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.
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.
|Ethnic Group||Carrier Rate||Affected Rate|
|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|
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.
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.
An organization that provides testing, evaluation, counseling, and support to people at risk of sickle cell disease.
10300 Carnegie Ave.
Cleveland, OH 44106
Phone: (216) 229-8600
A non-profit that helps families affected by beta thalassemia and advocates for research into better treatments for the disease.
330 Seventh Avenue Suite 900
New York NY 10001
Explanations of an extensive number of genetic diseases written for everyday people by the U.S. government's National Institutes of Health.
The NHLBI is the division of the government-run National Institutes of Health which deals with diseases of the blood, including beta thalassemia.
P.O. Box 30105
Bethesda, MD 20824-0105
Phone: (301) 592-8573
A division of Children's Hospital Oakland, the Center cares for thalassemia patients in the region along with research and outreach to families living with the disease.
747 52nd St.
Oakland, CA 94609
Phone: (510) 428-3885 x 4398
A non-profit that supports and advocates for research into the disease and educates the public about it.
231 East Baltimore St., Suite 800
Baltimore, MD 21202
Phone: (410) 528-1555
Secondary Phone: (800) 421-8453
An umbrella organization of 98 national thalassemia associations, it acts as a worldwide network for information and research. Its website has abundant information on the international scope of both the disease and the advocacy for a cure.
P.O. Box 28807
Nicosia 2083, Cyprus
Phone: 011 357 22 319 129 (from U.S.)
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