Beta thalassemia

Beta thalassemia is an inherited blood disorder that reduces the production of hemoglobin. Hemoglobin is the molecule in red blood cells that carries oxygen to cells throughout the body.

Symptoms of beta thalassemia occur when not enough oxygen gets to various parts of the body due to low levels of hemoglobin and a shortage of red blood cells (anemia). This disorder is classified as thalassemia major (also called Cooley's anemia) or thalassemia intermedia depending on the severity of symptoms. Of the two types, thalassemia major is more severe.

Signs and symptoms of thalassemia major appear in the first 2 years of life. Infants have life-threatening anemia and become pale and listless. They also have a poor appetite, grow slowly, and may develop yellowing of the skin and whites of the eyes (jaundice). The spleen, liver, and heart may be enlarged, and bones may be deformed. Adolescents with thalassemia major may experience delayed puberty.

Signs and symptoms of thalassemia intermedia appear in early childhood or later in life. Individuals with thalassemia intermedia have mild to moderate anemia and may also have poor growth and bone abnormalities.

Worldwide, beta thalassemia is considered a fairly common blood disorder, affecting thousands of infants each year. Beta thalassemia occurs most frequently in Mediterranean countries, North Africa, the Middle East, India, Central Asia, and Southeast Asia.

Mutations in the HBB gene cause beta thalassemia.

Hemoglobin consists of four protein subunits, typically two subunits called alpha hemoglobin and two subunits called beta hemoglobin. The HBB gene provides instructions for making beta hemoglobin.

Some mutations in the HBB gene prevent the production of beta hemoglobin. The absence of beta hemoglobin is referred to as beta-zero (B⁰) thalassemia. With other HBB mutations, some beta hemoglobin is produced but in lower than normal amounts. A reduced amount of beta hemoglobin is called beta-plus (B⁺) thalassemia.

The loss of beta hemoglobin leads to a diminished amount of hemoglobin. Without sufficient hemoglobin, red blood cells do not develop normally. The low number of mature red blood cells leads to complications of anemia and other medical problems.

Read more about the HBB gene.

Thalassemia major and thalassemia intermedia are inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but typically do not show signs and symptoms of the condition. Sometimes, however, carriers of the altered HBB gene have a mild anemia referred to as thalassemia minor.

In a small percentage of families, the HBB mutation is inherited in an autosomal dominant manner. In these cases, one copy of the altered gene in each cell is sufficient to cause the disorder.