Hereditary hemochromatosis (HH) is a group of genetic iron overload disorders 
that manifest with various symptoms, including hepatic dysfunction, diabetes, 
and cardiomyopathy. Classic HH type 1, which is common in Caucasians, is caused 
by bi-allelic mutations of HFE. Severe types of HH are caused by either 
bi-allelic mutations of HFE2 that encodes hemojuvelin (type 2A) or HAMP that 
encodes hepcidin (type 2B). HH type 3, which is of intermediate severity, is 
caused by bi-allelic mutations of TFR2 that encodes transferrin receptor 2. 
Mutations of SLC40A1 that encodes ferroportin, the only cellular iron exporter, 
causes either HH type 4A (loss-of-function mutations) or HH type 4B 
(gain-of-function mutations). Studies on these gene products uncovered a part of 
the mechanisms of the systemic iron regulation; HFE, hemojuvelin, and TFR2 are 
involved in iron sensing and stimulating hepcidin expression, and hepcidin 
downregulates the expression of ferroportin of the target cells. Phlebotomy is 
the standard treatment for HH, and early initiation of the treatment is 
essential for preventing irreversible organ damage. However, because of the 
rarity and difficulty in making the genetic diagnosis, a large proportion of 
patients with non-HFE HH might have been undiagnosed; therefore, awareness of 
this disorder is important.