Thalassemia
by Simra Bhat
1. Caused by
1.1. Alpha-thalassemia: Mutations or deletions in HBA1 or HBA2 genes on chromosome 16
1.2. Beta-thalassemia: Mutations in the HBB gene on chromosome 11
2. Classified into
2.1. α Thalassemia
2.1.1. Silent Carrier - 1 gene affected
2.1.2. α Thalassemia Trait - 2 genes affected
2.1.3. Hemoglobin H Disease - 3 genes affected
2.1.4. α Thalassemia Major - 4 genes affected
2.2. β Thalassemia
2.2.1. β Thalassemia major - 1 mutated gene
2.2.2. β thalassemia Intermedia - 2 partially functioning genes
2.2.3. β Thalassemia Major - 2 non functioning genes
3. Pathophysiology
3.1. Autosomal recessive inheritance.
3.2. Reduced hemoglobin production: Abnormal globin chain synthesis.
3.3. Ineffective erythropoiesis: Increased destruction of abnormal red blood cells.
3.4. Hemolysis: Red blood cells are destroyed prematurely.
3.5. Tissue hypoxia: Decreased oxygen-carrying capacity.
3.6. Iron overload: Increased absorption and transfusion-related iron accumulation.
4. Complicated by
4.1. Iron overload from repeated transfusions.
4.2. Heart disease and liver damage.
4.3. Bone deformities and osteoporosis.
4.4. Increased infection risk.
5. Manifests as
5.1. α Thalassemia
5.1.1. Silent carrier - asymptomatic
5.1.2. Trait - mild anemia
5.1.3. Hemoglobin H disease - moderate to severe anemia and splenomegaly
5.1.4. Hydrops Fetalis - fatal fetal anemia, edema and stillbirth
5.2. β Thalassemia
5.2.1. Minor - mild anemia
5.2.2. Intermedia - moderate anemia, iron overload, splenomegaly
5.2.3. Major - severe anemi, growth retardation, bone deformities, transfusion dependency