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Premium member Presentation Transcript PowerPoint Presentation: Abdullah ali alqarni Student of medicine Imam university Dr.firstname.lastname@example.org abdullah ali alqarniWhat is thalassemia?: Thalassemia is a group of inherited disorders of hemoglobin synthesis characterized by a reduced or absent output of one or more of the globin chains of adult hemoglobin . The name is derived from the Greek words Thalasso = Sea" and " Hemia = Blood" in reference to anemia of the sea . Reduction of α or β chain synthesis causes α or β- thalassaemia respectively. What is thalassemia? abdullah ali alqarniPowerPoint Presentation: There are many variations at the gene level but the picture of hypochromasia and microcytosis is universal. The degree of chain imbalance determines the clinical picture from severe anaemia to a clinically silent form. Thalassaemia may involve other globin chains but the α and β chains are clinically of greater importance. abdullah ali alqarniHemoglobin Review: Each complex consists of : Four polypeptide chains, non-covalently bound Four heme complexes with iron bound Four O2 binding sites Hemoglobin Review abdullah ali alqarniPowerPoint Presentation: abdullah ali alqarniGlobin Chains: Alpha Globin 141 amino acids Coded for on Chromosome 16 Found in normal adult hemoglobin, A1 and A2 Beta Globin 146 amino acids Coded for on Chromosome 11, found in Hb A1 Delta Globin Found in Hemoglobin A2--small amounts in all adults Gamma Globin Found in Fetal Hemoglobin Zeta Globin Found in embryonic hemoglobin Globin Chains abdullah ali alqarniPowerPoint Presentation: abdullah ali alqarniNormal HumanHaemoglobins: Normal HumanHaemoglobins Haemoglobin Structural formula Adult Hb-A 2 2 97% Hb-A 2 2 2 1.5-3.2% Fetal Hb-F 2 2 0.5-1% Hb-Bart’s 4 Embryonic Hb-Gower 1 2 2 Hb-Gower 2 2 2 Hb-Portland 2 2 abdullah ali alqarniThe common abnormal haemoglobins: The common abnormal haemoglobins Haemoglobin Structural formula Hb-S 2 2 6 glu val Hb-C 2 2 6 glu lys Hb-E 2 2 26 glu lys Hb-D Punjab 2 2 121 glu gln abdullah ali alqarniGenetics: Alpha globins are coded on chromosome 16 Two genes on each chromosome Four genes in each diploid cell Gene deletions result in Alpha- Thalassemias Also on chromosome 16 are Zeta globin genes—Gower’s hemoglobin (embryonic) Beta globins are coded on chromosome 11 One gene on each chromosome Two genes in each diploid cell Point mutations result in Beta- Thalassemias Also on chromosome 11 are Delta ( Hb A2) and Gamma ( Hb F) and Epsilon (Embryonic) Genetics abdullah ali alqarniChromosomes: Chromosomes Source: Thalassemia.com abdullah ali alqarniTypes of Thalassemia: There are two basic groups of thalassaemia . thalassemia: There are four types categorized according to the severity of their effects on persons with thalassemia. ß thalassemia: There are 3 types categorized according to severity: Thalassemia minor Thalassemia intermedia Thalassemia major Types of Thalassemia abdullah ali alqarniα -Thalassemia: α -Thalassemia An absence or deficiency of α -chain synthesis due to delation of α -genes. abdullah ali alqarniPathogenesis of α-Thalassaemia: Pathogenesis of α - Thalassaemia In normal individual HbA , HbA2 and HbF need α -chain for their formation. 4 genes of α -chain, each pair on short arm of chromosome 16 present with genotype α , α / α , α . In α - thalassaemia , delation of α -genes reduction or absence of synthesis of α -chain depending on number of α -gene delation . abdullah ali alqarniPowerPoint Presentation: ↓ α -chain synthesis free γ -chain in the fetus & β -chain in infant of 6 months, and continue in the rest of life . Complementary 4 γ and 4 β are aggregated Hb Bart ( 4 γ ) and HbH (4 β ), respectively. abdullah ali alqarniVariants of α-Thalassaemia: Variants of α - Thalassaemia Silent carrier Delation of single α -gene Genotype α / αα Asymptomatic Absence of RBC abnormality Thalasaemia trait Delation of 2 α -genes Genotype --/ αα Asymptometic , minimal or no anaemia Minimal RBC abnormalities abdullah ali alqarniPowerPoint Presentation: Hb H disease Delation of 3 α -genes Genotype --/- α 75% reduction of α -chain 25% α -chain synthesis small amount of HbF , HbA , & HbA 2 Fetus can survive Severe anaemia Severe RBC abnormalites Hydrops fetalis Delation of all α -genes Genotype --/-- Absence of α -chain synthsis Only Hb Bart ( γ 4 ) is produced (High affinity for O 2 and can not dissociate O 2 to tissue) abdullah ali alqarniPowerPoint Presentation: abdullah ali alqarniPowerPoint Presentation: abdullah ali alqarniPowerPoint Presentation: abdullah ali alqarniPowerPoint Presentation: abdullah ali alqarniPowerPoint Presentation: abdullah ali alqarniPowerPoint Presentation: abdullah ali alqarniβ-Thalassaemia: β - Thalassaemia An absence or deficiency of β -chain synthesis of adult HbA β Chain synthesis Hb-A γ and δ chain Hb-A = α 2 β 2 abdullah ali alqarniPowerPoint Presentation: β - thalassaemia major Mutation of normal β -gene β 0 -gene absence HbA increased HA 2 and HbF genotype – β 0 β 0 β - thalassaemia intermedia ↑ HbA 2 ↑ HbF ↓ HbA Genotype β + β + or β 0 β β - thalassaemia minor ↑HbA 2 HbA normal HbF normal abdullah ali alqarniPowerPoint Presentation: On the basis of synthetic ability β -genes are designated as β gene – can synthesize normal amount of β -chain β + gene – can synthesize reduced amount of β -chain β 0 gene – cannot synthesize β -chain abdullah ali alqarniPathophysiology of β-Thalassaemia: Pathophysiology of β - Thalassaemia Various mutation in β -gene Complete or partial absence of β -chain Decreased adult HbA α -chain synthesis remain normal Free complementary α -chain – unstable and precipitate within normoblasts as insoluble inclusions Cell membrane damage & impaired DNA synthesis apoptosis i.e. ineffective erythropoeisis abdullah ali alqarni70-80% marrow normoblasts undergo apoptosis: 70-80% marrow normoblasts undergo apoptosis Inclusion bearing red cells undergo sequestration & destruction in spleen abdullah ali alqarniPowerPoint Presentation: Transmission of ß thalassemia If a carrier ( thalassemia minor ) marries a non-carrier, on average half of their children will be carriers, but none will develop thalassemia major. abdullah ali alqarniPowerPoint Presentation: Transmission ß of thalassemia - Cont However if two carriers marry, in each pregnancy there is a 25% chance of a non-carrier child, a 50% chance of a carrier child (thalassemia minor), and a 25% chance of a child with thalassemia major. abdullah ali alqarniAn example of inheritance: a carrier married to a normal person: An example of inheritance: a carrier married to a normal person Source: Emirates Thalassemia Society abdullah ali alqarniPowerPoint Presentation: abdullah ali alqarniAn example of inheritance- Cont: marriage between two carriers: An example of inheritance - Cont : marriage between two carriers Source: Emirates Thalassemia Society abdullah ali alqarniPowerPoint Presentation: abdullah ali alqarniTypes of ß thalassemia: Thalassemia Minor ( Trait) . This can also be called (carrier state), meaning that the person carries the genetic trait for thalassemia. Such people usually practice normal life, but may suffer from a mild form of anemia. Types of ß thalassemia abdullah ali alqarniTypes of ß thalassemia- Cont: Thalassemia Intermedia . Caused by the reduced availability of beta chains in hemoglobin and can lead to moderate to severe anemia and an array of complications including bone deformities and splenomegaly. Types of ß thalassemia- Cont abdullah ali alqarniPowerPoint Presentation: abdullah ali alqarniTypes of ß thalassemia- Cont: Thalassemia Major ( Cooley's Anemia) . Caused by the unavailability of beta chains in hemoglobin leading to a very severe and fatal if left untreated anemia. It requires regular blood transfusions leading to iron-overload which is treated with chelation therapy to prevent death from organ failure. Types of ß thalassemia- Cont abdullah ali alqarniPowerPoint Presentation: abdullah ali alqarniPowerPoint Presentation: abdullah ali alqarniSigns & Symptoms: Thalassaemia Minor : Usually no signs or symptoms except for a mild anemia. Thalassaemia Major : 1. Paleness, Jaundice or yellow coloured skin. 2. Growth retardation. 3. Bony abnormalities specially of the facial bones. 4. Enlarged spleen and liver. Signs & Symptoms abdullah ali alqarniPowerPoint Presentation: abdullah ali alqarniPowerPoint Presentation: abdullah ali alqarniPowerPoint Presentation: abdullah ali alqarniPowerPoint Presentation: abdullah ali alqarniLaboratory diagnosis : Thalassemia minor: -Blood smear shows hypochromia and microcytosis (similar to Iron Deficiency Anemia). -Blood indices: MCV< 75 fl , Hb usually> 10, Hematocrit> 30%, RDW < 14%. -Hemoglobin A2 often elevated > 3%, sometimes reaching 7-8%. Laboratory diagnosis abdullah ali alqarniLaboratory diagnosis- Cont: Thalassemia major: -Blood smear shows profound microcytic anemia, with extreme hypochromia , tear drop, target cells and nucleated RBCs. -Hemoglobin may be very low at 3-4 g/dl. Laboratory diagnosis- Cont abdullah ali alqarniBlood picture of a ß thalassemia major patient : Blood picture of a ß thalassemia major patient Source: Cooley’s Anemia Foundation abdullah ali alqarniPowerPoint Presentation: abdullah ali alqarniAdult Reference Ranges for Red Blood Cells: Women Men Units 12.0-15.0 13.6-17.2 g/ dL Hemoglobin ( Hb ) 33-43 39-49 % Hematocrit (HCT) 3.5-5.0 4.3-5.9 ×10 6 /mm 3 Red cell count 0.5-1.5 0.5-1.5 % Reticulocyte count 76-100 76-100 fL Mean cell volume (MCV) 27-33 27-33 pg Mean cell Hb (MCH) 33-37 33-37 g/ dL Mean cell Hb concentration (MCHC) 11.5-14.5 Red cell distribution width (RDW) Adult Reference Ranges for Red Blood Cells abdullah ali alqarniPowerPoint Presentation: abdullah ali alqarniPowerPoint Presentation: abdullah ali alqarni You do not have the permission to view this presentation. In order to view it, please contact the author of the presentation.