Hb Beta Chain-Related Hemoglobinopathies (Beta-Thalassemia and Sickle Cell Disease)
Hb beta chain-related hemoglobinopathies are inherited blood disorders affecting hemoglobin, vital for carrying oxygen in red blood cells. Mutations in the HBB gene cause these disorders.
There are three main types:
Beta Thalassemia Major: Severe anemia occurs due to low beta globin protein, causing symptoms like poor growth, pain, and organ damage. Children show symptoms early and require frequent blood transfusions to survive.
Beta Thalassemia Intermedia: A milder form causing mild to moderate anemia. Symptoms are less severe than major thalassemia, and it might not be diagnosed until later in life.
Sickle Cell Disease: Abnormal beta globin proteins make red blood cells crescent-shaped. This leads to anemia, infections, fatigue, and pain. It can cause blockages in blood vessels, leading to organ damage and acute chest syndrome, a severe breathing problem.
Treatment for thalassemias includes blood transfusions every few weeks, but this leads to iron buildup, requiring chelation therapy. Bone marrow transplant can cure it but it comes with risks. Sickle cell disease has varying symptoms; the most severe form can be treated with bone marrow transplants and other newer therapies. Lifelong care involves managing symptoms, avoiding dehydration, infections, and excessive physical activity, and taking pain medications.
This group of conditions is caused by pathogenic (disease-causing) variants in the HBB gene and exhibits autosomal recessive inheritance. This means that both parents must be carriers to have a 25% chance to have a child with the condition. The risk of being a carrier is based on a person’s ancestry or ethnic background. For example, individuals of Ashkenazi Jewish descent have a 1 in 28 chance to be a carrier.
Studies have shown that individuals that are carriers for a HBB variant associated with beta thalassemia (β+ or β0) may be at risk for beta thalassemia intermedia if they are also carriers of one or more extra copies of the alpha globin gene. Alpha thalassemia testing may be useful for these individuals. Individuals with sickle cell trait can also experience symptoms during episodes of dehydration, high altitudes, and other circumstances.