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How to Investigate
the Carriers of Thalassaemai? |
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Dr. Androulla Eleftheriou
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Carriers of the Thalassaemia trait do not have a disease. |
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They have no physical or mental symptoms and do not require a special diet or medical treatment. The condition cannot become a serious disease over night. Indeed, most will be unaware that they are carriers unless specifically tested. However, some carriers may experience mild anemia, which may be inaccurately diagnosed as iron deficiency anemia, Laboratory tests can easily differentiate between the two.
Pregnant women carriers may experience moderate anemia, which is addressed by prescribing iron supplements during prengnancy.
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Why is it important to know
if u are a carrier ? |
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Although being a carrier of a thalassaemia trait has not adverse health effects, yet if a carrier has a child with another carrier, there is a one in four or 25% chance that child will have thalassaemia major. As the figure indicates, when both parents are carriers, for every pregnancy there is a one in four (25%) chance that the child will be affected by Thalassaemia major and a one in two (50%) chance that the child will carry the Thalassaemia trait, and a one in four (25%) chance that the child will be normal.
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Finding out a carrier
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Genetic counseling
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In most cased, simple laboratory tests can identify whether a |
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person carries the Thalassaemia trait. However, before laboratory tests are carried out, it is important that individuals receive genetic counseling where possible, providing them with information, advice and guidance on why they should be tested, and what the results of the test will mean for them, otherwise provision of this information should rely on a good health education programme. A genetic counselor will be specially trained, of the disease itself, including:
• Where to be tested.
• How to interpret test results.
• What it means to be a carrier, including operations available to two carriers planning to have children, or who have already conceived – i.e at-risk couples.
• The nature and treatment of Thalassaemia major or of any other hemoglobin disorder or genetic disease.
A councelor should provide information to individuals and couples, allowing them to decide for themselves how they wish to proceed. However, the advice offered by a counselor and the decision taken by at risk couple is often influenced by religious and cultural beliefs. TIF's publication “Prevention of Thalassaemia and other Hemoglobin Disorders” Volume I, may offer the reader more expert information on these issues.
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Laboratory testing to establish whether one is a carrier of the ß – Thalassaemia trait
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Laboratory tests for Thalassaemia include a routine blood count (CBC), which includes measuring the level of hemoglobin and other parameters related to the number and volume of red blood cells, know as Mean Corpuscular Volume (MCH). For example, in adults, an MCV of less than 75 maybe indicative of a carrier state (alternatively, this may indicate iron deficiency -- a further test will establish which is the case). MCV levels maybe lower in children and vary according to age. Red blood cells are also examined under a microscope. The red blood cells of a Thalassaemia carrier will be a paler shade of red and be various shapes (piokitocytosis), compared to normal red blood cells, which are a darker, red and round and concave in shape.
If further laboratory tests (such as Total iron binding capacity (TIBC) and Ferrritin) exclude iron deficiency, as the cause of a Lower MCV, additional tests are carried out to confirm the presence of the Thalassaemia trait and to determine it's type. Tests to determine the presence of the B-trait include a process known as hemoglobin electrophoresis, which enables quantitative measurement of HbA and HbA2, the main and minor components of adult hemoglobin respectively. Other hemoglobins normally persent in adult red blood cells such as foetel hemoglobins (HbF) may also be measured by electrophoresis. In most cases, the above tests are sufficient to determine wether an individual is a carrier. A process of exclusion or deduction usually identifies the presence of a- Thalassaemia trait people hwo have low MCV (not due to iron defficiency), a normal ß – Thalassaemia trait, and who are of the appropriate ethnic origin are presumed to be a – Thalassaemia carriers. In some circumstances, DNA tests need to be carried out in order to determine the presence or absence of the B-or a- Thalassaemia trait. Such genetic tests are beginning to be more widely used to test for the Thalassaemia trait.
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Who should have blood test?
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Given the importance of prevent
ing Thalassaemia and the fact that the disease occurs in virtually every part of the world, screening for the Thalassaemia trait should ideally be incorporated into a national prevention programme starting at an early age but certainly before marriage or pregnancy, in order to give individuals the greatest choice. At the very least, screening should be considered:
• When a relative is known to be a carrier or a Thalassaemia patient and/or.
In countries or when coming from countries known to have a high frequency of Thalassaemia.
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Consanguinity
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Consanguineous means having similar blood so, for example, a marriage between close relatives is referred to as a consanguineous. In many parts of the world, such marriages are encouraged and practiced. However, the closer the relationship of parents, the greater the risk that any children they have may be born with a congenital disorder such as Thalassaemia.
An unrelated couple had about a 98% chance of having a healthy child. Couple who are first cousins have about a 96% chance of having a healthy child. First cousins and first cousins whose parents and/or grandparents are also close relatives have about a 94% chance of having a healthy child.
