(Mediterranean anemia, thalassemia major and minor)
Thalassemias are a group of hereditary, microcytic, hemolytic anemias, which are characterized by a defective synthesis of hemoglobin. They are particularly common in the population of the Mediterranean as well as Africans and Southeast Asians. The symptoms and clinical signs can result of anemia, hemolysis, splenomegaly, and Knochenmarkhyperplasie when multiple transfusions were carried out, also of iron overload. The diagnosis is made through genetic testing and a quantitative analysis of hemoglobin. Among the measures when severe forms include transfusions, splenectomy, administration of chelating agents and stem cell transplantation.
Thalassemias are a group of hereditary, microcytic, hemolytic anemias, which are characterized by a defective synthesis of hemoglobin. They are particularly common in the population of the Mediterranean as well as Africans and Southeast Asians. The symptoms and clinical signs can result of anemia, hemolysis, splenomegaly, and Knochenmarkhyperplasie when multiple transfusions were carried out, also of iron overload. The diagnosis is made through genetic testing and a quantitative analysis of hemoglobin. Among the measures when severe forms include transfusions, splenectomy, administration of chelating agents and stem cell transplantation. Pathophysiology Thalassemia (a hemoglobinopathy; hemoglobinopathies) is the most common hereditary diseases of hemoglobin synthesis. It is the result of an imbalance in the synthesis of hemoglobin, the (, ? ?, ?, ?) by a decreased production of at least one of the globin chains is caused. The ?-thalassemia is caused by the reduced production of ?-polypeptide chains. The inheritance is done autosomal. Heterozygous carriers of the trait are asymptomatic and have a mild to moderate microcytic anemia (thalassemia minor). In homozygotes (?-thalassemia major or Cooley’s anemia) severe anemia developed with a Knochenmarkhyperplasie. The ?-?-thalassemia is a rare form of ?-thalassemia, wherein the production of both ?- and the ?-chain is disturbed. It can be used as heterozygous also be homozygous. In the ?-thalassemia decreased production of ?-polypeptide chains is available. It has a complex mode of inheritance, since the genetic control of the synthesis of ?-chains total of two different gene pairs (4 genes) subject. Heterozygous with a single gene defect (?-thalassemia 2 without symptoms) are usually clinically unremarkable. Heterozygous extensive damage in 2 of the 4 genes (?-thalassemia-1, characteristic carrier) tend to develop a mild to moderate microcytic anemia, but without a symptom development. Defects in 3 of the 4 genes have a much greater effect on the production of ?-chains, thereby tetramers are formed with an excess of ? chains (hemoglobin H) or in infants with ?-chains (hemoglobin Bart). Damage to all 4 genes lead to fetal death, since hemoglobin without ?-chains is not able to transport O2 (hydrops). In the dark-skinned people, the gene frequency is for ?-thalassemia at about 25%. Only about 10% have damage to two or more genes. Symptoms and signs The clinical picture of all thalassemia is similar but varies in its severity. In the ?-thalassemia major symptoms in the first and second year of life occur. It shows severe anemia and a transfusion and resorptionsbedingte iron overload. Patients have jaundice, leg ulcers and cholelithiasis (such as sickle cell anemia). Frequently you will find a partly massive splenomegaly. It can lead to sequestration in the spleen, which leads to increased destruction of transfused normal erythrocytes. By the hyperactivity of the bone marrow results in a thickening of the skull and cheekbones. The involvement of the bones increases the risk of pathological fractures and leads to growth disorders, which puberty occurs delayed or prevented. With an iron overload iron deposition in the heart muscle can lead to heart failure. Hepatic siderosis is typical and leads to hepatic impairment and cirrhosis. Patients who suffer from the hemoglobin disease often have symptomatic hemolytic anemia and splenomegaly. Diagnosis Upon suspicion test for anemia Peripheral blood smear electrophoresis DNA Test (prenatal) The suspected thalassemia, patients with an appropriate family history indicative thereof symptoms or clinical signs or microcytic hemolytic anemia. Suspicion of thalassemia laboratory tests for microcytic and hemolytic anemia, as well as a quantitative hemoglobin analysis should be performed. The bilirubin, iron and ferritin levels in serum are increased. often there is a severe anemia with hemoglobin values ??of ? 