A matter of screening
An inherited blood disorder that may cause anaemia or death if not treated.
THALASSAEMIA is an inherited disease, passed on from parents to children through the genes.
If only one parent has an abnormal gene, the child may have a thalassaemia trait/ minor and be a carrier. People with thalassaemia minor are usually healthy and most go through life unaware of their status unless they have a blood test to screen for thalassaemia. This is easily done by asking for a full blood count (FBC) test.
Studies show that thalassaemia minor affords some protection against malaria. Interestingly, thalassaemia is most commonly seen in people from South-East Asia, the Mediterranean and the Middle East – all regions that have malaria.
The abnormal thalassaemia gene produces a defective haemoglobin molecule in red blood cells (RBCs), which results in a low mean corpuscular volume (MCV) and low haemoglobin concentration in blood tests.
As a result of this defective haemoglobin, the RBC is unstable, with a shorter life.
The thalassaemic RBCs are smaller in volume, and lighter or paler than normal RBCs.
Normally, haemoglobin helps carry oxygen from the lungs to the body via blood circulation. In thalassaemia, due to lower haemoglobin concentration, less oxygen is carried to the body.
Types of thalassaemia
There are two types of thalassaemia: alpha thalassaemia and beta thalassaemia.
Haemoglobin (Hb) has two beta chains and two alpha chains of haemoglobin. The two beta chains are coded for by two genes, and the two alpha chains.
Alpha thalassaemia – Alpha thalassaemia has reduced or absent alpha globin chains. As there are four alpha genes, that means that there are four types of alpha thalassaemia:
• Silent alpha thalassaemia (minor/trait): one alpha gene missing
• Alpha thalassaemia minor (minor/trait): two alpha genes missing
• HbH disease or thalassaemia intermedia: three genes missing
• Alpha thalassaemia major: four alpha genes missing (causes hydrops foetalis where the foetus does not survive, or dies at birth)
Beta thalassaemia – Beta thalassaemia has reduced or absent beta globin chains. There are three forms of beta thalassaemia:
• Beta thalassaemia trait/minor: one gene missing
• Beta thalassaemia intermedia (a clinical diagnosis caused by different combinations of genetic factors)
• Beta thalassaemia major: two genes missing
Thalassaemia can be divided according to their Hb levels. These are classified as:
• Thalassaemia trait or minor (thalassaemia carriers) who are normal and do not need transfusions.
• Thalassaemia intermedia, where their Hb is lower than 10g/dl; may need blood transfusions off and on.
• Thalassaemia major – If both parents pass the abnormal genes to the child, the child will have a thalassaemia major.
Haemoglobinopathies are different from thalassaemia as these result from a point mutation (change) in the globin chain.
The commonest haemoglobinopathy in Malaysia is HbE, in which there is point mutation in the beta globin chain.
HbE does not cause any health problems. A person with HbE should be counselled not to marry a person with beta thalassaemia trait as they would have a one in four chance of having a child with HbE/beta thalassaemia, resulting in beta thalassaemia intermedia.
Another haemoglobinopathy is Hb Constant Spring (HbCS). It involves the alpha globin chain.
Screening objectives
It is important to screen the population for thalassaemia if we are to reduce the number of beta thalassaemia major cases in the country.
Many people have their FBC done some time in their lives. If their MCV is less than 76 femtoliters or the mean corpuscular haemoglobin (MCH) is less than 26 picogram, they should be screened for thalassaemia.
Even if the patient is elderly, a Hb analysis of her family members would help identify all her relatives who may have the same type of thalassaemia. Then the younger ones can be counselled not to marry someone with beta thalassaemia if they themselves have beta thalassaemia trait.
By screening and counselling the general population with beta thalassaemia trait, Malaysia can achieve its target of no more new babies born with beta thalassaemia major by 2025.
This is important because only beta thalassaemia major patients require monthly blood transfusions (RBC transfusions will cause iron overload, so patients also need daily iron chelating therapy to remove the excess iron) to survive.
As thalassaemia and haemogloginopathies are inherited diseases, children and siblings of an affected person are also likely to be affected. Therefore, the most cost-effective method of screening is to test all the family members of someone identified with thalassaemia.
How does one test for thalassaemia? First, do a FBC. If the MCV is less than 76 fl and/or the MCH is less than 26pg, a Hb analysis is done.
There are two types of Hb analysis:
1. HPLC or Hb electrophoresis 2. Reticulocyte smear for “H” inclusions and a smear to look for Hb precipitate and/ or DNA studies for alpha thalassaemia.
The test needs to be done only once in a lifetime as thalassaemia is an inherited condition.
A written diagnosis is given so that the patient can show it whenever he/she sees a doctor.
All government hospitals have automated haematology analysers. The test is cheap and is a useful tool in screening for thalassaemia.
Every pregnant woman has a FBC done, and thalassaemia can be identified if those with low MCV and MCH are further tested.
Pertinent points
• A Hb E carrier can marry anyone except those with beta thalassaemia as there is a one in four chance of having a child with Hb E/beta thalassaemia.
• To prevent thalassaemia major/thalassaemia intermedia:
> A person with beta thalassaemia trait is counselled NOT to marry another person with beta thalassaemia trait in order to prevent the occurrence of a child with beta thalassaemia major.
> A person with beta thalassaemia trait is counselled NOT to marry a person with HbE to prevent HbE/beta thalassaemia, a thalassaemia intermedia.
> A person with alpha thalassaemia minor is counselled NOT to marry another person with alpha thalassaemia minor or one with Hb Constant Spring to prevent HbH Disease, an alpha thalassaemia intermedia.
• A person with alpha thalassaemia CAN marry a person with beta thalassaemia.
• A person with alpha thalassaemia CAN marry a person with HbE.
• Carriers should attend counselling sessions to fully understand the disease and consider what they can do to safeguard their future.
Datin Dr G. Duraosamy is a consultant haematologist. This article is courtesy of Gribbles Pathology Malaysia. The information provided is for educational purposes only and should not be considered as medical advice. The Star does not give any warranty on accuracy, completeness, functionality, usefulness or other assurances as to the content appearing in this column. The Star disclaims all responsibility for any losses, damage to property or personal injury suffered directly or indirectly from reliance on such information.