Reference centiles for serum ferritin and percentage of transferrin saturation, with application to mutations of the HFE gene

Background: The gene that causes most cases of hereditary hemochromatosis i s designated HFE. Individuals with mutations in the HFE gene may have incre ased serum iron, transferrin saturation, and ferritin concentrations relati ve to individuals with the wild-type genotype. Methods: We generated reference centiles for percentage of transferrin satu ration and serum ferritin concentrations in normal (wild-type), healthy Cau casian adults. We then examined transferrin and ferritin concentrations rel ative to these centiles in 81 individuals homozygous for the major hemochro matosis mutation C282Y and 438 individuals with the compound heterozygous H FE genotype C282Y/H63D. Results: Serum ferritin concentrations, but not percentage of transferrin s aturation, in normal, healthy women tended to increase sharply as they prog ressed through menopause. Transferrin and serum ferritin centiles for norma l, healthy females were lower than the corresponding centiles in normal, he althy males. C282Y homozygotes had abnormally high transferrin saturation a nd 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 homo zygotes, with equal proportions of each. Conclusions: There are age- and sex-related differences in reference centil es for the percentage of transferrin saturation and serum ferritin concentr ations in normal, healthy adults. Individuals homozygous for the C282Y muta tion in the HFE gene have abnormal transferrin saturation and serum ferriti n values relative to the reference population; penetrance with the compound heterozygotes, as reflected by abnormal transferrin and ferritin values, i s less than with the homozygotes. (C) 2001 American Association for Clinica l Chemistry.