Hereditary hemochromatosis is an autosomal recessive disease of iron overload affecting 1 in 200-300 individuals of Northern European descent.1 The HFE gene mutations 845G->A (C282Y, cysteine to tyrosine at amino acid 282) and 187C->G (H63D, histidine to aspartic acid at amino acid 63) have been found in a majority of hereditary hemochromatosis cases in Caucasian populations.1 The identification of the C282Y homozygous mutation is most closely associated with hereditary hemochromatosis and with elevated ferritin and transferrin saturation levels.2 The importance of C282Y heterozygous mutations is controversial, including compound C282Y/H63D mutants, as is the presence of homozygous or heterozygous H63D mutations,1, 3 especially in the setting of secondary causes of iron overload. Of note, C282Y heterozygosity is present in up to 10% of the general population, and H63D heterozygosity in up to 24%.2 This assay will not detect rare mutations in the HFE gene that can be associated with hereditary hemochromatosis. Correlation of genetic findings with clinical and laboratory findings is required to make a diagnosis of hereditary hemochromatosis.
1. Lyon E, Frank EL. 2001 Clin Chem; 47(7):1147-56.
2. Adams PC, Reboussin DM, et al. 2005 N Engl J Med; 352(17):1769-78.
3. Olynyk JK, Cullen DJ, et al. 1999 N Engl J Med; 341(10):718-24.