AUSTRALIAN GASTROENTEROLOGY INSTITUTE (educational arm of the Gastroenterological Society of Australia)Website: www.gesa.org.au ... Copies reviewed November 2001HAEMOCHROMATOSIS(Inherited Iron Overload Disease)IntroductionIron in small quantities is essential to life, particularly for the function of haemoglobin, the blood protein which carries oxygen to the tissues. Normally iron is taken into the body from food via the intestine (known as "absorption"). Once the iron is absorbed the body has no way of getting rid of excess iron. Some people have a disease called haemochromatosis in which too much iron is absorbed. If this disease is not diagnosed and treated, iron can damage vital organs and shorten a person's life.What is Haemochromatosis?Haemochromatosis is a genetic (family inherited) disorder in which too much iron is taken into the body over and above the needs of the body. It is caused by an abnormal gene, recently described and called the HFE gene.A gene is a code for a family likeness or characteristic. There are millions of genes located on our 23 pairs of genetic material (called chromosomes) that we inherit from our parents, half from each parent.Individuals inheriting one haemochromatosis gene and one normal gene are called carriers. Their iron absorption may be slightly higher than normal but most do not absorb enough iron to cause any significant health problems. If two carriers marry, each of their children has a 25% chance of inheriting two haemochromatosis genes and a 50% chance of inheriting one haemochromatosis gene. Carriers can now be identified by a new gene test for the HFE gene.Individuals inheriting two haemochromatosis genes will absorb far too much iron. This iron slowly builds up in the liver, heart, pancreas and other hormonal glands and joints. It takes many years to build up iron to a level which causes damage to these organs, but by the time the damage occurs, it is often too late for the organ to repair itself and some permanent damage may remain.How common is Haemochromatosis?About one person in every 300 has the disease haemochromatosis while about 12% of our Australian population are carriers of one haemochromatosis gene. This means that in a city of the size of Sydney there are approximately 12,000 people affected by the disease and 400,000 people carrying one haemochromatosis gene. This makes haemochromatosis one of the commonest genetic diseases in our society, although many people are only mildly affected.What are the symptoms Haemochromatosis?Symptoms vary considerably among patients. The symptoms resemble those of many other medical conditions, making diagnosis difficult. The symptoms may include fatigue, weakness, weight loss, abdominal discomfort and joint pain. A tanned appearance, not due to sun exposure, may also occur. Other symptoms may develop later as a result of organ damage to the liver, heart (palpitations, shortness of breath, chest pain), pancreas (thirst or frequent urination as a result of diabetes), or other hormonal deficiencies (loss of sex drive or body hair). However, most young people with the disease have no symptoms or only minor symptoms in the early stages of the disease.Who may be at risk of Haemochromatosis? · Blood relatives of patients (particularly close relatives such as brothers, sisters and children). · Individuals with symptoms of the disease. · Individuals with diabetes, arthritis and certain heart problems. If you have some of the symptoms mentioned above, do not overreact and conclude that you have haemochromatosis because there are many other causes for such symptoms. See your family doctor and discuss your concerns.How is the diagnosis made?A blood relative of someone with haemochromatosis should have a simple blood test for the HFE gene to see if they are at high risk of haemochromatosis. This blood test is available (after discussion with your general practitioner) through usual pathology laboratories. In people without any family history of haemochromatosis, the two most useful initial blood tests are: · Serum transferrin saturation (best test). · Serum ferritin (may be normal early in the disease). These tests can be done on the one sample of blood. If the tests are abnormal on at least two occasions, a further blood test looking for the HFE gene may be all that is required to confirm the diagnosis of haemochromatosis. Some patients will require a liver biopsy to confirm the diagnosis and/or assess the degree of damage to the liver. Liver biopsy involves removal of a small piece of liver with a needle under local anaesthetic. It is a safe procedure when done by a medical practitioner experienced in the technique.Screening of relativesAfter a diagnosis of haemochromatosis is made, all close relatives over the age of 10 years should be screened for haemochromatosis. Close relatives include brothers, sisters, parents and children. Cousins, aunts and uncles should also be tested, although the risk is much lower. Family screening will include an examination by a doctor, with blood testing as described above, to determine which family members are likely to have the disease. In some cases, blood tests will need to be repeated in 2 years as sometimes the excess iron does not become