Too much or too little iron?

In general, people have a reasonable level of awareness about iron deficiency, which can lead to anaemia (a low number of red blood cells). However, iron overload (haemochromatosis) is a hereditary, or genetic, condition that affects one in 200 New Zealanders - it is far less well recognised, and it is reportedly underdiagnosed (on average, in New Zealand, it takes six years after the first GP visit for correct treatment to be started).

The symptoms of lethargy and fatigue are common to both iron deficiency and iron overload (and many other conditions), but if left untreated iron overload can have some serious long term health effects.

To complicate matters, anaemia (low red blood cell count) is not always necessarily due to iron deficiency; some types of anaemia actually cause iron overload, so it is possible to have both iron overload and anaemia at the same time. This makes accurate diagnosis by a doctor and blood iron testing crucial - mistakenly taking iron supplements for 'tiredness' when iron overload, and not anaemia, is behind the problem will make matters worse.

Who will have iron overload?

Most people absorb only as much iron as they need from iron-rich foods such as meat, seafood, grains and green vegetables, and the rest passes through the body. But about one in 200 New Zealanders has the disease called iron overload, or genetic haemochromatosis, a condition in which the body takes in and stores too much iron from the diet.

Because of the chemical properties of iron, it cannot be broken down and eliminated from the body. Haemochromatosis is genetic or acquired; it is not an infectious disease and therefore cannot be transmitted from one person to another.

Genetic haemochromatosis is hereditary - a mutated HFE gene is believed to be the cause. It is the most common genetic disease in the world - 38% of people of Celtic, Anglo and Northern European descent (according to a recent Christchurch study) have a mutated HFE gene, but they may not all have the disease itself.

There are no reliable estimates of how many Maori or Pacific Island people are affected, but the likelihood of iron overload is thought to be similar, particularly if there is a mixed racial background.

One in 200 people (0.5%) have two copies of this abnormal gene, one from each of their parents. Having two copies of the mutated gene is closely linked with developing iron overload - however, at present, a lot of these people have not been diagnosed as having iron overload (they are still 'accumulating' iron) or have not had iron-related health problems (if present) correctly diagnosed.

Males and females of all ages are prone to iron overload.

Some people with just one abnormal HFE gene may still develop symptoms of iron overload. This can happen if they are taking iron supplements or are eating a diet high in iron. Also, the causes of iron overload are still not fully understood and it appears there may be several other genes involved, some still unidentified, which may act together with the HFE gene to cause the disease.

Several other disorders can cause iron overload. These are much less common than genetic haemochromatosis, but it is also possible to have one or more of them as well as having genetic haemochromatosis. But whatever the cause, the long term consequences and the necessary treatment remain the same.

What is iron overload?

In small amounts, iron is essential for our bodies to work normally. Its main role is in forming haemoglobin (the molecule that binds oxygen) in red blood cells, which carry oxygen around the body. A normal diet contains more iron than we need and most of us absorb only as much as we need when food is digested in the intestine.

When too much iron is taken up it slowly builds up in various parts of the body, including the liver, heart and pancreas gland, and it becomes toxic to these organs. Eventually, these organs may become permanently damaged by the excess iron in them.

It is often many years before a person has any symptoms of iron overload, and when problems do arise the symptoms are frequently very vague and can be confused with those of many other conditions, including anaemia.

What are the symptoms?

Common persistent symptoms include:

• extreme tiredness
• general poor health
• weight loss
• joint pains
• pains in the belly
• loss of sex drive
• sometimes the skin has a 'sun-tanned' colour - it may take on a slate-grey or bronze appearance without sun exposure

Not every person with iron overload will have all of these symptoms, and often they can be mistaken for other conditions such as arthritis, stomach ailments or chronic fatigue syndrome.

What are the consequences of iron overload?

Having excess iron hinders the body's immune system, leaving a person prone to infections and illness. People who have iron overload at the same time as fighting other diseases (eg, cancer, hepatitis and AIDS) do not progress well until their iron level has been lowered.

If after prolonged iron overload the pancreas is affected, diabetic complications may occur. Heart problems such as angina, poor heart rhythm and shortness of breath can also happen. If the liver is affected, cirrhosis (which, if untreated, can lead to cancer) is also a possibility.

Other effects caused by having a high iron level over a long period include spleen problems, depression and neurological problems, and infertility. These conditions are not usually noticed before the age of 40 but can be prevented if iron overload is diagnosed and treated early on.

How is iron overload diagnosed?

When iron overload is suspected the diagnosis is first made using blood tests - an iron saturation test and a serum ferritin test. Most people with iron overload have an increased iron saturation (over 44%) and/or a raised serum ferritin level (over 150) which measures the amount of stored iron. The first of these two is the more specific test however.

For those with blood test results that suggest iron overload, a four to six week trial period of treatment (quantitative venesection) will make a 100% correct diagnosis of genetic haemochromatosis. Going through with this testing is important as early diagnosis can allow long term treatment to begin and organ damage to be prevented.

What is the treatment for iron overload?

Once diagnosed, iron overload is completely preventable. If it is detected before any damage to the body's organs has been caused by the toxic effects of a long term high iron level, then regular treatment to keep iron levels within a safe limit should ensure there is no future damage and will enable a normal life expectancy.

If damage to organs has occurred it is likely to be permanent and any additional treatment will depend on the type of damage caused. Therefore, a swift diagnosis of iron overload and quickly starting treatment to reduce iron levels and avoid future organ damage are high priorities. (There is no benefit in waiting to determine the exact genetic cause - the treatment is the same.)

Iron overload cannot be controlled by altering your diet, if you have genetic haemochromatosis. A balanced diet (including a little red meat) is recommended for general good health - but avoiding alcohol, vitamin C and multivitamin pills, and obviously iron supplements and or iron-fortified foods. Drinking tea with meals also helps by hindering iron absorption. (These diet changes should only be considered, together with your doctor, once he or she has determined whether you actually have iron overload.)

When iron overload is first diagnosed it may be necessary to remove about half a litre of blood every week for up to two years. Once the excess stored iron has been lowered, blood is removed three or four times a year, and your blood ferritin level will be measured regularly to make sure it stays at a safe level.

The New Zealand Blood Donor Service now accepts donations from people diagnosed with haemochromatosis as long as it meets all the normal criteria for safety. Until recently, most blood banks were throwing away such venesected blood, even though there are severe shortages.

Treatment: venesection

The treatment for keeping iron levels from increasing to unsafe levels is lifelong. It involves having blood taken out of the body (venesection), just like being a blood donor. When blood is removed, the body's response is to make more red blood cells to replace it, thus using up some of the stored iron.

Screening

Gene testing is available but it is not 100% accurate because many of the genes involved have not yet been identified. Therefore, routine screening is not recommended - you may have iron overload but the available gene tests can miss it.

If your close family members are known to be genetic carriers for iron overload (haemochromatosis), or have iron overload, you should ask your doctor about getting an iron studies and ferritin blood test done. The severe effects of long term iron overload can be avoided with advice and treatment, and diagnosis is easy and cheap.

If everyone had an iron test done each year, with treatment when necessary, no one would need to suffer the symptoms of iron overload.

Liver biopsy is not recommended. It is an invasive process and so it carries a level of risk, but it does not change how the patient is to be treated. Newer imaging techniques offer more information non-invasively.

Original material provided by New Zealand Haemochromatosis Support and Awareness Group and edited by everybody. Last updated August 2009.