Beta Thalassemia *

Osmosis

What is beta thalassemia?

Genetic disorder causing deficiency in production of β-globin chains of hemoglobin

Which populations are most commonly affected by beta thalassemia?

Mediterranean

What is the composition of hemoglobin?

Four globin chains (α

What is hemoglobin F (HbF)?

Fetal hemoglobin with 2 α and 2 γ chains

What is hemoglobin A (HbA)?

Major adult hemoglobin with 2 α and 2 β chains

What is hemoglobin A2 (HbA2)?

Minor adult hemoglobin with 2 α and 2 δ chains

What causes beta thalassemia?

Point mutations in the beta globin gene on chromosome 11

Which regions of the beta globin gene are commonly mutated?

Promoter sequences and splice sites

What is the effect of beta globin mutations?

Reduced (β+) or absent (β0) β-globin chain synthesis

What is the inheritance pattern of beta thalassemia?

Autosomal recessive

What defines beta thalassemia minor?

One mutated beta globin gene (usually asymptomatic)

What defines beta thalassemia intermedia?

Two mutated genes with reduced β-globin synthesis

What defines beta thalassemia major?

Two β0 mutations; no β-globin chains produced

What happens when there’s a β-globin chain deficiency?

Free α-chains accumulate and form intracellular inclusions

What is the result of α-chain accumulation in RBCs?

Membrane damage and hemolysis

What is extravascular hemolysis?

Destruction of RBCs by macrophages in the spleen

What complications result from hemolysis?

Jaundice and secondary hemochromatosis

How does hemolysis cause hypoxia?

Fewer RBCs to carry oxygen to tissues

How does hypoxia affect bone marrow and extramedullary tissues?

Stimulates RBC production

When do beta thalassemia major symptoms appear?

3 to 6 months of life

Why are symptoms delayed in beta thalassemia major?

Fetal hemoglobin (HbF) still binds free α-chains in early life

What are common beta thalassemia major symptoms?

Anemia (pallor

What are complications of secondary hemochromatosis?

Arrhythmias

What facial feature is associated with beta thalassemia major?

Chipmunk facies (enlarged forehead and cheek bones)

What skull X-ray finding is classic in beta thalassemia major?

‘Hair-on-end’ or crew-cut appearance

What are typical lab findings in beta thalassemia?

Low hemoglobin

What does peripheral smear show in beta thalassemia?

Microcytic

What lab values indicate iron status in beta thalassemia?

High serum iron

What does hemoglobin electrophoresis show in beta thalassemia?

Low HbA

What hemoglobin electrophoresis finding is seen in beta-thalassemia minor?

HbA2 >3.5%

What are the treatment options for beta thalassemia?

Blood transfusions

What is transfusion-dependent thalassemia?

Phenotypes requiring recurrent blood transfusions (major

What is non-transfusion-dependent thalassemia?

Phenotypes that do not require regular blood transfusions (minor

Why is iron chelation needed in thalassemia?

Prevent iron overload from frequent blood transfusions

What iron chelating agent is commonly used?

Deferoxamine

Why is splenectomy sometimes performed?

To reduce excessive hemolysis from splenomegaly

What is the key pathology in beta thalassemia?

Reduced or absent β-globin chain synthesis

What are the consequences of abnormal hemoglobin formation?

Ineffective oxygen transport and RBC destruction

What type of anemia results from beta thalassemia?

Microcytic anemia

What is another name for thalassemia?

Mediterranean anemia