According to Thalassemia International Federation, only about 200,000 patients with thalassemia major are alive and registered as receiving regular treatment around the world. However, accurate data on carrier rates in many populations are lacking, particularly in areas of the world known or expected to be heavily affected. 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. It has been estimated that about 1.5% of the global population (80 to 90 million people) are carriers of beta-thalassemia, with about 60,000 symptomatic individuals born annually, the great majority in the developing world. Population migration and intermarriage between different ethnic groups has introduced thalassemia in almost every country of the world, including Northern Europe where thalassemia was previously absent. The high gene frequency of beta-thalassemia in these regions is most likely related to the selective pressure from Plasmodium falciparum malaria. The highest carrier frequency is reported in Cyprus (14%), Sardinia (10.3%), and Southeast Asia. However, cardiac disease remains the main cause of death in patients with iron overload.īeta-thalassemia is prevalent in Mediterranean countries, the Middle East, Central Asia, India, Southern China, and the Far East as well as countries along the north coast of Africa and in South America.
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. Individuals with thalassemia intermedia may require splenectomy, folic acid supplementation, treatment of extramedullary erythropoietic masses and leg ulcers, prevention and therapy of thromboembolic events. Bone marrow transplantation remains the only definitive cure currently available. In some circumstances, spleen removal may be required. Treatment of thalassemia major includes regular RBC transfusions, iron chelation and management of secondary complications of iron overload. Genetic counseling is recommended and prenatal diagnosis may be offered. 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).
Diagnosis of thalassemia is based on hematologic and molecular genetic testing. Transmission is autosomal recessive however, dominant mutations have also been reported. 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 (beta 0) synthesis of the beta chains of hemoglobin (Hb). Thalassemia minor is clinically asymptomatic but some subjects may have moderate anemia. 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. Patients with thalassemia intermedia present later in life with moderate anemia and do not require regular transfusions. 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). 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. Individuals with thalassemia major usually present within the first two years of life with severe anemia, requiring regular red blood cell (RBC) transfusions. Three main forms have been described: thalassemia major, thalassemia intermedia and thalassemia minor.
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.