Before we discuss the different types of thalassaemia it would be usefull to cover some background information on haemoglobin disorders and DNA.

Haemoglobinopathies are a group of conditions affecting human blood - more specifically an important substance or protein called haemoglobin contained in the red blood cells, hence the name haemoglobin disorders or haemoglobinopathies.

These proteins constitute an important part of the human blood, which is the vital fluid that brings nourishment, such as oxygen (O2), hormones, proteins, fats and carbohydrates, to the body’s organs and tissues, and carries away waste substances such as carbon dioxide (CO2), urea and uric acid.


In adults, blood is exclusively produced in a special tissue called marrow, which is found in the central cavity of the bones (bone marrow). Blood consists of two major components:

  • Plasma, which is the yellow liquid that constitutes about 55% of the volume of blood and contains water, salts and important proteins.
  • 3 types of cells which are microscopic building blocks, trillions of which make up the human body.

The cells found in blood are:

  • The white cells or leucocytes
  • The platelets or thrombocytes
  • The red cells or erythrocytes

Each type of blood cell has specific functions and each contributes, in its own special way, to the well-being of the human organism, including protection against infection (white cells); limiting blood loss when a vessel is damaged (platelets); and provision of oxygen to tissues and vital organs (red cells).

Many diseases in humans are caused by abnormalities in the blood and these are categorized according to the component of the blood which is affected: white cell diseases, platelet diseases and red cell diseases.

Red cell diseases include amongst others the haemoglobinopathies or haemoglobin disorders, the most severe of which are alpha (α-) and beta (β-) thalassaemia and sickle cell disease.


Each cubic millimetre of human blood contains 4,500,000 – 5,000,000 red cells and each one of them is packed with 300 million molecules of haemoglobin -the substance that gives blood its red colour (because of a particular substance or metal it contains), and most importantly its oxygen carrying capacity (oxygen being essential for the growth and performance of the cells and organs of the human organism). The haemoglobin molecule itself consists of two major parts: (i) the globin and (ii) the haem:

Globin is a protein made up of smaller units, referred to as chains – the alpha (α) and the non-alpha such as beta (β), gamma (γ), and delta (δ) chains. The alpha (α) chains couple with equal amounts of beta (β) chains to make up the haemoglobin A (HbA), which is the main type of haemoglobin in adults and up to 10% of the haemoglobin of the foetus. Alpha chains also couple with other chains, making up the haemoglobins found at various stages of human life, from conception, through foetal life, to birth and after birth.

Globin Gene Cluster

The ‘haem’ part of the haemoglobin molecule contains iron – the metal that is essential for the growth and normal functioning of the cells and that gives blood its red colour. Iron has the capacity to easily bind and lose oxygen, providing the haemoglobin molecule with the capacity to carry and distribute oxygen to tissues and organs of the body. Adults have about 4g of iron in their body, 75% of which is used to synthesize the haemoglobin molecules of the red cells.

The level of haemoglobin found in a routine laboratory blood examination will, therefore, reflect the
level of the individual’s iron.


Haemoglobinopathies are genetic or hereditary disorders that are passed on from parents to children according to a specific pattern of inheritance known as “Mendelian recessive autosomal pattern of inheritance”. They are called genetic because all characteristics are passed on from parents to children through genes, which are the biological units of inheritance that provide all the information needed for controlling growth and development throughout human life. In the case of haemoglobinopathies, the contribution of genes is necessary from both parents (recessive inheritance) for the inheritance of these disorders, which can affect male and female children alike (autosomal).

Deoxyribonucleic Acid (DNA)

Deoxyribonucleic Acid (DNA)Deoxyribonucleic Acid is a chemical substance often referred to by its abbreviation, DNA, which constitutes the key component of genes, of which a great number are needed to carry out the many and complex biological functions of the human organism. Genes are linked together in the cell on long piles of DNA called chromosomes, of which there are 23 pairs, half inherited from one and half from the other parent.

In the case of adult haemoglobin, the production and synthesis of its α- and β-chains, which constitute its major component, is controlled by genes on specific chromosomes. Four α-genes on chromosome 16 and two non-α-genes, such as (β, γ and δ) on chromosome 11, are responsible for the production, in exactly equal numbers, of α- and β- chains, respectively.

The individuals who have a defect in one of the α-genes responsible for the production of α-chains, which may cause reduced production of these chains, are called α-thalassaemia carriers. If the defect involves more of the α-genes, then fewer α-chains are produced and the individual may be affected more significantly.

Similarly, a defect in the gene responsible for the production of β-chains may cause a small or a severe reduction of β-chains.The degree of β-chain reduction will determine whether an individual is only a β-thalassaemia carrier, or a patient with β-thalassaemia intermedia or major. 

In contrast to the thalassaemias, in which the defect in the genes results in reduced production of
α-and β- chains (α or β), there are conditions in which the defect in the genes results in the production of “wrong” kinds of proteins whose structure, as well as their function, are different from that of the adult common haemoglobin, (HbA). These are called abnormal or structural haemoglobin variants.

Extract from: 
Haemoglobin Disorders
By Androulla Eleftheriou (B.Sc., M.Sc., Ph.D, MBA)
And Michael Angastiniotis (MD, DCH)

The Major Haemoglobin Disorders are:

Alpha-Chain Disorders

ß-Chain Disorders

Sickle cell disorders


Sickle cell anaemia (HbSS)

HbH disease


alpha-thalassaemia Hydrops Fetails

HbSC disease

(=Hb Bart's Hydrops Fetails)

HbSD disease

alpha-chain variants


HbS/O Arab

Other rare sickling disorders


ß-thalassaemia major

ß-thalassaemia intermedia

HbE/ß-thalassaemia major

Other rare thalassaemias