β-thalassemia (beta-thalassemia)

beta-Thalassemia is typically associated with hypochromic, microcytic anemia. The severity of blood count changes depends on the number of disrupted beta-globin genes (b⁰) or their residual function (b⁺). In beta-thalassemia minor, mild microcytosis and hypochromia with erythrocytosis and occasionally slightly decreased hemoglobin concentration are observed. In beta-thalassemia intermedia or major, moderate to severe hypochromic anemia with hemoglobin concentrations sometimes below 7 g/dL are seen.

In carriers of additional alpha-thalassemia or hereditary HbF persistence (HPFH), the blood count changes are attenuated. On the contrary, patients with triplication (aaa/aa) or higher grade gain of an alpha-globulin gene have more pronounced symptoms.

The iron status in α-thalassemia is usually normal. In pronounced forms with hemolysis, ineffective erythropoiesis, and consequent need for repeated transfusions, iron overloads with elevation of ferritin occur.

Hemoglobin electrophoresis in beta-thalassemia minor shows HbA2 levels typically above 3.2% (b⁺) or above 3.6% (b⁰). In some patients, elevated HbF can also be detected (0.5-6%).  In patients with beta-thalassemia intermedia and major, HbA2 and HbF fractions are highly variable with normal to elevated HbA2 and HbF ranging from 10% to almost 100%.

Hb Lepore shows typical thalassemic blood count changes and in hemoglobin electrophoresis an abnormal hemoglobin fraction corresponding to a fusion transcript of delta- and beta-globins.

The most common causes of beta-thalassemia are single nucleotide variations in the HBB gene that can be detected by sequencing. In some cases, larger deletions in the beta-globin complex also underlie beta-thalassemia and are detected by multiplex ligation-dependent probe amplification (MLPA). This method also detects deletions affecting multiple genes of the beta-globin gene complex, e.g., δβ-thalassemia.