Beta thalassemia is a genetic blood disorder affecting hemoglobin production in red blood cells. Hemoglobin carries oxygen throughout the body. Individuals with this condition have reduced hemoglobin, leading to a shortage of red blood cells and anemia. Symptoms include pale skin, weakness, and fatigue. Beta thalassemia is prevalent in regions like the Mediterranean, Middle East, and Asia.
The HBB Gene and Hemoglobin Production
Beta thalassemia originates from mutations within the HBB gene on chromosome 11. This gene provides instructions for creating beta-globin, a protein component of hemoglobin. Normal adult hemoglobin consists of two beta-globin and two alpha-globin subunits, plus iron-containing heme molecules that bind oxygen.
Mutations in the HBB gene disrupt beta-globin production. Beta-zero (β⁰) thalassemia mutations completely prevent beta-globin production. Beta-plus (β⁺) thalassemia mutations result in reduced, but not absent, beta-globin. This deficiency in beta-globin hinders the proper formation of functional hemoglobin, leading to red blood cells that do not develop normally and are often abnormally small. This results in a shortage of mature red blood cells, which impairs oxygen delivery to tissues and contributes to anemia.
How Beta Thalassemia is Inherited
Beta thalassemia is inherited in an autosomal recessive pattern. This means that to develop the disorder, an individual must inherit two altered copies of the HBB gene, one from each parent. Males and females are equally affected, as the genes are not on sex chromosomes.
Parents who carry one altered copy of the HBB gene are referred to as “carriers” or have “beta thalassemia trait.” These individuals usually do not exhibit symptoms or may experience only mild anemia. However, carriers can still pass the altered gene to their children.
If both parents are carriers, there is a 25% chance their child will inherit two altered copies and be affected. There is a 50% chance the child will be a carrier, and a 25% chance the child will inherit two normal genes. In rare instances, beta thalassemia can be inherited in an autosomal dominant manner, where one altered gene copy is sufficient to cause symptoms.
Understanding Different Forms of Beta Thalassemia
The severity of beta thalassemia varies based on the HBB gene mutations inherited, categorized into three main forms.
Beta thalassemia major, also known as Cooley’s anemia, is the most severe form and often appears within the first two years of life. Individuals have mutations in both HBB gene copies, leading to severe deficiency or complete absence of beta-globin. This necessitates lifelong regular blood transfusions.
Beta thalassemia intermedia is moderately severe, with symptoms appearing later in childhood or adulthood. These individuals also have mutations in both HBB genes, but specific mutations allow for some beta-globin production. This results in milder anemia that may or may not require occasional blood transfusions.
Beta thalassemia minor, or beta thalassemia trait, occurs when an individual inherits only one altered HBB gene copy. People with beta thalassemia minor are asymptomatic or experience only mild anemia, often discovering their carrier status during routine blood tests.
Genetic Testing and Counseling
Genetic testing is important for diagnosing beta thalassemia and identifying carriers. DNA testing methods, such as polymerase chain reaction (PCR) and direct sequence analysis, detect specific mutations or deletions in the HBB gene. These tests confirm a diagnosis, determine the genotype, and help predict potential severity.
Genetic counseling is recommended for individuals and families at risk, especially those planning a family or with a family history of thalassemia. A genetic counselor helps individuals understand inheritance patterns, assess their risk of passing the condition to children, and explore reproductive options. Newborn screening programs in some regions also identify affected infants early, allowing for timely monitoring and intervention.