Severe β-depletion is a pure heterozygote of β0 or β+ depletion or a double heterozygote of β0 and β+ depletion, because β-chain production is completely or almost completely inhibited, so that the synthesis of HbA containing β-chain is reduced or disappeared, while the excess α-chain binds to γ-chain and becomes HbF (a2γ2), resulting in a significant increase of HbF. Due to the high oxygen affinity of HbF, it causes hypoxia in patient tissues. The excess a-chain is deposited in young erythrocytes and erythrocytes, forming a-chain inclusion bodies attached to the erythrocyte membrane and making it stiff, which is mostly destroyed in the bone marrow and leads to “ineffective hematopoiesis”. Some of the red blood cells containing inclusion bodies mature and are released into the peripheral bloodstream, but they are easily destroyed when they pass through the microcirculation, and these inclusion bodies also affect the permeability of the red blood cell membrane, resulting in a shortened life span of red blood cells. Causes of shortened erythrocyte lifespan: The disease is due to deletions or point mutations in the bead protein gene. There are 4 types of peptide chains that make up pearl proteins, namely α, β, γ and δ chains, which are encoded by their corresponding genes. The deletion or point mutation of these genes can cause the synthesis of various peptide chains to be impaired, resulting in changes in the components of hemoglobin. Usually, thalassemia is divided into 4 types, such as α, β, δβ and δ, among which β and α thalassemia are more common. β-thalassemia The human β-juicein gene cluster is located at 11p15.5. β-thalassemia (referred to as β-thalassemia) occurs mainly due to point mutations and, to a lesser extent, gene deletions. The gene deletion and some point mutations can cause complete inhibition of β chain production, which is called β0 thalassemia, while some point mutations cause partial inhibition of β chain production, which is called β+ thalassemia. β thalassemia has more mutations, and more than 100 kinds of mutation points have been found so far, 28 kinds have been found in China. There are six common mutations: ①β41-42 (-TCTT), accounting for about 45%, ②IVS-Ⅱ654 (C→T), accounting for about 24%, ③β17 (A→T), accounting for about 14%, ④TATA box-28 (A→T), accounting for about 9%, ⑤β71-72 (+A), accounting for about 2%, and ⑥β26 (G→A), i.e. HbE26, accounting for about 2%. Heavy β-depletion is a pure heterozygote of β0 or β+-depletion or a double heterozygote of β0 and β+-depletion, because the β-chain production is completely or almost completely inhibited, so that the synthesis of HbA containing β-chain is reduced or disappeared, while the excess α-chain combines with γ-chain and becomes HbF (a2γ2), which makes HbF increase significantly. Due to the high oxygen affinity of HbF, it causes hypoxia in patient tissues. The excess a-chain is deposited in young erythrocytes and erythrocytes, forming a-chain inclusion bodies attached to the erythrocyte membrane and making it stiff, which is mostly destroyed in the bone marrow and leads to “ineffective hematopoiesis”. Some of the red blood cells containing inclusion bodies mature and are released into the peripheral blood, but they are easily destroyed when they pass through the microcirculation, and these inclusion bodies also affect the permeability of the red blood cell membrane, resulting in a shortened life span of the red blood cells. For these reasons, the children present clinically with chronic hemolytic anemia. Anemia and hypoxia stimulate increased secretion of erythropoietin, which induces increased hematopoiesis in the bone marrow, thus causing skeletal changes. Anemia increases the absorption of iron from the intestine and, together with repeated blood transfusions during treatment, results in massive iron storage in the tissues, leading to iron-containing hemoglobin deposition. Mild-type geodystrophy is a heterozygous state of β0 or β+ geodystrophy, where the synthesis of β-chains is only mildly reduced, so its pathophysiological changes are extremely mild. Intermediate β-depletion is a double heterozygous state of some β+-depletion and pure heterozygous state of some variants of β-depletion, or double heterozygous state of two different variants of dyslipoproteinemia, and its pathophysiological changes are between heavy and light.