New advances in the diagnosis and management of thalassaemia

(image: Wikimedia Commons)

Thalassaemia, an inherited blood disorder is the result of a genetic defect that causes anaemia (an insufficiency of red blood cells). According to Dr Natasha Sewpersad, a clinical haematologist based at Inkosi Albert Luthuli Central Hospital in Durban "Thalassaemia affects mainly people of Mediterranean as well as south and south-east Asian descent. It is especially common where there is a high rate of intermarriage within a community."

People who carry a single abnormal gene are said to have thalassaemia minor and patients who inherit two abnormal genes have thalassaemia major, which is much more severe. Thalassaemia minor is generally asymptomatic, although some patients may suffer from mild anaemia.

"Patients with thalassaemia major usually present aged six months to one year with severe life-threatening anaemia.

It is a chronic lifelong condition requiring frequent blood transfusions - every three to four weeks for life," says Dr Yasmin Goga, a paediatric haematology consultant also based at Inkosi Albert Luthuli Hospital.

Testing for thalassaemia major

The initial suspicion that a patient has a haemoglobin disorder is seen in a test called a 'full blood count' (FBC). Says Sewpersad: "The patient will have a low haemoglobin level and the red cells will be pale and small. Iron deficiency anaemia shows a very similar picture, so it's important to rule this out before diagnosing thalassaemia. We are able to get around this by measuring iron levels in the body and can only diagnose thalassaemia once any iron deficiency has been treated."

In the presence of an abnormal FBC and normal iron status, more sophisticated tests are then carried out to confirm the diagnosis.

Dr Sewpersad feels that South Africa's incidence of thalassaemia major is not high enough to recommend routine testing of all newborns. However, a basic haemoglobin assessment should be undertaken at all antenatal visits.

"GPs, nurses and obstetricians must be taught to suspect thalassaemia minor in Asian women with low haemoglobin levels and appropriate tests must be carried out as outlined above. In summary, while routine screening is not recommended, at risk groups must nonetheless be identified."

Complications

The most important and serious complication of thalassaemia major is iron overload. The human body has no mechanism of excreting excess iron, and constant blood transfusions cause excess iron from donor blood to accumulate gradually in vital organs at increasingly toxic levels. "The organs affected are the liver, heart and all endocrine organs," says Sewpersad. "Patients are consequently at risk for heart and liver failure and numerous hormonal disorders. Drugs that remove - the technical term is 'chelate' - iron are therefore essential."

Significant advances have been made in the treatment of iron overload. "Previously iron chelation required that the patient be attached to a pump for 8-10 hours, five nights a week, with a small needle inserted into the skin.

However, the advent of oral iron chelators has revolutionised the management of iron overload states.

A non-invasive imaging technique known as T2* MRI has also had a positive impact on the diagnosis and management of iron overload, allowing it to be detected easily and addressed before it reaches potentially lethal levels. "This is a remarkable technology that allows us to assess the iron burden in cardiac tissue. A similar technology, the R2, is available for liver tissue. This test helps us identify severe iron burden and alerts us to the need for intensification of iron chelation therapy," says Dr Sewpersad.

"Bone marrow transplantation can offer patients with thalassaemia major a cure. However this procedure is only carried out in specialised centres and is also associated with some clinical risk," says Dr Goga.

"The good news is that the management of thalassaemia is continuously improving. Early diagnosis, proper iron chelation and supportive care now ensure that patients with thalassaemia major can live full lives with careers and families of their own. Research in this field is ongoing and further breakthroughs in the understanding of the genetics of the disorder may one day revolutionise our approach to thalassaemia major," notes Dr Sewpersad.

Genetic testing

Genetic testing for thalassaemia, which allows for conclusive diagnosis, is not routine in South Africa. In the prenatal setting, these tests are performed on the parents. If thalassaemia minor is diagnosed in both parents, the chance that the baby will have thalassaemia major is 25%. The parents are then counselled. The testing on the baby is only conclusive after 6-12 months of age, as during the first six months of life high levels of foetal haemoglobin protect the baby.

"Genetic testing may be of significance in the future when we wish to correlate response to chelation with specific genetic patterns, when gene therapy is more refined and the disorder can be rectified at a genetic level," concludes Dr Sewpersad.

Successful testing in Cyprus

The Mediterranean island of Cyprus, divided between Greek and Turkish ethnic groups, has the world's highest rate of thalassaemia. Approximately one in seven Cypriots - 15% of the population - is a carrier, and when two carriers have a child, there is a high chance their child will have the disease.

Few Cypriots can afford the treatment and the cost to the government to treat these children threatened to consume the entire budget of the health ministries.

