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

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.

Implementation of ironXS: a study of the acceptability and feasibility of genetic screening for hereditary hemochromatosis in high schools.

Hereditary hemochromatosis (HH), most often due to HFE C282Y homozygosity, is an iron overload disorder that can result in severe morbidity including hepatic cirrhosis. Predisposition to HH is easily diagnosed and morbidity is preventable by maintaining normal body iron and thus calls have been made to introduce community screening. The current study has been designed to assess the acceptability and feasibility of HH screening in high schools. Students (mostly 15-16 years of age) watched a purpose-designed DVD for education about HH. Those with parental consent were then offered cheek-brush screening for C282Y. Students completed a questionnaire prior to screening. The program was offered to 9187 students at 32 schools and 3489 (38%) had screening. Nineteen C282Y homozygotes (1 in 183) and 376 heterozygotes (1 in 9.3) were identified. More than 90% of students answered each of five knowledge questions correctly. Eight homozygotes (42%) had elevated transferrin saturation, but only two (10.5%) had marginally elevated serum ferritin (SF). We have shown that genetic screening for HH can successfully be offered in the high school setting. Ongoing research in this study will answer questions about the impact of high school students learning that they are at risk of HH.