Etiology

1. Primary (heriditary) hemochromatosis

2. Secondary iron overload (secondary hemochromatosis)

Primary (hereditary) hemochromatosis

• Classical and most frequent form: adult hemochromatosis type I

  • Homozygous or heterozygous for the HFE gene defect

    • Located on chromosome 6

    • Most commonly affects C282Y and H63D

    • Associated with HLA-A3 genotype

  • Inheritance: autosomal recessive with incomplete penetrance

• Further forms: Hemochromatosis types II–IV are also hereditary, but significantly less frequent.

HLA A3 as in HA3mochromatosis!

• Caused by iron overload

  • Transfusion-related (e.g., in individuals with beta-thalassemia major or other forms of chronic anemia requiring chronic transfusion)

  • Ineffective erythropoiesis

    • Thalassemia

    • Sickle-cell anemia

    • Sideroblastic anemia (e.g., hereditary sideroblastic anemia; anemia of chronic disease)

  • Excessive alcohol consumption

Alcohol increases the absorption of iron.