Thalassemia is hereditary hemoglobinopathies characterized by inhibition of the synthesis of chain protein molecules forming the structure of hemoglobin. This leads to damage to the erythrocyte membrane and destruction of red blood cells with the development of hemolytic crises. Signs are characteristic bone changes, hepatosplenomegaly, anemic syndrome. The diagnosis is confirmed by clinical and laboratory data (hemogram, hemoglobin, myelogram, electrophoretic method). Prenatal diagnosis is possible. In the treatment of thalassemia, hemotransfusion, desferal therapy, splenectomy, bone marrow transplantation are used.
ICD 10
D56 Thalassemia
Meaning
Thalassemia is a group of genetically determined blood diseases that develop with impaired synthesis of a- or β-chains of hemoglobin, accompanied by hemolysis, hypochromic anemia, microcytosis. In hematology, disease refers to hereditary hemolytic anemia – quantitative hemoglobinopathies.
Pathology are not uncommon in Africa, the Middle East, India and Indonesia and Central Asia. 300 thousand children are born with disease every year in the world. Depending on the form of pathology, the course of thalassemia can be severe, fatal or mild, asymptomatic. Just like sickle cell anemia, disease plays the role of a protective factor against malaria.
Causes
Thalassemia is a genetic disease with autosomal recessive inheritance. The direct cause of the pathology is various mutational disorders in the gene encoding the synthesis of a particular hemoglobin chain. The molecular basis of the defect may be the synthesis of abnormal matrix RNA, deletions of structural genes, mutations of regulatory genes or their ineffective transcription. The consequence of such disorders is a decrease or absence of synthesis of one of the polypeptide hemoglobin chains.
Thus, with b-thalassemia, beta chains are synthesized in insufficient quantities, which leads to an excess of alpha chains, and vice versa. Excessively produced polypeptide chains are deposited in erythroid cells, causing their damage. This is accompanied by the destruction of erythrocaryocytes in the bone marrow, hemolysis of erythrocytes in peripheral blood, death of reticulocytes in the spleen. In addition, with b-thalassemia, fetal hemoglobin (HbF) accumulates in erythrocytes, unable to transport oxygen to tissues, which causes the development of tissue hypoxia. As a result of bone marrow hyperplasia, deformity of the bones of the skeleton develops. Anemia, tissue hypoxia and ineffective erythropoiesis to one degree or another disrupt the development and growth of the child.
The homozygous form is characterized by the presence of two defective genes inherited from both parents. In the heterozygous variant of thalassemia, the patient is a carrier of a mutant gene inherited from one of the parents.
Classification
Taking into account the defeat of one or another polypeptide chain of hemoglobin , there are:
- a-thalassemia (with suppression of alpha-chain synthesis of HbA). This form can be represented by a heterozygous carrier of the manifest (α-th1) or mute (α-th2) gene; homozygous a-thalassemia (fetal dropsy with Barts hemoglobin); hemoglobinopathy H
- b-thalassemia (with suppression of the synthesis of HbA beta chains). It includes heterozygous and homozygous β-thalassemia (Cooley anemia), heterozygous and homozygous δß-thalassemia (F-thalassemia)
- γ-thalassemia (with suppression of the synthesis of gamma chains of hemoglobin)
- δ-thalassemia (with suppression of the synthesis of delta chains of hemoglobin)
- thalassemia caused by a violation of the structure of hemoglobin.
Beta-thalassemia is statistically more common, which, in turn, can occur in 3 clinical forms: small, large and intermediate. According to the severity of the syndrome, a mild form is distinguished (patients live to puberty), medium-severe (the life expectancy of patients is 8-10 years) and severe (the death of children occurs in the first 2-3 years of life).
Thalassemia symptoms
Signs of a large (homozygous) b-thalassemia manifests itself already during the 1-2 year of the child’s life. Sick children have a characteristic mongoloid face, a saddle-shaped bridge of the nose, a tower (quadrangular) skull, hypertrophy of the upper jaw, malocclusion, hepatomegaly and splenomegaly. Manifestations of anemia are pale or earthy-jaundiced skin color.
