A common disease which is under-diagnosed
The genetic defect that causes hereditary hemochromatosis is present at birth. However, the symptoms do not appear until later in life. This is because iron buildup occurs slowly throughout a person’s life. Symptoms usually begin in men in their late 30’s to 50’s. In women, symptoms usually start 10 to 15 years after menopause, when they no longer lose iron with menstruation.
Early Symptoms of Hemochromatosis
Early signs and symptoms of hemochromatosis are similar to those of many other common conditions, making it difficult to diagnose. The symptoms vary between different people and some people with hemochromatosis do not have any early symptoms. Symptoms may include:
- Joint pain, usually in the hands, hips, knees and/or ankles (this is one of the first and most common complaints of people with hemochromatosis)
- Chronic fatigue (this is one of the first most common complaints of people with hemochromatosis)
- Lack of energy
- Abdominal pain
- Loss of sex drive (libido), impotence
- Heart problems (heart flutters, irregular heart beat)
- Generalized darkening of skin color (bronzing)
- Lack of normal menstruation (amenorrhea), premature menopause
- High blood sugar levels
- Low thyroid function (hypothyroidism)
- Abnormal liver function test
- Shortness of breath
Advanced-Stage Symptoms of Hemochromatosis
If hemochromatosis is not detected early and treated, iron will continue to accumulate in the organs and eventually lead to serious conditions such as:
- Arthritis (osteoarthrithis, osteoporosis) knuckles, ankles and hips
- Liver disease, including an enlarged liver, cirrhosis, cancer, and liver failure
- Diabetes, high blood sugar
- Heart problems (irregular heartbeat, heart attack or congestive heart failure)
- Loss of period or early menopause
- Abnormal pigmentation of the skin, making it look gray or bronze
- Thyroid deficiency, hypothyroidism (which can cause depression)
- Damage to the adrenal glands
Hemochromatosis is Under-Diagnosed
Although hemochromatosis is common, the disease is often under-diagnosed for several reasons:
1. Physicians often overlook hemochromatosis as they concentrate on treating the conditions caused by hemochromatosis (arthritis, liver disease, heart disease, diabetes), rather than looking for the root cause of the disease.
2. Hemochromatosis has a wide range of possible symptoms, making the disease very difficult to diagnose symptomatically.
3. The early symptoms of hemochromatosis are vague and mimic the symptoms of many other diseases, so physicians do not think to test for it. As a result, the disease is often not diagnosed and treated in the early stages before organ damage has occurred.
4. The later stage symptoms of hemochromatosis do not occur until midlife, so detection and treatment often does not happen until it is too late.
5. There are no “textbook” symptoms of hemochromatosis.
If hemochromatosis is discovered early and treated before organ damage has occurred, a person can live a normal, healthy life.
Hemochromatosis is caused by a defect in a gene called HFE which is responsible for regulating the absorption of dietary iron by the body. The defective HFE gene is found in families with a history of hereditary hemochromatosis. A simple DNA test from a cheek swab sample can confirm whether a person has the defective HFE gene and be at risk of developing hemochromatosis.
DNA Testing for Hemochromatosis
Genetic testing can be done quickly and easily using a buccal brush (cheek brush) that is included in the DNA test kit. The brush is rubbed gently inside the mouth against the cheek for 10 seconds to collect a DNA sample for testing. The sample is sent back to the laboratory using the return package provided in the kit and results are available within 7 to 14 days.
Diagnosis of Hemochromatosis After Symtoms Have Already Appeared
While DNA testing can confirm a diagnosis of hemochromatosis, other test types can be used to determine whether symptoms of the disease have already appeared, how far the disease has progressed, and what types of treatment are required.
1. Blood iron tests
There are several blood tests that can detect iron overload in the body:
A measure of the amount of iron stored in the body. Blood ferritin levels are usually high in patients with hemochromatosis. However, other factors may also cause elevated ferritin levels, including liver disease, infection, cancer, heart disease, AIDS, metabolic disorders, and inflammatory conditions such as arthritis.
A measure of the amount of iron in the blood in order to determine the amount of free or unbound iron in the body.
Total iron binding capacity (TIBC)
TIBC is a measure of the total amount of iron that can be carried in the blood by transferrin, a protein that carries iron from one part of the body to another. It is a measure how well your blood can transport iron.
