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1. b Thalassaemia is a recessive gene caused blood disorder. As all recessive gene disorders, it is inherited as two forms: A person can inherit just one Thalassaemia gene and be a healthy CARRIER or inherit two Thalassaemia Genes, one from each parent, and have the full and devastating condition: Thalassaemia Major.
2. b Thalassaemia is referred to as being a single gene disorder and it is also classified as an autosomal gene disorder. The genes affected are a pair of b globin genes located on Chromosome 11.
3. These genes are responsible for the production of b globin, a complex protein that forms the
hemoglobin in the red blood cells.
4. In b Thalassaemia, the individual inherits mutated genes. The manner in which these mutations occur are many. In b Thalassaemia a majority of the mutations are gene deletions. The presence of these mutated genes in certain locations or populations may have due to a slow process of natural selection. Carriers of the Thalassaemia Gene have some protection against malaria. It is likely that a parasite that causes malaria and is carried by the mosquito may have been a likely natural selecting agent or vector. This is probably why the gene predominately affects people from the Mediterranean, South Asia (Pakistan, India, Sri Lanka and Bangladesh) and areas where there is a high incidence of malaria.
5. A Carrier is an individual who has inherited only one faulty (mutated) gene. A carrier's b-globin gene pair on chromosome 11 will have one good and one faulty gene in the b globin pair ( can be from either parent). A carrier's genes will thus be producing reduced quantities of b globin and his/her red blood cells will be smaller on account of reduced
hemoglobin being produced.
6. A Carrier can pass on their faulty genes to their child. If both partners are Carriers then there is a 25% chance at each pregnancy that their child could inherit two faulty genes, one inherited from each parent, and have the devastating full blown condition: Thalassaemia Major. This child will have no b-globins and thus have poor and unsustainable red blood cells.
7. You cannot “catch” Thalassaemia. You must inherit it. A Carrier will not develop Thalassaemia Major.
b (Beta) THALASSAEMIA CARRIER- CLINICAL FACTS
8. Human blood is made up of red blood cells that carry oxygen from the lungs to all parts of the body, white blood cells that fight infection, platelets that help seal up wounds and repair tissue. Blood also has other dissolved minerals and substances. Both the blood cells and others substance are all held in a yellow liquid called the blood plasma.
9. Thalassaemia affects red blood cells. A red blood cell is full of hemoglobin. This is an iron rich complex protein that binds with oxygen and gives blood its rich red colour.
Hemoglobin is made of Haem and the globins. Haem is a complex mixture of iron and protoporphyrin and the Globins are two complex proteins called a Globins and b Globins that link up with haem to give you
hemoglobin.
10. In a Carrier there will be less b Globins made as they only have one good gene. Less b Globins mean less
hemoglobin made. This individual’s red blood cells are smaller on account of the fact that less
hemoglobin is packed into the red blood cell. However, this individual is healthy and will not be aware of the condition. Only a simple blood test arranged by the GP can reveal a Carrier. b(Beta)Thalassaemia carriers are easily discovered by a
Hemoglobin electrophoresis test on a sample of blood.
11. In sharp contrast to their healthy Thalassaemia carrier parents, children with Thalassaemia Major have two faulty genes. They have no genes there to produce b globins. Their red blood cells will be formed poorly and they will have unsustainable adult
hemoglobin.
12. These children will develop severe anemia that is diagnosed as early as 2-6 months of age as the child's red blood cells will be poorly formed and are destroyed very rapidly. This child needs monthly blood transfusions and if not transfused they could die by age 2. Their is no effective cure and the treatment is life long and full of complications.
13. Because this child is unable to make their own hemoglobin, the additional blood they are getting in transfusions is destroyed without recycling of the iron into new red blood cells. This iron is retained by the body and a child with Thalassaemia Major faces long term ill health due to this iron overload. If this iron is not removed, the iron damages the organs and hormone systems/glands and the child dies by 20 years. Iron overload is a common cause of ill health and early death. The iron removing therapy requires daily injections. The treatment is given at home through a daily twelve hour continuous injections of a drug called Desferal delivered slowly via a syringe driver. In young children this is a painful and tiresome routine that the parents undertake every night. A Thalassaemia Major patient is constantly at risk of chronic illness related to excess retention of iron which can result in liver disease, diabetes, delayed puberty, stunted growth and other hormonal deficiencies. Early death is common place due to heart failure after complications due to non-compliance to treatment.
14. The psychological impact on a Thalassaemia Patient and his/her family can be devastating and it affects compliance. Early death due to non-compliance because of psychological fatigue is common place. Discrimination at school and from employers, obtaining and retaining employment and other career complications are encountered. The treatment costs the State up to an estimated £1 million to raise a child
to 30 years of age.
15. Financial penalties such as difficulties in obtaining mortgages, insurance cover and general loans can also place an enormous stress on the patient. Students can discuss this in light of their own career prospects and what this would mean to them.
16. b Thalassaemia can be tested, predicted and prevented. There are many ethical issues involved in this area. We will only cover the Science of the tests. The School or class can develop this further. The film GATTACA is recommended to all students as it covers many ethical issues. We can test the carriers by a simple blood test called the
hemoglobin electrophoresis. This is not a DNA test and is very easy and cheaper than DNA test. In the UK the GP should be able to carry out this test for you free. We can also test the developing baby,
fetus, in the womb to see if it has Thalassaemia Major. These tests are DNA based tests.
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1. Because b Thalassaemia is a recessive gene disorder, you need both parents to be carriers in order for them to have a child with Thalassaemia Major. As all recessive gene disorders, we have a Mendelian inheritance pattern. There is a 25% chance at each pregnancy that a couple where both partners are carriers could have a child with Thalassaemia Major. This means that they could still have children who are healthy.
2. It is the Mendelian Chance that in each pregnancy there is a 75% chance that the child is healthy. That is 25% chance that the child has no Thalassaemia genes, 50% chance that they have only one gene and are carriers like their parents and 25% chance that they have both genes and have the full condition.
3. Whether a couple chooses to test or not is a deeply personal matter. Many opinions will be expressed at a social and community level. The students are encouraged to find these out.
4. However, the choice to test the fetus is ideally first mentioned to an individual when he or she first goes for his/her own test to determine if they are carriers. This is usually part of the genetic
counseling exercise where an individual is found to be a carrier.
5. However, where both partners are found to be carriers, the couple should ideally be informed about testing the
fetus before they plan a family. A proper Genetic counseling exercise for the couple and even the whole family is an appropriate time to mention this.
6. The opportunity to test the fetus is first formally offered very early in a pregnancy. It is only offered to a couple when BOTH partners have been found to be Carriers and they both CHOOSE to test the
fetus and exercise an informed choice after considerable genetic counseling. The school can work on issues relating to cases where one partner may not agree to test whilst the other may. Or where the couple may choose to test and the family may oppose.
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The Medical Research Council, Research Update 15, Ethics and the Gene Map, comments: “Ethics is an intellectually respectable discipline but it is not like mathematics where there are typically definite right or wrong answers. What ethics can help people to do is to think clearly and rationally about the moral questions”.may be mild hypo chromic anemia. If there are deleted the patient has hemoglobin H disease and if all four are deleted the baby is stillborn (hydrous fetalis). Hemoglobin H is a beta-chain tetramer formed from the excess of chains. It is functionally useless. Treatment of hemoglobin H disease is similar to that of
beta-Thalassaemia of intermediate severity. In some patients the disorder is due to a combination of
alpha-Thalassaemia genes with genes, which produce a functionally useless globing chain, Hb Constant Spring. The combinations are shown in the information box.
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