C282Y/H63D Hemochromatosis Mutation Is Relevant When Comorbid Factors Are Present

Biochemical iron-overload expression is lower in C282Y/H63D compound heterozygotes than in C282Y homozygotes, but comorbid factors can lead to fibrosis in heterozygotes.

Among patients with hereditary hemochromatosis, those with homozygous C282Y mutations in the HFE gene are at the highest risk for significant iron overload and symptomatic disease. Patients with compound heterozygous C282Y/H63D mutations also are at increased risk for iron overload, but symptomatic disease seems to be less prevalent. Investigators retrospectively evaluated 91 patients with compound heterozygosity and 483 patients with homozygous C282Y mutations to determine the clinical significance of compound heterozygosity. Clinical expression, biochemical expression, histologic damage (iron deposition, fibrosis), and prevalence of HFE mutations among relatives were analyzed.

Fifty-two of the heterozygotes were asymptomatic on presentatio…

Reviewing Author

Atif Zaman, MD, MPH