Beta Thalassemia

Overview

• Genetic Disorder: Deficiency in beta-globin chains of hemoglobin.
• Hemoglobin Function: Oxygen-carrying proteins in red blood cells (RBCs).
• Prevalence: Common in Mediterranean, African, and Southeast Asian populations.

Hemoglobin Structure

• Components:
  • Hemoglobin is made of four globin chains, each with a heme group.
  • Types: Alpha, Beta, Gamma, Delta.
• Types of Hemoglobin:
  • Hemoglobin F (HbF): 2 alpha + 2 gamma chains.
  • Hemoglobin A (HbA): 2 alpha + 2 beta chains (major adult form).
  • Hemoglobin A2 (HbA2): 2 alpha + 2 delta chains (small fraction).

Pathophysiology

• Deficiency: Partial/complete beta-globin chain deficiency.
• Cause: Point mutation in the beta-globin gene on chromosome 11.
  • Mutations often occur in promoter sequences and splice sites.
• Inheritance: Autosomal recessive - two mutated gene copies required.

Types of Beta Thalassemia

• Beta Thalassemia Minor: One mutated gene; reduced/absent beta-globin.
• Beta Thalassemia Intermedia: Two mutated genes; reduced synthesis.
• Beta Thalassemia Major: Two beta-zero mutations; no beta-globin produced.

Symptoms and Complications

• Accumulation of Alpha Chains: Forms intracellular inclusions; damage RBCs.
• Hemolysis: RBC breakdown in bone marrow/spleen.
• Spilled Hemoglobin: Causes jaundice and secondary hemochromatosis.
• Hypoxia: Signals increased RBC production, causing bone marrow and spleen enlargement.
• Beta Thalassemia Minor: Typically asymptomatic.
• Beta Thalassemia Major: Symptoms develop in 3-6 months.
  • Anemia, jaundice, hepatosplenomegaly, growth retardation.
  • Complications: Arrhythmias, pericarditis, cirrhosis, hypothyroidism, diabetes mellitus.
  • Physical signs: "Chipmunk" faces, "hair on end" skull appearance.

Diagnosis

• Blood Tests: Low hemoglobin, decreased mean corpuscular volume (MCV), variable RDW.
• Peripheral Blood Smear: Microcytic, hypochromic RBCs, target cells.
• Lab Findings: High serum iron, ferritin, transferrin saturation.
• Hemoglobin Electrophoresis: Low HbA, increased HbF, HbA2.
  • In minor: HbA2 > 3.5%.

Treatment

• Not Always Required: Based on symptom severity.
• Blood Transfusions: Correct low hemoglobin levels.
• Categories:
  • Transfusion Dependent Thalassemia: Requires recurrent transfusions (e.g., major and some intermedia).
  • Non-Transfusion Dependent Thalassemia: Does not require regular transfusions (e.g., minor, mild intermedia).
• Iron Overload Management: Iron chelation agents like deferoxamine.
• Splenectomy: Considered for severe splenomegaly.

Conclusion

• Beta thalassemia is caused by a mutation on chromosome 11 leading to reduced or absent beta-globin synthesis.
• Recognized by physical features, blood tests, and genetic testing.
• Treatment varies based on severity, with a focus on managing anemia and iron overload.