The defeat of tubular bones is accompanied by a lag in growth and pathological fractures. It is possible to develop synovitis of large joints, calculous cholecystitis, ulcers of the lower extremities. The factor complicating the course of b-thalassemia is hemosiderosis of internal organs, leading to the development of cirrhosis of the liver, pancreatic fibrosis and, as a consequence, diabetes mellitus; cardiosclerosis and heart failure. Patients are susceptible to infectious diseases (intestinal infections, acute respiratory infections, etc.), the development of severe forms of pneumonia and sepsis is possible.
Small (heterozygous) b-thalassemia may occur asymptomatically or with minimal clinical manifestations (moderate enlargement of the spleen, slightly pronounced hypochromic anemia, complaints of increased fatigue). Similar symptoms accompany the course of the heterozygous form of a-thalassemia.
In the homozygous form of a-thalassemia, alpha chains are completely absent; fetal hemoglobin is not synthesized in the fetus. This form is incompatible with life, which leads to intrauterine fetal death due to developing dropsy syndrome or spontaneous termination of pregnancy. The course of hemoglobinopathy H is characterized by the development of hemolytic anemia, splenomegaly, severe bone changes.
Diagnostics
Thalassemia should be suspected in persons with a family history, characteristic clinical signs and laboratory indicators. Patients need to consult a hematologist and a medical geneticist.
Typical hematological changes are a decrease in the level of hemoglobin and color index, hypochromia, the presence of target-shaped erythrocytes, an increase in the level of serum iron and indirect bilirubin. Hb electrophoresis on cellulose acetate film is used to determine various hemoglobin fractions. When studying bone marrow punctate, attention is drawn to hyperplasia of the red hematopoietic germ with a high number of erythroblasts and normoblasts. Molecular genetic studies reveal a mutation in the a- or β-globin locus that disrupts the synthesis of the polypeptide chain.
On craniograms with large b-thalassemia, needle periostosis (the phenomenon of the “hairy skull”) is revealed. Transverse striation of tubular and flat bones, the presence of small foci of osteoporosis is characteristic. With the help of ultrasound of the abdominal cavity, hepatosplenomegaly, gallbladder stones are detected.
If thalassemia is suspected, it is necessary to exclude iron deficiency anemia, hereditary microspherocytosis, sickle cell anemia, autoimmune hemolytic anemia. In families with thalassemia patients, it is recommended to conduct genetic counseling of spouses and invasive prenatal diagnostics (chorion biopsy, cordocentesis, amniocentesis) to detect hemoglobinopathy in the early stages of pregnancy. Confirmation of homozygous forms of thalassemia in the fetus serves as an indication for artificial termination of pregnancy.
Thalassemia treatment
Therapeutic tactics for various forms are not the same. Thus, patients with minor b-thalassemia do not need treatment. On the other hand, patients with homozygous b-thalassemia from the first months of life require hemotransfusion therapy (transfusion of thawed or washed erythrocytes), administration of chelating iron-binding drugs (deferoxamine), glucocorticoids in the event of hemolytic crises. In all forms of thalassemia , folic acid and B vitamins are indicated .
With hypersplenism (especially against the background of hemoglobinosis H), removal of the spleen (splenectomy) is required. Due to the tendency to join infectious complications, mandatory vaccination against pneumococcal infection is recommended for patients. Bone marrow transplantation from a histocompatible donor is a promising method of treating thalassemia.
Forecast
The prognosis of large forms is unfavorable; patients die in infancy or at a young age. With a heterozygous asymptomatic form, the duration and quality of life in most cases do not suffer. Primary prevention of thalassemia includes the prevention of marriages between heterozygous carriers of the disease genes, and with a high genetic risk of giving birth to sick offspring – refusal of childbearing.
Literature
- Alpha-Thalassemia. Tamary H, Dgany O. 2005 Nov 1 [updated 2020 Oct 1]. In: Adam MP, Everman DB, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2023. link
- Abstracts of Presentations at the Association of Clinical Scientists 143rd Meeting Louisville, KY May 11-14,2022. [No authors listed] Ann Clin Lab Sci. 2022 May;52(3):511-525. link
- Sickle Cell Disease. Bender MA, Carlberg K. 2003 Sep 15 [updated 2022 Nov 17]. In: Adam MP, Everman DB, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2023. link
- Beta-thalassemia. Galanello R, Origa R. Orphanet J Rare Dis. 2010 May 21;5:11. link
