Thalassemia: Causes, Symptoms, Diagnosis, Treatment

Thalassemia (hereditary leptocytosis, Mediterranean anemia, large and small thalassemia) is a group of hereditary microcytic hemolytic anemia characterized by an anomaly of hemoglobin synthesis. They are especially typical for people of Mediterranean, African, Asian origin. Symptoms and complaints are caused by the development of anemia, hemolysis, splenomegaly, bone marrow hyperplasia and multiple transfusions with iron overload. The diagnosis is based on a quantitative analysis of hemoglobin. Heavy treatment includes blood transfusion, splenectomy, chelator therapy, stem cell transplantation.

Causes of the thalassemia

Thalassemia (hemoglobinopathy-b) is the most common hereditary disorder of hemoglobin synthesis. The result of an unbalanced synthesis of hemoglobin is the disruption of production of at least one polypeptide chain (b and y 5).

Beta-thalassemia is the result of a breakdown in the synthesis of beta-polypeptide chains. Type of inheritance autosomal, heterozygous patients are carriers and have asymptomatic anemia of mild or moderate severity (small thalassemia), with a homozygous form (large beta-thalassemia or Cooley anemia) develop severe anemia with bone marrow hyperplasia.

Beta-thalassemia is the result of a decrease in the synthesis of the beta-polypeptide chain, has more complexes of congenital anomalies, since the control of synthesis

Beta-chains are carried out by 2 pairs of genes (4 genes). The heterozygous form with one genetic defect [beta-thalassemia-2 (latent)] is usually not clinically manifested. In case of heterozygous form with defects in 2 of 4 genes [beta-thalassemia-1 (typical)], microcytic asymptomatic anemia develops from mild to moderate severity. Anomalies in 3 of the 4 genes to a greater extent damage the production of the beta chain, leading to the formation of tetramers with excess beta-chains (HbH) or in children of y-chains (Hb Barts). Anomalies in 4 genes result in death in utero, Hb with no b-chain is not capable of carrying O ₂. In blacks, the frequency of thalassemia is about 25%, but only 10% have an anomaly of more than 2 genes.

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Symptoms of the thalassemia

Clinical symptoms of thalassemia are similar, but vary in the severity of the manifestations. Large b-thalassemia occurs at the age of 1 to 2 years with symptoms of severe anemia, posttransfusion and absorption overload of iron. Patients have jaundice, ulcers on the legs and cholelithiasis (as in sickle cell disease). Typical is a massive splenomegaly. Sequestration of erythrocytes in the spleen can develop, which increases the destruction of transfused normal red blood cells. Hyperplasia of the bone marrow causes a thickening of the skull bones and paint protrusions. The involvement of tubular bones predisposes to pathological fractures, growth disruption and, possibly, a delay in sexual development. Accumulation of iron in the myocardium can lead to the development of heart failure. Typical is hemosiderosis of the liver, leading to impaired liver function and cirrhosis. Patients with HbH often have symptoms of hemolytic anemia and splenomegaly.

Diagnostics of the thalassemia

Thalassemia is suspected in patients with a family history, characteristic symptoms and signs of microcytic hemolytic anemia. If suspected of thalassemia, the studies recommended for microcytic and hemolytic anemia are performed with a quantitative determination of hemoglobin. There is an increase in serum bilirubin, iron and ferritin levels.

With large beta-thalassemia, severe anemia is detected, often with hemoglobin less than 60 g / l. The number of erythrocytes is increased in comparison with the level of hemoglobin, since there is a pronounced microcytosis of the cells. In the smear of peripheral blood, the changes characteristic for this diagnosis are determined: a large number of nucleated erythrocytes, target cells, small, pale erythrocytes, basophilic puncture.

A quantitative study of hemoglobin determines the increase in HbA, which is characteristic of small -tlasseemia. With a large beta-thalassemia, the level of HbF usually increases, sometimes up to 90% and HbA is usually increased by more than 3%. In -talassemia, the percentage of HbF and HbA is usually within normal limits, and the determination of one or two genetic anomalies characteristic of thalassemia excludes other causes of microcytic anemia. Disease of HbH can be established upon the detection of HbH or the Bartz fraction by electrophoresis of hemoglobin. It is possible to identify specific molecular changes, but this does not change the clinical management of the patient. For prenatal diagnosis and genetic counseling, gene mapping is performed.

If a bone marrow examination is performed (for example, to exclude other causes), the erythroid hyperplasia is determined in the myelogram. When radiography in patients with large beta-thalassemia, changes due to chronic bone marrow hyperplasia are determined. On the radiograph of the skull, the thinning of the cortical layer is determined, the expansion of the diplic spaces with the structure in the form of "sun rays" and the appearance of granules or the phenomenon of "ground glass". Tubular bones can have thinning of the cortex, expansion of the medullar space and foci of osteoporosis. Vertebral bodies can be characterized by the presence of a granule or the phenomenon of "ground glass". The phalanges of the fingers can be convex or rectangular in shape.

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Treatment of the thalassemia

Patients with small beta and beta-thalassemia do not need treatment. Splenomegaly can be effective in patients with HbH in the presence of severe anemia or splenomegaly.

Children with large beta-thalassemia should receive as few transfusions as possible to prevent iron overload. However, suppression of abnormal hemopoiesis with the use of periodic transfusions of erythrocyte mass can be effective in patients with severe manifestations of the disease. To prevent or reduce hemochromatosis, excess (transfusion) iron should be removed (for example, by chelation therapy). Splenectomy can reduce the need for transfusion therapy in patients with splenomegaly. Allogeneic transplantation of stem cells can be effective, but requires the presence of a histocompatible donor, in addition, the risk of complications, including fatal, with this method of treatment, as well as the need for prolonged immunosuppressive therapy limit its use.

Forecast

Life expectancy in patients with small beta-thalassemia or small beta-thalassemia is normal. The outlook for patients with HbH varies. In patients with large beta-thalassemia, life expectancy is reduced, only some patients survive to the sexually mature age or longer.

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