From the Guidelines
Thalassemias are a group of genetic disorders characterized by impaired production of hemoglobin, a protein essential for red blood cell function, resulting in ineffective erythropoiesis and profound anemia 1.
Key Characteristics
- Severe reduction or absent production of the β-globin chain constituent of hemoglobin (Hb) A, leading to an excess of α-globin chains 1
- Life-threatening anemia from approximately 1 to 2 years of age, requiring lifelong blood transfusions 1
- Iron overload due to frequent blood transfusions, necessitating lifelong iron chelation treatment to prevent or reverse iron-related complications 1
Diagnosis and Treatment
- Cardiac iron overload is a significant concern, with heart failure being the most common cause of death in β-thalassemia major (TM) 1
- Cardiac T2 magnetic resonance* is essential for estimating cardiac iron and identifying patients at risk of heart failure 1
- Iron chelation therapy with deferoxamine or deferasirox is crucial in preventing and managing iron overload 1
From the Research
Definition and Classification of Thalassemias
- Thalassemias are a group of genetic disorders that affect the production of hemoglobin (Hb), leading to varying degrees of anemia 2, 3, 4.
- They are characterized by anomalies in the synthesis of the alpha or beta chains of hemoglobin, resulting in variable phenotypes ranging from severe anemia to clinically asymptomatic individuals 3.
- The main forms of thalassemia include thalassemia major, thalassemia intermedia, and thalassemia minor, with different clinical presentations and treatment requirements 3, 5.
Pathophysiology and Clinical Features
- Thalassemias are caused by point mutations or deletions in the beta globin gene on chromosome 11, leading to reduced or absent synthesis of the beta chains of hemoglobin (Hb) 3.
- Ineffective erythropoiesis and red cell transfusions are sources of excess iron that can lead to iron overload and related complications, such as endocrinopathy, osteoporosis, cirrhosis, renal failure, and malignant transformation 6, 5.
- Clinical features of thalassemia include severe anemia, growth retardation, pallor, jaundice, poor musculature, hepatosplenomegaly, leg ulcers, and skeletal changes 3.
Diagnosis and Treatment
- Diagnosis of thalassemia is based on hematologic and molecular genetic testing, with genetic counseling and prenatal diagnosis recommended for affected families 3, 4.
- Treatment of thalassemia includes regular red blood cell transfusions, iron chelation therapy, and management of secondary complications of iron overload, as well as bone marrow transplantation in some cases 2, 3, 4.
- Novel therapeutic approaches, such as gene therapy and small molecule therapies, are being developed to address the underlying pathophysiology of thalassemia and improve treatment outcomes 2.