Beta-thalassemia

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

Early detection of myocardial dysfunction in poorly treated pediatric thalassemia children and adolescents: Two Saudi centers experience

Background & Objective: Cardiac complications are among the most serious complications in Beta Thalassemia Major Patients. Our aim was to evaluate the value of tissue Doppler imaging (TDI) for early detection of myocardial dysfunction in pediatric and adolescent patients with B-TM before development of overt heart failure or cardiomyopathy. Patients and methods: 100 thalassemic patients below 18 years old and 100 healthy, age & sex matched controls were enrolled in our case-control study. Cases were selected from those attending outpatient clinics and inpatient wards, King Abdulaziz University hospital and Alhada Armed Forces Hospital, Saudi Arabia, between January 2014 and January 2015. They were subjected to echo-Doppler examination for both septal and lateral walls of the basal mitral and tricuspid annuli assessing the systolic myocardial velocity (S wave), early diastolic myocardial velocity (Ea wave) and late diastolic myocardial velocity (Aa wave). Results: Patients with thalassemia have RV and LV dysfunction on the basis of abnormal TDI derived myocardial velocities. There was a statistically significant differences between patients and controls regarding (Aa) and (S) of the septal wall of the basal mitral annulus and (Ea) of the lateral wall of the mitral annulus. Also patients with thalassemia have significantly higher (S) of the basal tricuspid annulus. These abnormalities were not detected by conventional echo-Doppler. Conclusion: Clinically asymptomatic thalassemic children and adolescents who had normal global functions by conventional echo-Doppler were found to have abnormal left ventricular and right ventricular dysfunctions detected by TDI. TDI is superior to Echo-Doppler in detection of early myocardial damage in asymptomatic thalassaemic patients