Background: The gene that causes most cases of hereditary hemochromatosis is designated HFE. Individuals with mutations in the HFE gene may have increased serum iron, transferrin saturation, and ferritin concentrations relative to individuals with the wild-type genotype.
Methods: We generated reference centiles for percentage of transferrin saturation and serum ferritin concentrations in normal (wild-type), healthy Caucasian adults. We then examined transferrin and ferritin concentrations relative to these centiles in 81 individuals homozygous for the major hemochromatosis mutation C282Y and 438 individuals with the compound heterozygous HFE genotype C282Y/H63D.
Results: Serum ferritin concentrations, but not percentage of transferrin saturation, in normal, healthy women tended to increase sharply as they progressed through menopause. Transferrin and serum ferritin centiles for normal, healthy females were lower than the corresponding centiles in normal, healthy males. C282Y homozygotes had abnormally high transferrin saturation and serum ferritin values relative to the wild types. Compound heterozygotes appeared to be a mixture of individuals with unexceptional transferrin and ferritin values and those with abnormally large values similar to the homozygotes, with equal proportions of each.
Conclusions: There are age- and sex-related differences in reference centiles for the percentage of transferrin saturation and serum ferritin concentrations in normal, healthy adults. Individuals homozygous for the C282Y mutation in the HFE gene have abnormal transferrin saturation and serum ferritin values relative to the reference population; penetrance with the compound heterozygotes, as reflected by abnormal transferrin and ferritin values, is less than with the homozygotes.