Asymptomatic hemochromatosis subjects: genotypic and phenotypic profiles

Screening for hereditary hemochromatosis (HHC) by means of transferrin satu ration (TS) levels has been advocated and will identify many patients who a re asymptomatic. The purposes of this study were (1) to determine HFE genot ypes among asymptomatic HHC patients and correlate this profile with the de gree of iron overload and (2) to evaluate the relationship between mobilize d iron (mob Fe), age, serum ferritin (SF), and quantitative hepatic iron (Q HI) in this population. One hundred twenty-three asymptomatic HHC patients were evaluated; ail had quantitative phlebotomy to determine mob Fe and gen otyping for C282Y and H63D mutations. Liver biopsies with QHI determination s were performed an 72 of the 123 patients. Of the entire group, 60% were h omozygous for C282Y, and 13% were compound heterozygotes (C282Y/H63D), Amon g asymptomatic patients, the prevalence of homozygous C282Y is lower compar ed with previous studies that include clinically affected patients, Of thos e patients with more than 4 g mob Fe, 77% were homozygous C282Y, Asymptomat ic patients with lower iron burdens frequently had genotypes other than hom ozygous C282Y, There was no correlation between age and mob Fe in these pat ients; however, there was a correlation between mob Fe and both SF (r = 0.6 8) and QHI(r = 0.75). In conclusion, asymptomatic patients with moderate ir on overload had a different genotypic profile than was seen in advanced iro n overload. The significance of identifying patients with modest degrees of iron loading, who may not be homozygous for C282Y, must be addressed if ro utine TS screening is to be implemented. (C) 2000 by The American Society o f Hematology.