Case Note 1; Donating Blood To Keep Hereditary Haemochromatosis At Bay

3년 전



  • Iron is one of the most important minerals that we need to take on a daily basis to stay strong and healthy. Taking iron less than the recommended amount daily can predispose an individual to various medical consequences which could reduce their quality of life.

  • Iron is an essential component of a haemoglobin. It enables red blood cell to carry oxygens in the blood circulation system for distribution to all kind of cells in the body.

  • Without iron, haemoglobin will be incapable of transporting oxygen which could cause a variety of signs and symptoms such as iron-deficiency anaemia, hair loss, fatigue, weak immune system, pica etc. The majority of signs and symptoms are non-specific, which mean, if you experienced such, it could be something unrelated to iron deficiency.

But what happens if you have too much iron in the body?

  • If you have someone related to you (family, friends, your teacher, your cleaner or your lover) who had thalassemia major, you would realise after a few years of getting blood transfusions, the doctor would ask them to take some medication called the iron chelating agent.
  • Iron might be essential but if it exceeds the optimal amount needed by our body, it could become toxic. There are a few metabolic diseases which can be caused by excessive amount of iron accumulating in the body such as diabetes mellitus and hypothyroidism.

  • Without an iron chelating agent, people who need regular transfusion will have to endure the side effect of the treatment.

  • Today, I'm not going to talk about Thalassemia but I will share with all of you regarding a disease which would increase the amount of iron absorption in the small intestine causing multiple organs failure as a consequence of iron deposition.

  • Enter Hereditary Haemochromatosis


  • You might think, it is quite unfortunate for an individual to inherit such genes but this ailment is quite common among the Northern Europeans especially the Celtic. I mean it is estimated that 1 in 200 people have the disease while 1 in 10 people carry the disease.

  • The gene which is responsible for causing this ailment is called as the HFE gene. It can be found on the short arm of the chromosome 6 and mutation would lead to the substitution of amino acids in the 282nd position, yielding Tyrosine instead of Cysteine.

  • This changes the interaction between the TFR1 (a transferrin receptor) which plays an important part in the iron metabolism and the HFE protein.

  • The mutation which yields Tyrosine instead of Cysteine is the commonest kind which affects the production of HFE protein, hence, the iron metabolism. In some cases (rare), the mutation in the HFE gene yield Aspartic acid instead of Histidine in the 63rd amino acid's position.

Source: Wikimedia Author: Wellcome Images (CC BY 4.0)

  • Even though a large population in the Northern European inherited this disease, only a small portion suffer from the ailment. The reason behind this is still unknown but it can be due to multiple environmental factors such as diet.

  • Affected people were usually complaining of joints pain, a problem with erection and feeling lethargic at first. Later, signs of liver failure might develop. They will start to have cardiac problems, osteoporosis, diabetes mellitus, hypogonadism and hypoaldosteronism.

So, how does the iron overload happen?

  • Well, there are two theories which I know of that can explain why mutations in the HFE protein would lead to iron overload. The first theory concerns with an inappropriate increase in the transferrin signalling, while the second one, is lack of Hepcidin expression.

  • Now, there are a lot of words that you might not understand if I'm going to explain this deeply, so to avoid that, I will be summarising some of the important points from my own reading and understanding.

Source: Wikimedia Author: DFID - UK Department for International Development (CC BY 2.0)

  • For the first theory, the reason why there is an iron overload is due to an inappropriate signalling by the carrier protein called transferrin. Transferrin carries iron in the blood and this particular protein would be aided by HFE proteins.

  • When the level of iron is low, HFE proteins will bind to transferrin to increase the amount of iron release into the blood from the intestine. Based on that information, we would know that transferrin was abundant during iron deficiency.

  • A mutated HFE protein, however, will bind to the transferrin regardless the level of iron in the blood. The signal sent by the transferrin would allow the intestine to release iron as if there is a lack of that particular micronutrient in the blood circulation. This would, in fact, lead to iron overload.

  • Even though the theory sounds valid, there are a lot of people who have mutated HFE protein but didn't manifest any sign and symptoms of iron overload. Some people who manifest such symptoms could have normal HFE proteins. There must be some kind of alternatives theory which could explain that.

  • This brings us to the second theory, lack of Hepcidin expression. As opposed to the transport protein called Transferrin, the expression of Hepcidin will inhibit absorption of iron into the bloodstream.

  • There is 4 type of genes which control the expression of Hepcidin which are Hemojuvelin, HFE, Hepcidin and Transferrin. I'm not going to make it complicated, just know that mutation to any of the 4 genes will reduce the expression of Hepcidin.

  • This would lead to a decrease of iron absorption inhibition which would lead to iron overload.

  • Excess iron would be deposited on various organs leading to diseases depending on the site of accumulation; heart (dilated myocardiopathy), pancreas (diabetes mellitus), thyroid (hypothyroidism) etc.

Meet Mr H

Source: Wikimedia Author: Senior Airman Shane Karp

  • Mr H is an 83 years old gentleman who presented to the hospital complaining of abdominal pain. After an hour of history taking and physical examination, the doctor in charge run some investigations by sending some blood sample to the laboratory.

  • He was found to have Hereditary Haemochromatosis along with a liver mass filled with iron diagnosed as liver cancer without any sign of cirrhosis (scarring of the liver). This is quite strange since liver cancer is usually accompanied by liver scarring.

  • The liver is usually the first organ affected by the disease due to its role as the iron storage in the form of ferritin or haemosiderin. In this elderly gentleman, he experiences neither symptoms nor signs of the liver, heart, kidney or any organ failure that might cause by the disease process.

  • Some people might not have been implicated in the disease process but eventually, they will at a later age (40-50 years old) but for this gentleman, he was diagnosed at the age of 83 years old.

  • After a detailed history taking, it was revealed that this gentleman donated blood regularly since he was 20 years old. It is one of the many benefits of blood donation; saving people with Hereditary Haemochromatosis.

  • Currently, the most effective treatment to treat this ailment is a procedure called bloodletting. There are other ways that we can use to maintain the level of iron in the blood circulation such as taking a low-iron diet, taking iron chelating agents etc. but venesection is the most effective of all.

  • People who are diagnosed with Hereditary Haemochromatosis will need venesection once in every 2-3 months to maintain haematocrit level at an acceptable position. Since this gentleman has been donating blood quite regularly since he was 20 years old, he has been living healthily without him knowing it.

  • It was one of the most useful benefits of blood donation that can be seen.


  • I hope you learned something from this article. If there is anything wrong with the information provided in the article, leave your comment in the section below. I appreciate your help and support.

Thank you.


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