Introduction
This topic covers normal hemoglobin and the inherited disorders of the red cell: thalassemias (quantitative globin defects), sickle cell disease (abnormal hemoglobin HbS), and the red-cell membrane and enzyme defects hereditary spherocytosis and pyruvate kinase deficiency, with their clinical and genetic characteristics and medical genetic counselling (MGC).
Thalassemias
Thalassemias are a group of inherited anemias caused by reduced or absent synthesis of globin chains that make up hemoglobin. Unlike sickle cell disease (a qualitative defect in Hb structure), thalassemias are quantitative defects of hemoglobin production. The imbalance between α- and β-chain synthesis leads to unstable hemoglobin, destruction of red cell precursors in the bone marrow, and chronic hemolytic anemia.
They are especially prevalent in the Mediterranean, Middle East, Africa, and Asia, where the carrier state is common because it provides partial protection against malaria. Inheritance is autosomal recessive.
Normal Hemoglobin Synthesis
- Adult hemoglobin (HbA) = α₂β₂.
- α-globin genes → chromosome 16 (2 per chromosome, total 4).
- β-globin gene → chromosome 11 (1 per chromosome, total 2).
- A balanced production of α- and β-chains is essential.
- Any defect → excess of the opposite chain → precipitation, RBC damage, and anemia.