Sickle beta thalassemia

Other Names: Hemoglobin sickle-beta thalassemia; Hb S beta-thalassemia; Sickle cell - beta-thalassemia disease; HbS - beta-thalassemia; HbS-beta-thalassemia syndrome; Sickle cell-beta-thalassemia disease syndrome

Sickle beta thalassemia is an inherited condition that affects hemoglobin, the protein in red blood cells that carries oxygen to different parts of the body. It is a type of sickle cell disease. A heterozygous state in which a person has a hemoglobin s allele along with a beta-thalassemia allele. The severity of the condition is determined to a large extent by the quantity of normal hemoglobin produced by the beta-thalassemia gene.

Cause

Sickle beta thalassemia is caused by changes (mutations) in the HBB gene. HBB encodes a component of hemoglobin called "beta globin". Different mutations in HBB impact the production of hemoglobin in various ways. One specific mutation leads to an abnormal form of hemoglobin (called hemoglobin S) that causes red blood cells to form a "sickle" or crescent shape. Other mutations reduce the production of beta globin, which leads to low levels of functional hemoglobin and a low number or mature red blood cells (beta thalassemia).

People affected by sickle beta thalassemia have a different mutation in each copy of the HBB gene: one that produces hemoglobin S and a second that is associated with beta thalassemia. Depending on the beta thalassemia mutation, people may have no normal hemoglobin (called sickle beta zero thalassemia) or a reduced amount of normal hemoglobin (called sickle beta plus thalassemia). The presence of sickle-shaped red blood cells, which often breakdown prematurely and can get stuck in blood vessels, combined with the reduction or absence of mature red blood cells leads to the many signs and symptoms of sickle beta thalassemia.

Inheritance

Autosomal recessive inheritance, a 25% chance

Sickle beta thalassemia is inherited in an autosomal recessive manner. This means that to be affected, a person must have a mutation in both copies of the responsible gene in each cell. People affected by sickle beta thalassemia inherit a different mutation in the HBB gene from each parent: one that produces sickle hemoglobin (called sickle trait) and a second that results in reduced levels of functional hemoglobin (called beta thalassemia). The parents of an affected person usually each carry one mutated copy of the gene and are referred to as carriers. Carriers typically do not show signs or symptoms of the condition. When two carriers of an autosomal recessive condition have children, each child has a 25% (1 in 4) risk to have the condition, a 50% (1 in 2) risk to be a carrier like each of the parents, and a 25% chance to not have the condition and not be a carrier.

Signs and symptoms

Signs and symptoms of sickle beta thalassemia may include:

• Anemia (low levels of red blood cells)
• Repeated infections
• Frequent episodes of pain
• Pulmonary hypertension
• Acute chest syndrome (pneumonia-like condition due to entrapment of infection or sickle cells in the lungs)
• Stroke
• Enlarged spleen and/or liver
• Heart murmurs
• Delayed puberty
• Slowed growth
• Jaundice

The symptoms of sickle beta thalassemia vary in severity based on the amount of normal hemoglobin made. Affected people may have no normal hemoglobin (called sickle beta zero thalassemia) or a reduced amount of normal hemoglobin (called sickle beta plus thalassemia). Although these two forms share many of the same features, people with sickle beta zero thalassemia are generally more severely affected than those with sickle beta plus thalassemia. For example, people with sickle beta plus thalassemia generally experience less frequent episodes of pain and are less likely to develop stroke, pulmonary hypertension and acute chest syndrome.

Diagnosis

In the United States, babies affected by sickle beta thalassemia are often diagnosed at birth through newborn screening. In the absence of newborn screening, a diagnosis is usually suspected in infants or young children with signs and symptoms associated with the condition. Specialized laboratory tests that measure the amounts of abnormal hemoglobin in the blood and/or genetic testing to identify changes (mutations) in the HBB gene can be used to confirm a diagnosis. Diagnostic tests include DNA sequencing, hemoglobin electrophoresis, and high-performance liquid chromatography. Carrier testing for at-risk relatives and prenatal testing are possible if both disease-causing mutations in the family are known.

Treatment

Treatment for sickle beta thalassemia is supportive and usually depends on the signs and symptoms present in each person. It is generally recommended that all affected people drink plenty of water; avoid climate extremes, activities that lead to inflammation and extreme fatigue; and stay up-to-date on all immunizations. Because sickle beta thalassemia is associated with a variety of health problems, affected people are usually followed closely by their healthcare provider with regular physical examinations that may include specialized laboratory tests and imaging studies (i.e. chest X-ray, transcranial doppler ultrasound, ECG). Blood transfusions may be prescribed on a regular basis for affected people with a history of or risk factors for stroke and other specific health problems, such as pulmonary hypertension. Hydroxyurea, a drug approved by the U.S. Food and Drug Administration for the treatment of sickle cell disease, can decrease the frequency and severity of pain episodes; reduce the need of blood transfusions; and increase life span.

Prognosis

The long-term outlook (prognosis) for people with sickle beta thalassemia varies depending on the severity of the condition. Sickle beta zero thalassemia (no normal hemoglobin) is usually associated with a worse prognosis and more severe disease course than sickle beta plus thalassmia (a reduced amount of normal hemoglobin). Although sickle cell diseases, including sickle beta thalassemia, can be fatal and are often associated with a shortened life span, early detection and the introduction of new treatment options have lead to significant increases in life expectancy and survival of people with these conditions.

NIH genetic and rare disease info

• NIH info on Sickle beta thalassemia

Sickle beta thalassemia is a rare disease.

Sickle beta thalassemia Resources
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