By Lau Hui Chong
(Published in’Campus & Beyond’, a weekly column written by Swinburne academics in the Borneo Post newspaper)
Thalassemia is one of the most prevalent genetically inherited diseases today. Although it is more prominent in the Mediterranean region, Africa and some parts of Asia, approximately 150 to 200 million people or 4.5% of the world’s population are carriers of thalassemia. In Malaysia alone about 5% of the population are at risk of thalassemia transmission.
The disease is a result of errors in the production of haemoglobin, a globular protein which is extremely important in the transportation of oxygen in the body. Each red blood cell contains about 300 million molecules of haemoglobin. Each molecule of haemoglobin contains two subunits, namely the alpha and beta, which are necessary for the proper binding of oxygen in the lungs and the delivery of this vital gas to the tissues in other parts of the body. The lack of these subunits is due to the errors in the genes on the appropriate chromosomes.
Thalassemia may be passed on from parent to child in an autosomal recessive pattern. This means two copies of an abnormal gene must be present for the disease to develop. If each parent carries one copy of the recessive gene, also known as carrier, there is a possibility that their child will have thalassemia. If only one parent has the gene, the child is potentially a carrier.
The human cell contains 23 sets of chromosomes which are responsible for the normal functioning of the cell and thus, the body. Chromosome 16 is responsible for the production of the alpha haemoglobin subunit while chromosome 11, the production of beta subunit. The lack of a particular subunit determines the type of thalassemia, either alpha or beta thalassemia. Mutations on either of these chromosomes will lead to the production of a dysfunctional haemoglobin molecule. It will cause deficiency in red blood cells to carry enough oxygen. There are approximately 100 types of mutation of chromosome 11 and these lead to severe forms of thalassemia.
For people with thalassemia, routine blood transfusion and iron chelation therapy (to remove the excess iron from the body), is necessary. Generally, people with thalassemia die early in the first decade of life due to prolonged anaemia which leads to bone deformities, organ enlargement and dysfunction. However, due to advancement in technology, those undergoing regular and proper treatment might have a longer life span of about 20 to 30 years.
Thalassemia is classified into two types: thalassemia minor is a carrier and may either have no or show negligible symptoms of anaemia; and thalassemia major, where anaemia is most severe. General signs and symptoms include pale skin, weakness and chronic fatigue due to anaemia. For the first two years of life, the child develops severe anaemia followed by growth retardation. Eventually, the spleen, liver and heart become larger than normal and bones are deformed. The child may not live beyond the first 10 years.
The first step of diagnosis involves clinical examination such as signs and symptoms, family history and blood tests including a full blood count. In the past, diagnosis was only carried out with basic biochemical tests such as complete blood count, peripheral blood smear, iron binding capacity and haemoglobin electrophoresis.
However, with advances in science and technology, a more accurate method known as DNA analysis has been developed to identify the recessive allele at the molecular level. This procedure has now been used extensively and has taken precedence over conventional diagnostic methods. Moreover, like most genetically inherited diseases, thalassemia can be detected while the baby is still in the womb. This is done by sampling the amniotic fluid in the placenta by a method called amniocentesis. This has helped to reduce the incidence rate of thalassemia. However, as with other diseases detected via this method, once the disease is confirmed, other issues arise as to the fate of the unborn child.
Generally, the standard treatment involves blood transfusion and iron chelation therapy. However, there are limitations in these methods because of the possibility of infection and side effects. New methods focus on blood and bone marrow stem cell transplant where abnormal stem cells are replaced with healthy ones from a donor. Although it gives hope to the thalassemia patient this procedure is rather risky and chances of getting a matching donor are low.
Scientists are currently working on the possibility of inserting a normal haemoglobin gene into the stem cells of the bone marrow, a method used in the treatment of cystic fibrosis, another genetically inherited disease. If the patient’s stem cells successfully uptake the normal gene to make or express the normal haemoglobin molecule, the disease will be eliminated. Known as gene therapy, this method would be the ideal alternative to conventional methods such as blood transfusion and bone marrow transplant.
Professor Dr Le Bolch, an American scientist and gene therapist at Harvard Medical School and his colleagues have been working on the expression of normal haemoglobin producing genes in mice. This has been proven to be quite successful. Clinical trials on humans have been carried out in France and will be carried out in the United States in the near future. Although there are still some concerns on the safety of this approach, obstacles especially on the vectors used, side effects and effectiveness of the expression, gene therapy offers a potential curative approach for thalassemia. On-going molecular studies and intensive clinical trial and monitoring should eventually solve the doubts and queries on gene therapy.
Lau Hui Chong is a lecturer with the School of Engineering, Computing and Science at Swinburne University of Technology Sarawak Campus. She can be contacted at firstname.lastname@example.org.