Introduction - Genetic Blood Disorder "β-Thalassaemia"
(Courtesy Thalassaemia International Federation and Colin Dunwell)
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.
Haemoglobin disorders or 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.
Haemoglobin is a protein that consists of the alpha (α) and beta (β) parts or chains and which are in turn produced by the α-globin genes and β-globin genes respectively. Hence the diseases caused by haemoglobin abnormality either with regards to its production or its structure are divided into α-chain diseases (or α-globin gene) diseases and β-chain (β-globin gene) diseases. These genes are found on chromosomes 16 and 11 respectively.
Patients with β-thalassaemia major, the most severe form of thalassaemia, cannot make normal adult haemoglobin, which is made up of equal numbers of α- and β-chains, and as a consequence cannot produce normal red blood cells (RBCs). In these individuals, i.e. those with β-thalassaemia major, each red blood cell contains much less haemoglobin, because the β-globin genes are not working or functioning properly and thus do not or produce very small amounts of β-chains. Consequently, there are far fewer red cells than the normal range. This causes anaemia, which is severe in these patients.
Thalassaemia is a form of inherited autosomal recessive blood disorder characterized by abnormal formation of hemoglobin. The abnormal hemoglobin formed results in improper oxygen transport and destruction of red blood cells. Thalassaemia is caused by variant or missing genes that affect how the body makes hemoglobin, the protein in red blood cells that carries oxygen. People with thalassaemia make less hemoglobin and have fewer circulating red blood cells than normal, which results in mild or severe anemia. Thalassaemia will be present as microcytic anemia.
Thalassaemia can cause complications, including iron overload, bone deformities, and cardiovascular illness. However, this same inherited disease of red blood cells may confer a degree of protection against malaria (specifically, malaria caused by the protozoan parasite Plasmodium falciparum), which is or was prevalent in the regions where the trait is common. This selective survival advantage of carriers (known as heterozygous advantage) may be responsible for perpetuating the mutation in populations. In that respect, the various thalassaemias resemble another genetic disorder affecting hemoglobin, sickle-cell disease.
This genetic condition which although carried by approximately 7% of the world's population is more prevalent not only in Asian cultures but also in certain areas of the Mediterranean such as countries like Cyprus. Sickle Cell is found more amongst the Afro Caribbean races but is a similar genetic condition. Research will hopefully find a cure but the incidence is set to rise in future years with the growing economic conditions in countries such as India and Pakistan. (In the past many foetuses did not even reach birth.) Not all children develop the severe variety of the disease and treatments are much better than in the past.
Frequently Asked Questions
Courtesy Thalassemia Foundation of Canada
What Is Thalassaemia?
(also known as Mediterranean anemia, or Cooley’s Anemia) is a genetic blood disease. People born with this disease cannot make normal hemoglobin (anemia) which is needed to produce healthy red blood cells.
Origin of disease and who carries Thalassaemia?
People of Chinese, South Asian, Middle Eastern, Mediterranean or African origin.
What is Thalassaemia Minor?
People with a thalassaemia mutation only in one gene are known as carriers or are said to have thalassaemia minor. Thalassaemia minor results in no anemia or very slight anemia. People who are carriers do not require blood transfusion or iron therapy, unless proven to be iron deficient.
What is Thalassaemia Major?
Children born with thalassaemia major usually develop the symptons of severe anemia within the first year of life. Lacking the ability to produce normal adult hemoglobin, children with thalassaemia major:
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are chronically fatigued
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fail to thrive, and
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do not grow normally
Prolonged anemia will cause bone deformities and eventually will lead to death within the first decade of life. The only treatment to combat severe anemia is regular blood transfusions.
How can Thalassaemia be treated?
Regular blood transfusions allow patients with thalassaemia to grow normally and be active. Unfortunately, transfusions result in deadly accumulation of iron in the heart and liver. If the excess iron is not removed then the patients may suffer from a premature death due to iron overload.
Nowadays, drugs designed to remove excess iron (iron chelators) have significantly changed the prognosis of thalassaemia. Excess iron is very harmful, causing serious heart, endocrine and liver complications, which can even be fatal. Excess iron is removed in a process known as iron chelation using special drugs (iron chelators). Today, these are desferioxamine (Desferal), desferasirox (Exjade), deferiprone (Ferriprox, L1) (Courtesy Thalassaemia International Federation). Patients can grow and develop normally, with relatively normal heart and liver functions. Patients are living longer and having families of their own. Medical advances continue and promise to improve the life expectancy and quality of life further for those living with thalassaemia.
Current treatments allow thalassaemia patients to live relatively normal lives, however, a cure remains to be found. The genetic cause of thalassaemia was one of the first genes discovered in the 1970′s, yet 30 years later, gene therapy still eludes thalassaemia patients.
Do you carry Thalassaemia?
