[Novel aspects of pathogenesis of hereditary hemochromatosis].

Patients with hereditary hemochromatosis (HC) may present a plenty of clinical symptoms, thus are referred to various specialists and may prone a significant diagnostic dillema. The molecular basis of hemochromatosis is more complex than expected. In 1996 HFE gene was identified and its main mutations (C282Y and H63D) were described as well as their high frequency in population of European descent. Them: Most patients with clinical symptoms of hemochromatosis are homozygous for C282Y but it is also clear that some families are linked to rarer conditions, named "non-HFE hemochromatosis". Between 2000-2004 other genes involved in iron homeostasis were intensively studied, leading to recognition of hepcidin (HAMP) - the most important iron hormone, hemojuvelin (HJV), transferin receptor 2 (TfR2) and ferroportin. Recent findings led to novel hypothesis on potential digenic modes of inheritance or the involvement of modifier genes. Hepcidin plays a central role in mobilization of iron, HFE, TfR2 and HJV playing a modulating role in its production, related to the body's iron status. It has also been demonstrated that HAMP negatively regulates cellular iron efflux by affecting the ferroportin cell surface availability. The result of such a wide investigations is OMIM classification of hereditaty hemochromatosis, typing four types of the disease.