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Published on: September 6, 2017
Choosing wisely-directed HFE testing improves diagnostic yield and test utilization in hereditary hemochromatosis
Landry E Nfonsam1, Betty-Ann Hohenadel2, Menaka Pai3
1Molecular Genetics Laboratory, Hamilton Regional Laboratory Medicine Program, Hamilton Health Sciences, Hamilton, Ontario, Canada; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
Background:
Appropriate laboratory test utilization is essential for sustainable clinical and laboratory practice. HFE-associated hereditary hemochromatosis is a common cause of iron overload in individuals of Northern European ancestry and is primarily associated with the p.(Cys282Tyr, C282Y) variant and, less frequently, p.(His63Asp, H63D). In 2019, Choosing Wisely Canada (CWC) recommended restricting HFE genotyping to patients with elevated ferritin and transferrin saturation (>45%) or a documented family history. We evaluated the impact of implementing these criteria at the point of order entry, on test utilization and diagnostic yield.
Methods:
We retrospectively compared HFE genotyping data from three years before (June 2019-June 2022) and three years after (June 2022-June 2025) CWC implementation in a tertiary-care molecular diagnostics laboratory.
Results:
Post-implementation, overall testing volume decreased by 40%. Despite reduced volume, detection of clinically significant genotypes increased substantially: C282Y homozygotes increased from 7.6% to 14.8% (+95%), and C282Y/H63D compound heterozygotes increased from 5.8% to 9.1% (+57%).
Conclusions:
Implementation of CWC-based pre-analytical criteria significantly improved diagnostic yield while reducing unnecessary testing. These findings support guideline-directed HFE genotyping as an effective laboratory stewardship strategy in clinical biochemistry and genetics.
