Iron overload disease

Iron overload disease, or haemochromatosis, is a disorder in which the body absorbs too much iron.

Alternative names

haemochromatosis, iron storage disease

What is iron overload disease?

Iron is an essential mineral for normal functioning of the body, but it can also be toxic in excessive quantities. Iron overload disease, or haemochromatosis, is a disorder in which the body is unable to regulate iron absorption, with the result that excess iron accumulates in the body.

Over time, as too much iron builds up in the tissues, it can damage many parts of the body, such as the joints and organs like the liver, pancreas and heart. Left untreated, iron overload can lead to a variety of serious medical problems, including heart disease, diabetes, liver cancer and arthritis.

What causes iron overload disease?

Iron overload disease may be caused by several different genetic or acquired disorders.

Genetic causes

Most cases of iron overload are the result of genetic disorders. Iron overload disease caused by genetic abnormalities is called hereditary haemochromatosis.

Mutations (changes or defects) of one specific gene, HFE, account for about 80 percent of all iron overabsorption disorders. It seems that this abnormal gene carries the “blueprint” for the production of a defective protein that causes the gut to absorb too much iron. The excess iron then enters the bloodstream and eventually gets deposited in different parts of the body.

People inherit two copies of most genes, one from each parent. If you inherit two copies of the defective HFE gene, your risk of developing iron overload disease is very high. If you only inherit one defective copy, you are a “carrier” i.e. you can pass the defective gene on to your children, but you are unlikely to suffer any symptoms yourself. However, some studies have shown that carriers have above average concentrations of iron in their blood, which could increase their risk for iron overload, and might be problematic if they suffer from another liver-damaging disease, such as hepatitis or alcoholism.

Nongenetic causes

Haemochromatosis is only one of several iron loading diseases. A number of other causes of excess body iron have been found, including chronic liver disorders caused by hepatitis, alcoholism and other metabolic disorders; frequent blood transfusions and disorders that cause chronic anaemia. Iron overload can also be caused by excessive dietary iron intake from, for example, supplements and fortified foods.

Who gets iron overload disease and who is at risk?

Public health studies suggest that between one and 10 percent of people have excess iron in their bodies.

Iron overload may be as high as 30 percent in some specific groups:

• Caucasians i.e. people of European descent
• People with chronic hepatitis
• People who have received multiple blood transfusions
• Hispanics
• African Americans
• Black races from Africa

The HFE gene defect is one of the most common human genetic disorders known: between one in 8 and one in 10 people are carriers, and about one in 200 individuals have the double defective gene for hemochromatosis. Siblings of people diagnosed with the disorder have a 25 percent chance of developing the condition.

Although the HFE gene defect occurs with the same frequency in both males and females, men are likely to develop symptoms of iron overload earlier than women. Typically, symptoms first appear in men between the ages 30 and 50 and after age 50 (after menopause) in women. It seems that since women lose iron through blood loss during menstruation, they will develop organ damage from iron accumulation on average 15 to 20 years later than men.

Symptoms and signs of iron overload disease

Initial symptoms of iron overload disease may be vague, and may be similar to those of many other conditions. Common early symptoms may include:

• Fatigue and lack of energy
• Abdominal pains
• Joint pain (especially in the hands, feet, hips and knees)
• Chronically sore muscles
• Decreased sex drive
• Heart problems
• Unexplained weight loss

Many people with iron overload disease have no symptoms.

Numerous other symptoms may occur as iron accumulates in different parts of the body and leads to a variety of serious complications.

Complications of Iron Overload Disorder

Examples of conditions that result from iron deposition in the following organs and tissues:

• Liver: scarring of the liver (cirrhosis), hepatitis and increased risk of liver cancer and liver failure.
• Pituitary gland and testicles: shrinkage of the testicles, impotence and sterility.
• Pancreas: decreased insulin production resulting in diabetes mellitus.
• Heart: congestive heart failure, irregular heartbeat and atherosclerosis.
• Skin: bronze or gray discoloration.
• Joints: arthritis.
• Brain: Excess iron may possibly play a role in certain psychological problems.
• Hypothyroidism – as a result of deposition in the thyroid

How is iron overload disease diagnosed?

Until recently, health professionals thought that iron overload disease was a very rare disorder, and did not screen for it regularly. As a result, and also because its symptoms may be vague and variable, it has often gone undiagnosed. Research estimates that 90 to 95 percent of people with iron overload have not been diagnosed or treated. Diagnosis previously relied on symptoms of end-stage disease, but nowadays iron overload disease can be diagnosed long before the serious associated conditions develop.

Medical and family history, physical examination, and routine blood tests may help identify iron overload as the cause of symptoms. However, a transferrin saturation test is usually used to screen for early-stage haemochromatosis. This test measures levels of blood iron and ferritin (a blood protein that indicates the amount of iron stored in the body), which are usually high in people with hemochromatosis.

A liver biopsy (tissue sample) or genetic testing may be appropriate to confirm the diagnosis.

