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# Thalassemias - Diverse group of disorders which manifest as anemia of varying degrees. - Result in defective production of globin chain of Hb molecule. - Distribution is worldwide. - May be either homozygous defect or heterozygous defect. - Globin chains are structurally normal (in contrast to he...

# Thalassemias - Diverse group of disorders which manifest as anemia of varying degrees. - Result in defective production of globin chain of Hb molecule. - Distribution is worldwide. - May be either homozygous defect or heterozygous defect. - Globin chains are structurally normal (in contrast to hemoglobinopathy), but have imbalance in production of the two types of globin chains. - Results in overall decrease in amount of Hb produced and may induce hemolysis. - Two major types of thalassemias: - Alpha (a) - Caused by defect in rate of synthesis of alpha chains. - Beta (B) - Caused by defect in rate of synthesis in beta chains. ## Genetics of Thalassemia - Adult hemoglobin is composed of two alpha and two beta chains. - Alpha thalassemia usually caused by gene deletion; Beta thalassemia usually caused by point mutation. ### Thalassemia | | | | | | :-------- | :-------- | :-------- | :-------- | | **Alpha** | **Alpha** | **Beta** | **Beta** | | **Thalassaemia** | **Thalassaemia** | **Thalassaemia** | **Thalassaemia** | | **Major** | **Minor** | **Major** | **Minor** | | 4 genes are involved in making the alpha hemoglobin chain | | 2 genes are involved in making the beta hemoglobin chain | | | **Alpha Thalassaemia Major** | **Alpha Thalassaemia Minor** | **Beta Thalassaemia Major** | **Beta Thalassaemia Minor** | | :------------------------- | :--------------------------- | :---------------------------- | :-------------------------- | | 1 mutated gene Carrier of Thalassaemia | 2 mutated genes Alpha-Thalassaemia Trait | 2 mutated genes Cooley Anaemia Mild to moderate manifestations | 1 mutated gene Mild manifestations | | 3 mutated genes Moderate to severe manifestations | 4 mutated genes Rare Usually early death | | | ## Beta Thalassemia - Beta thalassemia will not manifest at birth since there is predominance of Hb F (production of Beta chain will occur only at 3 - 6 months after birth) - B chain gene is located at chromosome 11 - Homozygous form results in severe transfusion dependent anemia ## Classical Syndromes of Beta Thalassemia - Silent carrier state: mildest form of beta thalassemia (heterozygous with very mild mutation).