Serum transferrin saturation
This test determines the percentage of the transferrin that is being used to transport iron. Transferrin saturation is calculated by dividing serum iron by TIBC. The transferrin saturation is between 20 and 45 percent in healthy individuals.
An elevated transferrin saturation percentage or serum ferritin level points to iron overload. Serum iron and transferrin saturation are abnormally high in patients who are affected by hereditary hemochromatosis.
2. Liver biopsy
Before the availability of genetic testing for hemochromatosis, liver biopsy was previously widely used to diagnose hemochromatosis. With the availability of DNA testing for hemochromatosis, liver biopsy is now rarely needed to make the diagnosis of hereditary hemochromatosis.
During the biopsy, a tiny piece of tissue is removed from the liver using a thin needle. The liver biopsy can determine the extent of liver damage and determine how much iron is being stored in the liver.
Patients with hemochromatosis who have a normal liver biopsy result can live a normal healthy life once treatment for hemochromatosis is initiated. However, if cirrhosis is already present as a result of hemochromatosis, it is too late to reverse the effects and longevity is decreased.
3. Other tests
- Liver function tests, blood sugar levels to find out whether you have diabetes or liver disease.
- Alpha-fetoprotein levels, a blood test that looks for higher levels of a protein that occurs with liver cancer.
- Electrocardiogram (ECG) to look at the electrical activity of the heart.
- CT scan, MRI, and ultrasound
Once hemochromatosis is detected, treatment is simple and effective. If hemochromatosis is detected and treated at early stages, the serious complications caused by hemochromatosis such as liver disease, heart disease, arthritis, and diabetes can usually be prevented.
Removing excess iron
Hemochromatosis is treated by removing excess iron from the body in order to bring the body’s iron level back down to normal. The excess iron is removed by removing blood or donating blood at blood banks. This process is called “phlebotomy”.
Depending on the severity of the iron overload, blood is initially taken once or twice a week for several months to a year, sometimes longer. The goal is to bring the blood ferritin down to normal levels.
Once the iron level has returned to normal, blood is removed approximately every 2 to 4 months for life. This will help to maintain iron at normal iron levels and prevent further iron build-up.
The benefits of therapeutic phlebotomy in hemochromatosis are as follows:
1. It prevents the development of liver cirrhosis and liver cancer if the disease is discovered and treated early.
2. It improves liver function in patients who have already developed advanced cirrhosis.
3. It improves and/or completely resolves symptoms of weakness, abdominal pain, joint pain, and fatigue.
4. It improves the function of the heart in patients with mild and early heart disease.
5. It prevents further accumulation of iron in organs, thus preventing further organ damage.
Effectiveness of Treatment
The outlook for people who have been detected early and treated is excellent. If the treatment is started before the organs have been damaged by iron build up, complications of hemochromatosis such as liver disease, heart disease, diabetes and arthritis can be prevented and the person can have a normal life expectancy.
The general outlook is highly dependent upon the degree of organ damage that has already occurred before treatment begins. The earlier hemochromatosis is detected and treated, the better the outcome.
People who are detected too late and begin treatment after organ damage has already occurred may have a shortened life expectancy due to complications of the damage already done to the organs. For example, when treating a person with early stage liver disease, the prognosis is good and the person is very likely able to have a normal life expectancy. However, if the liver has already been damaged by cirrhosis or scarring of the liver, the person’s chances of developing liver cancer increases significantly, even with treatment.
Diet and Lifestyle
If you have tested positive for hereditary hemochromatosis, the following recommendations for diet and lifestyle may help you to live a healthier life.
1. Do not take iron pills and multivitamin supplements that contain iron
Iron supplements can further elevate your body’s iron levels and contribute to disease. Eating foods that contain iron is fine.
2. Do not take vitamin C supplements
Vitamin C increases the amount of iron that your body absorbs from the foods that you eat. Eating fruits and vegetables that contain vitamin C is fine.
3. Limit the amount of red meat in your diet
Red meat contains a high level of iron that is easily absorbed.
4. Avoid alcohol
Alcohol increases the absorption of iron and can increase the risk of developing cirrhosis and liver cancer. Limit the amount of alcohol that you drink. If you already have liver damage, refrain from consuming any alcoholic beverages as it may cause further liver damage.
5. Avoid raw shellfish
People with hereditary hemochromatosis are susceptible to infections. Raw shellfish may occasionally be contaminated with bacteria. Cooking food at high heat destroys bacteria which is harmful to people with hemochromatosis.
