Non-expressing homozygous C282Y carriers and haemochromatosis

After the detailed description of 311 patients with iron overload by J H Sheldon in 1935,1 people assumed that iron overload and haemochromatosis were synonymous and that iron overload throughout the body defined and caused the clinical disease. Iron overload was determined by liver biopsy, autopsy, and response to therapeutic phlebotomy. In the 1970s, newer blood tests such as serum ferritin and transferrin saturation became part of the diagnostic testing for iron overload.23 In 2005 data from the Hemochromatosis and Iron Overload Screening (HEIRS) Study introduced genetic testing and showed that approximately 57% of female C282Y homozygotes and 20% of male C282Y homozygotes had a normal serum ferritin and/or transferrin saturation without apparent iron overload.4 Transferrin saturation was found to be highly variable within individuals,5 and serum ferritin had mostly false positive results in patients without iron overload. Magnetic resonance imaging became a new tool to assess iron overload in the …