Thalassemia can be divided into two categories according to the different pathogenic gene mutations: α-thalassemia and β-thalassemia. α-thalassemia refers to thalassemia caused by pathogenic mutations in the α-globin gene. Similarly, β-thalassemia refers to thalassemia caused by pathogenic mutations in the β-globin gene.

The α-globin gene is located on chromosome 16. Normal human chromosomes have two copies of the α-globin gene arranged in tandem. Two chromosomes means four copies of the α-globin gene. If there is a pathogenic mutation in α-globin, it may lead to thalassemia, which is mainly manifested as a reduction in the number of α-globin copies, which may be 1, 2, 3, or even 4. It is most common in Asian and African Americans. Among them, the common α-globin deletions in Chinese are mainly: -SEA, -α3.7, and -α4.2.

The reduction in α-globin synthesis results in a relative excess of β-globin chains and a reduction in the total production of hemoglobin. The reduction in total hemoglobin production produces the typical thalassemia microcytic anemia. However, the relative excess of β-globin production produces a hemoglobin tetramer composed entirely of β-globin tetramers, known as Hb H. Although Hb H is somewhat soluble, it is more easily oxidized and has a higher affinity for oxygen than normal Hb A.   Not only does this result in inefficient delivery of oxygen to tissues, but oxidized Hb H tends to accumulate in erythrocytes, resulting in an extravascular hemolytic anemia that can lead to splenomegaly. Hb H also appears to induce a degree of ineffective erythropoiesis.

The β-globin gene is located on chromosome 11. Normal people have one copy of β-globin on each chromosome 11, and a total of two copies of the β-globin gene. The β-globin gene mutation is mainly due to abnormal coding, which makes it impossible to synthesize β-globin, or the synthesized β-globin cannot bind to α-globin, and thus cannot form normal, functional hemoglobin. β-thalassemia is generally caused by mutations in β-globin. Common mutations in Chinese people include: CD41-42, IVS-2-654, CD17, -28, CD26, CD71-72, CD43, -29, Int, CD14-15, CD27-28, -32, -30, IVS-1-1, IVS-1-5, CD31 and Cap.