Haemoglobin is the component in red cells that is responsible for transporting oxygen from the lungs to all parts of the body. Normal haemoglobin comprises two α globin chains and two β globin chains, and each of these protein chains carry an iron-containing haem group which binds to oxygen.
Haemoglobinopathies are a group of inheritable conditions which affect the quantity and/or structure of the haemoglobin. The most common haemoglobinopathy in Singapore and Southeast Asia is thalassaemia.
In each individual, there are four α genes (two inherited from each parent) and two β genes (one inherited from each parent). They signal the production of the α globin chains and β globin chains respectively in haemoglobin.
Persons with thalassaemia mutations of the α globin genes (α thalassaemia) have reduced production of α globin chains and those with thalassaemia mutations of the β globin genes (β thalassaemia) have reduced production of β globin chains, resulting in decreased quantities of haemoglobin.
There are different types of thalassaemia, which are primarily classified into two main categories:
1. Alpha Thalassaemia: This type occurs when there is a mutation or deletion in one or more of the four genes responsible for making alpha-globin, a component of haemoglobin. The severity depends on how many genes are affected:
2. Beta Thalassaemia: This occurs when one or both of the genes responsible for producing beta-globin are mutated. It is categorised as:
The symptoms and complications of thalassaemia will depend on its severity. This is determined by the number of globin genes involved and the type of thalassaemia mutations.
Persons with thalassaemia trait could have mild anaemia but usually do not have symptoms or complications from thalassaemia. These persons may have only one β globin gene affected by thalassaemia (β thalassaemia trait) or at most two α globin genes affected by thalassaemia (α thalassaemia trait).
Persons with non-transfusion dependent thalassaemia (NTDT) would usually have moderate anaemia and may experience intermittent symptoms of anaemia such as giddiness or breathlessness as well as intermittent transfusions. They usually experience enlargement of the liver and spleen which may sometimes cause abdominal discomfort. They may also develop other complications related to the thalassaemia, such as high blood pressure in the lungs which can cause breathlessness and decreased effort tolerance. Extra sites for production of haemoglobin outside of the bone marrow such as in the spine can cause back pain, lower limb weakness and numbness. They may also develop ankle/foot ulcers. Persons with NTDT may have both β globin genes mutations, causing only a mild decrease in the production of β globin chains. Hb H disease is when three α globin genes are mutate.
Persons with transfusion dependent thalassaemia (TDT) would usually have severe life-threatening anaemia, and require regular blood transfusion for survival from less than 2 years old. Persons with TDT would usually have both β globin genes affected by severe mutations, resulting in absent or negligible β globin chains.
As α globin chains are also needed to produce foetal haemoglobin, foetuses with all four α globin genes affected by thalassaemia mutations would have a very severe form of α thalassaemia, known as Bart's hydrops fetalis. Without intervention, foetuses with Bart's hydrops fetalis usually die during the pregnancy or soon after birth. The mother carrying the foetus with Bart's hydrops fetalis may also experience serious complications.
You should see a doctor if you experience persistent fatigue, weakness or shortness of breath. These symptoms may indicate anaemia, which can be linked to thalassaemia. If there is a family history of thalassaemia or unexplained anaemia, it is important to seek medical advice for proper testing and diagnosis.
Thalassemia is a genetic condition and cannot be prevented.
Screening for thalassaemia in couples who are planning to have children or are expecting a child is recommended. If both parents carry the same type of thalassaemia mutations (i.e. both have α thalassaemia or both have β thalassaemia) they are at risk of having children with clinically significant thalassaemia. Antenatal testing of their foetuses for thalassaemia mutations may be carried out by the foetal maternal specialists using specialised procedures.
Thalassemia is a genetic condition and is caused by mutation in the genetic material of cells that make haemoglobin which is involved in the transportation of oxygen. This mutation can be passed from parents to their children.
The main risk factors for thalassaemia include:
Family history: If either parent carries the genetic mutations responsible for thalassaemia, there is a higher likelihood of inheriting the condition. This is especially true for both alpha and beta thalassaemia.
Ethnic background: People of certain ethnicities are at higher risk. Thalassaemia is most common among those of Mediterranean, Middle Eastern, South Asian and African descent due to the higher prevalence of the genes that cause this condition in these populations.
Carrying the thalassaemia gene: Even if an individual does not show symptoms, they may be a carrier of the thalassaemia trait (thalassaemia minor) and can pass it on to their children.
Initial screening for thalassaemia involves blood tests such as
In SGH, we have a specialist Thalassemia Clinic with a dedicated multidisciplinary team consisting of doctors, nurses and social workers.
NTDT patients will need regular monitoring for complications. Some may need intermittent blood transfusion when there are exacerbations of anaemia during pregnancies, infections, or in preparation for surgeries. Some may also need more regular transfusions for specific periods of their lives to prevent or treat complications associated with the thalassaemia such as delayed growth and development. They may develop iron overload from increased gut absorption, and/or transfusions which can affect the heart, liver and endocrine system. Medications are available to chelate iron to prevent the adverse impact on the functions of these organs.
TDT patients need regular blood transfusions every 3- to 5-weekly. They also need regular monitoring for complications from iron loading as a result of the frequent transfusion. Iron chelation therapy is needed to prevent the adverse impact of the iron on the functions of the heart, liver and endocrine system. Haematopoietic stem cell (HSC) transplant is potentially curative and may sometimes be carried out on TDT patients if there is an eligible matched HSC donor (usually a sibling). Such transplants are usually performed during childhood when the transplant outcomes may be better. Gene therapy is another potentially curative treatment that is studied – it currently remains experimental in most parts of the world.
Treatment depends on the severity of the condition. Mild cases may not require treatment, while more severe cases need regular blood transfusions, iron chelation therapy to manage iron overload and in some cases, haematopoietic stem cell transplants for a potential cure.
Women with thalassaemia or those carrying the trait may experience complications during pregnancy, such as worsening anaemia. In severe cases like Bart's hydrops fetalis, the condition can lead to life-threatening outcomes for the foetus and complications for the mother.
Yes, genetic testing can identify whether individuals carry the thalassaemia trait. This is particularly helpful for couples planning to have children, as it can assess the likelihood of passing on thalassaemia mutations to their offspring.
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