Lecture on Beta Thalassemia

Introduction

• Topic: Beta Thalassemia (Microcytic Anemia)
• Symptoms: Tiredness, paleness, murmur (flow murmur), angina, exercise intolerance, fatigue.
• Prevalence: Common in Italy, the Mediterranean, Middle Eastern, and Asian populations.

Hemoglobin Structure

• Hemoglobin: Two alpha subunits, two beta subunits (tetramers).
• Thalassemia: Defect in globin chain synthesis.
• Consequences of defective globin synthesis:
  • Decreased hemoglobin → anemia.
  • Unbalanced hemo tetramers → precipitation in RBCs leading to hemolysis by spleen macrophages (ineffective erythropoiesis).

Beta Thalassemia Genetics

• Chromosome: 11 (Alpha-thalassemia involves chromosome 16).
• Remembering mechanism: Drawing beta (β) and 11.
• Types:
  • Mild: Due to splicing defect.
  • Severe: Due to nonsense mutation causing early stop codons.
• Beta Thalassemia Variants:
  • Heterozygous: Beta thalassemia minor.
  • Homozygous: Thalassemia intermedia, beta thalassemia major.

Beta Thalassemia Minor

• Characteristics:
  • Increased number of microcytic RBCs.
  • Often asymptomatic or minor anemia.
  • Hemoglobin electrophoresis: Slight decrease in Hemoglobin A, increase in Hemoglobin A2 and F.
• Differential Diagnosis: Different from alpha thalassemia trait (normal hemoglobin electrophoresis).

Beta Thalassemia Major (Cooley’s Anemia)

• Characteristics:
  • Zero beta globin production.
  • Alpha homotetramers precipitate, causing ineffective erythropoiesis and hemolytic anemia.
  • Responses:
    • Bone marrow expansion (medullary erythropoiesis).
    • Extramedullary hematopoiesis in spleen and liver (hepatosplenomegaly).
    • Skeletal changes (hair on end appearance, chipmunk facies).
  • Treatment: Blood transfusions (leading to iron overload and hemosiderosis).
  • Bilirubin metabolism: Increase in unconjugated bilirubin → jaundice.

Beta Thalassemia Intermedia

• Characteristics:
  • Intermediate severity between minor and major.
  • Often co-inherited with alpha thalassemia trait.
  • Less homotetramers and hemolysis compared to major form.
  • Increase in Hemoglobin F (fetal hemoglobin: alpha + gamma chains).

Conclusion

• Understanding Beta Thalassemia is crucial for exams.
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