Classification of Thalassaemias

Classification of the Thalassaemias is a potentially detailed topic due to the complex inheritance and different clinical presentations. A simplified classification of these rare diseases can be presented under two headings:

• the types of abnormal haemoglobin and their inheritance
• the clinical presentations

Haemoglobin abnormalities

Haemoglobin A, which comprises 98% of the body’s normal haemoglobin, is composed of two alpha and two beta polypeptide chains. Polypeptides are the building blocks of proteins. The configurations of the alpha and beta chains are controlled by genes inherited from both parents. In the Thalassaemias the production of the alpha and/or beta chains may be defective. Red cells containing defective chains are unstable and tend to disintegrate in the blood stream, a process called haemolysis. The oxygen carrying capacity of the blood is reduced due to a deficiency of normal haemoglobin, and the person may become anaemic. The body responds by increasing production of red cells in the bone marrow.

Thalassaemia is classified on the basis of the defective polypeptide chains.

Beta-Thalassaemia

Beta-Thalassaemia occurs when there is decreased synthesis of the beta polypeptide chains. If the abnormal gene for the condition is inherited from one parent the affected person is described as a carrier or as having the Thalassaemia trait. They usually have no ill effects from the condition or have a mild anaemia that is asymptomatic. This condition is called Thalassaemia minor.

If the abnormal gene for beta polypeptide synthesis is inherited form both parents a much more severe anaemia develops in the affected child. This is known as beta Thalassaemia major or Cooley’s anaemia.

Alpha-Thalassaemia

Inherited abnormalities of the alpha peptide chains also occur; these are known as alpha-Thalassaemia. The pattern of inheritance is more complex since there are more genes controlling the synthesis of alpha chains. People with alpha-Thalassaemia trait may have mild anaemia but are usually asymptomatic. Some types of alpha-Thalassaemia cause mild-moderate anaemia e.g. haemoglobin H, which may cause symptoms and require treatment. The most severe types of alpha Thalassaemia are usually incompatible with life, the foetus dies in the uterus or affected babies die soon after birth (alpha Thalassaemia major).

Other types of Thalassaemia

E-Beta Thalassaemia occurs when abnormal haemoglobin, Haemoglobin E, occurs with beta-Thalassaemia. It is found in people from Southeast Asia and causes a moderately severe anaemia. In some patients this results in a Thalassaemia Major type clinical picture and in others it behaves clinically more like Thalassaemia Intermedia.

Sickle beta Thalassaemia may occur in communities where one parent carries the Thalassaemia trait and the other the sickle cell trait – click here for Sickle Cell guidance. The severity of the resultant anaemia varies between individuals. Sickle beta Thalassaemia behaves clinically like sickle cell disease.

Clinical classification of Thalassaemias

(Beta) – Thalassaemia major

In this clinical group normal haemoglobin production is reduced to such a degree that severe anaemia is inevitable. Normal growth and development can only be sustained from infancy by regular blood transfusions. Without these death occurs in early childhood. People in this group may be described as having transfusion dependent Thalassaemia.

(Beta)-Thalassaemia intermedia

People in this clinical group produce reduced amounts of haemoglobin and have long-term anaemia. However survival and normal growth/ development are possible without regular blood transfusions. These individuals survive into late childhood or adulthood. They may however require blood transfusions at times, and they may develop other complications due to long-term anaemia. Because they are chronically anaemic they absorb too much iron from the diet and develop iron overload even without blood transfusions. Complications of iron overload such as diabetes tend to occur in the 20s. Once iron overload has developed they will require treatment – see treatment section.

Thalassaemia minor

People in this group have only mild to moderate anaemia. They usually have no symptoms and live normal lives. They may be known to have the condition because of a family history of Thalassaemia, screening or as an incidental diagnosis when a routine blood test is taken for the investigation of another medical condition.

Diagnosis of Thalassaemia

Diagnosis is made by blood tests that identify the type and amount of abnormal haemoglobin (s).

Amended May 2009