Background: The gene that causes most cases of hereditary hemochromatosis is designated HFE. Three mutations exist at this locus at a relatively high gene frequency.
Objective: To determine the gene frequency of the three HFE mutations and to relate genotypes to various clinical and laboratory variables.
Design: Observational study.
Setting: Health appraisal clinic.
Patients: 10 198 adults who registered for health appraisal and consented to DNA examination for hemochromatosis. Consenting patients were slightly older and had attained a slightly higher educational level than nonconsenting patients.
Measurements: Extensive medical history and laboratory tests, including complete blood count, transferrin saturation, and other chemistries; serum ferritin levels; and HFE genotype.
Results: In white participants, the gene frequencies were 0.063 for the C282Y mutation, 0.152 for the H63D mutation, and 0.016 for the S65C mutation. Gene frequencies were lower in other ethnic groups. In participants with HFE mutations, the average serum transferrin saturation and ferritin levels were slightly increased, as were mean hemoglobin levels and mean corpuscular volume. A transferrin saturation of 50% had a sensitivity of only 0.52 (95% CI, 0.345 to 0.686) and a specificity of 0.908 (CI, 0.902 to 0.914) for detection of homozygosity. A ferritin level of 200 µg/L in women and 250 µg/L in men had a sensitivity of 0.70 (CI, 0.540 to 0.854) and a specificity of 0.803 (CI, 0.796 to 0.811). The prevalence of iron deficiency anemia was lower in women who carried HFE mutations.
Conclusions: Screening for transferrin saturation and ferritin levels does not detect all homozygotes for the major hemochromatosis mutation. Heterozygotes for HFE mutations had a lower prevalence of iron deficiency anemia.