Similarly, the additional risk of having a affected child falls sharply the more distant the relationship between the parents. About 2-3 children in 1,000 born to unrelated parents have a recessive disorder. From 2-20 chilren in 1,000 born to related parents have a recessive disorder, depending on how closely the parents are related.
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The choice available for an “at-risk” couple Prental testing.
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Where a woman carrying the B- Thalassaemia trait is considering having a child is already pregnant, her partner (if not aware of his carrier status) should be tested at once to find out if he also has the Thalassaemia trait. If they are both carriers, the couple may decide to proceed with Planning a family or, if already pregnant, may consider continue the pregnancy and wether this is possible, then proceed with testing the foetus for Thalassaemia, possibly deciding to terminate pregnancy if the foetus is affected. The choices considered by “at-risk” couples include separation, adopting, proceeding to invitro fertilization with foreign healthy sperm or ova. Or parents mainly due to religeous beliefs may decide not to find out the status of the child and continue with the pregnancy.
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Testing a foetus for Thalassaemia
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There are three types of ytests that can determine wether an unborn child has Thalassaemia
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Amniocentesis
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Amniocentesis is performed in the second trimester of pregnancy, after about 15 (18-22) weeks gestation. Using ultrasound as a guide, a trained obstetrician inserts a very thin needle through the mother's abdomen to withdraw 2-3 tablespoons of amniotc fluid. The foetal cells(cells from the unborn child) present in the fluid are then analyzed in the laboratory to determine wether the feotus has Thalassaemia.
The test is used when the pregnancy is advanced. It poses no significant risk to the mother. However, the test may cause a miscarriage – from a few days to a few weeks after the test.
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Cordocentesis
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Under Ultrasound guidance, a fine needle is inserted through the abdomen into the foetal unbilical cord. Bout 2-3 ml of blood is aspirated and foetal blood is separated out in the laboratory. In skilled hands 100% pure foetal cells are obtained from the first attempt in the majority of the cases. Causes of failure in obtaining pure foetal blood include early gestational age is also the most important cause of occurrence of serious complications in cordocentesis.
Globin chain separation with gel electrophoresis is the usual lanboratory method of detection. Early and specific diagnosis by molecular methods had almost completely replaced cordocentesis which is now mainly indicated only in pregnant patients who report late, in those in whom CVS is inconclusive and when previous studies of at risk couples are not available.
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Chorionic Villus Sampling (CVS)
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CVS can be performed somewhat earlier than amniocentesis, at about 10-11 weeks gestation. Using ultrasound as a guide, the specialist obstrician removes a small sample of the Chorionic Villi – cells that condition the same genetic information as the foetus and which will eventually form the placenta. The cells are removed either by a thin needle inserted through the mother's abdomen. (Tranabdominal) or a thin catheter inserted through the vagina (transcervical). The cells are then analyzed and a diagnosis is made. As with amnicentesis CVS poses no signifiacant risk to the mother. However, there is again a small risk of a miscarriage. If a miscarriage does occur, it can be difficdult to know wether it was due to CVS, because many miscarriages happen naturally at around 12 weeks of pregnancy.
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There may be an increased risk of the baby's limbs being malformed if CVS is done very early in pregnancy – i.e before the 8 weeks after the last menstual period. However, there is no evidance of an increased risk of any malformation when CVS is carried out after the last menstrual period. This is why the procedure is generally carried out after the eginning of the 10 th week after the last period.
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How genetic testing works?
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Amniocentesis and CVS are both based on DNA testing and involve identifying or excluding the genetic anormality(mutation) present in parents – the most accurate means of diagnosing inherited disease. However, as with all tests, there is a possilbility of error, albeit a very small one.
The genes for the characteristics we inherit, including hemoglobin, are made of DNA. Every tissue in the body, including a baby's placenta, contains a persons entire DNA pattern. In case of CVS, for example, laboratory scientists study the hemoglobin genes contained in the DNA of cells from the Chorionic Villi to see if the baby will be normal, a Thalassaemia carrier or will have Thalassaemia major. Analysis of the sample usually takes about a week. If the test show that the baby is affected, the couple may decide to end the pregnancy. The role of the genetic councelor and obstetrician in these cases is extremely important. Even at this state, decisions have been taken by the couple to continue with the pregnancy accepting the lifelong treatment of the affected child. If pregnancy termination is the choice, however this is done in one of the two ways, depending on the stage of the pregnancy |
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Late termination
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The procedure for termination a pregnancy at over 14 weeks involves inducing labour by inroducing hormones(prostaglandin) into the omb. The labour may last for several hours and the procedure is much more upsetting for the woman that an early terminartion Again, thist type of termination does not effect the women's ability to become pregnant again.
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Other Approaches
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Prenatal diagnosis and the termination of pregnancy are controversial. Unfortunately, however, prevention cannot rely on the identification of carries alone and screening cannot be effective and successful in the absence of prenatal diagnosis and pregnancy termination. Other methods of prevention are being developed such as analysis of foetal cells in the mother's blood. This however has limitations and cannot offer to-date a reliable
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