Primary, genetic hemochromatosis

The term “hereditary hemochromatosis” (HH) encompasses a number of autosomal recessive inborn errors of iron metabolism with excessive iron absorption and pathological tissue iron deposition [1,2].

0.3–0.5% and 8–12% of Caucasian White populations are homozygous and heterozygous for HFE-HH, respectively. HFE mutations are found in 64–90% of clinically apparent HH cases across Europe and the USA. The penetrance of the disruption seems to be 25–50%.

So far, five genes have been identified to cause HH (HFE/6p21.3, TfR2/7q22, SLC40A1/2q32, HEMP/19q13.1, HJV/1q21) [2,3].

Over decades, increased iron absorption in homozygous HH leads to progressive iron deposition in tissues, due to impaired hepcidin function [2,3], and to subsequent organ damage due to iron-catalyzed formation of toxic radicals. When untreated, HH leads to hepatic failure and cirrhosis,...