Beta Thalassemia Lecture Notes

Overview

• Beta Thalassemia is a genetic disorder leading to deficient production of beta-globin chains of hemoglobin.
• Oxygen-carrying proteins in red blood cells (RBCs) are affected.
• Prevalent in Mediterranean, African, and Southeast Asian populations.

Hemoglobin Structure

• Hemoglobin consists of four globin chains, each bound to a heme group.
• Globin Chains:
  • Alpha
  • Beta
  • Gamma
  • Delta
• Types of Hemoglobin:
  • Hemoglobin F (HbF): 2 alpha + 2 gamma chains (fetal hemoglobin)
  • Hemoglobin A (HbA): 2 alpha + 2 beta chains (major adult form)
  • Hemoglobin A2 (HbA2): 2 alpha + 2 delta chains (small fraction of adult hemoglobin)

Genetic Basis

• Cause: Point mutation in the beta-globin gene on chromosome 11.
• Mutation Sites: Promoter sequences and splice sites lead to reduced or absent beta-globin synthesis.
• Inheritance: Autosomal recessive disorder requiring two mutated gene copies.

Types of Beta Thalassemia

• Beta Thalassemia Minor: One mutated gene, often asymptomatic.
• Beta Thalassemia Intermedia: Two genes with reduced beta-globin synthesis.
• Beta Thalassemia Major: Two beta-zero mutations (no beta-globin production).

Pathophysiology

• Alpha Chain Accumulation: Free alpha chains form inclusions damaging RBC membranes.
• Hemolysis: RBC breakdown in bone marrow or spleen (extravascular hemolysis).
• Consequences:
  • Jaundice: Due to excess unconjugated bilirubin.
  • Secondary Hemochromatosis: Due to iron deposits.
  • Hypoxia: Fewer RBCs lead to increased RBC production, causing bone and organ enlargement.

Clinical Presentation

• Beta Thalassemia Minor: Typically asymptomatic.
• Beta Thalassemia Major:
  • Symptoms develop at 3-6 months (after fetal hemoglobin phase).
  • Anemia Symptoms: Pallor, shortness of breath, fatigue.
  • Other Symptoms: Jaundice, hepatosplenomegaly, growth retardation.
  • Complications: Arrhythmias, pericarditis, cirrhosis, hypothyroidism, diabetes mellitus.
  • Physical Appearance: Chipmunk faces, skull x-ray shows 'hair on end' or 'crew cut' appearance.

Diagnosis

• Blood Tests:
  • Low hemoglobin level.
  • Decreased mean corpuscular volume (MCV).
  • High red blood cell distribution width (RDW) - normal in minor cases.
• Peripheral Blood Smear: Microcytic, hypochromic RBCs, target cells.
• Lab Tests:
  • High serum iron, ferritin, and transferrin saturation.
• Hemoglobin Electrophoresis: Low HbA, increased HbF and HbA2 levels.

Treatment

• Blood Transfusions: Correct low hemoglobin levels.
• Categories:
  • Transfusion-Dependent Thalassemia: Requires recurrent blood transfusions (e.g., beta thalassemia major).
  • Non-Transfusion-Dependent Thalassemia: Does not require regular transfusions (e.g., minor and intermedia with milder symptoms).
• Iron Overload Management:
  • Use of iron-chelating agents like Deferoxamine.
• Splenectomy: When splenomegaly leads to excessive hemolysis.

Summary

• Beta Thalassemia: Autosomal recessive disorder affecting beta-globin chain production.
• Types: Minor, Intermedia, Major.
• Significant Symptoms: Chipmunk faces, hair on end appearance, hepatosplenomegaly, jaundice.
• Management: Transfusions, iron chelation, splenectomy.