globinopathies

Globinopathies are inherited disorders caused by abnormalities in the globin chains of hemoglobin, either structural changes in the globin proteins or quantitative defects in the synthesis of alpha or beta globin chains. They include both hemoglobin variants and thalassemias, and they affect the oxygen-carrying capacity of blood and the survival of red blood cells.

The major forms include alpha- and beta-thalassemias, which result from reduced synthesis of alpha or beta globin chains, and structural variants such as sickle cell disease (HbS) and other hemoglobinopathies like HbC, HbD, HbE. Less common conditions involve unstable or fusion globin chains that destabilize hemoglobin.

Pathophysiology: imbalances in globin chain production or abnormal globin structure lead to ineffective erythropoiesis and chronic hemolytic anemia. In HbS, polymerization of deoxygenated hemoglobin causes red blood cell sickling, increased hemolysis, and vascular occlusion with potential organ damage.

Clinical features often include chronic anemia with fatigue, pallor, and growth delay; skeletal changes in thalassemias; splenomegaly; and, in sickle cell disease, vaso-occlusive crises, acute chest syndrome, stroke risk, and infection susceptibility. Diagnosis is typically based on blood counts, abnormal red cell indices, and hemoglobin electrophoresis or HPLC, with genetic testing used to confirm specific mutations.

Management is supportive and disease-modifying where possible, including transfusions with iron chelation for iron overload, hydroxyurea for sickle cell disease, and curative options such as hematopoietic stem cell transplantation or gene therapy in select cases. The burden varies by genotype and access to care; newborn screening improves early detection. Globinopathies remain a major public health issue in regions with high prevalence of thalassemias or hemoglobin variants.