7. BETA THALASSEMIA.pptxmust view slides

Beta thalassemia must view slides

1. Beta Thalassemia 11/27/2023 11:38 1

2. Beta Thalassemia Introduction There are more than 200 of mutation within the beta globin gene found worldwide to produce beta thalassemia. Beta thalassemia are caused by mutation on chromosome 11 that affect all aspect of beta globin production. Beta thalassemia can either be ß° or ß + ß + is a reduction in beta chain production ß° is a total absence of beta chain production Homozygous ß° thalassemia is associated with a predominance of; Hb F No Hb A Variable amounts of Hb A 2 . In individuals with homozygous ß + thalassemia Hb A are variable Hb F is increased Hb A 2 is normal, decreased , or elevated 11/27/2023 11:38 2

3. Pathophysiology of Beta Thalassemia The molecular defects in β thalassemia result in absent or reduced β chain production. Alpha chain synthesis is unaffected and hence there is imbalanced globin chain production leading to an excess of α chains. In the absence of their partners, they are unstable and precipitate in the red cell precursors, giving rise to large intracellular inclusions, which interfere with red cell maturation. Hence, there is a variable degree of intramedullary destruction of red cell precursors (i.e. ineffective erythropoiesis). 11/27/2023 11:38 3

4. Pathophysiology of Beta Thalassemia Those red cells that mature and enter into the circulation contain α chain inclusion, which interfere with their passage through the microcirculation, particularly in the spleen. These cells, which show a variety of abnormalities of membrane structure and permeability, are prematurely destroyed and thus the anaemia of β thalassemia results from both ineffective erythropoiesis and a shortened cell survival. The anaemia acts as a stimulus to erythropoietin production and this causes expansion of the bone marrow, which may lead to serious deformities of the skull and long bones. Because the spleen is being constantly bombarded with abnormal red cells, it hypertrophie 11/27/2023 11:38 4

5. Beta Thalassemia There are 3 general categories of beta thalassemia that range from mild to severe; Beta thalassemia minor Beta thalassemia intermedia Beta thalassemia major Sometimes, a gene change for beta thalassemia can happen along with a gene change for sickle cell disease condition called sickle beta thalassemia or S beta thalassemia 11/27/2023 11:38 5

6. i . Beta T halassemia M inor Beta thalassemia minor is also called beta thalassemia trait. This condition is caused by one gene change. Most people with this form of condition have no signs or symptoms, or they may have mild anaemia. They can pass the gene change on to their children . In this condition, one of the two beta globin genes is mutated but the lack of beta protein is not great enough to cause problems in the normal functioning of the Hb. Alpha chain production continues at a near normal rate. The alpha chains combine with the available beta chains resulting in decreased levels of Hb A. There still remains of excess alpha chains and this may stimulates the increased production of delta chains. The alpha and delta chains combine to form increased amounts of Hb A 2 . 11/27/2023 11:38 6

7. Beta T halassemia M inor If there is still an excess of alpha chains the normal mechanism which switches off gamma chain production does not function correctly and the rate of gamma chain production will be greater than in a normal adult. This results in the formation of increased amounts of Hb F. A person with this condition simply carries the genetic trait for thalassemia and have a 50/50 chance to pass the gene to their offspring, who would also have thalassemia minor and will usually experience no health problems other than possible mild anemia 11/27/2023 11:38 7

8. ii. Beta T halassemia I ntermedia This condition is caused by two gene changes. It generally causes mild to moderate anaemia . In this condition, an affected person has two mutated. The lack of beta protein in the Hb is great enough to cause a moderately severe anaemia . The significant signs and symptoms are; Fatigue Shortness of breath Bone deformities Mild jaundice Enlargement of the spleen. 11/27/2023 11:38 8

9. Beta Thalassemia Intermedia There is a wide range in the clinical severity of this condition, and the borderline between thalassemia intermedia and the most severe form (thalassemia major) can be confusing. The deciding factor seems to be the degree of anaemia and the amount of blood transfusions required by the patient. The more dependent the patient is on blood transfusions, the more likely he or she is to be classified as thalassemia major. 11/27/2023 11:38 9

10. iii. Beta thalassemia major Beta thalassemia major is also called Cooley’s anaemia , named after the doctor who first described it in 1925. This condition occurs on average in one in four offspring if both parents are carriers of the beta thalassemia trait. Either no β chain ( β o ) or small amounts ( β + ) are synthesized Beta thalassemia Major is the most severe form of beta thalassemia in which there is a complete lack of beta globin production, preventing the production of significant amounts of Hb A. This is a severe imbalance of globin chain synthesis where the alpha globin chain is far greater than the beta chain. There is therefore an excess unpaired alpha-globin chains aggregate to form precipitates that damage red cell membranes leading to premature destruction of erythroid precursors. 11/27/2023 11:38 10

