Hemoglobinopathies

Hemoglobinopathies are a group of inherited disorders affecting the structure or production of hemoglobin, the protein that carries oxygen in red blood cells. They arise from mutations in the globin genes and are a major cause of inherited anemia worldwide. Most are inherited in an autosomal recessive manner, though some variants and de novo mutations occur. Disorders are commonly classified into qualitative (structural) abnormalities of globin chains and quantitative disorders resulting in reduced synthesis of one or more chains.

Qualitative disorders include structural variants such as hemoglobin S (HbS), HbC, HbD, and HbE, which can cause increased red cell destruction or abnormal oxygen delivery and, in certain cases, vaso-occlusion. Quantitative disorders include alpha-thalassemia and beta-thalassemia, characterized by reduced or absent production of alpha or beta globin chains and varying degrees of anemia.

Pathophysiology involves instability or polymerization of abnormal hemoglobin in low oxygen (as in HbS), leading to hemolysis and vascular occlusion, or imbalanced globin chain production causing ineffective erythropoiesis and hemolysis.

Clinical features range from asymptomatic carrier states to severe anemia with pain crises, infections, organ damage, growth retardation, and vaso-occlusive complications such as stroke or acute chest syndrome.

Diagnosis relies on newborn screening in many regions, followed by complete blood count, and confirmatory testing with hemoglobin electrophoresis or high-performance liquid chromatography and molecular testing as needed.

Management is disease-specific and may include regular transfusions and iron chelation for severe thalassemias, disease-modifying therapies such as hydroxyurea for sickle cell disease, vaccination and infection prophylaxis, and curative options like allogeneic stem cell transplantation or gene therapies in selected patients. Genetic counseling and prenatal testing are important for at-risk families. See also sickle cell disease and thalassemia.