LONG-TERM FOLLOW-UP OF 2 CASES OF HEMOCHR OMATOSIS RESPECTIVELY HOMOZYGOUS FOR THE HIS63ASP AND CYS282TYR MUTATIONS

A 45-year-old Greek patient was found to have a moderate iron overload (ferritin 1213 mu g/l, serum iron 21.5 mu mol/l, transferrin saturati on 40%). He underwent 12 phlebotomies of 450 cc over an 8-year period and ferritin was normalized (267 mu g/l) after the seventh. Study of t he HLA-H gene in leukocyte DNA showed that the patient is homozygous f or the His63Asp mutation while no modification was found at position 2 82. This case is compared with that of a 50-year-old Swiss male presen ting a severe iron overload (ferritin 7660 mu g/l, serum iron 36.5 mu mol/l, transferrin saturation 97%). Although this patient has undergon e 77 phlebotomies (450 cc each time) over a 2-year period, he continue s to have a high ferritin level (2200 mu g/l). HLA-H gene analysis sho wed the absence of codon 63 mutation and the presence of Cys282Tyr mut ation in the homozygous state. The study of these two cases indicates that penetrance of the His63Asp mutation in the homozygous state is ve ry low as compared to Cys282Tyr and results in moderate iron accumulat ion, probably without organ damage. This genotype must be looked for w henever moderate iron overload is present.