Anemia due to thalassemia: overview of the different forms and therapy of the gene defect
The body needs oxygen, which the red blood cells ( erythrocytes ) transport from the lungs to the individual cells . In the case of the genetic disease thalassemia, the transport of the O 2 molecules through the blood does not work to the required extent. The defect leads to a change in the iron-containing protein hemoglobin (hematocrystalline, hematoglobin). The erythrocytes need the latter in order to bind the oxygen.
Medicine distinguishes between different variants of thalassemia. Hemoglobin is made up of a chain of several components. Depending on the modified building block affected, doctors differentiate between alpha and beta thalassemia. The described genetic defect leads to anemia, which manifests itself in the form of headaches, dizziness, tiredness and a pale complexion. After the diagnosis, in severe cases, therapy consisting of blood transfusions and medication begins.
Thalassemia major requires blood transfusions or bone marrow transplantation
In summary, mutations on the globin chains trigger the genetic disease thalassemia. In Europe, beta thalassemia predominates. If the genetic defect affects both inherited alleles, thalassemia major is present.
The homozygous form of the disease explained represents the more serious variant. The hemoglobin concentration in the blood drops sharply. Therefore, there is a need for regular blood transfusions. In addition, the patients receive medication for iron elimination. Complete healing of thalassemia major requires bone marrow transplantation (hematopoietic stem cell transplantation).
Thalassemia leads to dysfunction of hemoglobin
The oxygen contained in the inhaled air does not remain in the lungs. Instead, the O 2 molecules reach the erythrocytes. The red blood cells then transport the oxygen to the target locations via the bloodstream. In order to bind the oxygen, the hematocrystalline supports the described transport. If there is a functional disorder in the hematoglobin that is formed, this affects the oxygenium transport.
The disease thalassemia causes such dysfunction in the hemoglobin. This is a genetic defect that leads to defective formation of hematoglobin. Often the changes in the hematocrystalline arise due to point mutations.
The protein-containing part of hemoglobin is called globin. It consists of a total of four chains:
- Alpha-Globin,
- Beta-Globin,
- Gamma-Globin,
- Delta-Globin.
Thalassemia is due to reduced or non-existent formation of functional hemoglobin. As a result of the disease, globin components mutate; the resulting altered hematocrystalline loses its ability to function with regard to oxygen transport.
Difference between alpha and beta thalassemia
Medical diagnosis differentiates between two different forms of the disease explained: alpha and beta thalassemia. Both variants express themselves in the first years of life. Those affected are conspicuous by their pale face. In addition, anemia causes headaches, dizziness and tiredness. Patients tend to get out of breath quickly. You have trouble concentrating.
In alpha thalassemia, the gene defect (on chromosome 16) affects the globin alpha chains of the same name. As a result, there is an excess of beta or gamma globins. Conversely, beta thalassemia refers to an error in the production of beta globin. A genetic defect on chromosome 11 causes the globin mutations in thalassemia.
Variants of beta thalassemia
Beta thalassemia is the most common form of the disease presented. It occurs predominantly in Europe, while alpha thalassemia is more likely to be found in Asia. Medicine distinguishes between two different forms of thalassemia in the beta variant:
- Thalassaemia minor,
- und Thalassaemia major.
If beta thalassemia affects the genes inherited from both parents, it is thalassemia major. Doctors refer to these alternatively as a homozygous form or as Cooley anemia or Mediterranean anemia. The production of the beta-globin chains does not occur. The resulting erythrocytes are in an extremely unstable and defective state. Ultimately, ineffective erythropoiesis (technical term for the formation of erythrocytes) develops.
In the heterozygous form Thalassemia minor, the gene defect only affects one of the two alleles. The term refers to a comparatively mild variant of thalassemia. In the patient, the symptoms appear in a very weak form or do not occur at all. Therefore, there is usually no need for therapy.
Information on Thalassemia major
With regard to European patients and the effects, thalassemia major is therefore the disease with the greatest relevance. For this reason, detailed information on the homozygous form of the disease follows below.
Beta-thalassemia is usually inherited in an autosomal recessive manner. The genetic defect becomes apparent shortly after birth. In addition to the listed consequences of anemia such as dizziness, headaches or fatigue, there are other serious symptoms associated with thalassemia major.
At the age of a few months, the affected patients show a significantly enlarged spleen and liver. Growth disorders, malformations of the bones and considerable damage to the organs occur later. In addition, patients tend to have a yellow discoloration of the skin.
Severe anemia is considered to be an important symptom of thalassemia major in terms of diagnostics. Anemia is reflected in a low concentration of hemoglobin in the blood. Consequently, a laboratory analysis of the hematocrystalline provides information about the disease. The externally visible symptoms are similar to those of iron deficiency anemia. However, iron levels in thalassemia patients are not abnormal.
Therapy with blood transfusion or bone marrow transplantation
In the case of the homozygous form of thalassemia, a lifelong blood transfusion is required. Otherwise, the disease will end in death at an early age. The transfusions take place over a period of two to six weeks. According to an article published in Deutsches Ärzteblatt, the repeated drop in the hemoglobin concentration below 8 g/dl is considered an indicator for the start of therapy.
In the course of the symptomatic therapy of thalassemia through transfusions, the iron level in the blood rises too much. Therefore, the doctors supplement the treatment with the administration of drugs that stimulate iron excretion. If the serum ferritin concentration repeatedly exceeds the limit of 1,000 ng/ml, the iron elimination therapy begins. Nevertheless, there is a risk that an excess of iron will damage the body. At the same time, there is a risk of side effects from the drugs administered for iron elimination.
Bone marrow transplantation is the only option to cure the severe form of thalassemia. The required intervention is considered to be highly risky. In addition, the therapy requires the availability of a suitable donor.
Accompanying symptoms: enlargement of the bone marrow and spleen
In view of the ineffective erythropoiesis, the body tries to compensate for the deficiency on its own. The latter leads to overproduction in the form of greatly increased erythropoiesis in the bone marrow. The medulla ossium expands by a multiple of the usual size.
The thalassemia leads to what is known as erythroid hyperplasia (pathological expansion of the bone marrow). As a result, the bones also enlarge. The latter leads to a brittle and thus significantly weakened skeleton. This results, among other things, in an increased risk of bone fractures.
The spleen is responsible for breaking down the erythrocytes. Due to the overproduction, the number of erythrocytes to be broken down increases. This causes the spleen to become overactive, causing it to enlarge. This results in the risk of excessive breakdown of white blood cells, which triggers a weakened immune system.
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