18 January 2007
Hereditary haemochromatosis is a condition in which the iron levels in the blood are too high, associated with heritable mutations in the HFE gene which are common in Caucasian populations. Although the complications that can result from iron overload are severe (such as cirrhosis and cancer of the liver), and there is a simple and effective intervention to prevent such end-stage disease (regular blood-letting), the utility of population screening for the condition is questionable, because the disease shows very low penetrance. Although most individuals with clinical iron-overload are homozygous for HFE mutations (the most common variants being C282Y and H63D), a substantial proportion of homozygotes remain asymptomatic.
For any proposed genetic screening programme the potential benefit, in terms of disease prevention, must be weighed against the potential negative effects on those found to carry relevant mutations, in terms of psychological wellbeing. However, a study reported in a recent edition of Genetics in Medicine did not look at patients found to have mutations or clinical signs associated with risk of hereditary haemochromatosis, but rather those found to have ’indeterminate’ results – HFE genotypes and/or iron levels in the blood with uncertain associations with disease risk [Anderson RT et al. (2006) Genet Med. 8(11):681-7].
The researchers compared levels of psychological well-being and health anxieties among over 1000 such patients with that of healthy controls, having no HFE mutations or elevated iron levels. They found that confusion existed among participants about what their reported test results actually meant, particularly among those who received indeterminate results (19.5% compared with 5.4% of controls). More of this group believed that they had haemochromatosis mutations and/or clinical disease, and such beliefs were associated with poorer outcomes in terms of health and mental well-being. The authors conclude that “when screening results are vague or indeterminate regarding risk of disease, people may conclude that they have an abnormality that threatens their health and, as a result, feel less well and worry more”.
Comment: The authors of this paper also note that conventionally, trivial or indeterminate risk results are not reported to screening participants, precisely in order to prevent the sort of psychological harms outlined above. Some would argue that this approach is inappropriate as it entails undermining patient autonomy and withholding information that may, in the future, be useful to assess disease risk. However, in this particular instance - given that only a small proportion of those found to be homozygous for the HFE mutations associated with haemochromatosis are likely to be at genuine risk of clinical disease - these results would seem to strengthen the argument that population screening should not be introduced.