A more accurate test for iron overload is measuring the iron content of liver tissue obtained by a biopsy. The liver is usually the first organ to accumulate excess iron, which can eventually lead to cirrhosis and liver cancer. The doctor numbs the area with local anaesthetic, and then inserts a needle through the right lower rib cage into the liver, sometimes using ultrasound for guidance. The sample obtained is studied under a microscope for liver damage, and its iron content measured.

Imaging procedures, such as magnetic resonance imaging (MRI) or computed tomography (CT) scans, may also help determine if iron accumulation has occurred in different organs.

If the cause of the condition is genetic, a DNA test for the HFE gene mutation can help to confirm diagnosis and be used to screen family members. A diagnostic service for hereditary haemochromatosis has recently been established in South Africa. If you are diagnosed with or suspected to have iron overload disease, then all your blood relatives should also be screened for the disorder. Relatives can be diagnosed with 100% accuracy. The procedure is fairly simple and inexpensive.

Additional tests and procedures may be necessary to assess advanced tissue complications caused by iron overload, and to decide on appropriate treatment for these.

How is iron overload disease treated?

Phlebotomy

Iron overload disease can be simply and effectively treated using a procedure called phlebotomy, in which blood is regularly withdrawn from the arm veins to reduce excess iron stores in the body. Phlebotomy is similar to donating blood: it can be done at a blood bank or outpatient clinic, and the amount you give is the same (a pint, or about half a litre). The difference is that phlebotomy is usually done once or twice weekly, and continues for several months until your blood iron levels test normal, or even slightly below. Your doctor will also check that your levels of ferritin return to the lower end of the normal range, so that there is no danger of iron reaccumulating. Once these levels are reduced, you will begin maintenance therapy, giving blood every one to four months. This therapy must be continued for life if the consequences of the disease are to be avoided. Sometimes a long-term catheter is placed in a blood vessel to assist with the phlebotomy procedure.

Hormones and medications may also be used to speed removal of iron from your system.

Diet

Diet modification can help reduce iron absorption and achieve normal body iron levels. If you have iron overload disease, you should avoid iron-rich foods, iron supplements and vitamin C supplements (vitamin C increases iron absorption). You should also avoid eating raw shellfish, which may be infected with bacteria to which people with iron overload are particularly susceptible.

In addition to iron level reduction, you should also receive treatment for any of the complications of iron overload.

Can iron overload disease be prevented?

Iron overload disease is fully preventable when it is diagnosed and treated early enough. The availability of the effective screening blood test and the identification of the haemochromatosis gene have made widespread testing possible.

If you are a blood relative of someone with iron overload, you should be checked for the disorder every time you have a general medical examination (at least once a year) for the rest of your life. Some medical experts are even recommending that blood iron and ferritin levels be included in routine screening blood tests for all adults.

There is debate as to whether there should be widespread genetic screening for the defective HFE gene. Not everyone with hereditary hemochromatosis has the same gene mutation. For example, people of African descent are more likely to have African iron overload disease, which seems to be caused by a different mutation. It is also not clear that everyone with a pair of the defective genes will develop the disease.

It is not effective (or wise) to try to prevent the disorder by cutting down on iron in the diet, unless you have been diagnosed with iron overload and instructed to do so by your doctor. Some iron is vital for health, and many high iron-content foods contain other important nutrients. It is important not to take excessive amounts of iron supplements, however.

Greater awareness of this disorder by both the public and health professionals could lead to earlier treatment and avoidance of serious illness.

What is the outcome of iron overload disease?

When iron overload disease is diagnosed early, it is easily treated and damage to organs can be completely prevented. You can return to normal health and enjoy a normal life expectancy. The tendency to overabsorb iron will remain, but maintenance treatment can ensure that the iron does not reaccumulate.

Undetected and untreated excess iron eventually kills after inflicting injury to a variety of body organs. The outcome for people who already have organ damage at the time of diagnosis depends on the severity of the damage. Usually, further damage can be prevented by removing the excess iron as quickly as possible. Sometimes the damage can even be reversed. In people where the disease has caused cirrhosis, treatment can still improve other problems such as heart function, skin colour and diabetes. The cirrhosis is irreversible, however, and the risk of developing liver cancer remains high, even once excess iron is removed and the iron level is normalised. About 25% of people with haemochromatosis who have cirrhosis develop liver cancer, and treatment should include monitoring for this.

Very advanced organ damage may require transplantation. Organs most likely to be transplanted as a result of iron overload are the liver, heart and pancreas. Joint replacement may be necessary in advanced cases of arthritis.

Excess iron can also compromise the immune system. Many diseases, such as AIDS, cancer and hepatitis, will have a poor outcome unless excess iron is removed.

When to call the doctor

Consult your doctor if you are concerned that you may have symptoms of iron overload disease, if you are a blood relative of someone who has been diagnosed with the condition, or if you would like to know more about the screening process.

(Reviewed by Prof. Don du Toit, University of Stellenbosch)