1.Dr. Vijay Marakala, MBBS, MD. Assistant professor BIOCHEMISTRY SIMS & RC

2. Hemoglobinopathies are disorders of Hb resulting from changes in the amino acid sequence of one of the globin chains or lack /decreased production of globin chains 3. Hemoglobin S Hemoglobin C Methemoglobinemia Thalassemia 4. Abnormal -globin chains GLUTAMIC ACID in the 6th position of -globin chain is replaced by VALINE Substitution due to point mutation 5. SICKLE CELL ANEMIA Homozygous Inherited 2 mutant - globin genes Polymerization of RBCs Sickle shaped RBCs SICKLE CELL TRAIT Heterozygous One normal gene Asymptomatic 6. Hemolytic anemia Tissue damage Pain Infection Protection against malaria 7. Microscopy Microcytic hypochromic anemia Sickling of RBCs Hb Electrophoresis Presence of HbS Decreased or absence of HbA & HbF Molecular RFLP 8. Blood transfusion For anemia Iron overload Cirrohosis Anti-sickling agents Hydroxyurea Sodium cyanate Aspirin 9. Substitution of glutamic acid by lysine in the 6th -chain RBCs do not sickle Mild hemolytic anemia 10. Substitution occurs in either proximal or distal histidine by tyrosine Iron will be in ferric form forming methemoglobin Oxygen binding is decreased Cyanosis Alpha 58 His Tyr [Hb M Boston] Beta 92 His Tyr [Hb M Hyde Park] 11. Thalassemia are group of inherited disorders of Hb synthesis characterized by lack or decreased synthesis of or globin chains Absence or reduced output of one or more globin chains of Hb 12. Found most frequently in the Mediterranean, Africa, Western and Southeast Asia, India and Burma Distribution parallels that of Plasmodium falciparum 13. On the basis of Globin chains - Thalassemia Impaired - chain production - Thalassemia Impaired - chain production On the basis of Inheritance Homozygous - Thalassemia major - Thalassemia major Heterozygous - Thalassemia minor - Thalassemia minor 14. -Thalassemia Different types of gene deletions. Rarer because alpha chain deficiency is incompatible with life 15. - Thalassemia Silent carrier - / No effects Trait - /- --/ Mild anemia Hb H disease --/- Moderate anemia Barts hydrops fetalis --/-- Severe Fetal death /Normal 16. Thalassemia Minor / 0 / + Mild anemia Intermedia 0/ + Moderate anemia Major 0/ 0 +/ + Severe anemia 0 = no production of the chain + = diminished production of the chain /Normal 17. 1- Anemia : Microcytic and hypochromic 2- Excessive hemolysis 3- Hyperplasia of the bone marrow and extramedullary erythropoiesis 18. In both thalassemia and hemoglobinopathy therapy is usually supportive rather than curative 19. Time of presentation Related to degree of severity Usually in first few years of life Untreated severe thalassemia --/--: Prenatal or perinatal death --/- & --/ : Normal life span with chronic hemolytic anemia 20. Untreated thalassemia Major: Death in first or second decade of life Intermedia: Usually normal life span Minor/Minima: Normal life span 21. 1- Palliative transfusion: It is just to keep patient surviving 2- Hypertransfusion: Maintain a hemoglobin level of 9 to 10 g/dl To reduce extramedullary erythropoiesis 3- Supertransfusion: Maintain a hemoglobin level >12 g/dl in an effort to suppress all erythropoiesis. 22. Chelation therapy with Deferoxamine 23. Alternative treatment Activation of fetal hemoglobin genes Bone marrow transplantation 24. Antenatal diagnosis. DNA diagnosis is based on PCR amplification of fetal DNA 25. HEMOGLOBIN DERIVATIVES Compounds that are formed by combinations of ligands with hemoglobin 26. HEMOGLOBIN DERIVATIVES Oxyhemoglobin Deoxyhemoglobin Carbaminohemoglobin Methemoglobin Carboxyhemoglobin Sulfhemoglobin 27. Mutation in the globin chain Deficiency of methemoglobin reductase Decreased supply of NADPH Combination of oxidizing chemicals 28. C A U S E S Smoking Exposure to coal mining Environmental pollution