Genetic hemochromatosis - from molecular genetics to the clinical diagnosis

More than 90% of patients with genetic hemochromatosis carry a characterist ic mutation in the HFE-gene (C282Y). HFE modulates the iron uptake by the t ransferrin receptor. Duodenal crypt cells of HFE-knockout mice show low int racellular iron concentrations which lead to an upregulation of the divalen t metal transporter and enhanced iron uptake by duodenal enterocytes. Heter ocygosity for the C282Y mutation appears to alter the course of other liver diseases like porphyria cutanea tarda and nonalcoholic steatohepatitis.