Beta-thalassemia

The beta thalassemia mutations are often found in regions of the world where malaria has been common (in the past or the present). This is because people who are carriers for beta-thalassemia or a related hemoglobin condition have a slight change in shape to their red blood cells. This change in shape does not affect the function of the red blood cell so they do not have any symptoms. However the change in shape does result in the individual being less susceptible to malaria.

In areas where malaria is common, these carriers have a survival advantage. They are less likely than their counterparts to contract malaria and thus more likely to survive and to reproduce. When they have children, they have a 1 in 2 (50%) chance with each child of passing on the mutation. Thus the mutation increases in frequency in the population over time. As the mutation increases in frequency, it becomes more likely that two people who are carriers for the mutation will both pass down the mutation to a child who will be affected with beta thalassemia.

Cooley’s Anemia Foundation
330 Seventh Avenue #900
New York NY 10001
Phone: 800-522-7222 (toll-free)
Fax: 212-279-5999
Email: info@cooleyanemia.org
www.cooleysanemia.org

Thalassaemia International Federation (TIF)
PO Box 28807
Nicosia 2083 Cyprus
Phone: +357 22 319129
Fax: +357 22 314552
Email: thalassaemia@cytanet.com.cy
www.thalassaemia.org.cy

National Haemoglobinopathy Registry
MDSAS NHR Administrator
5 Union Street
City View House
Manchester M12 4JD
United Kingdom
Phone: 0161 277 7917
Email: support@mdsas.com
www.nhr.nhs.uk

If untreated, affected children usually have growth problems and delays (failure to thrive) and expansion of the bone marrow. Untreated, thalassemia major also leads to heart failure and liver problems. It also makes a person more likely to develop infections.

The most common secondary complications are those related to iron overload from having frequent blood transfusions. Because individuals with beta-thalassemia often require frequent transfusions, over time, an influx of iron-containing hemoglobin from chronic blood transfusions can lead to a buildup of iron in the body, resulting in liver, heart, and hormone problems. Iron overload can be prevented by adequate iron chelation, a procedure where excess iron is removed from the body.

Various conditions may have signs and symptoms similar to those seen in beta thalassemia. Such conditions include sideroblastic anemias and congenital dyserythropoietic anemias. Beta thalassemia can also occur along with other features as part of a larger syndrome such as in X-linked thrombocytopenia with thalassemia or beta thalassemia-trichothiodystrophy.

The United States blood supply is among the safest in the world. The Food and Drug Administration (FDA) has in place a five-layer safeguard system to help ensure the safety of blood given to recipients.

These safeguards are not perfect – for example, sometimes an infection has an "incubation period" during which it may not be detected by any known tests – but they are effective at keeping blood safety at a very high level. The most recent studies suggest the risk of HIV or hepatitis C from blood transfusions is about 1 in 1,000,000. The risk of hepatitis B infection, however, is somewhat likelier. Thalassemia patients should make sure that they receive leukoreduced (white blood cells removed) red blood cells, in order to reduce the risk of transfusion reactions. This is standard practice in the United States.

If you and your partner are both carriers for beta-thalassemia, each baby that you have with this partner is at 25% risk of having beta-thalassemia.

With improved screening programs, non-invasive iron measurement, better methods of measuring iron’s impact, a safer blood supply and more drug treatment options, people with thalassemia are surviving into their fifth decade and beyond.

The estimated number of worldwide births of patients with beta thalassemia major every year is about 22,989. The total annual incidence of symptomatic individuals is estimated at 1 in 100,000 throughout the world.

Beta thalassemia is a life-long disease. People with beta thalassemia have abnormal hemoglobin, which is a part of a red blood cell that carries oxygen to all areas of the body. In people with beta thalassemia, low levels of hemoglobin lead to a lack of oxygen in many parts of the body. Affected individuals also have a shortage of red blood cells (anemia), which can cause pale skin, weakness, fatigue, and more serious complications. Individuals with thalassemia often require frequent blood transfusions or hospitalization.

Beta-thalassemia is also known as Cooley’s anemia and Mediterranean anemia. It may also be referred to as thalassemia major and thalassemia intermedia.

Mutations in the HBB gene cause beta thalassemia. The HBB gene provides instructions for making a protein called beta-globin. Beta-globin is a component of hemoglobin. A lack of beta-globin leads to a reduced amount of functional hemoglobin. Without sufficient hemoglobin, red blood cells do not develop normally, causing a shortage of mature red blood cells. The low number of mature red blood cells leads to anemia and other associated health problems in people with beta thalassemia.

Children and adults with beta-thalassemia have normal intellectual development.

Thalassemia intermedia is milder than thalassemia major. The signs and symptoms of thalassemia intermedia appear in early childhood or later in life. Affected individuals have mild to moderate anemia and may also have slow growth and bone abnormalities. They may or may not need transfusions. If they do, they usually require transfusions at a lower frequency than those with thalassemia major.

The signs and symptoms of thalassemia major appear within the first 2 years of life. Children develop life-threatening anemia. They do not gain weight or grow at the expected rate (failure to thrive). Children may also develop yellowing of the skin and whites of the eyes (jaundice). Untreated affected individuals may have an enlarged spleen, liver, and heart, and their bones may be misshapen. Some adolescents with thalassemia major experience delayed puberty. Many people with thalassemia major have such severe symptoms that they need frequent blood transfusions to replenish their red blood cell supply.

