Beta-thalassemia
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Open Access
- 21 May 2010
- journal article
- review article
- Published by Springer Science and Business Media LLC in Orphanet Journal of Rare Diseases
- Vol. 5 (1), 11
- https://doi.org/10.1186/1750-1172-5-11
Abstract
Beta-thalassemias are a group of hereditary blood disorders characterized by anomalies in the synthesis of the beta chains of hemoglobin resulting in variable phenotypes ranging from severe anemia to clinically asymptomatic individuals. The total annual incidence of symptomatic individuals is estimated at 1 in 100,000 throughout the world and 1 in 10,000 people in the European Union. Three main forms have been described: thalassemia major, thalassemia intermedia and thalassemia minor. Individuals with thalassemia major usually present within the first two years of life with severe anemia, requiring regular red blood cell (RBC) transfusions. Findings in untreated or poorly transfused individuals with thalassemia major, as seen in some developing countries, are growth retardation, pallor, jaundice, poor musculature, hepatosplenomegaly, leg ulcers, development of masses from extramedullary hematopoiesis, and skeletal changes that result from expansion of the bone marrow. Regular transfusion therapy leads to iron overload-related complications including endocrine complication (growth retardation, failure of sexual maturation, diabetes mellitus, and insufficiency of the parathyroid, thyroid, pituitary, and less commonly, adrenal glands), dilated myocardiopathy, liver fibrosis and cirrhosis). Patients with thalassemia intermedia present later in life with moderate anemia and do not require regular transfusions. Main clinical features in these patients are hypertrophy of erythroid marrow with medullary and extramedullary hematopoiesis and its complications (osteoporosis, masses of erythropoietic tissue that primarily affect the spleen, liver, lymph nodes, chest and spine, and bone deformities and typical facial changes), gallstones, painful leg ulcers and increased predisposition to thrombosis. Thalassemia minor is clinically asymptomatic but some subjects may have moderate anemia. Beta-thalassemias are caused by point mutations or, more rarely, deletions in the beta globin gene on chromosome 11, leading to reduced (beta+) or absent (beta0) synthesis of the beta chains of hemoglobin (Hb). Transmission is autosomal recessive; however, dominant mutations have also been reported. Diagnosis of thalassemia is based on hematologic and molecular genetic testing. Differential diagnosis is usually straightforward but may include genetic sideroblastic anemias, congenital dyserythropoietic anemias, and other conditions with high levels of HbF (such as juvenile myelomonocytic leukemia and aplastic anemia). Genetic counseling is recommended and prenatal diagnosis may be offered. Treatment of thalassemia major includes regular RBC transfusions, iron chelation and management of secondary complications of iron overload. In some circumstances, spleen removal may be required. Bone marrow transplantation remains the only definitive cure currently available. Individuals with thalassemia intermedia may require splenectomy, folic acid supplementation, treatment of extramedullary erythropoietic masses and leg ulcers, prevention and therapy of thromboembolic events. Prognosis for individuals with beta-thalassemia has improved substantially in the last 20 years following recent medical advances in transfusion, iron chelation and bone marrow transplantation therapy. However, cardiac disease remains the main cause of death in patients with iron overload.Keywords
This publication has 90 references indexed in Scilit:
- Pregnancy and -thalassemia: an Italian multicenter experienceHaematologica, 2009
- Association of globin gene quadruplication and heterozygous thalassemia in patients with thalassemia intermediaHaematologica, 2009
- Cholelithiasis in thalassemia majorEuropean Journal of Haematology, 2008
- Genome-wide association study shows BCL11A associated with persistent fetal hemoglobin and amelioration of the phenotype of β-thalassemiaProceedings of the National Academy of Sciences of the United States of America, 2008
- Improved survival of thalassaemia major in the UK and relation to T2* cardiovascular magnetic resonanceJournal of Cardiovascular Magnetic Resonance, 2008
- Combined chelation therapy in thalassemia major for the treatment of severe myocardial siderosis with left ventricular dysfunctionJournal of Cardiovascular Magnetic Resonance, 2008
- Reversal of heart failure in thalassemia major by combined chelation therapy: a case reportEuropean Journal of Haematology, 2004
- Basal and Stimulated Levels of Growth Hormone, Insulin-like Growth Factor-I (IGF-I), IGF-I Binding and IGF-Binding Proteins in Beta-Thaiassemia MajoJournal of Pediatric Endocrinology and Metabolism, 2004
- Elastic tissue abnormalities resembling pseudoxanthoma elasticum in β thalassemia and the sickling syndromesBlood, 2002
- Variability in hepatic iron concentration measurement from needle-biopsy specimensJournal of Hepatology, 1996