Pathophysiology

• The HFE gene regulates iron homeostasis (see “Iron” in the articles on trace elements).

• HFE gene defect (homozygous) → defective binding of transferrin to its receptor → ↓ hepcidin synthesis by the liver → unregulated ferroportin activity in enterocytes → ↑ intestinal iron absorption → iron accumulation throughout the body → damage to the affected organs

In hereditary hemochromatosis, decreased hepcidin leads to iron overload. In secondary hemochromatosis, iron overload leads to increased hepcidin immediately after a blood transfusion (unless liver fibrosis or cirrhosis, which leads to decreased hepcidin synthesis, is present).