Objective: Hereditary hemochromatosis (HH) is a genetic condition characterized by increased iron absorption. Most HH cases are homozygous for the C282Y mutation in the HFE gene, but accurate prevalence data for the Norwegian population is lacking. In population studies, serum transferrin saturation (TS) is commonly used as a screening test. However, the sensitivity and specificity of TS in this setting is not well documented. The purpose of this study was to determine the prevalence of the C282Y mutation in the general population, and to evaluate the diagnostic accuracy of the TS test as a screening criterion for finding C282Y homozygotes.
Materials and methods: The hemochromatosis screening study in Nord-Trøndelag county, Norway (the HUNT2 study) comprised 65,238 participants. The HUNT biobank contains biological material and data from the participants, and 5000 individuals were randomly selected. Genotyping of the common HFE gene mutations was successful for 4827 samples, from which TS data existed for 4804 individuals. From these data we calculated the population frequency of the C282Y mutation, and the sensitivity and specificity of TS measurements.
Results: The prevalence of C282Y homozygosity in the population was 0.75%. Using 55% (men) and 50% (women) as decision limits, the sensitivity of two consecutive elevated TS measurements was 90.0% for men and 55.0% for women, whereas the specificity was 99.6% and 99.4%, respectively.
Conclusion: An unbiased estimate of the C282Y homozygote prevalence in Norway is 0.75%. Two measurements of TS is an accurate screening test for C282Y homozygosity in men, but not in women.