Thalassemia

Thalassemia is a hereditary blood disorder characterized by decreased synthesis of globin chains, the protein components that make up hemoglobin.

Normal Hemoglobin Structure

Normal adult hemoglobin (HbA) consists of two alpha and two beta globin chains. The genes responsible for producing these chains include:

• Four alpha globin alleles (two copies each of HBA1 and HBA2 genes)
• Two beta globin alleles (one copy each of the HBB gene)

Thalassemia Minor

Thalassemia minor occurs when there are mutations in one or two alpha alleles, or a single mutation in a beta allele. This results in a mild reduction of the affected globin chain.

Clinical Presentation

• Usually asymptomatic or very mild anemia
• Slight fatigue in some cases
• No organ damage or growth delays

Laboratory Findings

• Presence of target cells on blood smear
• Low/normal red cell distribution width (RDW)
  • High in Iron deficiency anemia
• Persistent microcytosis (small red blood cells)
• Normal white blood cell and platelet counts
• Elevated Hemoglobin A2

Diagnosis and Management

Hemoglobin electrophoresis is the primary diagnostic tool used to distinguish between alpha and beta thalassemia minor. Treatment is usually not necessary for this mild form of the condition.

Thalassemia Major

Thalassemia major represents the severe form of the disease, occurring when all alpha or all beta alleles are mutated or deleted. This results in severe reduction or complete elimination of the affected globin chain.

Types

The condition is classified based on the affected globin:

• Alpha thalassemia major (also known as hemoglobin Bart (Hb) (gamma tetramers) hydrops fetalis syndrome) → caused by mutations in alpha globin genes (HBA1, HBA2)
  • Presents at birth - Hemoglobin F (2 alpha, 2 gamma) utilizes alpha globin
• Beta thalassemia major → caused by mutations in the beta globin gene (HBB)
  • After 6 months - Hemoglobin F dies and beta chains are utilized.

Clinical Presentation

Patients with thalassemia major typically develop symptoms in early childhood and present with:

• Severe anemia
• Fatigue, pallor, and poor growth
• Bone deformities, particularly affecting facial and skull bones
• Hepatosplenomegaly (enlarged liver and spleen)
• Jaundice
• Delayed puberty
• Elevated Hemoglobin A2

Treatment Approaches

Management of thalassemia major requires comprehensive care including:

Primary Treatments:

• Regular blood transfusions administered every few weeks to maintain adequate hemoglobin levels
  • Iron chelation therapy to prevent iron overload from repeated transfusions
• Folic acid supplementation to support red blood cell production

Potential Curative Treatment:

• Bone marrow or stem cell transplant offers the possibility of a cure in select patients