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Clinical Review

Diagnosis and management of hereditary haemochromatosis

BMJ 2011; 342 doi: (Published 19 January 2011) Cite this as: BMJ 2011;342:c7251

Rapid Response:

Why is haemochromatosis so common?

Dear Editor,

Van Bokhoven and co-authors provide a comprehensive account of
haemochromatosis1. It is important to state however, that haemochromatosis
is also associated with an increased risk of infection2. It is unclear if
iron overload per se compromises the immune system or if the iron rich
host facilitates pathogenic invasion2. This increased risk of infection is
significant for two reasons. Clinicians must bear this in mind when
treating patients with haemochromatosis. Secondly it may also hold the key
to the conundrum of the near exclusivity of the haemochromatosis genes to
European populations3. These same genes are very rare in African and Asian

The authors state that the prevalence of the haemochromatosis zygote is
0.4%. The Hardy-Weinberg analysis reveals a carrier rate of 1 in
8.4. Injurious genes tend not to be so prevalent; unless carriers or
homozygotes enjoy a selective advantage over competitors. The high
frequency of the haemochromatosis "mutation" within the European
population is difficult to explain. In atavistic man iron storage would
protect against blood loss in parturition, warfare, hunting or
malnutrition. This would not explain the exclusivity of the gene to the
European population.

I recently suggested that in more tropical climes this advantage would be
outweighed by the ramifications of infection by more pernicious pathogens
such as Plasmodium and other parasites4. The iron-rich host would be at
increased risk and would endanger the whole population. His iron-laden
tissue would be able to support a greater number of parasites and hence
increase his infectivity and the reproductive efficacy of the pathogen.

Iron dietary supplementation has been shown to increase the risk of
malaria infection, when administered in isolation without malarial
surveillance and treatment5. I also posit that sickle cell disease,
thalassaemia and erythrocyte enzymopathies are respectively biophysical,
quantitative and biochemical means of withholding iron, within the blood,
from invading pathogens4.

However haemochromatosis results in low macrophage iron content thus
impeding the propagation of intracellular microbes such as Mycobacterium
tuberculosis, Salmonella typhi, and Chlamydia pneumoniae2. It appears that
complex infective selective pressures may have shaped the global
distribution of the haemochromatosis genes.

1. Bokhoven MA, van Deursen C Th B M, Swinkels DW Diagnosis and
management of hereditary haemochromatosis BMJ 2011 342:c7251.

2. Khan FA, Fisher MA, Khakoo RA. Association of hemochromatosis with
infectious diseases: expanding spectrum. Int J Infect Dis. 2007

3. Adams PC, Reboussin DM, Barton JC, McLaren CE, Eckfeldt JH,
McLaren GD, Dawkins FW, Acton RT, Harris EL, Gordeuk VR, Leiendecker-
Foster C, Speechley M, Snively BM, Holup JL, Thomson E, Sholinsky P;
Hemochromatosis and iron-overload screening in a racially diverse
population New England Journal of Medicine 2005;352:1769-78.

4. Uzoigwe OF. The distribution of the parasitic fauna dictates the
distribution of the haemochromatosis genes. Med Hypotheses. 2010; 75:415-

5. Ojukwu JU, Okebe JU, Yahav D, Paul M. Oral iron supplementation
for preventing or treating anaemia among children in malaria-endemic
areas. Cochrane Database Syst Rev. 2009 Jul 8;(3):CD006589.

Competing interests: No competing interests

31 January 2011
Ossie F Uzoigwe
Medical Writer
8 Harcourt Crescent, Sheffield