Hereditary haemochromatosis: to screen or notBMJ 1999; 319 doi: https://doi.org/10.1136/bmj.319.7209.531 (Published 28 August 1999) Cite this as: BMJ 1999;319:531
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To the Editor - Recent publications in the BMJ have highlighted the
problems in population screening for haemochromatosis 1 2. These include
interpretations of the genotype phenotype correlation and concerns about
the practicalities and organisation of screening programmes.
first degree relatives of affected individuals is recommended and
genotyping is a potentially more efficient way of identifying at risk
individuals although it is not sufficient in isolation and needs to be
followed by biochemical testing 3. There is evidence that referrals for
haemochromatosis mutation testing throughout Europe are increasing4 .This
increase is for both diagnostic and family testing.
This increase in the number of tests may be proceeding in an unplanned and
uncoordinated way. Anecdotal evidence from regional genetic centres in
the UK and examination of one centre's referral pattern for
haemochromatosis also show an increase. The majority of referrals will be
of relatives. A recent unpublished survey of the genetic centres in the UK
indicated that all of the respondents (83% response rate) would offer
genetic testing for haemochromatosis although 6% would pass the referral
on to another speciality (haemotology or hepatology) for both genetic
testing and biochemical screening. When asked specifically about testing
of unrelated spouses of carriers all respondents indicated they would
offer carrier testing in this situation, presumably to clarify offspring
Genetic haemochromatosis is inherited as an autosomal recessive and it is
common in recessive conditions to offer cascade testing of family members
with carrier testing of partners.The purpose of the testing normally being
to detect at risk carrier couples in order to offer informed reproductive
choice. A cascade approach to testing for haemochromatosis including
testing of spouses will detect many more carriers than at risk
individuals. The significance of carrier status in relation to iron
overload is not particularly clear and in addition the clinical importance
of the specific mutations remains to be elucidated.
Advocating family testing as a strategy for screening for haemochromatosis
may be justified but its implementation deserves as much consideration as
that accorded to population screening. Genetic haemochromatosis is one of
the first of the more common conditions where genotyping can be used to
identify those at risk in order to initiate treatment. The lack of
coherent strategies for delivery of this service to the population does
not bode well for the utilisation of genotyping for risk factors for more
common diseases in the future.
1 Haddow J E, Bradley L A. Hereditary haemochromatosis: to screen or
not BMJ 1999 319:531-532
2 Allen K, Williamson R. Screening for hereditary haemochromatosis
should be implemented now. BMJ 2000 320:183
3 Olynyk J K, Cullen D J, Aquila S, Rossi E, Summerville L and Powell
L W. A population based study of the clinical expression of the
haemochromatosis gene. The New England Journal of Medicine 1999 341:718-
4 The European and UK Haemochromatosis Consortia: Diagnosis and
management of haemochromatosis since the discovery of the HFE gene: a
European experience. British Journal of Haematology 2000 108:31-39
Wessex Clinical Genetic Service,
Princess Anne Hospital,
Southampton SO16 5YA
Dr William Rosenberg
Cell and Molecular Medicine,
Mailpoint 811, Level D South Block,
Southampton General Hospital,
Southampton SO53 1ER
Competing interests: No competing interests
The recent editorial in the BMJ on population screening for
haemochromatosis raises interesting issues, but incorrectly concludes the
time for population screening is not ripe because of uncertainties about
the proportion of homozygotes who will express symptoms of the disease.
Haemochromatosis has been recognised as a clinical entity for more than
150 years, but the gene that is mutated was only identified in 1996.