6. Drink tea and coffee
Coffee and many teas (black, green, oolong) contain a chemical called tannin. Tannin helps to minimize the absorption of iron by your body.
7. Avoid foods that are enriched with iron
Avoid foods that are enriched with iron such as certain breakfast cereals, breads, and snacks.
Other Important Activities
- Get regular check-ups to monitor the amount of iron in your blood.
- Get immunized against hepatitis A and B. Hepatitis can contribute to liver disease.
- Get regular phlebotomies as needed to help control the iron levels of your body.
- Exercise regularly. Include at least 30 minutes of moderate exercises that increase your heart rate into your daily schedule.
Hereditary hemochromatosis is a deadly but treatable disease which is found predominantly in individuals of European descent. The gene mutation most commonly associated with hemochromatosis is C282Y. Almost 85 to 90% of all individuals who are clinically affected with hemochromatosis test positive for the C282Y gene mutation, and studies have shown that in non-clinically diagnosed individuals, 10 to 33% of individuals who test positive for 2 copies of the C282Y mutation eventually go on to experience the morbidity associated with hereditary hemochromatosis.
The strong genetic association of this disease with the C282Y mutation, and the striking prevalence of this mutation in individuals of European ancestry has led researchers to investigate the history of C282Y, including the location in Europe where it first originated and how this mutation eventually spread throughout Europe. To tackle this study, scientists have conducted large scale screenings for the C282Y mutation in various indigenous populations throughout Europe in an effort to pinpoint the population distribution pattern of C282Y and retrace its mode of spread.
To follow is a table summarizing the distribution frequencies of C282Y in indigenous populations in various regions of Europe:
Table 1. Population Frequency of C282Y mutation in various regions of Europe
|COUNTRY #||INDIVIDUALS SCREENED||C282Y ALLELE FREQUENCY|
|Sweden (Sami People)||151||2.0|
|UK (N.E. England)||117||7.7|
|UK (Jersey Islands)||411||8.3|
|UK (Orkney Islands)||103||4.9|
The population studies conducted to date show a very interesting and distinct distribution pattern for the C282Y marker in Europe. The highest frequencies of this mutation are found along the coastline of Europe. Furthermore, the frequency of C282Y is highest in Western Europe and declines significantly moving east. Also, the frequency is highest in Northern Europe and declines significantly moving south.
DNA studies have also shown that the C282Y mutation likely first arose in Europe approximately 60 to 70 generations ago. Assuming that each generation is 20 to 25 years, that would place the origin of this mutation to approximately 1200 to 1750 years ago, with subsequent rapid spread along the coastline of Europe and disseminating from Northern and Western Europe. The timing and pattern of spread of this mutation has a very close correlation to the migration of Vikings and locations of Viking settlements in Europe beginning around the same time, resulting in the “Viking hypothesis” for the C282Y marker which suggests that the C282Y mutation is associated with Vikings.
Further studies to investigate the “Viking Hypothesis” found that C282Y is found in greatest frequencies in regions that are known to be Viking settlements. For example C282Y is found in high frequencies in the Scandinavian countries including Iceland and the Faeoroe Island, which are known to be colonized by Vikings. Further support of the Viking Hypothesis was indicated by studies which showed that the lowest frequencies of C282Y were found in regions of Europe that were not affected by Vikings such as Central Europe, the Balkans, the Mediterranean countries and Russia.
The genetic studies to date suggest that the C282Y mutation first arose in Europe and was spread by Vikings and later by the Normans throughout Europe, indicating a genetic link between hereditary hemochromatosis and Viking ancestry. Moving forward, ongoing studies in the research community will focus on forensic DNA testing of Viking skeletons to obtain definitive proof of the origins of the C282Y mutations and solidifying a Viking link to this prominent European genetic disease.
Olsson, K., Konar, J., Dufva, I., Ricksten, A., Raha-Chowdhury, R.. (2010). Was the C282Y mutation an Irish Gaelic mutation that the Vikings helped disseminate? HLA haplotype observations of hemochromatosis from the west coast of Sweden. European Journal of Haematology, 86, 75-82.
Milman, N., and Pedersen, P.. (2003). Evidence that the Cys282Tyr mutation of the HFE gene originated from a population in Southern Scandinavia and spread with the Vikings. Clinical Genetics, 64, 36-47.