11. Beta thalassemia major The profound anaemia typically is associated with erythroid hyperplasia and extramedullary haematopoiesis . At birth the baby with thalassemia major seems entirely normal. Most children with this thalassemia major seem s healthy at birth but develop severe anaemia during the first few years of life. The anaemia begins to develop and becomes progressively more and more severe. They seems normal because the predominant Hb at birth is still Hb F. Hb F has two alpha chains and two gamma chains. It has no beta chains so the baby is protected at birth from the effects of thalassemia major. Without treatment, they can develop liver, bone and heart problems.  11/27/2023 11:38 11

12. Beta thalassemia major The infant fails to thrive (to grow normally) and often has problems feeding (due to easy fatigue from lack of oxygen, with the profound anaemia ), bouts of fever (due to infections) to which the severe anaemia predisposes the child and diarrhea and other intestinal problems. The clinical severity of these conditions are: Ineffective erythropoiesis Intravascular haemolysis . Intramedullary death severe microcytic hypochromic anaemia . 11/27/2023 11:38 12

13. Beta thalassemia major Without treatment, the spleen, liver, and heart become enlarged, and bones can become thin and brittle, the result is death before age twenty. This anaemia requires lifelong regular blood transfusions and considerable ongoing medical care. Over time, these frequent transfusions lead to excessive amounts of iron in the body. Left untreated, this excess iron can deposit into the liver, heart and other organs and can lead to a premature death from organ failure 11/27/2023 11:38 13

14. Geographic Distribution Geographically, thalassemia is considered as one of the most common genetic disorders world wide. The highest prevalence is in the Mediterranean region, parts of North and West Africa, the Middle East, the Indian subcontinent, southern Far East and southeastern Asia, especially Thailand and southern China. In Africa, thalassemia are rare, except for some isolated pockets in West Africa, notably Liberia, and in parts of North Africa. They are however common in the other Arab countries such as Libya, Tunisia, Algeria and Jordan. Thalassemia is also common in the kingdom of Saudi Arabia along the coastal strip of the Red Sea and in the Eastern Province. The Saudi Ministry of Health at a point designed a protocol for premarital testing after the royal decree in December 2003, which was implemented by a February 2004. In Europe, the highest concentrations of the disease are found in Greece, including the Greek islands and in some parts of southern Italy 11/27/2023 11:38 14

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16. Clinical Presentations 1. Severe anaemia becomes apparent at 3-6 months after birth when the switch from γ - to β -chain production should take place. 2. Enlargement of the liver and spleen occurs as a result of excessive red cell destruction, extramedullary haemopoiesis and later because of iron overload. The large spleen increases blood requirements by increasing red cell destruction and pooling, and by causing expansion of the plasma volume. 3. Expansion of bones caused by intense marrow hyperplasia 4. The patient can be sustained by blood transfusions but iron overload caused by repeated transfusions is inevitable. Each 500 mL of transfused blood contains approximately 250 mg iron. 5. Infections can occur for a variety of reasons. In infancy, without adequate transfusion, the anaemic child is prone to bacterial infections. 6. Osteoporosis may occur in well-transfused patients. It is more common in diabetic patients with endocrine abnormalities and with marrow expansion resulting from ineffective erythropoiesis 11/27/2023 11:38 16

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21. LABORATORY DIAGNOSIS OF THALASSEMIA 11/27/2023 11:38 21

22. LABORATORY DIAGNOSIS OF THALASSEMIA 1. Heterozygous beta thalassemia When heterozygous beta thalassemia is present with Hb S The clinical symptoms of Hb S/ β and Hb S/ β + are very different. Hb S/ β is more severe than Hb S/ β + condition Hb S/ β resembles sickle cell anaemia . In both Hb S/ β and Hb S/ β + , tests for Hb S are positive. 2. Homozygous beta thalassemia. The homozygous forms of beta thalassemia are easily recognized by the haematological change with very high level of Hb F and Hb A 2 values. There is microcytic hypochromic red cells and elevated level of Hb A 2 3. Causes beta thalassemia trait. Raised Hb A 2 and Hb F levels and target cells can help to differentiate this condition from iron deficiency anaemia . Hb A 2 value may be reduced to borderline or normal values when beta cell trait co-exists with iron deficiency due to reduced Hb A 2 synthesis. The tests should be repeated after 3–4 months treatment with iron if beta cell trait is suspected. 11/27/2023 11:38 22

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24. Laboratory Diagnosis of Thalassemia Thalassemia and abnormal Hb diagnosis require a combination of laboratory tests including the measurement of RBC indices and quantification of Hb A 2 and Hb F. The HPLC and Hb electrophoresis system can distinguish thalassemic diseases and the carriers. These systems give both qualitative and quantitative analyses of Hb components with good precision and reproducibility. Specific thalassemia mutation can be detected by DNA analysis Cases that mutation cannot identify by previous molecular analysis technique will be sent for DNA sequencing. 11/27/2023 11:38 24

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28. Hb Electrophoresis 11/27/2023 11:38 28

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33. Thank You 11/27/2023 11:38 33