Beta-thalassemia

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...

A Melting Curve Analysis–Based PCR Assay for One-Step Genotyping of β-Thalassemia Mutations

“…Each year, approximately 40,000 infants positive for ␤-thalassemia major are reported in areas endemic for thalassemia, which include the Mediterranean countries, parts of north and west Africa, the Middle East, India, and southeast Asia including southern China. 3,4 In China, the estimated incidence of carriers of ␤-thalassemia is as high as 7% in the Guangxi Province, and 1% to 6% in populations elsewhere in the endemic areas of southern China. [5][6][7][8] ␤-Thalassemia is a severe disease, and its treatment requires many resources, both medical and financial.…”

New film‐coated tablet formulation of deferasirox is well tolerated in patients with thalassemia or lower‐risk MDS: Results of the randomized, phase II ECLIPSE study

“…Compliance with iron chelation therapy can influence the frequency and severity of iron overload-related complications, 1 with demonstrated improvement in organ dysfunction and survival in patients compliant with iron chelation therapy. [2][3][4][5][6] The once-daily oral deferasirox dispersible tablet (DT) formulation (Exjade ® ), available since 2005, offered an improved option over parenteral deferoxamine (Desferal ® ), providing greater compliance, patient satisfaction, and health-related quality of life.…”

Acute cardiac decompensation in a patient with beta‐thalassemia and diabetes mellitus following cessation of chelation therapy

“…Hypogonadotropic hypogonadism is the most frequent endocrine complication in patients with iron overload and thalassemia 3. There is a close association between insulin resistance (IR) and testosterone deficiency 27.…”

“…Chelation therapy is used to mitigate against these complications. Endocrine complications from repeated transfusion include secondary hypogonadism (prevalence of 35–55%) 3, short stature (31–35%), diabetes mellitus (6–10%), primary hypothyroidism (3–11%), and hypoparathyroidism (1–7%) 3, 4. Iron deposition cardiomyopathy is the leading cause of morbidity and mortality in patients with thalassemia with consequent congestive cardiac failure accounting for up to 70% of deaths in patients with thalassemia 3.…”

“…Endocrine complications from repeated transfusion include secondary hypogonadism (prevalence of 35–55%) 3, short stature (31–35%), diabetes mellitus (6–10%), primary hypothyroidism (3–11%), and hypoparathyroidism (1–7%) 3, 4. Iron deposition cardiomyopathy is the leading cause of morbidity and mortality in patients with thalassemia with consequent congestive cardiac failure accounting for up to 70% of deaths in patients with thalassemia 3. The coexistence of diabetes in patients with thalassemia leads to an increased risk for myocardial fibrosis 5, while diabetes and hypogonadism are independently associated with myocardial iron loading 6.…”