Thalessemia

1. Thalessemia

2. Pathogenesis • Genetically determined • Heterogenous group of disorder • Reduced synthesis of one or more types of normal haemoglobin polypeptide chains

4. Demographics: Thalassemia • Found most frequently in the Mediterranean, Africa, Western and Southeast Asia, India and Burma

5. Normal Haemoglobin • HbA - α2β2 • HbA2 - α2δ2 • HbF – α2γ2

6. Each goblin chain have separate genetic control α –thalassaemia affect α-chain synthesis β –thalassaemia affect β-chain synthesis

7. β-Thalassaemia β Chain synthesis An absence or deficiency of β-chain synthesis of adult HbA Hb-A γ and δ chain Hb-A = α2β2

8. Pathophysiology of β-Thalassaemia 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

9. 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 • β0 gene – cannot synthesize β-chain

10. β-thalassaemia major • Mutation of normal β-gene β0-gene  absence HbA  increased HA2 and HbF • genotype – β0β0 • β-thalassaemia intermedia • ↑HbA2 • ↑HbF • ↓HbA • Genotype β+β+ or β0β • β-thalassaemia minor • ↑HbA2 • HbA normal • HbF normal

11. Symptoms • Inadequate production + ineffective erythropoiesis + haemolysis Anaemia • hemolysis hyperbillirubinemia jaundice • To compensate anaemia extramedullary haemopoiesis in liver,spleen  Hepatosplenomegaly • ↑Erythropoiesis marrow expansion & thinning of cortex of skull bone Thalassaemia facies/bone pain • Iron overload—increased absorption and transfusions  Endocrine disorders, Cardiomyopathy, Liver failure

12. management • Regular blood transfusions • Iron chelation-desferroxamine SC infusion/oral • Splenectomy • Monitor for complications of iron overload-LFT,ECHO,Thyroid functions,growth (pituitary can be damaged)

13. Normal Thalassaemia

17. α-Thassaemia An absence or deficiency of α-chain synthesis due to delation of α-genes.

18. 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 • In α-thalassaemia, delation of α-genes reduction or absence of synthesis of α-chain depending on number of α-gene deletion.

19. ↓α-chain synthesis free γ-chain in the fetus & β-chain in infant of 6 months, and continue in the rest of life. • Complementary 4γ and 4β are aggregated  Hb Bart (4γ ) and HbH (4β ), respectively.

20. 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

21. Hb H disease • Delation of 3 α-genes • Genotype --/- α • 75% reduction of α-chain • small amount of HbF, HbA, & HbA2 • Fetus can survive • Severe anaemia • Hydrops fetalis • Delation of all α-genes • Genotype --/-- • Absence of α-chain synthsis • Only Hb Bart (γ4) is produced • Incompatible with life

22. Inheritance • Autosomal recessive • Inc incidence in consanguineous marriages • Can be prevented by detecting carriers

25. Laboratory Diagnosis of Thalassaemia

27. Laboratory Findings • Hb – low • RBC count – Markedly decreased • MCV, MCH, MCHC – reduced • Blood picture-abn RBC • Hb electrophoresis –can demonstrate the types of Hb present

28. Peripheral Blood Film Normal

29. Thalassaemia slides

31. Thank you