Retired GP, Doug Jenkinson shares his thoughts on newly published research, which shows significantly increased risk from sepsis in C282Y homozygotes.

I retired as a GP in 2011, but since I was diagnosed with genetic haemochromatosis three years ago I have taken a great interest in new research on the subject. This has been easy thanks to Google Scholar which automatically emails details of newly published papers about Haemochromatosis.

Very recently I felt a surge of excitement when I was sent information about a paper that was published in May 2024 in the well know international journal ‘Blood’. The research findings were completely new, seemed very soundly based, and of great relevance to anyone with C282Y genetic haemochromatosis. The researchers, based in Copenhagen, were able to study blood specimens from 142,188 Danish men and women that had been taken over several decades as part of several population health studies.

The purpose of the research was to investigate if there was any connection between the amount of iron in the body and infections. Bacteria need iron to grow and reproduce, so it was logical to investigate whether low iron levels or high iron levels in the human body made infection more or less likely.

One way to investigate this kind of thing is to take advantage of the masses of computerised data that now exist. Although it is a rather crude method of investigation, the large numbers make it possible to identify connections even though it was never the purpose of the recordings in the first place. This is what the Danish scientists did.

They looked for connections between substances that anyone with haemochromatosis will be very familiar with, serum iron, ferritin, transferrin saturation, and haemochromatosis genes C282Y and H63G.

Although some of the findings were important to specialists in this field, the somewhat shocking finding which is of relevance to haemochromatosis sufferers was that homozygous C282Y subjects were twice as likely to die from sepsis. Risk of bacterial infections in general are increased, but to a lesser extent. They found no increased risk for compound heterozygous C282Y/H63D subjects.

These findings were true whether the haemochromatosis had been treated or not, and equally true for people who had not even had their haemochromatosis diagnosed.

Sepsis is also known as septicaemia or blood poisoning. It happens when a bacterial infection escapes from tissue and gets into the blood. It rapidly causes a particular kind of shock, making blood pressure fall and endangering organs like brain and kidneys that can become permanently damaged. With modern treatments 90% of sufferers will survive. It can be difficult to diagnose, especially by the inexperienced.

If this applies to you, what do you need to do about it? You now know this fact, but you can be sure that 99% of doctors you come across will not, and possibly never will. It is small print knowledge that is difficult to memorise alongside all the other things that have to be thought about. If it gets confirmed by other studies, which I feel sure it will, it may come up on a computer your doctor may be using, but that is way into the future. Until then it is up to you or your representative to point out do any doctor that is treating you for a bacterial infection that your C282Y haemochromatosis type makes you susceptible to develop sepsis.

The probable reason for the susceptibility is to do with the abnormal gene that characterises type 1 haemochromatosis. We know that that this gene is responsible for producing abnormal hepcidin hormone that is unable to properly control the absorption of iron from the gut. It is also unable to properly regulate the flow of iron from certain body cells for the same reason. When bacteria invade our bodies, one of the body’s responses is to reduce this flow of iron from cells, which in unaffected people slows the growth of many bacteria.

Here are the identification details of the paper and a link to a brief abstract.

Mottelson M, Glenthøj A, Nordestgaard BG, Ellervik C, Petersen JB, Bojesen SE, Helby J. Iron, haemochromatosis genotypes, and risk of infections: a cohort study of 142,188 general population individuals. Blood Journal. 2024 May 10:blood-2023022235.

A personal note...

I was intrigued by this paper. I knew that the UK Biobank study had shown men with haemochromatosis were more likely to suffer pneumonia and that some infections were thought to be more common in sufferers and perhaps some less common. I also knew of theoretical risks from abnormal hepcidin and its role in response to infection.

I also knew that I had personally suffered erysipelas on several occasions as an adult. Erysipelas is a nasty kind of skin infection that can lead to sepsis, and it used to kill people before antibiotics. I had always recovered with antibiotics, but I felt I must have some susceptibility for it to keep recurring. Later in life I suffered actual sepsis. Once after a prostate biopsy and I recovered well with intravenous antibiotics. It happened again several years later, after a prostate operation this time. On that occasion I nearly died. 

Above : a photograph of Erysipelas (red swelling) on the leg, but it can occur elsewhere on the body, too.

So I am now very wary if I get a skin infection and will be shouting out my susceptibility to my doctor if I get another bad one. In the past nobody might have taken much notice, but now it had been demonstrated and published in a major medical journal I can quote the evidence. That is important.

I do not know that my haemochromatosis was the cause of these infections or not. These things could easily have happened without haemochromatosis, and they do, all the time, to people. As time passes and more research is done, the situation will undoubtedly become clearer.

Doug Jenkinson
Retired GP
June 2024