SCIENTIFIC BACKGROUND
Beta thalassemia is an autosomal recessive inherited hematological disorder caused by a quantitative synthesis disorder of the β-globin chains of hemoglobin. It is estimated that approximately 3% of the world's population are carriers of beta thalassemia, but the prevalence varies widely among ethnic groups. A particularly high prevalence is found in Mediterranean countries, parts of Asia, the Middle East, and West Africa.
Human hemoglobin consists of different types of hemoglobin, each composed of 4 globin chains (each two identical chains form a tetramer). Hemoglobin A (HbA), which is predominant in adults at approximately 97%, is composed of 2 α- and 2 β-globin chains. In beta thalassemia, synthesis of the β-chains is reduced or completely absent, resulting in an excess of free α-chains that exhibit high instability. Their precipitation leads to premature hemolysis of erythrocytes or their precursors already in the bone marrow.
The homozygous form of beta thalassemia is also called thalassemia major, the heterozygous form is called thalassemia minor. The minor form usually shows only mild, hypochromic microcytic anemia, and significant clinical symptoms are not usually observed. In the intermediate form of beta thalassemia (thalassemia intermedia), the severity ranges between thalassemia minor and major.
Symptoms of thalassemia major, also known as Cooley anemia, usually appear in the first months of life, as soon as fetal hemoglobin (HbF) is replaced by adult hemoglobin (HbA). Clinically, infants are characterized by failure to thrive, hepatosplenomegaly and jaundice, with severe microcytic hypochromic anemia and abnormal erythrocyte morphology. In untreated patients, the increased but ineffective erythropoiesis leads to characteristic skeletal changes, especially in the cranial bones, due to widening of the medullary canals. Symptomatic therapy of the major form is performed by regular blood transfusion. To avoid iron overload with the risk of hemosiderosis, additional therapy with iron resorption inhibitors is indicated. Since August 2020, there is the possibility of a treatment for adults who require transfusion with the active ingredient luspatercept. The only causal treatment option remains bone marrow transplantation.
Variant forms occur in association with combined heterozygosity with abnormal hemoglobins such as sickle cell hemoglobin (HbS) or Hb Lepore.
Most heterozygous carriers of beta thalassemia are detected by chance during routine screening. In the blood analysis, a microcytosis and/or a hypochromia, or sometimes a lowered Hb value, is observed. In the course of diagnosis, an iron deficiency should first be excluded by determining serum ferritin, which is the most frequent cause of hypochromic microcytic anemia. In advance, the Mentzer index can already be used to estimate whether it is more likely an iron deficiency anemia or a beta thalassemia.
If iron deficiency is excluded, the presence of hemoglobinopathy can be investigated by Hb differentiation. In many cases, the question of a predisposing carrier of a hemoglobinopathy arises only in the context of conceiving a child, either because of a positive family history or because of ethnic origin. In the case of an already existing pregnancy, a rapid diagnosis is important in order to be able to assess the risk of a severe form of hemoglobinopathy in offspring as early as possible.
Since hemoglobinopathies can occur in a wide variety of combinations, hematologic findings should always be compared with molecular genetics results and checked for validity.
References
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