Many people from the areas of the world where thalassaemia is common carry the gene for it on one chromosome (that is, they have thalassemia minor). You may believe that your blood has been tested for this specific gene but testing for thalassaemia requires a special blood test. To be tested your doctor must order a blood test called HEMOGLOBIN ELECTROPHORESIS which can identify a carrier of thalassaemia.
If you, your parents or ancestors are from an area of the world where thalassaemia is common, PLEASE REQUEST hemoglobin electrophoresis blood test from your doctor.
It is important to identify yourself as a possible carrier of thalassaemia (thalassaemia minor). A person with thalassaemia minor has a 25%(1 in 4) chance of having a baby with thalassaemia major if his/her mate also has thalassaemia minor.
What are the tests to identify a carrier?
Diagnosis involves:
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A full blood count to measure the size and volume of red blood cells
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Examination of the shape of the RBC under a microscope
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A procedure known as electrophoresis to measure the quantity of adult haemoglobins HbA and Hb A2
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Sometimes other specific tests at the ‘’molecular DNA’’ level, to confirm results. A person that has the genetic defect in one of the two genes inherited from his/her mother and father is called a carrier of β-thalassaemia or a carrier of β-thalassaemia minor or a carrier of the trait or stigma of β-thalassaemia or heterozygote for β-thalassaemia.
How do you inherit Thalassaemia?
If both parents carry thalassaemia minor, their children may have thalassaemia minor, or they may have completely normal blood, or they may have thalassaemia major. In each pregnancy there is a one in four (25%) chance that their child will have normal blood, a two in four (50%) chance that the child will have thalassaemia minor or a one in four (25%) chance that the child will have thalassaemia major.
How can we prevent Thalassaemia?
Please share the information on this website with others. Show it to your family, friends, neighbours, coworkers or anyone who has origins from areas where thalassaemia is common. Be sure to ask your doctor to test you for thalassaemia minor. Increased awareness is the key, please do your part by spreading the word.
Gene Therapy - A future cure for Thalassaemia
Inheritance Pattern of Beta Thalassaemia (Courtesy Thalassaemia International Federation)
When the two β- and the four α-globin genes that produce normal adult haemoglobin (HbA, α2β2) work or function normally, the individual is not a carrier and does not have a haemoglobin disorder.
If one gene of the two β-globin genes is not working or functioning perfectly well, then the individual is called a carrier of β-thalassaemia.
Below, the reader will be able to understand how partners pass on to their children the β-globin genes
Pattern A
When one of the parents carries a non-functional β-globin gene, i.e. when he/she is a β-thalassaemia carrier and the other parent carries 2 functional β-globin genes, then each child born to these parents (i.e. at every pregnancy) has a one-in-two (50%) chance of inheriting the non-functional β-globin gene from the carrier parent as shown here.
Pattern B
Partners who both carry a non-functional β-globin gene are referred to as an “at-risk” couple and at each pregnancy, the risks involved are as follows:
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a one-in-four (25%) chance that the child will inherit two non-functional β-globin genes (- -), one from the mother and one from the father, and therefore have β-thalassaemia major/intermedia, the full-blown disease, also known as Mediterranean Anaemia or Cooley’s Anaemia or homozygous for β-thalassaemia
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a one-in-two (50%) chance that the child will be a carrier of β-thalassaemia
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a one-in-four (25%) chance that the child will have completely functional β-globin genes as seen here.
EPIDEMIOLOGY
(Courtesy Thalassaemia International Federation)
Did you know that...?
(World Bank 2006, report of a joint WHO-March of Dimes meeting 2006)
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Approximately 7% of the global population is a carrier for Haemoglobin disorders
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A carrier of a pathological Hb gene encounters no health problems
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Between 300,000 – 500,000 children are born annually with a severe haemoglobin disorder
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About 80% of affected children are born in middle and low income countries
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About 70% are born with sickle cell and the rest with thalassaemia disorders
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50 – 80% of children with sickle cell anaemia and 50,000 – 100,000 children with β-thalassaemia major die each year in low and middle income countries
Origin of Thalassaemia
Thalassaemia was originally thought to be a disease limited to the Mediterranean region, in countries such as Greece, Italy and Cyprus. Hence, the name given to the disease: Mediterranean Anaemia or thalassaemia (Greek compound word: thalassa meaning sea or Mediterranean Sea and aemia meaning anaemia). Later it was recognized that thalassaemia was and still is particularly prevalent in areas in which malaria is or was endemic.
The malaria parasite is an infectious agent carried by some types of mosquitoes, including mainly the anopheles type and enters the human body through a mosquito bite. The malaria parasite causes a serious infectious disease in humans by attacking the red blood cells.
It is thought that in areas where malaria was endemic, humans underwent a small genetic change or adjustment in their DNA which gave them an advantage over those in whom this change did not occur, i.e. this change made them more resilient to the malaria infection.
This is because important changes occurred in the environment of the red cells following this genetic change that did not allow the parasite to survive and multiply causing illness and death. This adjustment led to what we today know as the β-thalassaemia carrier status.
