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 Hb-A γ and δ chain Hb-A = α2β2
An absence or deficiency of β-chain synthesis of adult HbA
β Chain synthesis
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 intermedia
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 β0 β
β-thalassaemia minor
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 Hydrops fetalis 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