Thalassemia is a group of inherited blood disorders caused by mutations in the genes responsible for hemoglobin production.
These mutations result in the reduced production of one of the globin chains (alpha or beta), leading to imbalanced globin chain production, ineffective erythropoiesis, and hemolysis.
Thalassemia is categorized into alpha and beta thalassemia based on the affected globin chain.
Types of Thalassemia
1. Alpha Thalassemia
Alpha thalassemia results from deletions or mutations in the HBA1 and HBA2 genes, which encode the alpha-globin chains.
The severity of the condition depends on the number of affected alpha-globin genes:
Silent Carrier: One gene affected; usually asymptomatic.
Alpha Thalassemia Trait: Two genes affected; mild anemia.
Hemoglobin H Disease: Three genes affected; moderate to severe anemia.
Hydrops Fetalis: All four genes affected; usually fatal in utero or shortly after birth.
2. Beta Thalassemia
Beta thalassemia results from mutations in the HBB gene, which encodes the beta-globin chain.
It is classified based on the severity of symptoms and the amount of functional beta-globin produced:
Beta Thalassemia Minor (Trait): One gene affected; mild anemia.
Beta Thalassemia Intermedia: Two genes affected; moderate anemia with variable severity.
Beta Thalassemia Major (Cooley's Anemia): Two genes affected; severe anemia requiring regular blood transfusions.
Pathophysiology
Thalassemia results from imbalanced globin chain production, leading to ineffective erythropoiesis (production of RBCs) and hemolysis (destruction of RBCs).
The excess unpaired globin chains form precipitates that damage RBC membranes, causing premature cell death.
This leads to chronic anemia, which stimulates increased erythropoietin production and expansion of the bone marrow, causing skeletal deformities and other complications.
Symptoms
Symptoms vary depending on the type and severity of thalassemia:
1. Mild Thalassemia (Trait):
Often asymptomatic or mild anemia.
2. Moderate to Severe Thalassemia:
Severe anemia: Fatigue, weakness, pallor.
Growth retardation and delayed puberty.
Bone deformities: Especially in the face and skull.
Splenomegaly: Enlarged spleen causing discomfort and risk of rupture.
Jaundice: Due to increased hemolysis.
Frequent infections.
Iron overload: Due to repeated blood transfusions and increased intestinal absorption, leading to organ damage (heart, liver, endocrine glands).
Diagnosis
Thalassemia is diagnosed through:
Complete Blood Count (CBC): Shows low hemoglobin and abnormal RBC indices.
Hemoglobin Electrophoresis: Identifies abnormal hemoglobin types and quantifies hemoglobin fractions.
Genetic Testing: Confirms mutations in globin genes.
Peripheral Blood Smear: Shows microcytic, hypochromic RBCs with target cells and other abnormalities.
Treatment
Treatment varies based on the severity of thalassemia:
1. Mild Thalassemia:
Usually requires no treatment, but regular monitoring is recommended.
2. Moderate to Severe Thalassemia:
Regular Blood Transfusions: To maintain hemoglobin levels and prevent complications.
Iron Chelation Therapy: To remove excess iron from the body and prevent organ damage.
Folic Acid Supplements: To support RBC production.
Splenectomy: Surgical removal of the spleen if it becomes excessively enlarged or if hemolysis is severe.
Bone Marrow Transplant: Potential cure for some patients, especially children with severe thalassemia.
Gene Therapy: Experimental treatment with the potential for curing the disease.