What is the difference between alpha (α) thalassemia and beta (β) thalassemia?

From the Guidelines

Alpha thalassemia and beta thalassemia are distinct genetic blood disorders that differ primarily in the globin chain of hemoglobin affected, with alpha thalassemia resulting from mutations in the alpha-globin genes and beta thalassemia from mutations in the beta-globin genes. The key difference between the two conditions lies in the specific globin chain affected, leading to varying degrees of severity and clinical manifestations. Alpha thalassemia, resulting from mutations in the alpha-globin genes on chromosome 16, can range from silent carrier status to fatal hydrops fetalis, depending on the number of affected genes 1. In contrast, beta thalassemia, involving mutations in the beta-globin genes on chromosome 11, is typically classified as minor, intermedia, or major, with beta thalassemia major often presenting with severe anemia in infancy requiring lifelong transfusions 1.

Key Differences

• Genetic Basis: Alpha thalassemia is caused by mutations in the alpha-globin genes, while beta thalassemia is caused by mutations in the beta-globin genes.
• Severity: The severity of alpha thalassemia varies widely based on the number of affected genes, while beta thalassemia is classified into distinct severity categories.
• Clinical Manifestations: Beta thalassemia major often presents with severe anemia in infancy, while alpha thalassemia's clinical manifestations vary based on the number of affected genes.
• Treatment Approaches: The treatment approaches for alpha and beta thalassemia differ, with beta thalassemia major often requiring lifelong transfusions and alpha thalassemia requiring varying levels of medical intervention based on severity.

Laboratory Findings and Treatment

Both conditions cause an imbalance in globin chain production, leading to ineffective red blood cell production. However, the specific laboratory findings and treatment approaches differ based on which globin chain is affected. For example, beta thalassemia major often requires cardiac monitoring and treatment for iron overload, as seen in the consensus statement from the American Heart Association 1. In contrast, alpha thalassemia may require prenatal diagnosis and monitoring for fetal anemia, as outlined in the Society for Maternal-Fetal Medicine clinical guideline 1. Gene therapy has also been explored as a potential treatment option for both conditions, with promising results in mouse models 1.

From the Research

Difference between Alpha and Beta Thalassemia

• Alpha thalassemia is caused by reduced or absent synthesis of alpha globin chains, while beta thalassemia is caused by reduced or absent synthesis of beta globin chains 2.
• The clinical presentation of alpha and beta thalassemia varies depending on the genotype, ranging from a silent or mild carrier state to severe, transfusion-dependent or lethal disease 3.
• Alpha thalassemia major with hemoglobin Bart's usually results in fatal hydrops fetalis, while beta thalassemia major causes hemolytic anemia, poor growth, and skeletal abnormalities during infancy 2.
• Beta thalassemia intermedia is less severe than beta thalassemia major and may require episodic blood transfusions, while alpha thalassemia intermedia, or hemoglobin H disease, causes hemolytic anemia 2, 4.

Clinical Manifestations and Treatment

• Thalassemia should be suspected in patients with microcytic anemia and normal or elevated ferritin levels, and hemoglobin electrophoresis may reveal common characteristics of different thalassemia subtypes 4.
• Treatment of thalassemia includes transfusions, iron chelation therapy to correct iron overload, hydroxyurea, hematopoietic stem cell transplantation, and luspatercept 4.
• Management of patients with alpha-thalassemia is primarily supportive, addressing either symptoms or complications of the disease, or its transfusion-dependence 3.
• Novel therapies are also in development, including curative gene manipulation techniques and disease modifying agents that target ineffective erythropoiesis and chronic hemolytic anemia 3.

Prognosis and Complications

• Persons with thalassemia trait have a normal life expectancy, while persons with beta thalassemia major often die from cardiac complications of iron overload by 30 years of age 2.
• Thalassemia complications arise from bone marrow expansion, extramedullary hematopoiesis, and iron deposition in peripheral tissues, affecting the skeletal system, endocrine organs, heart, and liver 4.
• Life expectancy of those with thalassemia has improved dramatically over the past 50 years with increased availability of blood transfusions and iron chelation therapy, and improved iron overload monitoring 4.