Alpha Thalassemia: Symptoms, Diagnosis, and Treatment - PDF

Thalassemia Presented by Dr.Sahar Gamal Elbager Assistant Professor of Haematology UMST  Thalassemia Definition: Thalassemia is a heterogenous group of disorders disorders characterized by genetically determined reduction in the rate of normal globi...

Thalassemia Presented by Dr.Sahar Gamal Elbager Assistant Professor of Haematology UMST  Thalassemia Definition: Thalassemia is a heterogenous group of disorders disorders characterized by genetically determined reduction in the rate of normal globin chain synthesis. Sahar Gamal Elbager 2 Sahar Gamal Elbager 3  Genetics Haemoglobin A is made up of 2 alpha and 2 beta chains Synthesis of alpha chains is controlled by 2 gene clusters on chromosome 16. Synthesis of beta chains is controlled by gene on chromosome 11. Sahar Gamal Elbager 4 Genetics Sahar Gamal Elbager 5  Classification of Thalassemia Thalassemia are autosomal recessive disorders. According to the deficient globin chain thalassemia classified to 1.Alpha thalassemia Silent carrier Thalassemia trait HbH disease Hb Barts/Hydrops foetalis syndrome Sahar Gamal Elbager 6  Classification of Thalassemia 2. Beta thalassemia Thalassemia major Thalassemia intermedia Thalassemia minor Sahar Gamal Elbager 7  Alpha thalassemia α chains of globin are not/partly synthesized. It is required for both HbA and HbF. Majority of α thalassemia cases result from thalassemia cases result from gene deletions. Others 1) Mutation which cause aberrant splicing 2) Mutation of chain terminator codon 3) Mutation which causeSaharinstability Gamal Elbager of α globin 8 Classification Alpha thalassemia Sahar Gamal Elbager 9 Classification Alpha thalassemia Sahar Gamal Elbager 10 Inheritance Sahar Gamal Elbager 11  Pathophysiology in Alpha Thalassemia I. Reduced biosynthesis of alpha chain II. Beta and gamma chain produced Fetus 1. ϒ tetramer, α absent 2. Unable to carry and deliver oxygen 3. Intra uterine hypoxia Foetal death 4. Still birth Sahar Gamal Elbager 12 Pathophysiology in alpha thalassemia Adult 1. Formation of beta tetramer, present in developing normoblast 2. Moderatly ineffective erythropoiesis 3. Hb H inclusion in red cells, cannot dissociate oxygen in tissue 4. Spleen trap this cells 5. Tissue hypoxia 6. Hemolytic anemia 13  HB BARTS’ Hydrops Foetalis Syndrome Deletion of all 4 genes. Intrauterine death of such a baby or if born, dies wihin first 2 hour. Hb barts’ (γ4): ϒ chains has high affinity for oxygen) therefore , does not dissociate oxygen resulting in sever tissue hypoxia foetal death. foetal Sahar Gamal Elbager 14 α-Thalassaemia: Hydrops Fetalis Sahar Gamal Elbager 15 Peripheral smear Sahar Gamal Elbager 16  Hb H --/-alpha Anemia, Hb 7-11g/dl Reticulocyte count 4 - 15 % Icterus and hepatosplenomegaly Lab findings Anisopoikilocytosis Hypochromia Sahar Gamal Elbager 17  Hb H Microcytosis Target cells Inclusions bodies Hb electrophoresis: demonstrates fast moving HbH band in n the range of 5-35 %. Hb H also demonstrate on HPLC. Sahar Gamal Elbager 18 Sahar Gamal Elbager 19 Hb H Inclusions bodies  α -Thaassemia Trait Deletion of two (-α /-α) (--/ αα ) Clinically normal Hb 9-12 g/dl MCV ↓ MCH ↓ Mild microcytosis and hypochromia  Hb electrophoreisis Hb bart : not demonstrable  They are often mistakenly diagnosed as having iron deficiency anaemia. ( RDW is useful marker) Sahar Gamal Elbager 21  SILENT CARRIER Deletion of one globin gene (- α/αα) People with this condition are usually haematologically and clinically normal Confirmation by DNA analysis. Sahar Gamal Elbager 22 Thank you Sahar Gamal Elbager 23