• History & Background
• ...is a Blood Disorder
• ...is a Genetic Disorder
• ...Reason for Genetic Mutation

History & Background

Thalassaemia Major has existed in the world for hundreds of years. Dr. Thomas Cooley and Dr. Pearl Lee recognized it as a clinical entity only in 1925. Dr. Cooley and Dr. Lee described five cases of Thalassaemia Major, giving details of the condition, its causes and its effects. Being the first to detect the disorder as a form of anaemia, it came to be called as Cooley’s Anaemia.

It was found that this condition existed in large numbers in the areas bordering the Mediterranean Sea - a belt starting from Italy to Greece to Cyprus to Turkey - and then into Iraq, Iran, Pakistan and India. ‘Thalas’ means ‘the sea’ in Greek and therefore ‘Thalassaemia’ meant ‘anaemia found near the sea’.

Thalassaemia is the term that is widely used all over the world. But to give the historical perspective of its detection and geographical perspective of its prevalence, it is also referred sometimes as ‘Cooley’s Anaemia’ or ‘Mediterranean Anaemia’.

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...is a Blood Disorder

Blood is made up of the following components:

Red Blood Cells
Red Blood Cells (RBCs) give the red colour to blood. RBCs have a substance called haemoglobin, which plays the role of carrying the oxygen that we breathe in, to the various tissues of the body.

White Blood Cells
White Blood Cells are the defense mechanism of the body. Whenever the body is subjected to attacks from outside, WBCs swing into action and protect the body. They identify, destroy and remove any foreign material that has entered the body.

Platelets
Platelets are cells, which play the role of helping in clotting of blood. Whenever there is an injury platelets play a very important part in arresting the loss of blood by enabling the process of clotting.

Plasma
Plasma is the fluid part of Blood. It enables blood to flow, and plays the role of a carrier. It carries the RBCs, WBCs and Platelets. It also plays the role of carrying nutrients to the various parts of the body, and takes out the waste matter.

Thalassaemia Major is a disorder, which affects the Red Blood Cells in the Blood. The RBCs are full of haemoglobin, which carry the oxygen that we breathe, to the various tissues of the body. Haemoglobin is made up of ‘haem’ (iron component) and ‘globin’ (protein component). Two Alpha and two Beta chains form globin.

In the case of Thalassaemia Major, there is a reduction in the number of Beta Chains. This leads to improper globin synthesis, and lack of haemoglobin, leading to premature destruction of the RBCs. The child will not be able to carry oxygen to the various tissues of the body. This will prove fatal to the child unless it is monitored and treated properly.

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..is a Genetic Disorder

Every physical characteristic and function of the human body is controlled by a pair of genes. Genes are present in every cell of our body. You have two of every kind of gene, one passed on by your mother, the other passed on by your father. One of these two genes tends to dominate and the other is recessive. The characteristic/function acquired by a person depends on which parent’s gene dominates. There could be some characteristic where the mother’s gene dominates, whereas in other characteristics the father’s gene may. Among many other pairs of genes, you have two genes that control how haemoglobin is made in each of your red blood cells.

1. ‘Normal’ people are normal because they have two normal genes for haemoglobin. In other words, both parents have passed on normal genes for haemoglobin.
2. Persons with Thalassaemia Minor (also called ‘carriers’) have one normal gene and one altered gene for haemoglobin. They are healthy because the normal gene becomes the dominant gene. One of the parents has passed on the altered gene. Therefore, atleast one parent is definitely a Thalassaemia Minor.
3. People with Thalassaemia Major have two altered genes for haemoglobin. This means that both parents have passed on the altered gene. Therefore both parents have to be ‘carriers’.

If both partners in a marriage are Thalassaemia Minor, there are the following possibilities:

1. Both mother and father pass on the normal gene – child is ‘normal’.
2. Mother passes on the normal gene and father passes on the altered gene – child is a ‘carrier’.
3. Mother passes on the altered gene and father passes on the normal gene – child is a ‘carrier’.
4. Both mother and father pass on the altered gene – child is Thalassaemia major (serious problem).

Thus a Thalassaemia Major child is born only if both the mother and the father are Thalassaemia Minor.

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Causes of the ‘Altered’ Gene

Researchers have been able to identify the pair of altered genes, which cause a reduction in Beta Chains, leading to Thalassaemia Major. These genes are located on chromosome No. 11. Though it is difficult to pin-point the causes, it is clear that the genes underwent a mutation gradually over a few generations.

When one looks at the regions of the world that have a high incidence of Thalassaemia, one can see that these are the same areas that have had a problem of malaria. It is therefore being hypothesized that due to successive generations being subjected to malaria, the gene has undergone a mutation due to successive generations being subjected to malaria. This hypothesis has gained ground also because of the fact that people carrying the altered gene are known to have a lesser risk against malaria.

In short, many successive generations of the population being subjected to malaria has resulted in a genetic mutation. The ‘altered’ gene now gives improper instruction leading to a reduction in ‘beta’ chains resulting in improper synthesis of ‘globin’. The consequent lack of haemoglobin results in premature destruction of Red Blood Cells, leading to inability to deliver oxygen to the various tissues of the body.