In: Hemochromatosis7 Jun 2012
Nonexpressing homozygotes comprise only 6% of the C282Y homozygotes evaluated at the London Health Science Centre, but seven of 16 (44%) homozygous subjects in our population screening study showed no expression. Although voluntary blood donation may have contributed to the higher number of nonexpressing homozygotes in this study, none of these patients were super-donors, and we understand that during blood donation, there is compensatory iron reabsorption and donors are not left with a net iron deficit. If blood donation were the major factor affecting expression, these C282Y homozygotes would have had very low iron burdens that could be managed with fewer than 10 venesections during their lifetimes. Recent studies by Barton et al have suggested that blood donation does not have a major effect on the clinical expression of hemochromatosis. Furthermore, there were more non-blood donors than blood donors in this series, and other large population screening studies have demonstrated a normal serum ferritin concentration in 25% to 50% of discovered C282Y homozygotes. Other factors affecting nonexpression include other modifying genes, as has been suggested in knockout mouse models. Guidelines for the follow-up of nonexpressing homozygotes have not been clearly established.
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