What is haemochromatosis?

Haemochromatosis is a hereditary iron storage disease which can lead to chronic damage to important organs. Iron storage disease means that the body stores too much iron. The hereditary form of haemochromatosis is by far the most prevalent hereditary disease in our latitudes. Every 10th person is a carrier of a mutated gene and one in 200 - 400 has an increased risk of developing the disease.

Normally the iron balance of the body is in exact equilibrium i.e. the quantity of iron which is absorbed from the food (ca.1-2 mg) matches the amount that is lost by excretion. In hereditary haemochromatosis there is a chronic positive iron balance since the body continuous to absorb excessive amounts of iron (4-5 mg) despite the filled iron stores. This excess iron can neither be utilized nor excreted and must therefore be deposited in various tissues (liver, heart, pancreas, pituitary gland and joints). After a time severe cell damage occurs which can finally lead to liver cirrhosis, diabetes, joint pain and a bronze discolouration of the skin in old age. 

	Figure: In haemochromatosis the inner organs such as the liver shown here have a dark red-brown colour. Figure by courtesy of Dr. T. Takahashi, Third Department of Internal Medicine, Niigata University School of Medicine, Niigata, Japan.

What is the cause of hereditary haemochromatosis?

The disease is caused by an increased absorption or iron from the upper small intestine. This is due to a mutation in the genetic material, the so-called Hfe gene.
A mutation is the technical term used to describe a change in the blueprint of certain genes compared to the original version. Each person always has two genes (chromosomes) for a particular trait one of which is inherited from the mother the other from the father. If both genes are identical for this trait, then it is referred to as homozygocity. If they are different the carrier is heterozygous for this trait. The hereditary disease is usually more pronounced in homozygous carriers compared to heterozygotes.

There are two clinically relevant mutations for haemochromatosis which can nowadays be detected with the GenoType® Hereditary Haemochromatosis test.

What are the symptoms of hereditary haemochromatosis?

First uncharacteristic symptoms are often described by the affected individuals as tiredness, depression, irritability, abdominal pain, susceptibility for infections and impotence.
The persistent deposition of iron in the organs results in many clinical symptoms particularly in patients that are more than 40 to 50 years old. The excessive amount of iron deposited in the liver damages the liver cells and the normal liver tissue is replaced by scar tissue which is referred to as cirrhosis of the liver. Excessive depositing of iron also occurs in the pancreas which damages the insulin forming cells. This results in the development of a so-called "bronze diabetes". Other symptoms are cardiac dysrhythmia, bronze skin colour and joint pain. Men are affected about 10-times more frequently and at an earlier age than women since women suffer from iron loss during menstruation, pregnancy and breast feeding. 

Treatment of haemochromatosis

The treatment of haemochromatosis simply consists of  periodic blood donations which help to remove the excess iron from the body. The duration and frequency of the phlebotomies primarily depends on the stage of the disease and has to be continuously accompanied by a check of the haemoglobin and serum ferritin concentrations. After normal values have been achieved, the iron concentration must be kept at this level by regular monitoring and blood donations at longer intervals. If the therapy is carried out before the clinical symptoms occur, it is possible to prevent organ damage. The life expectancy of the patients is normal if appropriate treatment is started at an early stage.

Figure: The simplest treatment for haemochromatosis is to periodically donate blood.

Why is early detection so important?

Haemochromatosis often remains undiscovered or is diagnosed too late since not all patients develop the full blown disease and it is difficult to make an appropriate differential diagnosis on the basis of the uncharacteristic early symptoms. Even classical laboratory parameters (transferrin, serum ferritin, liver biopsy) can indeed be normal in individual patients. In young haemochromatosis patients the amount of stored iron may not yet be pathologically elevated due to the age. Even women present a relative good iron balance due to the periodic blood loss during menstruation.  Hence it is extremely important to know the genetic constellation of a patient in order to initiate timely therapeutic measures. If the disease is detected in time, it is not likely to lead to a reduction in the life expectancy whereas the prognosis of the disease without treatment is poor.

Who should have a genetic analysis?

Nowadays a molecular genetic analysis can be used to rapidly and simply test whether a genetic predisposition for developing haemochromatosis is present. Recent diagnostic systems such as the GenoType® hereditary haemochromatosis test from Hain Lifescience, Nehren allow your family doctor to reliably detect the iron storage disease. Hence the doctor can determine whether the individual patient is a carrier for this hereditary disease. The patient will be informed in detail about the consequences of such a test result and which therapeutic measures may be necessary. 

The test should be used for:

• patients with unusual transferrin and serum ferritin values
  
  
• patients with haemochromatosis
  
  
• young persons with a family history of such disorders
  
  
• women (laboratory diagnosis is often difficult due to the iron loss)
  
  
• patients with chronic viral hepatitis
  

What happens if I already suffer from haemochromatosis?

Patients that have already been diagnosed for haemochromatosis should undergo a gene analysis to differentiate between hereditary and acquired haemochromatosis. Even if the laboratory tests are pathological (high serum ferritin values > 150-200 ng/dl, transferrin saturation > 45 %) a mutation analysis should be carried out for confirmation. If one parent is a homozygotic carrier of the mutation then it is absolutely essential to examine all first degree relatives since if they are found to be positive the early implementation of therapeutic measures can prevent the impending organ damage when the finding is positive. It is often only the gene test which brings certainty particularly for women and young patients since the classical laboratory values are often ambiguous in such cases.