Haemochromatosis, or GH (Genetic Haemochromatosis, is a genetic disorder causing the body to absorb an excessive amount of iron from the diet: the iron is then deposited in various organs, mainly the liver, but also the pancreas, heart, endocrine glands, and joints.

Normally the liver stores a small amount of iron for the essential purpose of providing new red blood cells with iron, vital for health. When excessive quantities of iron are stored in the liver it becomes enlarged and damaged. Deposits of iron may also occur in other organs and joints, causing serious tissue damage.

For a long time it was believed that the disorder was rare, so GH was seldom considered as a possible diagnosis. However, recent surveys of people of Northern European origin have shown a prevalence of 1 in 400 likely to be at risk of developing iron overload. GH is now recognised as being one of the most common genetic disorders.

The Society was set up to provide support and information for those affected by GH. Members recieve information leaflets, treatment record cards, a 'handbook', quarterly newsletter and the opportunity to attend the AGM and hear medical professionals give their updates. More information on the society follows.

WHAT ARE THE SYMPTOMS?

Chronic fatigue, weakness, lethargy
Abdominal pain; sometimes in the stomach region or the upper right hand side, sometimes diffuse
Arthritis; may affect any joint but particularly common in the knuckle and first joint of the first two fingers
Diabetes (late onset type)
Liver disorders; abnormal liver function tests, enlarged liver, cirrhosis
Sexual disorders; loss of sex drive, impotence in men, absent or scanty menstrual periods and early menopause in women, decrease in body hair
Cardiomyopathy; disease of the heart muscle (not to be confused with disease of the arteries of the heart)
Neurological/psychiatric disorders; impaired memory, mood swings, irritability, depression
Bronzing of the skin, or a permanent tan

Most of these symptoms are found in other disorders. Chronic fatigue may be ascribed to after-effects of a viral infection or to psychological causes, and abdominal pain to irritable bowel syndrome. Similarly liver disorders may be put down to excessive alcohol intake, even in someone who is only a moderate drinker. However, if the above symptoms are present, GH should also be considered as a diagnosis.

Most individuals who have GH will, in due course, develop at least one or two of the above symptoms, although possibly in a very mild form. There may be a long phase of the condition where there are no symptoms. However, if arthritis is found only in the first two finger joints this is highly suggestive of GH.

HOW IS HAEMOCHROMATOSIS INHERITED?

Inherited disorders are caused by defective genes in the cells which make up the body. Genes, which are made of DNA, contain the information the body needs to develop from the egg and to maintain itself in good working order. There are about 30,000 genes and every cell in the body, except sperm and egg cells, contains two copies of each. One of these copies is inherited from the mother and one from the father.

In 1996 the HFE gene was identified as the major gene affected in Haemochromatosis. A small change (mutation) is present in both copies of the gene in over 90% of those diagnosed with GH. GH is a 'recessive' disorder. The risk of absorbing excess iron will only occur if both copies of the gene are abnormal. If only one copy is defective, an individual will be perfectly healthy but will be a 'carrier'. This means he or she will be able to pass on the abnormal gene to a son or daughter.

Sperm and egg cells have only one copy of each gene, and on average half the eggs or half the sperm of a carrier will contain the defective version. By contrast, ALL the eggs or sperm of an individual in whom both gene copies are defective and who, as a result, suffers from GH, will carry the abnormal gene.

To develop GH you have to inherit a defective gene from both your parents. This can happen in three ways:

It should be emphasised that the proportions given in examples 1 and 2 are averages for the whole population: in any particular family where both parents are carriers (example 1) it would be possible for all children to be affected, all to be carriers, or for all to be normal.

WHAT ARE THE DIAGNOSTIC TESTS?

WHAT IS THE TREATMENT ?

The simple and effective treatment consists of regular removal of blood. Known as venesection therapy or phlebotomy, the procedure is the same as for blood donors. Every pint of blood removed contains a quarter of a gram of iron. The body then uses some of the excess stored iron to make new red blood cells. Venesection will usually be performed once a week, depending on the degree of iron overload. Treatment may need to be continued at this frequency for up to 2 years, occasionally longer. During the course of treatment, the serum ferritin levels are monitored, indicating the size of the remaining iron stores. Treatment should usually continue until the serum ferritin level reaches 20µg/l (indicating minimal or absent iron stores).

This is not the end of the story. Excess iron will continue to be absorbed so the individual will need occasional venesections (maintenance therapy), on average every 3 to 4 months, for the rest of his or her life. Monitoring of transferrin saturation and serum ferritin is used to assess whether venesection is required more or less often. The transferrin saturation should be maintained below 50% and the serum ferritin below 50µg/l.

HOW EFFECTIVE IS THE TREATMENT?

Venesection treatment will cause tissue iron to be mobilised and iron stores will return to normal. However, it will not cure some serious clinical conditions such as diabetes or cirrhosis if they are already present at the time treatment is started. This emphasises the need for early diagnosis.

Fatigue, lethargy and abdominal pain should decrease.
Cardiomyopathy should improve providing cardiac damage is not severe. In severe cases iron chelation treatment can reverse congestive heart failure.
Bronzing of the skin should fade.
Cirrhosis will stay the same.
Sexual dysfunction and arthritis do not usually improve. Indeed arthritis may appear later even if absent at the time of diagnosis and treatment.
Providing there is not a massive, long-standing iron overload present at the time treatment is started; those who undergo treatment have a normal life expectancy.

WHAT ABOUT DIET?

It is not possible to treat GH with a low iron diet. A nutritional natural diet is recommended. As some foods affect the way the body absorbs iron, we suggest you:

+ Avoid vitamin supplements or tonics containing iron, and breakfast cereals heavily fortified with iron. Large doses of vitamin C should also be avoided, as it makes the process of depositing iron in some organs easier and enhances the absorption of iron from the diet.
+ Reduce intake of offal (liver, kidney etc.) and red meat. The rate of iron absorption from red meat is 20 to 30% whereas vegetables and grains have less iron and a 1 to 20% rate of absorption.
+ Minimise alcohol intake, particularly with meals, as it may increase iron absorption and it can also cause liver disease. Tea and all milk products taken with a meal reduce the amount of iron absorbed.

Our Aims

+To SUPPORT people with GH by providing help with their problems and ensuring that their relatives are tested in due time. The quarterly newsletter provides news and views from members in the UK and from around the world. Opportunities to meet other members living nearby are arranged if they wish.

+To promote AWARENESS among the health professions, patients and their families, the general public and policy makers so that the condition may be diagnosed and treated in time. There is also a need to overcome the misconceptions that GH is rare, that only middle-aged men are at risk, and women are seldom affected until their menopause.

+To encourage and support RESEARCH, and provide resource material for the allied medical professions. The Society keeps up to date on the latest studies.

Medical Advisors
Professor T. M. Cox, University of Cambridge School of Clinical Medicine
Dr. J. S. Dooley, Centre for Hepatology, The Royal Free Hospital, London
Professor M. J. Pippard, Ninewells Hospital and Medical School, University of Dundee
Professor R. Williams, CBE, Director of the Institute of Hepatology, University College London Medical School

Scientific Advisor
Professor M. Worwood, University of Wales College of Medicine, Cardiff