Hemochromatosis is an iron overload disorder. The affected individual stockpiles iron in the body to the extent that it accumulates to an undesirable amount at various locations, causing harm to the normal functioning of the tissue in which it is stored.
The main causes which result in hemochromatosis are as mentioned below:
Both primary and secondary hemochromatosis has been reported, the former being far more common. Primary or hereditary hemochromatosis exists in several forms, of which Type 1 is the most common. The organs in which iron is usually stored include the heart, the liver, the skin, the pancreas, and the joints. The human metabolism is that iron excretion is more or less stable regardless of intake and absorption. As a result, excessive iron cannot be expelled through a natural course, when it is significantly increased in hemochromatosis. This leads to progressive and often irreversible damage to the tissues, which results due to iron overload, and could become fatal, unless the condition is treated well in time.
Hereditary Type 1 hemochromatosis is among the commonest of genetic diseases found in the USA and is especially prominent among individuals of North European descent.It is caused by mutations in the HFE gene, the ones being found most often includes C282Y and H63D. However, hemochromatosis as a whole is due to mutations in one of several genes, the more frequently found ones being HAMP, HFE, HJV, SLCO40A1, and TFR2 genes. Type 2 hemochromatosis is the result of the abnormality in the HJV or the HAMP genes, while the TFR2 gene mutation causes Type 3. Abnormality of the SLC40A1 gene is the reason for Type 4.
All these genes are alike in coding for proteins which regulate iron absorption, transport, and storage in the body. When they are abnormal, excessive absorption, overriding regulatory mechanisms in the gut wall can lead to high levels of iron in the serum and altered patterns of iron storage in the body’s tissues, with toxic effects on their functions. One of these proteins is the liver hormone called hepcidin, which cannot function normally in hemochromatosis
The inheritance of the genes responsible for Types 1, 2 and 3 are autosomal recessive, and therefore each parent must pass on one abnormal copy of the gene before the child is clinically affected. The parents are typically carriers with one mutated copy of the gene each, and with no features of the condition. Type 4 is inherited in an autosomal dominant fashion and so if one abnormal gene copy is transmitted to the offspring will have the disease. This type is usually seen in offspring of parents are also affected. Overall, however, not more than one in ten individuals with two copies of the gene mutation actually show significant signs and symptoms of hemochromatosis.
In keeping with the genetics and the time of onset, there are different clinical forms of hemochromatosis, such as: