Beta thalassemia is a genetic blood disorder that affects the body’s ability to produce hemoglobin. Hemoglobin is the protein in red blood cells; the cells that carry oxygen throughout the body.Â
There are three main forms of beta thalassemia: minor, intermedia, and major. Beta thalassemia minor typically causes mild anemia and often does not require treatment. Beta thalassemia major, also known as Cooley’s anemia, is the most severe form and requires regular blood transfusions and medical care.Â
Individuals with beta thalassemia intermedia have moderate anemia and may need occasional blood transfusions.
Approximately 1.5% of the global population, or around 80 to 90 million people, are carriers of beta thalassemia, with 60,000 to 70,000 affected infants born annually. Alpha thalassemia, a similar condition, is similarly widespread, particularly in tropical and subtropical regions.Â
Beta Thalassemia major was first described in 1925 by Cooley and Lee as a severe form of anemia, marked by splenomegaly and bone deformities due to the early onset of anemia caused by reduced hemoglobin synthesis. The highest frequency occurs in a region known as the “thalassemia belt,” spanning countries along the Mediterranean, parts of Africa, the Middle East, the Indian subcontinent, and Southeast Asia.
Hemoglobin is a protein in red blood cells that helps carry oxygen from the lungs to the rest of the body. It also helps bring carbon dioxide (a waste product) back to the lungs to be breathed out.
Hemoglobin is very important because oxygen is needed by all the cells in your body to produce energy and function properly. Without enough hemoglobin, your body can’t get enough oxygen, which can make you feel tired, weak, and short of breath. Hemoglobin also helps keep the blood’s pH level balanced, which is important for maintaining overall health.
Hemoglobin is made up of four protein chains, known as globin chains, which form a structure called a tetramer. These chains are paired to form two types of subunits, typically two alpha (α) chains and two non-alpha chains. The composition of hemoglobin changes at different stages of development, and the specific types of globin chains involved include:
The hemoglobin beta (HBB) gene is a gene located on chromosome 11 that provides instructions for making the beta-globin protein, a key component of hemoglobin. The HBB gene specifically produces the beta-globin chains that pair with alpha-globin chains (produced by the HBA gene) to form normal hemoglobin (HbA) in adults.
Mutations in the HBB gene can disrupt the production of beta-globin, leading to conditions such as beta-thalassemia and sickle cell anemia. In beta thalassemia, HBB mutations reduce or stop beta-globin production, causing anemia and other health issues due to insufficient and dysfunctional hemoglobin.
Beta thalassemia is inherited in an autosomal recessive manner, meaning a person must inherit two copies of the mutated gene—one from each parent—to develop the severe form of the disorder. Suppose an individual inherits only one mutated gene. In that case, they are considered carriers (also known as having beta thalassemia minor) and may exhibit mild anemia but generally live a normal life.
Carriers have a 50% chance of passing the mutated gene to their children, while two carriers have a 25% chance of having a child with beta-thalassemia major and a 50% chance of having a child who is a carrier.
Beta thalassemia and sickle cell anemia are both genetic disorders affecting hemoglobin, but they are distinct conditions. In beta thalassemia, the body cannot produce enough beta chains for hemoglobin, leading to anemia due to reduced production and increased breakdown of red blood cells.Â
Sickle cell anemia, on the other hand, is caused by a specific mutation in the hemoglobin gene that leads to the production of abnormal hemoglobin (HbS). This causes red blood cells to become rigid, sticky, and sickle-shaped, leading to blockages in blood vessels and further breakdown of the cells.Â
While both conditions cause anemia and are inherited in an autosomal recessive manner, their underlying genetic mutations and clinical manifestations are different. Beta thalassemia primarily results in reduced hemoglobin production, whereas sickle cell anemia affects the shape and function of the hemoglobin itself.
Treatments also vary between the two, with beta-thalassemia often requiring regular blood transfusions and sickle cell anemia focusing on preventing pain crises and managing complications.
Currently, beta thalassemia is not considered completely curable in most cases. However, certain advanced treatments, such as bone marrow or stem cell transplants, have the potential to offer a cure for some patients, particularly those with severe forms like beta thalassemia major.
Bone marrow transplants involve replacing the patient’s defective bone marrow with healthy marrow from a compatible donor, which can then produce normal red blood cells. This procedure is complex, and finding a compatible donor can be challenging. It also carries risks, including rejection and infection.Â
Gene therapy is an emerging field that shows promise in treating beta-thalassemia by introducing normal copies of the beta-globin gene into the patient’s stem cells. While still in the experimental stages, early results have been promising for reducing or eliminating the need for regular blood transfusions.Â
A 2021 paper described a gene editing technique using Cas9/AAV6 that replaces the entire HBA1 gene with a full-length HBB gene in stem cells from β-thalassemia patients. One complication in beta-thalassemia stems from erythrotoxic accumulation and aggregation of the beta-globin-binding partner, alpha-globin.
This method restores the balance between β-globin and α-globin proteins, allowing the production of normal adult hemoglobin in the patient’s red blood cells. The edited stem cells also showed long-term success in producing healthy blood cells in mice, providing a potential new treatment approach for curing beta-thalassemia.
Beta thalassemia causes anemia, a condition characterized by a deficiency in the number or quality of red blood cells. This anemia results from the body’s inability to produce sufficient amounts of functional hemoglobin due to the defective or absent production of beta-globin chains.
In beta thalassemia major, the severe form of the disease, anemia is particularly pronounced. This leads to symptoms such as fatigue, weakness, pale skin, and growth delays in children. Without treatment, the anemia can be life-threatening.Â
Individuals with beta thalassemia intermedia experience moderate anemia, which can vary in severity, while those with beta thalassemia minor typically have mild anemia or may be asymptomatic.
The anemia in beta-thalassemia occurs because the imbalance between alpha and beta chains in hemoglobin leads to ineffective red blood cell production (ineffective erythropoiesis) and increased destruction of the red blood cells. To manage anemia, treatment may include regular blood transfusions, especially in severe cases, and iron chelation therapy to prevent iron overload caused by the transfusions.
Beta thalassemia is a genetic disorder that affects the production of hemoglobin, the protein responsible for carrying oxygen in red blood cells. There are three forms: minor (mild anemia), intermedia (moderate anemia), and major (severe anemia requiring regular transfusions).
Around 1.5% of the global population are carriers of the condition, with high prevalence in regions like the Mediterranean, Middle East, and Southeast Asia. Hemoglobin, made of alpha and beta chains, is crucial for oxygen transport.
Mutations in the HBB gene reduce beta-globin production, causing anemia. Beta thalassemia is inherited in an autosomal recessive manner, and while treatments like blood transfusions and bone marrow transplants help manage the disease, new treatments such as gene therapieoffer hope for a potential cure.
