Background: Screening for hereditary hemochromatosis is traditionally done by using serum iron studies. However, mutation analysis of the hemochromatosis-associated HFE gene has recently become available.

Objective: To compare the cost-effectiveness of no screening with four screening strategies that incorporate HFE gene testing or serum iron studies.

Design: Cost-effectiveness analysis.

Data sources: Published literature.

Target population: Siblings and children of an affected proband.

Time horizon: Lifetime from 10 years of age (children) or 45 years of age (siblings).

Perspective: Societal.

Intervention: 1) Serum iron studies. 2) Gene testing of the proband. If the proband is homozygous (C82Y+/+), the spouse undergoes gene testing; if he or she is heterozygous (C82Y+/-), the children undergo gene testing. 3) Gene testing of the proband; if he or she is homozygous, relatives undergo gene testing. 4) Direct gene testing of relatives.

Outcome measures: Cost per life-year saved and incremental cost-effectiveness ratio.

Results of base-case analysis: In children, HFE gene testing of the proband was the most cost-effective strategy for screening one child (incremental cost-effectiveness ratio, $508 per life-year saved). HFE gene testing of the proband followed by testing of the spouse was the most cost-effective strategy for screening two or more children (incremental cost-effectiveness ratio, $3665 per life-year saved). In siblings, all screening strategies were dominant compared with no screening. Strategies using HFE gene testing were less costly than serum iron studies.

Results of sensitivity analysis: Despite varying the prevalence of mutations and regardless of the cost of the genetic test in one- and two-way sensitivity analyses, HFE gene testing remained cost-effective.

Conclusions: HFE gene testing for the C282Y mutation is a cost-effective method of screening relatives of patients with hereditary hemochromatosis.