non-alcoholic steatohepatitis). Liver biopsy is still used to determine iron content in the liver, but MRI and ultra sound techniques are now available to help determine liver iron content. The Iron Disorders Institute Scientific Advisory Board does not recommend liver biopsy for patients whose serum ferritin is below 1,000ng/mL at the time of diagnosis.
Liver biopsy procedure is where a needle is inserted into the liver to obtain a tissue sample. A pathologist stains the sample with Prussian blue, which causes the iron to be seen. Liver biopsy remains the Gold Standard for determining the extent of liver damage such as fibrosis, cirrhosis or liver cancer.
Helpful Tip
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The Physician's Reference Chart, which include a diagnosis algorithm, ferritin reference ranges, genetic patterns, diet recommendations, liver biopsy recommendations and phlebotomy frequency. Purchase this chart from our
Iron Store.
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