The thalassemias are inherited blood disorders characterized by decreased haemoglobin production.


There are two main types of thalassaemia:

  • α-thalassaemia (or alpha thalassaemia) occurs when a gene or genes related to the α-globin protein are missing or changed (mutated), and
  • β-thalassaemia (or beta thalassaemia) occurs when similar gene defects affect production of the β-globin protein.

There are many forms of thalassaemia:

Each one of the above mentioned types has many different subtypes. Therefore, both α- and β- thalassaemia include the following three forms:

  • Thalassaemia major
  • Thalassaemia intermedia
  • Thalassaemia minor (or thalassaemia trait)

There are transfusion-dependent (TDT) and non-transfusion dependent forms of thalassaemia (NTDT).


In the physiological situation, the globin chains are a balanced combination of the α-globin chains to the non-α-globin chains, which are mainly β-chains, which, coupled with α-chains form adult haemoglobin (HbA), or with δ-chains, forming a minor fraction of adult haemoglobin (HbA2) or γ-chains, forming the fetal haemoglobin (HbF).

Any reduced production of one of the globin chains while the other chains are normally produced, means that there will be an accumulation of the other (unpaired) globin chains, within the developing red cell. In this way if α-globin chains are not produced in adequate amounts there will be an accumulation of β-globin chains (α-thalassaemia); if β-globin chains are inadequately produced then α-globin chains will accumulate (β-thalassaemia).

These excess globin chains precipitate in the red cell and cause its destruction. This results in anaemia (reduced availability of haemoglobin to carry oxygen), and the production of many unhealthy red cells in the bone marrow cavity where they are normally produced – this is called ineffective production of red cells (ineffective erythropoiesis). The anaemia results usually in the need to correct it by blood transfusion.

In the most severe forms of beta thalassaemia the anaemia is so severe that unless it is corrected regularly by blood transfusion the patient will die early in life (mostly in infancy). The condition is then known as transfusion dependent thalassaemia or TDT. Other cases may be able to survive with occasional or no blood transfusions, known as non-transfusion thalassaemia or NTDT (see figure).

It should be noted, however, that TDT and NTDT are fluid categories based on clinical parameters and variations. Modifiers of disease may shift a patient from one group to another during their lives – thus these designations should primarily represent patients’ ‘current’ clinical status with the understanding that they are interchangeable. NTDT encompasses three clinically distinct forms: β-thalassaemia intermedia, haemoglobin E/β-thalassaemia (mild and moderate forms), and α-thalassaemia intermedia (haemoglobin H disease).

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