Haemoglobin, which forms more than 50% of the red blood cell cytoplasm, is the carrier molecule of oxygen from the lungs to various tissues in our body.
It is a complex molecule that is made up of 4 separate globin chains. two of them are called alpha chains, and the other two are called beta chains.
Haemoglobin has a pocket to bind O2, which allows it to act as a transport protein.
There are several types of haemoglobin molecules in our body.
The kind containing 2 alpha chains and 2 beta chains I mentioned earlier is called HbA.
This is also the most common type of haemoglobin.
However, during the foetal period and even up to 6 months after we are born, the predominant kind of haemoglobin is HbF.
In HbF, there are 2 gamma chains instead of the beta chains.
Other less common types of haemoglobins like HbA2 are also seen at various stages of our life cycle.
Thalassaemias
Thalassaemias result from reduced production of haemoglobin due to a defect in the synthesis of one or more of the globin chains.
Depending on where the defect is, there are two types of thalassaemias, alpha and beta.
Beta Thalassaemia
The genetic information needed to produce alpha chains is recorded in the 11th chromosome in humans.
There is one gene on each copy of chromosome 11.
Due to a mutation occurring in one point of the gene, it could become non-functional and lose the ability to produce beta globin chains. One or both of the genes could get affected, resulting in 2 clinical pictures.
- 1 gene affected: beta thalassaemia minor
- both genes affected: beta thalassaemia major
In beta thalassaemia minor, as there is still one functional gene remaining, the body is able to compensate and keep the Hb concentration at a near normal level.
The Hb level could be normal or slightly reduced.
These people will usually show no clinical symptoms, but may become anaemic during pregnancy due to further haemodilution.
Beta thalassaemia major on the other hand, is dangerous.
They will have severe anaemia with obvious splenomegaly, hepatomegaly and changes in the skeletal system as the body tries to compensate.
That these symptoms will appear only after a few months from birth, as during the initial period the child’s prominent type of haemoglobin will be HbF, which does not contain any beta chains.
Beta thalassaemia major patients will become transfusion dependant in their first year of life, and are likely to die during the second or third decades of their lives.
Most of the time, their deaths are due to endocrine and cardiac complications caused by the iron overload from frequent transfusions.
There is also a third subset of beta thalassaemia called thalassaemia intermedia.
These patients will have symptoms of anaemia, but will not need regular blood transfusions.
Alpha Thalassaemia
The genetic information needed to produce alpha chains is recorded in the 16th chromosome in humans.
Unlike for beta chains, there are four genes altogether coding for alpha chains, 2 on each copy of chromosome 16.
Alpha thalasaemia occur usually due to whole gene deletions.
Point mutations are rare, unlike in beta thalassaemia. According to how many genes get deleted, there are several kinds of thalassaemias.
- 1 or 2 genes deleted: alpha thalassaemia trait
- 3 genes deleted: HbH disease
- all 4 genes deleted: hydrops fetalis
Alpha thalassaemia trait is usually a symptomless condition requiring no treatment.
HbH disease, where only one alpha globin allele is functioning results in moderate to severe anaemia which might require blood transfusions occasionally.
Deletion of all 4 alleles is not compatible with life beyond the foetal stage.
Foetal death occurs. This condition is also called hydrops foetalis.
Unlike beta chains, alpha chains are a part of both HbA and HbF, hence it will affect the foetal stages of life as well.
The diagnostic tests for alpha and beta thalassaemias are somewhat different.
Beta thalassaemia can be diagnosed using a process called haemoglobin electrophoresis.
It is a test that measures the different types of haemoglobin in the blood.
Usually there is a HbA predominance, followed by small amounts of HbA2 and HbF.
In patients with beta thalassaemia the levels of the other two types of haemoglobins will increase with a reduction in HbA.
Another technique that can be used in confirming beta thalassaemia is High Performance Liquid Chromatography (HPLC).
Alpha thalassaemia however cannot be diagnosed so simply as that.
As alpha chains are a part of all types of haemoglobins, all forms of Hb will be decreased.
The diagnosis requires DNA studies and molecular diagnostic techniques.
The blood picture will be quite similar to iron deficiency anaemia in thalassaemia trait patients.
Hypochromic microcytic cells will be evident and target cells will also be seen with poikilocytes.
A special feature of HbH disease is the presence of golf ball inclusions. They are actually precipitated beta tetramers formed due to the deficiency in alpha chains.
A full blood count or blood picture may direct you towards suspecting thalassaemia, but a diagnostic test is necessary before the initiation of treatment.
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