Hereditary hemochromatosis is an inherited disorder of iron metabolism in the 
Caucasian population with an autosomal recessive inheritance and a prevalence 
between 1 in 200 and 1 in 500. Until the discovery of HFE gene the diagnosis of 
hemochromatosis required documentation of iron overload or family linkage using 
HLA testing. The discovery of HFE gene has established the foundation for a 
better understanding of iron homeostasis and has changed hemochromatosis 
management: liver biopsy, gold standard diagnostic, was replaced by genetic test 
and it was suggested that population screening using genetic testing might be 
ideal for HFE related hemochromatosis. Considered for long time a unitary 
disease, a monogenic disorder characterized by excess tissue deposits of iron 
and subsequently organ damage, hemochromatosis is in fact a polygenic disease 
with many faces. The Online Mendelian Inheritance in Man database has lists four 
types of hereditary hemochromatosis, each of them caused by a different gene 
mutation (hepcidine, hemojuvelin, transferring receptor 2, ferroportin). The 
basic features shared by iron overload disorders associated with mutation in 
HFE, hepcidine, hemojuvelin, transferring receptor 2, ferroportin gene indicate 
that they are genetic variation of the same syndrome. Hereditary hemochromatosis 
must be distinguished from the other syndrome of iron overload and the classic 
term hereditary hemochromatosis should be reserved only for HFE related 
hemochromatosis.