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Haemochromatosis, also spelled hemochromatosis, is a hereditary disease characterized by improper processing by the body of dietary iron which causes iron to accumulate in a number of body tissues, eventually causing organ dysfunction. It is the main iron overload disorder.
Haemochromatosis is notoriously protean, i.e. it presents with symptoms that are often initially attributed to other diseases.
Symptoms may include:
Males are usually diagnosed after their forties, and women about a decade later, owing to regular iron loss by menstruation (which ceases in menopause).
A first step is the measurement of ferritin, the tissue form of accumulated iron which is shed into the blood. Other markers of iron metabolism are the iron carrying protein transferrin (decreased), transferrin saturation (increased) and serum iron (increased).
When these investigations point at Haemochromatosis, it is debatable whether a blood count, renal function, liver enzymes, electrolytes, glucose (and/or an oral glucose tolerance test (OGTT)).
Based on the history, the doctor might consider specific tests to monitor organ dysfunction, such as an echocardiogram for heart failure.
Haemochromatosis is one the most common inheritable genetic defects, especially in people of northern European extraction, with about 1 in 10 people carrying the defective gene. The prevalence of haemochromatosis varies in different populations. In Northern Europeans it is of the order of one in 400 persons. Other populations probably have a lower prevalence of this disease. It is presumed, though genetic studies, that the "first" haemochromatosis patient, possibly of Celtic ethnicity, lived 60-70 generations ago. Around that time, when diet was poor, the presence of a mutant allelle may have provided a heterozygous advantage in maintaining sufficient iron levels in the blood. With our current rich diets, this 'extra help' is unnecessary and indeed harmful.
Mutations of the HFE gene account for 90% of the cases. Homozygosity for the C282Y mutation is the most important one, although the H63D mutation can contribute to disease (substantially less than C282Y). Carriers of a single copy of either gene have a very slight risk of haemochromatosis when other factors contribute, but are otherwise healthy. Even if an individual has both copies of the abnormal gene the risk of actual clinical haemochromatosis is still quite low (? about 20%). This is called incomplete penetrance.
Other genes that cause haemochromatosis are the autosomal dominant SLC11A3/ferroportin 1 gene and TfR2 (transferrin receptor 2). They are much rarer than HFE-haemochromatosis.
Recently, a classification has been developed (with chromosome locations):
The normal distribution of body iron stores
People with the abnormal genes do not reduce their absorption of iron in response to increased iron levels in the body. Thus the iron stores of the body increase. As they increase the iron which is initially stored as ferritin starts to get stored as a breakdown product of ferritin called haemosiderin and this is toxic to tissue.
Early diagnosis is important because the late effects of iron accumulation can be wholly prevented by periodic phlebotomies (comparable in volume to blood donations). Treatment is initiated when ferritin levels reach 300 micrograms per litre (or 200 in nonpregnant premenopausal women).
Every bag of blood (450-500 ml) contains 200-250 milligrams of iron. Phlebotomy is usually done at a weekly interval until ferritin levels have returned to normal. After that, 1-4 donations per year are usually needed to maintain iron balance.
Other parts of the treatment include:
According to some, a one-time study of iron levels early in adult life would be sufficient to evaluate an individual. There is, however, a tendency for iron to accumulate over time. It is therefore doubtful whether screening should be undertaken at all, irrespective of timing problems. Only the most severe cases would be detected by a one-time ferritin check.
There exist other causes of excess iron accumulation, which have to be considered before Haemochromatosis is diagnosed.
The disease was first described by diabetes: Glycosurie, diabète sucré. Clinique médicale de l'Hôtel-Dieu de Paris, 2nd ed, Paris, 1865, 2: 663-698. He did not make the link with iron accumulation. This was done by cirrhosis
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