Hb beta chain-related hemoglobinopathy

What is Hb Beta Chain-related Hemoglobinopathy?

Hb beta chain-related hemoglobinopathies are a group of inherited blood disorders that affect hemoglobin, the major component of red blood cells which carries oxygen throughout the body. Hemoglobin is made up of two different proteins, alpha and beta. Mutations of the HBB gene can result in reduced levels of beta proteins (thalassemias), or the formation of structurally abnormal beta proteins (sickle cell disease and other hemoglobinopathies).

People with Hb beta chain-related thalassemia do not produce enough beta protein—and in some cases do not produce it at all—resulting in a shortage of red blood cells (anemia). Without sufficient numbers of properly functioning red blood cells, the organs of the body do not receive enough oxygen. There are three main types of beta thalassemia. In the most severe form, thalassemia major (also called Cooley's Anemia), a child will begin to show symptoms of severe anemia late in the first year of life. The lack of oxygen can cause him or her to be pale, listless, tired, and irritable. The child's spleen, liver, and heart may be enlarged, which is made noticeable by a swollen abdomen and yellowed skin. The child's overall growth will be slowed and his or her bones may be thin, brittle, and/or deformed. Without frequent blood transfusions, the condition can be life-threatening at an early age.

Beta thalassemia intermedia, a less severe form of the condition, 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. People with thalassemia intermedia require fewer blood transfusions and use them to improve the quality of their lives.

Sickle cell disease is a type of hemoglobinopathy caused by two Hb S mutations, or one copy of the Hb S mutation along with a beta thalassemia mutation. People with sickle cell disease produce an abnormal type of beta protein. This results in red blood cells having a stiff crescent shape resembling a sickle. The sickled blood cells die prematurely, causing a person to feel weak and tired, a condition known as anemia. People with sickle cell anemia develop symptoms including anemia, repeated infections, shortness of breath, fatigue, jaundice, and bone pain starting in early childhood. These sickled cells also get stuck in small blood vessels, blocking blood flow and causing serious medical complications such as blood-starved organs or tissue deterioration. The most recognizable symptom is episodes of acute back, chest, or abdominal pain called "crises."

There are other types of Hb beta chain-related hemoglobinopathies that can be considerably milder in presentation. These include mutations of hemoglobins C, E, D-Punjab and O-Arab. Interactions between beta globin proteins and these mutations can alleviate or exacerbate the effects of the individual variants. A consultation with a hematologist is useful in predicting phenotype.

How common is Hb Beta Chain-related Hemoglobinopathy?

Mutations of the HBB gene are considered common worldwide, with an estimated prevalence of 1/100,000 affected individuals. Thalassemias are most common in people of Mediterranean descent, especially in those from Sardinia and Cyprus. In Cyprus, 1 in 7 people are carriers of beta thalassemia, a rate which prompted a successful government-run disease prevention program. Beta thalassemia is also commonly found in the Middle East and Asia.

Sickle cell disease is common in people 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, approximately 1/10 people are carriers of sickle cell.

{% comment %} Not sure if this table contains the current values, I've copied it from beta thalassemia {% endcomment %}

{% prevalence_table %} Cypriot | 1 in 7 | 1 in 170 Sardinian | 1 in 8 | 1 in 240 Italian | 1 in 31 | 1 in 3,700 Middle Eastern | 1 in 34 | 1 in 4,500 Southeast Asian | 1 in 35 | 1 in 4,800 East Asian | 1 in 62 | 1 in 15,000 Indian | 1 in 64 | 1 in 16,000 {% endprevalence_table %}

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 people 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, people with beta thalassemia require a procedure called chelation therapy in which a medication is taken to eliminate excess iron from the body. These individuals require frequent monitoring by a physician to assess the efficacy of transfusion/chelation therapy. In a small minority of people, a bone marrow transplant from a sibling or other suitable donor has been able to cure the disease. This procedure, however, is risky and could even be fatal.

The symptoms of sickle cell disease can vary in severity, depending upon the mutations that a person carries. The Hemoglobin S mutation (sickle cell disease) is associated with the most severe symptoms. Sickle cell anemia 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 anemia 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.

People with sickle cell anemia, 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. Nutrional therapy and pain medications are also useful.

What is the prognosis for a person with Hb Beta Chain-related Hemoglobinopathy?

The prognosis is entirely dependent on the specific type of hemoglobin disorder, and an accurate diagnosis coupled with treatment. Lifespan can be shortened, but varies and may even be normal depending on disease severity.