Thalassemia: Overview, causes and symptoms

The typical symptom of thalassemia is hypochromic, microcytic anemia of varying severity.

Mild forms (thalassemia minima or minor) are asymptomatic or show only minor changes in the blood count (microcytosis, hypochromia, erythrocytosis, occasionally anemia) and do not require treatment or further monitoring. However, these forms are relevant in family planning.

More severe forms (thalassemia intermedia or major) are usually accompanied by marked hemolytic anemia and require more intensive care and treatment, depending on the type and severity of thalassemia.

Thalassemias result in blood count changes similar to iron deficiency, which should also be excluded in hypochromic, microcytic anemia. Patients from countries with a high incidence of thalassemia also have a higher than average incidence of iron deficiency.

Thalassemia is most frequent among individuals with genetic origins from countries around the equator, Africa, the Near and Middle East, and Southeast Asia. Due to migration, thalassemia is nowadays also regularly encountered in Western countries such as in Europe or North America.

Different forms of thalassemia can be inherited with each other or together with structural hemoglobin variants (e.g., HbS in sickle cell disease, HbE, HbD, HbC) and thus occur simultaneously in a patient.

The nomenclature of thalassemias is based on the globin gene affected and the severity of the resulting clinical symptoms. The most common forms are alpha-(α-) thalassemia and beta-(β-) thalassemia.

Thalassemia is caused by decreased or completely abolished production of globin chains due to variants in the corresponding globin genes or their regulatory regions. This quantitative defect in the production of one type of globin chain leads to an imbalance between the different globin chains. The consequence is an excess of one type of normal globin chain. The biochemical consequences are damage to the erythrocyte precursors, resulting in ineffective erythropoiesis, or damage to the mature erythrocytes, resulting in hemolysis and subsequent anemia.

Detection or exclusion of thalassemia is accomplished by an interplay of blood count measurement, hemoglobin electrophoresis, and molecular genetic methods.