beta globin-related hemoglobinopathy (including beta thalassemia and sickle cell disease)

What are Beta Globin-related Hemoglobinopathies (Including Beta Thalassemia and Sickle Cell Disease)?

Beta globin-related hemoglobinopathies (including beta thalassemia and sickle cell disease) are a group of inherited blood disorders that affect hemoglobin, a major component of red blood cells that are responsible for carrying oxygen throughout the body. Hemoglobin is made up of two different protein chains, the alpha and beta chains. Harmful genetic changes in the HBB gene can result in reduced levels of beta chains (thalassemias) or the formation of structurally abnormal beta globin proteins (sickle cell disease and other hemoglobinopathies).

There are three main types of beta globin-related hemoglobinopathies: a severe form of beta thalassemia called beta thalassemia major, a milder form of beta thalassemia called beta thalassemia intermedia, and sickle cell disease. There are other types of hemoglobinopathies that can be considerably milder in presentation as well. A consultation with a hematologist is useful in predicting expression of these diseases.

Individuals with beta globin-related thalassemia produce insufficient amounts of beta globin protein and in some cases do not produce it at all, resulting in a shortage of red blood cells (anemia). Without enough properly functioning red blood cells, the tissues of the body do not receive adequate oxygen. This results in several symptoms, including poor growth, pain, and organ damage.

Beta Thalassemia Major

In beta thalassemia major (also known as Cooley's anemia), a child will begin to show symptoms of severe anemia in the first two years of life. The lack of oxygen can cause children to be pale, tired, and irritable. The child's spleen or liver may be enlarged (hepatosplenomegaly), which is made noticeable by a swollen abdomen and yellowing of the skin (jaundice). This condition also causes delayed growth and misshapen bones. Without frequent blood transfusions, this can be a life-threatening condition at an early age.

Beta Thalassemia Intermedia

This is a less severe form of beta thalassemia that causes mild to moderate anemia and a wide spectrum of possible health problems. Symptoms are similar but less severe than beta thalassemia major, including bone deformities and an enlarged spleen. Individuals with thalassemia intermedia require fewer blood transfusions but may develop other symptoms such as leg ulcers and reduced bone mass leading to osteoporosis. Diagnosis of thalassemia intermedia may not be made until later in life.

Sickle Cell Disease

Sickle cell disease is a type of hemoglobinopathy caused by specific harmful genetic changes in the HBB gene that result in abnormal beta globin protein structure. This results in red blood cells that have a stiff crescent shape resembling a sickle. The sickled blood cells die prematurely, causing anemia, repeated infections, shortness of breath, fatigue, jaundice, and bone pain starting in early childhood. These sickled cells can also cause blockages in small blood vessels, reducing blood flow and causing serious medical complications such as blood-starved organs or tissue failure. The most recognizable symptom in children is foot or hand pain, and episodes of acute back, chest, or abdominal pain are common in adults.

Individuals with sickle cell disease may also experience delayed growth, delayed puberty, gallstones, and heart disease. Blockage of blood vessels in the lung can cause acute chest syndrome, which is associated with difficulty breathing, chest pain, and fever. Acute chest syndrome is a major cause of death in sickle cell disease.

Additional Considerations For Carriers

Studies have shown that individuals that are carriers of a harmful genetic change in HBB 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.

How common are Beta Globin-related Hemoglobinopathies (Including Beta Thalassemia and Sickle Cell Disease)?

The incidence of beta globin-related hemoglobinopathies in the population ranges from 1 in 200 to 1 in 25,000 births. Thalassemias are most common in individuals of Mediterranean descent, especially in those from Sardinia and Cyprus, as well as individuals from the Middle East and Asia. Sickle cell disease is common in individuals from Africa, the Mediterranean, the Arabian Peninsula, India, and Central and South America.

How are Beta Globin-related Hemoglobinopathies (Including Beta Thalassemia and Sickle Cell Disease) treated?

The most common treatments for beta thalassemia are blood transfusions, which provide a temporary supply of healthy red blood cells to bring oxygen to the body. Among individuals with thalassemia major, transfusions may take place every two to three weeks. While these transfusions can be lifesaving and life-enhancing, they result in a toxic buildup of iron in the blood. To counteract this side effect, individuals with beta thalassemia require chelation therapy, which helps eliminate excess iron from the body. These individuals require frequent monitoring by a physician to assess the progress of transfusion and chelation therapy. In a small minority of individuals, a bone marrow transplant from a sibling or other suitable donor has been able to cure the disease.

The symptoms of sickle cell disease can vary in severity, depending upon the harmful HBB change that an individual carries. In some patients, sickle cell disease can be cured with bone marrow transplants from a sibling or other suitable donor. For patients who are not candidates for bone marrow transplantation, sickle cell disease requires lifelong care to manage and limit the frequency of crises.

Individuals with sickle cell disease, particularly children, should drink plenty of water, avoid demanding physical activity, avoid too much sun exposure, and get all appropriate vaccines and immunizations. Preventing dehydration and avoiding infection can fend off crises and may prevent the sickling of red blood cells. Nutritional therapy and pain medications are also useful.

What is the prognosis for a person with Beta Globin-related Hemoglobinopathies (Including Beta Thalassemia and Sickle Cell Disease)?

The prognosis for an individual with a beta globin-related hemoglobinopathy depends entirely on the specific type of hemoglobin disorder and the harmful genetic changes in the HBB gene. A shortened lifespan is possible, but lifespan varies significantly and may even be normal, depending on disease severity. Early treatment can extend a patient's average lifespan by a decade or more.