Deposition of iron in skin produces the darker pigmentation noticed in light-skinned persons. Persons with anemia from ineffective erythropoiesis that can be seen with thalassemias can absorb excessive iron. Persons with refractory anemias requiring chronic transfusion therapy will also accumulate excessive iron. Genetic studies suggest that this mutation arose in a Celtic population in Europe 60 to 70 generations ago and may have had a selective advantage to a population at risk for iron deficiency. A single mutation, a substitution of cysteine to tyrosine at amino acid 282, called C282Y, is responsible for most cases.
Treatment is removal of iron by phlebotomy.
Family members also need to be screened by genetic testing with a blood sample to identify affected members before tissue damage develops.