In normal iron regulation, iron is absorbed in the intestine, and ferroportin transports iron from the cells of the intestinal lining into the bloodstream. Iron in the bloodstream is then bound by transferrin, which carries the iron to target cells. Iron is stored in cells and blood serum in a protein called ferritin. Reticuloendothelial macrophages, which can phagocytose red blood cells, are important in the iron recycling process. Ferroportin is upregulated in the reticuloendothelial macrophages after phagocytosis occurs so that iron from the degraded red blood cells can be released into the bloodstream and transported to other types of cells as needed. Hepcidin, a protein synthesized in the liver in response to iron or inflammation, is a regulator of ferroportin expression. When hepcidin binds ferroportin, ferroportin is phosphorylated, endocytosed, tagged with ubiquitin, and degraded. More than 39 mutations to the SLC40A1 gene have been identified in patients with type<unk>  hemochromatosis. The misregulation of ferroportin in type<unk>  hemochromatosis can involve a failure of ferroportin to be properly expressed at the cell membrane, or it can involve a failure of ferroportin to respond to negative regulation by hepcidin.<unk> A is characterized by impaired iron export in cells. Reticuloendothelial macrophages are most affected. Iron accumulates preferentially in Kupffer cells, which are located in the liver, and serum ferritin increases; less iron is available for circulating transferrin, a protein that binds iron and transports it through the bloodstream to cell receptors. This means that, while iron is trapped in certain types of tissues, it cannot be transported to tissues where it is needed. The accumulation of iron in tissues due to impaired iron export can lead to increasing transferrin iron saturation and liver parenchymal iron overload in advanced stages of the disease. More ferritin is produced to suppress oxidative cell damage, although the amount of ferritin that cells can accumulate is limited.<unk> B is characterized by abnormal iron release from macrophages and enterocytes because the mutant ferroportin is resistant to the hepcidin protein, which serves a regulatory function in wild-type ferroportin. Intestinal iron absorption and release of iron from macrophages is increased. Thus, this form of the disease leads to elevated transferrin saturation levels. Systemic iron overload results, and liver iron deposition is primarily in the hepatocytes.
Hemochromatosis type 4
Haemochromatosis type 3
Hereditary haemochromatosis
Juvenile hemochromatosis
Wilson's disease
Wilson–Mikity syndrome
Type 3c diabetes
Niemann–Pick disease, type C