What is Thalassaemia?

Thalassaemia is an inherited blood disorder that leads to decreased haemoglobin production. Thalassaemia is primarily of 2 different types:

a. α-thalassaemia (or alpha thalassaemia) occurs when a gene or genes related to the α-globin protein are altered or deleted (mutated).

b. β-thalassaemia (or beta thalassaemia) occurs when similar gene defect affects the production of the β-globin protein.

Thalassaemia may be manifested in many forms. Each of the types mentioned above can be further broken down into different subtypes.  Both α-thalassaemia (or alpha thalassaemia) and β-thalassaemia (or beta thalassaemia) include the following 3 subtypes:

Thalassaemia major

Thalassaemia intermedia

Thalassaemia minor (also known as thalassaemia trait).

Patients with thalassaemia may or may not require blood transfusions. Patients requiring blood transfusions are said to have transfusion dependent thalassaemia (TDT). Patients who do not require periodical blood transfusions are said to have non transfusion dependent form of thalassaemia (NTDT).

Physiology of Haemoglobin

Physiologically, the globin chains  are formed by a balanced combination of α and non α-globin chains, i.e. the β-  globin chains, γ-globin chains and δ-globin chains. The α-globin chains form the adult haemoglobin (HbA) when coupled with the β-globin chains. The α-globin chains together with δ-globin chains form a small fraction of the adult haemoglobin (called HbA2) and the fetal haemoglobin (HbF) when it is coupled with the γ-globin chains). 

When there is decreased production of one of the globin chains but the other globin chain is normally produced, there will be an excess accumulation of the other unpaired globin chains within the developing red blood cells (RBC’s). This means that when α-globin chains are not adequately produced there will be an excess accumulation of β-globin chains (leading to α-thalassaemia) and when β-globin chains are are not adequately produced there will be an excess accumulation of α-globin chains (leading to β-thalassaemia).

The excess globin chains accumulating in the red blood cells (RBC’s) cause its breakdown also known as ‘haemolysis’. This leads to decreased availability of haemoglobin to transport oxygen to different parts of the body, causing ‘anaemia’. 

Transfusion dependent thalassaemia (TDT) and non transfusion dependent thalassaemia (NTDT) are quite fluid terminologies.  A patient who may not require transfusions initially (NTDT) may start requiring transfusions based on clinical parameters. So, these terms are often interchangeable. NTDT may manifest in any of these 3 clinically different forms:

β-thalassaemia intermedia

Haemoglobin E/β-thalassaemia (mild and moderate)

α-thalassaemia intermedia