Letters

Should asymptomatic haemochromatosis be treated?

Alternative strategies to appropriate diagnosis need testing

Consequences of screening must be made known

Update from Seamark and Hutchinson

Alternative strategies to appropriate diagnosis need testing

EDITORThe contributions by Seamark and Hutchinson on the role of testing for and treatment of hereditary haemochromatosis highlight important issues about this disease and more generally about the clinical application of new genetic discoveries.¹ Uncertainties about the definition of disease are highlightedshould it be based on genotype, abnormal biochemistry, or symptoms, and, consequently, at what point does a predisposition to disease become genuine disease? This is a reflection more generally of the genetics of disease predisposition and the management of disease risk. Inevitably if we treat the risk of a diseasebe it by venesection for raised concentrations of ferritin or with tamoxifen in women with a family history of breast canceronly a proportion of patients will benefit and some will be harmed.²

We should be cautious about developing screening strategies for hereditary haemochromatosis for the general population. Proponents of population screening argue that it is common (based on a genetic definition of disease) and that prospective cohort studies show that early treatment results in normal life expectancy.³ For ethical reasons there will probably never be evidence from randomised controlled trials of venesection compared with watchful waiting in people with raised concentrations of ferritin. There is, however, sufficient uncertainty about expression of disease in C282Y homozygotes in the general population, and the role of gene/gene and gene/environment interaction in determining penetrance to postpone population screening until we know the results of large cohort studies of C282Y homozygotes from the general population.

In the meantime, primary care must still be aware of the possibility of misdiagnosing hereditary haemochromatosis and labelling patients with the diagnostic category of end stage disease such as cardiac failure or cirrhosis. The case of the patient (MH) described could be an example of this and we question the title of "asymptomatic haemochromatosis." Her case also shows a potential role for general practitioners in supporting shared decision making in patients who have received a diagnosis of hereditary haemochromatosis, given the uncertainties about management. MH was diagnosed using a case finding approach to the diagnosis of haemochromatosis, and this has been proposed as a reasonable course of action while we wait the results of population studies of hereditary haemochromatosis.⁴ The cost effectiveness of early diagnosis of hereditary haemochromatosis through systematic case finding and the positive predictive value of specific symptoms or symptom clusters in primary care require further investigation. In this way we may be more likely to define a group of people with hereditary haemochromatosis who would benefit from their diagnosis.

Jon Emery, Cancer Research Campaign primary care oncology research fellow. 
Imperial Cancer Research Fund General Practice Research Group, University of Oxford, Institute of Health Sciences, Oxford OX3 7LF jon.emery{at}dphpc.ox.ac.uk

Peter Rose, general practitioner. 
Mill Stream Surgery, Oxford OX10 6RL

Consequences of screening must be made known

EDITORThe contributions by Seamark and Hutchinson and the accompanying commentaries by Heath and McMullins raised some interesting points that could be extended to all screening programmes, both current and projected.¹ The most important of these is the principle that people without symptoms need to have the consequences of being screened explained to them before the screening test. It is not entirely clear whether the patient described was actually aware of these consequences and, if she had been, whether she would have agreed so readily to undergo screening. Health professionals have a tendency to overstate the benefits of screening and to underplay the less welcome consequences of it. ^{2 3} Although there are signs that this paternalistic attitude is changing, there is some way to go.⁴

In the paper there seems to be a difference in emphasis between the two general practitioners and the hospital specialist. Both general practitioners seem to place more importance on the quality of life, whereas the specialist views the less tangible benefit of a serum concentration of ferritin that is within normal limits to be important. The patient herself shares the attitude of the general practitioners and sees little benefit in being treated for a disease she may never have had any problem with and for which the treatment, in her view, is worse than the disease itself.

As screening tests become more sensitive there is a danger that many more individuals may encounter this problem. Screening tests are often described to the general public and politicians as the way forward. In reality the life expectancy gains achieved through screening may be less than is generally appreciated. Care must be taken that participants understand this before they undergo the tests, and not afterwards. The paper by Seamark and Hutchinson goes some way to redressing the balance.

John Nottingham, consultant histopathologist. 
George Eliot Hospital NHS Trust, College Street, Nuneaton, Warwickshire CV10 7DJ jfnottingham{at}doctors.org.uk

Update from Seamark and Hutchinson

EDITORWe used the term asymptomatic haemochromatosis as MH had no symptoms attributable to the condition and it would not have been found apart from the screening programme she took part in. She had no disturbance of liver function, no family history, her haemoglobin concentration was normal and there was no indication to check serum concentration of ferritin.

MH and her family have a strong sense of civic duty, hence their participation in diabetes research. This research did not specifically counsel about haemochromatosis, but when a potentially treatable condition was found it was decided that MH should be informed.

With regard to MH's family, her father was not known to have haemochromatosis although he did have diabetes. As MH is homozygous for C282Y her father must have either been a carrier or had undiagnosed haemochromatosis. Her brother has diabetes, but does not have haemochromatosis (although he could be a carrier). One sister and her children have neither diabetes nor haemochromatosis, although the sister has had thyroid disease. MH's other sister does not have diabetes but has recently been diagnosed as having haemochromatosis. Despite knowing far more about the condition than MH did two years ago she is about to start venesection.

We both believe that possibly more explanation would have been helpful in the initial stages, and we have since been sent some useful booklets and videos. CS feels that it is not usually helpful to paint the worst picture for patients at the start of treatment and so only gradually let MH know that the treatment might take longer than initially hoped. MH would also like to clarify what she meant when she wrote "not letting my doctor down"; she really meant that she would have regretted wasting everyone's time, she was not trying to earn "Brownie points."

Two years on we both feel more positive, and we meet less regularly for venesection and to talk about our travels and the paper. MH's latest serum concentration of ferritin was 30 µg/l (normal range 10-110 µg/l). MH realises that the treatment is for life, but it is less intrusive and she plans to return to Ascension in 2001 and New Zealand in 2002.

The aim of our paper was to promote discussion, which we have achieved, and to highlight that although venesection is safe and, some would say, easy, it does have important effects on the patient and staffing implications that should be taken into account if population screening for haemochromatosis is ever planned.

Clare J Seamark, general practitioner. 
Margot Hutchinson, retired headmistress. 
Honiton Group Practice, Marlpits Lane, Honiton, Devon EX14 2NY