Thalassaemia

Red blood cells are very important because they contain a substance called haemoglobin, which carries oxygen from the lungs to the rest of the body. Haemoglobin is produced in the bone marrow (a spongy material found inside larger bones) using the iron that the body gets from food.

In thalassaemia, haemoglobin production is abnormal, leading to anaemia and a reduced oxygen-carrying capacity. If your body doesn't receive enough oxygen, you can feel tired, breathless, drowsy and faint. If left untreated, the most serious types of thalassaemia can cause other complications, including organ damage, restricted growth, liver disease, heart failure and eventually death. Symptoms of anaemia include lethargy (a lack of energy), tiredness and breathlessness, particularly after exercise.

In England, beta thalassaemia major (BTM) is thought to affect around 1,000 people, with an estimated 300,000 people being carriers.

It most commonly affects people of Cypriot, Indian, Pakistani, Bangladeshi and Chinese origin. In the UK, eight out of 10 babies born with thalassaemia have parents of Indian, Pakistani or Bangladeshi ancestry

Thalassaemia is caused by alterations (mutations) in the genes that make haemoglobin.

Haemoglobin is made up of matching chains of proteins, which are named after Greek letters of the alphabet. To work properly, haemoglobin needs a pair of alpha chain proteins and a pair of beta chain proteins.

A mutation that affects the alpha chain causes alpha thalassaemia, and a mutation that affects the beta chain causes beta thalassaemia. These are now known as Transfusion Dependent Thalassaemia (TDT) and Non Transfusion Dependent Thalassaemia (NTDT).

The alpha chains are produced by four genes, two on each chromosome 16, which are inherited as pairs. The severity of the condition will depend on how many of those genes have been altered. If one gene is mutated, there's little or no effect. If two genes are mutated (one on each chromosome), there may be symptoms of mild anaemia. This condition is known as the alpha thalassaemia trait, a person with thalassaemia trait is also known as a carrier.

If two people with the alpha thalassaemia zero trait (when two genes on the same chromosome are altered) have a child, there's a one in four chance of the child inheriting the most severe form of alpha thalassaemia.

If three genes are mutated, the result will be a condition called haemoglobin H (HbH) disease. Someone with this condition will have lifelong (chronic) anaemia and may require regular blood transfusions, but not always.

If all four genes are mutated, the result will be the most severe form of alpha thalassaemia, known as alpha thalassaemia major. Infants with this condition are unable to produce normal haemoglobin and are unlikely to survive through pregnancy. There have been some cases of unborn babies being treated with blood transfusions while still in the womb, but this type of treatment has a low success rate and is not commonly undertaken.

Unlike alpha genes, there are only two beta genes, one each on chromosome 11.

Beta thalassaemia can range from moderate to severe. The most severe form of the condition is known as transfusion dependent thalassaemia (TDT)/ beta thalassaemia major (β thalassaemia major), where both beta genes are affected. People with TDT will require blood transfusions for life starting from a few weeks to months old.

Beta thalassaemia intermedia (βThal int) is the milder form of the condition, which is also known as non-transfusion-dependent thalassaemia (NTDT). The symptoms of NTDT will vary from person to person. Some people will experience symptoms of mild anaemia, while others will need blood transfusions.

These pages mainly focus on β Thal Major/ TDT, which is the most common and severe form of the condition in the UK.

Thalassaemia is an inherited condition, which means it is passed on to you from your parents.

It's not known exactly what causes the genetic mutations associated with thalassaemia. However, it's likely they've survived because carriers of the condition (both alpha and beta thalassaemias) are protected against malaria.

This is why thalassaemia and other related genetic blood disorders, such as sickle cell anaemia, are more common in parts of the world where malaria is a problem, including certain Mediterranean countries such as Greece, Cyprus and Italy, the Middle East, Asia and sub-Saharan Africa.

Individuals with thalassaemia syndromes are encouraged to obtain genetic counseling before starting a family. More information can be found at:

http://www.nhs.uk/Conditions/pregnancy-and-baby/Pages/screening-sickle-cell-thalassaemia-pregnant.aspx

Living with TDT can be challenging. You'll need to have regular check-ups to assess and reduce the risk of possible complications.

As well as the chronic anaemia complications of thalassaemia can include:

• Iron overload – people with TDT need blood transfusions from an early age. This causes individuals to become overloaded with iron. The excess iron from the transfusions causes an accumulation of iron within the blood as well as in the organs. If left untreated, serious and potentially life threatening problems can occur. This can range from cirrhosis of the liver to diabetes. In order to treat this, individuals are given chelation therapy (see below) in order to remove the excess iron. Iron overloading also occurs in NTDT as they have increased gastrointestinal absorption of iron
• An enlarged spleen – where the spleen has problems recycling red blood cells, making it grow larger
• Hormone complications – including delayed puberty and restricted growth
• Heart complications – such as an irregular or disturbed heartbeat (arrhythmia)
• Liver complications – such as hepatitis (swelling of the liver) or an enlarged liver (fibrosis)