Hemochromatosis (HC) is an iron-loading disorder caused by a genetically determined failure to prevent unrequired iron from entering the body. It is characterized by progressive parenchymal iron overload with potential for multiorgan damage and disease. Hepcidin, the iron hormone, normally limits iron transfer from the intestine and macrophages into the bloodstream. Pathogenic mutations in genes involved in hepcidin synthesis in the liver (HFE, TfR2, HJV, and HAMP) may all cause HC. Depending on the gene involved and its role in hepcidin regulation, the phenotype of HC varies, ranging from the rare HJV- and HAMP-juvenile forms characterized by massive iron loading with severe heart and endocrine disorders, to the late-onset phenotype dominated by liver disease and usually associated with HFE and, rarely, with TfR2 mutations. Homozygosity for the C282Y polymorphism of HFE is associated with the most common form of HC. Although C282Y homozygosity is frequent in Caucasians, its clinical expression is low and requires concurrence of host-related and environmental factors to cause disease. Phlebotomy is effective in preventing complications and improves survival in all forms of HC. © 2012 Blackwell Publishing Ltd.
Hemochromatosis / Pietrangelo, A.. - (2012), pp. 675-682. [10.1002/9781118321386.ch90]