Thalassemia

Thalassemia is a heterogeneous group of heredi- cally conditioned hypochromic anemia with different severity of the flow, which is based on a disruption in the structure of the globin chains. Numerous types of thalassemia with a variety of clinical and biochemical manifestations are associated with a defect in any of the polypeptide chains (α, β, γ, 5). Unlike hemoglobinopathy in thalassemia, there are no abnormalities in the chemical structure of hemoglobin, but there is a distortion in the quantitative ratios of HbA and HbF. For some types of α-thalassemia, tetrameric forms occur, such as HbH (β = 4), Hb Bart's ( γ = 4). Synthesis of polypeptide chains can be completely absent, which is noted at β ⁰ type of β-thalassemia, or characterized by partial insufficiency (β ⁺ type).

The molecular pathogenesis of thalassemia syndrome is expressed in the excess synthesis of α- or β-chains of hemoglobin. A correlation was established between the excess of synthesized α-chains in β-thalassemia and the survival of erythroid cells. Reduced survival of erythroid cells with excessive synthesis of α-chains with a large form of β-thalassemia leads to inefficient erythropoiesis.

It has been shown that isolated chains of hemoglobin, especially α-chains, are more labile and less resistant to denaturing effects than hemoglobin tetramer. Their oxidation and subsequent aggregation cause damage to the membrane. This process is accompanied by peroxide oxidation of lipids and proteins of the erythrocyte membrane by highly active free oxygen radicals formed during self-oxidation of isolated chains. Both processes cause the death of the erythroid cell.

Fetal hydrops with hemoglobin Barth

Fetal hydropsis with Bart's hemoglobin is the most severe form of α-thalassemia due to homozygous α-thalassemia-1 (all four genes are affected, two on each chromosome) and thus no functional hemoglobin, with the exception of the embryonic stage, is produced on which synthesizes α-like chains. Free β-globin forms tetramers, called HB Bart, with very high affinity for oxygen. HB Barta does not release hemoglobin in the fetal tissue, which causes tissue asphyxia, edema, congestive heart failure and a clinical picture of dropsy.

Bart's hemoglobin occurs almost exclusively in South-East Asia, where cis-deletion of α-globin genes is predominant. Children with fetal edema are not viable, death occurs either in utero, or in the first hours of life. When examined, the fetus is pale, swollen, with a massive and friable placenta. There are petechiae on the skin. There are defects in lung development. The heart is enlarged, the hypertrophy of both ventricles is expressed. Thymus gland enlarged. The enlargement of the liver is more pronounced than the spleen. Defined ascites, effusion in the pleura and pericardium, often non-admission of testicles and ginspadia. In various tissues and organs, hemosiderin deposits are found due to severe hemolysis in the fetus. The level of total hemoglobin is 30-100 g / l. Hemoglobin composition: hemoglobin Bart 70-100% with traces of hemoglobin Portland; HbH, HbA, HbA ₂, HbF are absent. In the blood, sharp erythroblastemia with hypochromic macro-cells, target cells, expressed aniso- and poikilocytosis.

[1], [2], [3], [4]

Beta-thalassemia

Beta-thalassemia (β-tal) is a heterogeneous group of diseases characterized by a decrease or lack of synthesis of β-globin chains. Depending on the severity of the condition, 3 forms of β-thalassemia are isolated: large, intermediate and small. The severity of clinical manifestations is directly proportional to the degree of imbalance of the globin chains.

Beta-thalassemia

[5], [6], [7], [8], [9], [10], [11]

Alpha-thalassemia

Alpha-thalassemia is a group of diseases common in Southeast Asia, China, Africa, the Mediterranean. Two almost identical copies of the α-globin gene are on chromosome 16. In 80-85% of cases of α-thalassemia, one or more of these four genes are lost. In the remaining patients, these genes persist, but do not function.

Clinical manifestations of α-thalassemia correlate with the degree of disruption of α-globin chain synthesis, but they are usually less pronounced than in β-thalassemia. This is due, first, to the fact that the presence of four α-globin genes contributes to the formation of an adequate number of α-chains until three or four genes are lost. Significant imbalance of hemoglobin chains occurs only if three of the four genes are affected. Secondly, aggregates of β-chains (β1-tetramers are formed when α-chains are deficient) are more soluble than α ₄ -tetramers, and therefore even in patients with significantly impaired α-globin synthesis with α-thalassemia, hemolysis is much weaker, and erythropoiesis more effective than β-thalassemia.

Alpha-thalassemia

[12], [13], [14], [15]

Hemoglobinopathy H

Hemoglobinopathy H - arises from the loss or dysfunction of three α-globin genes. The clinical picture is the same as with the intermediate form of β-thalassemia. The disease manifests by the end of the first year of life with moderate chronic hemolytic anemia (Hb 80-90 g / l); on the background of intercurrent diseases or when taking medications hemolytic crises can develop with a drop in hemoglobin level up to 40 g / l, requiring blood transfusions. There may be a lag in physical development, a Mongoloid type of face, jaundice, hepatosplenomegaly. In blood tests - hypochromic anemia, reticulocytosis, microcytosis, aniso- and poikilocytosis, target red blood cells. Most red blood cells contain HbH, which is β ₄ -tetramers formed with an excess of β-chains, and is detected by electrophoresis in the gel as the most mobile fraction. HbH precipitates mainly in mature red blood cells, which is accompanied by moderate hemolytic anemia. With hemoglobin electrophoresis, the level of HbH is 5-30%. Barm's hemoglobin is also determined in various amounts. The content of HbA _{2 is} decreased, HbF - in normal amounts or slightly increased (up to 3%).

Thalassemia Treatment

Indications for the beginning of transfusion therapy:

• a large form of β-thalassemia, hemoglobinopathy H with a hemoglobin level below 70 g / l;
• intermediate and large forms of β-thalassemia, hemoglobinopathy H with a hemoglobin level of 70-90 g / l with a marked lag in physical development, the presence of bone changes, a significant increase in the spleen.

How is thalassemia treated?