As a result, Cypriots on both the Greek and Turkish sides of the island introduced prevention programmes. In Greek Cyprus, the programme was run by the Cypriot Orthodox Church, which mandated premarital genetic testing followed by genetic counselling if both partners were carriers. For those who did conceive, prenatal testing was available.

These prevention programmes were remarkably successful. In 1985, Greek Cyprus achieved its goal of zero births of babies afflicted with the most severe form of the disease. Today, the birth rate in all of Cyprus has decreased to fewer than five cases per year from an expected rate of 70-80 cases without the use of prevention programmes.

Reference
1. https://www.counsyl.com/campaign/raising-awareness-beta-thalassemia

Thalassaemia fact sheet

• Thalassaemia is a hereditary genetic disorder of the blood.
  
• In people with thalassaemia, the production of normal haemoglobin is partially or completely suppressed, resulting in lack of red blood cells and thus anaemia.
  
• Thalassaemia affects mainly people of Mediterranean as well as south and South-East Asian descent. In South Africa, it is seen mainly in the Indian and Greek community.
  
• There are two main types of the disease - thalassaemia major and thalassaemia minor. Thalassaemia Major is a chronic condition requiring lifelong medical management, while the Thalassaemia minor is less severe and largely asymptomatic. Those with thalassaemia minor are often termed 'carriers'.
  
• Thalassaemia major is inherited via two mutated genes, one from each parent. It presents in childhood, usually between the ages of six months and one year. Children who do not receive treatment for thalassaemia major will die within their first decade.
  
• A multidisciplinary medical team needs to be involved in the care of a patient with thalassaemia major. The team should comprise a haematologist, endocrinologist, cardiologist, psychologist and dedicated nursing staff, as thalassaemia can have cardiac and endocrine/hormonal complications. Patients also require counselling and psychological support.
  
• The initial suspicion that a patient has a haemoglobin disorder is seen in a test called a 'full blood count'. Because iron deficiency anaemia shows a very similar picture, it's important to rule it out before diagnosing thalassaemia. Thalassaemia is only diagnosed once any iron deficiency has been treated.
  
• In the presence of an abnormal full blood count and normal iron status, more sophisticated tests are then done to confirm the diagnosis of thalassaemia.
  
• The primary treatment for thalassaemia major involves regular blood transfusions at 3-4-week intervals. This is necessary to maintain haemoglobin at normal levels and treat the anaemia.
  
• Blood transfusion exposes thalassaemia patients to a variety of risks, including infections. The most important is 'iron overload' consequent on the intake of iron from the donor blood.
  
• The human body lacks a mechanism for excreting excess iron, which means thalassaemia major patients need to undergo what is called 'chelation therapy' to remove the toxic iron build-up from their bodies.
  
• Together with blood transfusions, chelation therapy is the most important element in the treatment of thalassaemia.
  
• There have been significant advances in chelation therapy in recent years. Iron chelation once required that the patient be attached to a pump for 8-10 hours per night, five nights a week, with a small needle inserted into the skin. The advent of more convenient oral iron chelation treatments, in the form of a tablet that is taken dissolved in a glass of water, has greatly improved patients' quality of life.
  
• A non-invasive imaging technique known as T2* MRI has also had a positive impact on the diagnosis and management of iron overload, allowing it to be detected easily and addressed before it reaches potentially lethal levels. This technology is about to become available locally.
  
• The definitive treatment for thalassaemia major is a bone marrow transplant, which can cure the condition. The best match would be from a sibling. However, the procedure is not without risk and is only undertaken in specialist centres.
  
• The prognosis for thalassaemia minor is excellent and the management of thalassaemia major is improving all the time. Early diagnosis, proper iron chelation and supportive care now ensure that patients with the condition can live full lives with careers and families of their own.
  
• While thalassaemia cannot be eradicated in the same way as an infectious disease, a decreased incidence can be achieved by education of GPs and obstetricians about diagnosis of thalassaemia and who should be tested for the condition, notably possible carriers who are thinking of having children. Iron deficiency anaemia tends to be over diagnosed, while thalassaemia minor is often missed. This is dangerous if the diagnosis is missed in two people wishing to have a child, as there is then a high risk of the child being born with thalassaemia.
  
• The South African Thalassaemia Association is an excellent source of information on the condition and is committed to helping thalassaemia patients endure the rigours of their treatment and experience the joys of growing up, choosing careers and even having families of their own.

Compiled from information provided by haematologists, Drs Natasha Sewpersad and Yasmin Goga, Inkosi Albert Luthuli Central Hospital, and Sunil Soni, chairperson: South African Thalassaemia Association.