apparent until later life. Early diagnosis and treatment of family members with the disease is essential to prevent organ damage.Is there are treatment?Yes, By removing about 500ml of blood, as in blood donation, usually once a week, the body is stimulated to make more blood and this uses up the excess iron. This is called "venesection treatment". Depending on the amount of iron in the body, the initial treatment may take one or two years. Blood tests are done to monitor the iron removal. Once the excess iron has been removed, venesections are done about four times a year to prevent iron building up again.Treatment should continue for the rest of the person's life.Venesection treatment must only be done by medical or nursing staff experienced in this technique. Venesections can be done at some hospitals, some pathology laboratories or some general practices. On occasions, venesections can be organised through blood banks, after referral from a specialist. Immediately prior to a venesection, rest for 15 minutes and drink 500ml of fluid. After the venesection, stand up slowly and sit in a chair for 15 minutes, keeping pressure on your arm for 5 minutes where the needle was inserted.How effective is the treatment? What is the outcome?There is good evidence that with removal of excess iron, patients feel better, stronger, their tan colour lessens, liver size decreases, diabetes may improve and heart function improves. If treatment has been commenced early, damage to the liver and other organs may be completely prevented. If cirrhosis (liver scarring) is present it is usually not reversed by treatment, but should not get worse. Without venesection treatment, iron continues to build up and organ damage continues. It is not possible to treat haemochromatosis with a low iron diet, since iron is present in most foods, and it is the iron already in the body which will cause damage. However, it is advised that patients with haemochromatosis do not take iron tablets of any type, nor vitamin tablets containing iron or vitamin C (ascorbic acid) as vitamin C can increase iron absorption. People with haemochromatosis may also consider reducing red meat intake (eg. to approximately 90-120 g/day). Alcoholic drinks in small quantities (eg. two glasses or less per day) are not usually harmful, but if there is liver damage your doctor may advise you to have no alcohol.Are there support groups?Yes. Some large hospitals have support groups for patients and relatives with liver diseases and haemochromatosis. If not, you could contact the :Haemochromatosis Society of Australia,412 Musgrave Road,Coopers Plains,QLD, 4108Tel: (07) 3345 7583)or the Australian Gastroenterology Institute:145 Macquarie Street,Sydney,NSW, 2000This brochure is provided as a public service and was prepared by an expert committee of the Australian Gastroenterology Institute and endorsed by the Australian Liver Association.First Edition 1992; Second Edition 1999.Lifting an iron curtainIron is an essential nutrient for most cells, because iron-containing proteins are necessary to produce energy. Iron-overload, however, can damage most organs, and so cells need a way to fine-tune levels of iron. Excess iron in nerve cells has been implicated in many neurodegenerative human disorders, including Parkinson's disease and Friedreich's Ataxia. Mice have now been engineered to lack a gene (IRP2) involved in iron metabolism. These mice show progressive deterioration of the nervous system like that seen in people with Multiple System Atrophy (also known as Parkinson's Plus). However, the damaged brain areas in people affected by other iron-overload-related conditions differ from those in the mice. So it is unlikely that IRP 2 is involved in these human diseases. However, the finding suggests that the study of other genes involved in iron metabolism may provide clues to the causes of these disorders.Nature Genetics, February 2001 http://www.simr.org.uk/pages/advances/02-2001/Iron overload linked to liverLike most nutrients, iron is good for people - in the right doses. When the body has enough iron, our cells stop absorbing it from food; if there is too little, they absorb more. This system breaks down in the most common inherited disease in the Western world: haemochromatosis, which affects about one in every 250 people and is often fatal if it is not recognised and treated. Sufferers of haemochromatosis have inherited a defective copy of a gene called Hfe from each parent. The new study, involving DNA "chips" and mice, shows that the link between Hfe and iron is probably in the liver, rather than the intestine. The study is changing our understanding of how haemochromatosis develops. The scientists developed strains of mice without Hfe, or with the mutant version found in haemochromatosis. Both strains absorbed too much iron and exhibited the symptoms of the disease. The DNA chips were used to compare cells taken from these mice and their healthy cousins. They discovered that a molecule called hepcidin in the liver wasn't being activated properly. Nature Genetics May 2003http://www.simr.org.uk/pages/advances/2003/may/ Notice: Microsoft has no responsibility for the content featured in this group. Click here for more info.
| |
|
|
