Hb beta chain-related hemoglobinopathy

What Are Hb Beta Chain-Related Hemoglobinopathies?

Hb beta chain-related hemoglobinopathies 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. Mutations of 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 Hb beta chain-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.

Beta Thalassemia Major

Individuals with Hb beta chain-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 a sufficient number of properly functioning red blood cells, the tissues of the body do not receive enough oxygen. This can result in a number of symptoms, including poor growth, pain, and organ damage.

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 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, and causes mild to moderate anemia and a wide spectrum of possible health problems. The types of symptoms are the same as with thalassemia major, including bone deformities and an enlarged spleen, though these are typically not as severe. Thalassemia intermedia may not be diagnosed until later in life.

Individuals with thalassemia intermedia require fewer blood transfusions but may develop other symptoms such as leg ulcers and reduced bone mass leading to osteoporosis.

Sickle Cell Disease

Sickle cell disease is a type of hemoglobinopathy caused by specific mutations in the HBB gene that result in abnormal beta globin protein structure. This results in red blood cells having 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 deterioration. The most recognizable symptom in children is foot or hand pain, while episodes of acute back, chest, or abdominal pain is common in adults.

Individuals with sickle cell disease may also experience delayed growth and 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.

There are other types of hemoglobinopathies that can be considerably milder in presentation. These are caused by different mutations in the HBB gene. The complex interactions between different beta globin proteins can explain some of the wide diversity in symptoms and severity observed in hemoglobinopathies. A consultation with a hematologist is useful in predicting expression of this disease.

Additional Considerations for Carriers

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.

How Common Is Hb Beta Chain-Related Hemoglobinopathy?

Mutations of the HBB gene have an estimated prevalence of 1 in 100,000 affected individuals. Thalassemias are most common in individuals of Mediterranean descent, especially in those from Sardinia and Cyprus. In Cyprus, the prevalence is 1 in 7, while in Sardinia prevalence is 1 in 8. Beta thalassemia is also commonly found in the Middle East and Asia.

Sickle cell disease is common in individuals from Africa, the Mediterranean, the Arabian Peninsula, India, South America, and Central America. The large percentage of carriers in these regions is attributed to the sickle cell mutation's protective effect against malaria. In the African American population, prevalence is 1 in 10, while in Africa it is as high as 1 in 3 to 1 in 4.

How Is Hb Beta Chain-Related Hemoglobinopathy Treated?

The most common treatment for beta thalassemia is 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 life-saving 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. This procedure, however, is risky and can even be fatal.

The symptoms of sickle cell disease can vary in severity, depending upon the HBB mutations that an individual carries. The hemoglobin S mutation (sickle cell disease) is associated with the most severe symptoms. Sickle cell disease can be cured with bone marrow transplants, but the procedure is extremely risky, both because the drugs needed to make the transplant possible are highly toxic and because it can be difficult to find suitable donors. For patients who are not candidates for bone-marrow transplantation, sickle cell disease requires lifelong care to manage and control symptoms and limit the frequency of crises. Fortunately, a better understanding of how to manage the illness has extended patients' average lifespan by a decade or more.

Individuals with sickle cell disease, particularly children, should drink plenty of water, avoid demanding physical activity and 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 an Individual with Hb Beta Chain-Related Hemoglobinopathy?

The prognosis for an individual with Hb beta chain-related hemoglobinopathy is entirely dependent on the specific type of hemoglobin disorder, the mutations in the HBB gene, and an accurate diagnosis coupled with treatment. Lifespan can be shortened, but varies significantly, and may even be normal depending on disease severity.