Alpha thalassaemia

Alpha thalassaemia is a form of thalassaemia where at least one of the four alpha genes is missing or defective. This is inherited and genetic, which means that you get it from one or both of your parents.

There are several types of alpha thalassaemia. The type you have depends on how many of the four genes are missing and whether the missing gene(s) comes from one parent or both.

Red blood cells in people with thalassaemia are smaller and paler than in people without thalassaemia. This is because they contain less haemoglobin.

This does not matter too much in milder forms of alpha thalassaemia (when you miss one or two of the alpha genes). Your body will still usually make more red blood cells to keep your haemoglobin levels within, or close to, the normal range. It is when you miss three of the four genes that you may experience some problems.

If all four alpha genes are missing, a developing foetus won’t be able to make haemoglobin and it will need a blood transfusion to survive.

Genes are made of DNA. Each gene (on its own or in partnership with other genes) has a certain function. For example, a gene responsible for blue eyes or curly hair.

Most genes occur in pairs, where one is inherited from your father and one from your mother. A heterozygote is a person who has inherited two different copies of a particular gene. The faulty gene from one parent and the healthy one from the other. A homozygote is a person who has the same copy of a faulty gene, usually one from each parent.

If you are a carrier of thalassaemia, it means that you carry the faulty genes that cause thalassaemia. But you don’t show signs or symptoms of the full disease. Being a carrier is also known as having thalassaemia trait.

A person with alpha plus thalassaemia trait (heterozygote) is missing one of the four genes. They would have smaller, paler red cells than usual. But they would be healthy and wouldn’t suffer any ill effects from this (such as anaemia). 

Alpha plus thalassaemia is very common. About one in three people who originate from Africa or the Indian sub-continent carry it. It is also common among people from the Mediterranean area, the Middle East or South-East Asia. Some North Europeans are also affected.​​​​​​​

A person with alpha plus thalassaemia trait (homozygote) is missing two of the four genes. One gene is missing from the pair inherited from the mother, and the other from the pair inherited from the father. The person would have smaller, paler red cells than usual, and they might be mildly anaemic. Other than that they would be healthy and wouldn’t suffer ill effects from this.

A person with alpha zero thalassaemia trait (heterozygote) is missing two of the four genes. But both genes are missing from the genes inherited from one parent. The person would have smaller, paler red cells than usual, and they might be mildly anaemic. Other than that they would be healthy and wouldn’t suffer ill effects from this. This trait is mostly seen in people whose ancestry is from Greece, Turkey, Cyprus and South-East Asia.

It is important to identify people with alpha zero thalassaemia before they start a family. This is because they are at risk of having a child affected by alpha thalassaemia major if their partner also has alpha thalassaemia trait (heterozygote). See Alpha thalassaemia major section on the next page. 

A person with haemoglobin H (HbH) disease is missing three of the four genes. Two genes are missing from the genes inherited from one parent, and one gene is missing from the genes inherited from the other parent. The person would have smaller, paler red cells than usual, and they would be anaemic. Most people with HbH are healthy, but they experience difficulties when the body is physically stressed. For example, in pregnancy, when they are unwell or with intense exercise. Some people may need transfusions in these circumstances.

Here all four genes are missing.

If two people with the alpha zero thalassaemia gene make a baby, there is 1 in 4 risk that their baby will have alpha thalassaemia major.

As a developing foetus needs alpha genes to grow, it will become severely anaemic and die before being born without a blood transfusion.

Babies who have had a blood transfusion in the womb and are born with alpha thalassaemia major need lifelong treatment. 

The NHS antenatal screening programme includes blood tests to identify couples that are at risk of passing two alpha zero thalassaemia genes to their children. This is done by testing the mother’s blood when she registers her pregnancy.

Ideally, couples who are at risk should know this before they get pregnant. The initial test would be a regular blood count to see if the cells are small and pale. This can be done before pregnancy through the following routes:

• the GP
• the haemoglobinopathy genetics service at UCLH
• local sickle cell and thalassaemia centres
• your haematologist.

The only way to diagnose alpha thalassaemia and find out the type you have is through genetic testing.

As most of the alpha thalassaemia conditions don’t make people unwell, genetic testing is rarely done. For example, it can be carried out if it is unclear why your red cells are small and pale.

But genetic testing is vital to identify couples where both potential parents may carry the alpha zero thalassaemia gene. It provides information about their own risk of having a child with alpha zero thalassaemia.

There may be a few reasons why this has been missed:

• If you are an alpha thalassaemia carrier, your red blood cells will be smaller and paler compared to those of someone who isn’t. But your red blood cell count won’t be much different. This may make you a little anaemic but it won’t cause any other problems.
• The special test (called a haemoglobinopathy screen) you may have had to test for sickle cell disorder and beta thalassaemia has come back normal.

Genetic testing to diagnose alpha thalassaemia is not always offered if the iron stores and the haemoglobinopathy screen are normal.

Iron and vitamins

If you are a carrier of alpha thalassaemia and you are anaemic, your diet should be rich in iron and vitamins. This will help to make sure that your anaemia doesn’t get worse.

You should only take iron medicine if a special blood test (iron profile or ferritin) shows that you are short of iron. Taking iron medicine when you are not short of iron can lead to a build-up of iron in your organs. This can lead to organ failure.

A baby can only be affected by alpha thalassaemia major if both parents have alpha zero thalassaemia trait or HbH disease. This should be picked up through a blood test in pregnancy. The pregnant woman’s blood test result would alert the healthcare team to check the father of the baby. It is also possible and recommended to have these tests before becoming pregnant.

If you are a carrier of alpha zero thalassaemia or have HbH disease, your partner can have a blood test for haemoglobin disorders. This can be done at their GP or local sickle cell and thalassaemia centre. If your partner is also a carrier, you can ask your GP for an appointment with a specialist counsellor. You will then have a chance to discuss what it means to be at risk of having a child with a serious haemoglobin disorder.

NHS sickle cell and thalassaemia (SCT) screening programme

Website: gov.uk/guidance/sickle-cell-and-thalassaemia-screening-programme-overview
UK Thalassaemia Society
Tel: 020 8882 0011
Email: office@ukts.org
Website: ukts.org

University College London Hospitals NHS Foundation Trust cannot accept responsibility for information provided by external organisations.

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