On a genetic testing registry, there are 98 tests available for HBB gene in a total of 49 commercial labs in the US. The list of laboratories for genetic testing can be found:
http://www.ncbi.nlm.nih.gov/gtr/tests/?term=beta-thalassemia

There are also other related hemoglobin diseases, which, like beta-thalassemia, are also caused by an abnormality in the structure of hemoglobin (hemoglobinopathy). This includes hemoglobin E (HbE/beta thalassemia), hemoglobin C (HbC/beta thalassemia), and hemoglobin S (HbS/beta thalassemia), a condition that resembles sickle cell anemia and is sometimes referred to as sickle beta thalassemia disease

Yes. Prenatal diagnosis for pregnancies at increased risk is possible if the mutation in HBB gene in the family is known. Testing in the pregnancy can be done by invasive procedures, such as CVS or amniocentesis. To find a genetic counselor near you who can discuss prental testing, visit the National Society of Genetic Counselors Find a Genetic Counselor website.

Beta-thalassemia is on the Recommended Universal Screening Panel (RUSP) for newborn screening in the USA. The RUSP is a list of conditions, including 32 core conditions and 26 secondary conditions, which a national committee recommends that every baby in the USA should be screened for.

As of June 2019, there are clinical studies involving beta-thalassemia that are open and recruiting patients. To find up-to-date applicable clinical trial information, visit clinicaltrials.gov and search "Beta-thalassemia."

Currently, there is no cure for beta-thalassemia, but there are treatments and medications available to manage symptoms. Bone marrow transplant and cord blood transplant have been used in cases where a compatible donor is found. Blood transfusion and iron chelation are essential to overall well-being and health in individuals with beta-thalassemia.

It has been estimated that about 1.5% of the global population (80 to 90 million people) are carriers of beta-thalassemia.

There are several tests that are conducted to confirm a suspected case of thalassemia, including a Complete Blood Count (CBC) and a hemoglobin electrophoresis. These should be followed by a genetic analysis for both beta thalassemia and alpha thalassemia, even if initial results already indicate that either beta thalassemia or alpha thalassemia is a likely diagnosis.

Serum ferritin levels give a good general idea of how well chelation therapy is working, but they only measure the iron in the blood, they don’t necessarily tell you how much iron is in your heart and liver. MRI (magnetic resonance imaging) machines use non-invasive iron measurement technology to measure the amount of iron in your liver (using technology called R2) and in your heart (using technology called T2). However, for patients who can’t use this technology, a liver biopsy can provide valuable information.

The U.S. government monitors the potential transmission of diseases that may occur through transfused blood. The Centers for Disease Control and Prevention (CDC) has two programs that address this issue. First, through its established Universal Data Collection system, CDC screens for blood-borne pathogens like hepatitis and HIV. In addition, CDC developed the Thalassemia Data and Blood Specimen Collection system to help detect further known and emerging infections that may affect people who get frequent transfusions, such as those with severe forms of thalassemia.

The Cooley’s Anemia Foundation is an organization dedicated to raising money to fund research, provide patient resources, and improving the lives of patients living with Beta-thalassemia. Their donation portals can be found at cooleysanemia.org.

The March of Dimes also accepts donations towards research to prevent birth defects and childhood illnesses. marchofdimes.org

Beta thalassemia is a common blood disorder worldwide. Thousands of infants with beta thalassemia are born each year. Beta thalassemia occurs most frequently in people from Mediterranean countries, North Africa, the Middle East, India, Central Asia, and Southeast Asia. The highest incidences of beta thalassemia are reported in Cyprus, Sardinia, and Southeast Asia.

Normal red blood cells are round, concave and of equal shape and sizes. Red blood cells in patients with beta-thalassemia are weak, pale, and of variety of shapes and sizes. These changes can be seen under microscope during blood analysis in a laboratory.

If a person is a carrier of beta-thalassemia, they are sometimes said to have thalassemia trait or thalassemia minor. Carriers are healthy but may have a mild anemia. They require no medical treatment. The fact that an individual is a carrier only becomes important if their partner is also a carrier for beta-thalassemia or another hemoglobin variant and they have a pregnancy together. In that case, there is a chance (up to 25%, or 1 in 4) that the baby may be born with beta-thalassemia or another hemoglobinopathy (blood disorder like sickle cell disease).

Provided that a multidisciplinary team is available, pregnancy is possible and safe, and usually has a favorable outcome in women with beta-thalassemia. An increasing number of women with thalassemia major and thalassemia intermedia may, therefore, have children. Pregnant women should receive counseling regarding the risks and benefits of the use of iron chelation drugs during pregnancy.

The Cooley’s Anemia Foundation offers several different ways to connect with others living with beta-thalassemia. There are 11 local chapters under the Cooley’s Anemia Foundation. The foundation also hosts an annual Care Walk for the beta-thalassemia foundation to raise money and connect patients and families. Visit [link url="www.cooleysanemia.org” target=”_blank”>www.cooleysanemia.org to find resources nearest to you.

Beta thalassemia is classified into two types depending on the severity of symptoms: thalassemia major and thalassemia intermedia. Of the two types, thalassemia major is more severe.

Some mutations in the HBB gene prevent the production of any beta-globin. The absence of beta-globin is referred to as beta-zero (B0) thalassemia. Other HBB gene mutations allow some beta-globin to be produced but in reduced amounts. A reduced amount of beta-globin is called beta-plus (B+) thalassemia. Having either B0 or B+ thalassemia does not necessarily predict disease severity.