Genotype-based screening for hereditary haemochromatosis. I: Technical performance, costs and clinical relevance of a...

In 2001, we initiated a pilot study on DNA-based screening of hereditary haemochromatosis (HH) in Germany. A total of 5882 insurants of the German sickness fund Kaufmannische Krankenkasse-KKH requested information on this project, and 3961 of these individuals provided blood samples for testing of the HFE mutation C282Y. Of these, 3930 samples were successfully tested with two independent test methods, and the results were communicated to the referring doctors. In all, 67 of the tested individuals were homozygous for C282Y. Partially, this high rate (1.7%) can be explained by the fact that 42.6% of the homozygotes already knew their clinical diagnosis HH before sending the blood sample. Iron accumulation with further signs or symptoms of HH was present in eight of 34 newly diagnosed C282Y homozygous individuals. Two major aspects of our study were the analytic validity and the direct laboratory costs of different test methods. Of 7860 tests performed, 7841 (99.6%) gave correct results. The overall error rate was 0.24% (95% CI: 0.15-0.38%). The analytic specificity of the tests methods with respect to the detection of homozygosity for C282Y was 100% (7726 of 7726 nonhomozygous test challenges, 95% CI: 99.95-100%), while the analytic sensitivity was 97% (130 of 134 homozygous test challenges, 95% CI: 92.5-99.2%). The direct costs ranged from 11.20-16.35 \[euro] per test method. We conclude that the test methods for C282Y are robust, highly sensitive and specific, and that a DNA-based HH-screening program can be performed at reasonable laboratory costs.