6 g / dl at the ?-thalassemia major. The erythrocyte count is increased relative to hemoglobin level, as this is clearly microcytic cells. Usually the peripheral blood smears are diagnostic. They show a variety of nucleated erythroblasts target cells and small, pale red blood cells and a basophilic stippling or diffuse basophilia of the erythrocytes. The quantitative hemoglobin tests, the increase of hemoglobin A2 is diagnostic of the ?-thalassemia minor. In the ?-thalassemia major hemoglobin F is usually increased, in some cases up to 90%, and the hemoglobin A2 values ??are usually> 3%. In the ?-thalassemia, the proportion of hemoglobin F and hemoglobin A2 is generally normal. The diagnosis of a single or dual genetic defect is made using genetic tests and often a diagnosis of exclusion of other causes of microcytic anemia. Hemoglobin H disease may be provided in the hemoglobin electrophoresis on the detection of a rapidly migrating hemoglobin Bart H or a fraction. The specific molecular defect can be determined, but it does not affect the type of treatment. Recombinant DNA techniques of gene mapping (v. A. PCR) are now standard in prenatal diagnosis and genetic counseling. If a bone marrow examination performed (eg. As to exclude other causes) due to anemia, so this significant hyperplasia of erythropoiesis seen. X-ray examinations that are carried out for other reasons in patients with ?-thalassemia major, show changes due to the chronic bone marrow hyperactivity. The skull bone may comprise a thinning of the cortex, extended Diploeräume and granulated or milk glass-like appearing changes. In addition, a brush skull due to Trabekelveränderungen may be detectable. The bones also show a thinning of the cortex as well as extensions of the medullary canal and regions with osteoporosis. The vertebral bodies appear granulated or ground glass-like. The phalanges may have rectangular or biconvex shapes. Prognosis patients with ?- or ?-thalassemia minor have a normal life expectancy. The prognosis for patients with hemoglobin H disease is different. In patients with ?-thalassemia major, life expectancy is shortened, and only a few reach puberty or adulthood. Occasionally treatment splenectomy occasionally red blood cell transfusion and chelation therapy rarely allogeneic stem cell transplantation patients with a ?- or ?-thalassemia minor require no special treatment. Splenectomy can be helpful when a hemoglobin H disease causes severe anemia or splenomegaly. Children with ?-thalassemia major should receive as little transfusions as possible in order to avoid iron overload. Nevertheless, the suppression of the disturbed hematopoiesis may be clinically useful by periodic red blood cell transfusions in particularly severely affected patients. In order to prevent iron overload or delay, has to be removed (eg., Via a continuous iron chelation) excess (transfused) iron. Splenectomy can help patients with splenomegaly, to reduce the need for transfusion. Allogeneic stem cell transplantation has been successfully performed, but requires a histocompatible donor. However, the mortality and morbidity of this method limiting their clinical value. Important points thalassemias result from the decreased production of at least one globin polypeptide chain (?, ?, ?, ?); the resulting abnormal erythrocytes are microcytic often unusually shaped and prone to hemolysis (causing anemia). An often massive splenomegaly is common and can result in a Milzsequestrierung that accelerates the destruction of red blood cells (including transfused RBCs). Iron overload occurs due to the increased absorption (due to defective erythropoiesis) and the often frequent transfusions frequently. The diagnosis is made on the use of hemoglobin electrophoresis. Treatment should be as few transfusions as possible, the iron overload should be monitored and chelate should be used if needed. Splenectomy can help patients with splenomegaly, to reduce the need for transfusion. Allogeneic stem cell transplantation is effective, but requires a histocompatible vote and has significant risks; it should only be performed when the forecast would otherwise be poor.