To tell or not to tell – what to do about p.C282Y heterozygotes identified by HFE screening

Abstract

Hereditary hemochromatosis (HH) is a common preventable disorder of iron overload that can result in liver cirrhosis and reduced lifespan. Most HH is due to homozygosity for the HFE p.C282Y substitution. We conducted a study of screening for p.C282Y in high schools where p.C282Y heterozygotes (CY) individuals were informed of their genotype by letter. We studied whether these individuals understood the implications of their genotype, whether this resulted in anxiety or reduced health perception and whether cascade testing was higher in families of CY than wild-type homozygous (CC) individuals. We found 586 of 5757 (1 in 10) screened individuals were CY. One month after receiving their result, 83% correctly answered that they have one copy of p.C282Y. There was no adverse change in anxiety or health perception from prior to screening to 1 month after receiving results. Significantly more family members of CY individuals than CC individuals were informed about HH and had testing for HH. In conclusion, we found that informing CY individuals of their genotype does not increase anxiety and the implications are generally well understood. This leads to cascade testing in a minority of families. CY individuals should be informed of their genetic status when identified by population screening.

Highly accurate molecular genetic testing for HFE hereditary hemochromatosis: results from 10 years of blinded proficiency surveys by the College of American Pathologists

“…A recent publication investigating whether test results for HFE C282Y heterozygosity were associated with increased patient anxiety or harm indicated that these results were being appropriately interpreted as associated with no increased risk of disease. 21 However, it is possible that the observed PT survey heterogeneity in clinical interpretations of HFE genotyping may also be reflected in clinical diagnostic laboratory test reports that go to clinicians, and some misinterpretation of results may then ensue. There may be a need for further consensus and standardization in this area.…”

Diagnosis and treatment of hereditary hemochromatosis: an update

“…Concerns have been raised by some authors that screening may cause psychological and social stress and can be expensive considering the relatively low prevalence and incomplete penetrance. However recent studies have shown that there are minimal psychological effects of screening [146][147][148][149]. Additionally, studies outside the United States where insurance and health care access and coverage are less of a concern have suggested that practical reasons such as lack of awareness and access to screening programs are the major reasons for non-participation in screening programs [150].…”