Clinical haemochromatosis, defined by the presence of abnormal serum iron
indices, has consistently been estimated to affect between 1/200 and 1/500
Caucasians. The incidence of homozygotes for the more severe and common
of the two mutations, C282Y has been shown to be approximately 1 in 250 ,
in all Caucasian populations studied. The number of individuals with the
major predisposing genotype is at most double that of the clinical
A likely "favourable ratio" of one individual benefiting for every two
commenced on prophylactic phlebotomy on the basis of genotype tips the
scales in favour of population-based genetic screening. If gene testing
is offered, many individuals at high risk will be identified pre-
symptomatically and therefore will avoid serious but preventable
We believe that genetic population screening is a correct strategy because
haemochromatosis is common, preventable and treatable. Pre-symptomatic
screening would result in haemochromatosis becoming a rare clinical entity. Testing can be undertaken in pre-symptomatic adults aged below 30, and
prevention (regular blood donation) is not onerous. A simple and
inexpensive mouthwash test is all that is required for DNA analysis for
the affected gene. Unlike other gene tests, there are few ethical issues
involved to be balanced against the clinical benefits.
As for screening for high cholesterol or hypertension, the public health
issue revolves around the risk-benefit ratio. The link between risk
factor (C282Y homozygosity) and disease expression is tighter for
haemochromatosis, and the medical management (regular blood donation) is
far less onerous and costly, than the lifelong daily medication prescribed
for hypertension or hypercholesterolaemia. We believe there is an ethical
imperative to implement screening for the major mutation causing
haemochromatosis now to benefit all of those at risk, rather than wait
years for confirmation of what is highly likely from the incidence
1 Haddow JE, Bradley, LA. Hereditary Haemochromatosis: to screen or
not. BMJ 1999;319:531-532.
2 Leggett BA, Halliday JW, Brown NN, Bryant S, Powell LW.
Prevalence of haemochromatosis amongst asymptomatic Australians. Br J
Haematol 1990; 74: 525-30.
3 Bradley LA, Haddow JE, Palomaki G, Haddow, J, Robertson N, Ferrrie
R. Heriditary haemochromatosis mutation frequencies in the general
population. J Med Screen 1996;3:171-7.
4 Allen KJ, Williamson R. Should we genetically test everyone for
haemochromatosis? J Med Ethics 1999;25:209-214.
Competing interests: No competing interests
In their editorial on screening for hereditary haemochromatosis,
Haddow and Bradley consider that a ratio of 1 patient benefiting for every
10 treated is unacceptable (1). I wonder, therefore, what they would make
of the considerably higher ratios found in screening for pre-malignant
disease of the uterine cervix?
The NHS Cervical Screening Programme in England labels over 250,000
women per annum as having an abnormal cervical smear. Of these women, about 120,000 each year
are treated in order to prevent an estimated 800 deaths annually from the disease,
a ratio of 150 to 1(2,3). Many of these women believe that they have had a
life threatening cancer; they have not. In fact up to 14% have no evidence
of cervical intraepithelial neoplasia at all (2). Given that nearly half
of consultant pathologists and biomedical scientists employed in the
cervical screening programme admit to overcalling cervical smears for fear
of missing serious disease, then this percentage is likely to increase
(4). The cost benefit ratio of cervical screening in the UK will therefore
deteriorate further as more and more women are subjected to unnecessary
At risk of being considered politically incorrect, perhaps it is time
to think the unthinkable and to seriously reconsider whether the present
cervical screening programme continues to represent a cost effective
health intervention? At a cost of over £100,000 per life saved, almost
half of consultant pathologists in the UK believe it is not (4).
Dr. John Nottingham, FRCPath.
1. Haddow JE, Bradley LA. Hereditary haemochromatosis: to screen or
BMJ 1999; 319:531-2.
2. Statistical bulletin. Cervical Screening Programme, England: 1997-
98. Department of Health. London. January 1999.
3. Quinn M, Babb P, Jones J, Allen E, on behalf of the United Kingdom
Association of Cancer Registries. Effect of screening on the incidence of
and mortality from cancer of the cervix in England: evaluation based on
routinely collected statistics. BMJ 1999; 318: 904-8.
4. Brown DC, Griffiths D. A survey of biomedical scientists and
consultant pathologists involved in the cervical screening programme.
Cytopathology 1999; 10: 229-239.
Competing interests: No competing interests