Beta Hemoglobinopathies (Beta-thalassemia and Sickle Cell)

Beta-globin is part of a larger part of a protein found in red blood cells. This larger protein, hemoglobin, is what helps carry oxygen throughout the body. If the hemoglobin is not formed correctly, or at all, it affects the amount of red cells that are available for the body to use and how oxygen is distributed to the body. There are two major genetic disorders that are associated with beta-globin. The first is sickle cell disease, which affects the formation of hemoglobin and changes the shape of red blood cells from their normal circular shape to a half-moon/crescent shape. It is an inherited disorder characterized by anemia, joint pain, and a shortage of red blood cells. In some individuals with sickle cell disease their organs such as their lungs, liver and kidneys may be damaged. The amount of the pain, organ damage, and swelling varies among individuals with sickle cell disease. The second disorder is beta-thalassemia (BT), where the production of beta-globin is decreased, thus affecting the function of hemoglobin. This causes a lack of oxygen and iron buildup inside the body. Effects of the more severe form of BT, thalassemia major (Cooley’s anemia) can be seen within the first six months to 2 years of age. Children affected with BT fail to gain weight or grow at normal rates, may have diarrhea, enlarged organs, or irritability. Symptoms of the less severe form of BT, thalassemia intermedia, typically appear anytime from childhood into adulthood. They tend to be similar to those of thalassemia major, but milder. Chelation therapy and blood transfusions are necessary for those more severely affected for normal growth and development, but may only be needed on occasion for those mildly affected individuals. Life expectancy for sickle cell disease and beta-thalassemia is variable, but can be prolonged with proper treatment and management. Both genetic conditions are caused by mutations in the HBB gene.

Both sickle cell disease and BT are inherited in an autosomal recessive manner. This type of inheritance requires the presence of two copies of a pathogenic variant in the gene for a person to have the genetic disease. Both parents must be carriers of a pathogenic variant in the gene in order to be at risk to have an affected child. The child must inherit a pathogenic variant from each carrier parent in order to be affected. There is a 1 in 4 chance that a baby will inherit two mutated copies of the gene and be affected when both parents are carriers.

People who have sickle cell trait, or people who are carriers of sickle cell disease, usually don’t have signs of the disease although they can acquire problems from extreme exercise, dehydration, or high altitude. Carriers of BT are not at risk for any symptoms other than having a slightly lower red cell count. They are often referred to as having thalassemia minor. In both cases carriers do have a higher risk of having children affected with each condition. Testing of reproductive partners, with consideration to their ethnicity, is recommended for carriers of sickle cell trait or BT.

Sickle cell disease is common in the African American population as well as individuals from sub-Saharan Africa, India, Saudi Arabia and the Mediterranean (examples: Greece and Italy). It is estimated 1/12 African Americans have sickle cell trait. It is estimated that over 100,000 people have sickle cell disease in the Unites States. Beta-thalassemia occurs in about 1 in 100,000 newborns worldwide, but it is more common in the Mediterranean, Middle Eastern, Central Asian, Southeast Asian, and Indian populations.

Genetics Home Reference: Sickle cell disease (http://ghr.nlm.nih.gov/)
NIH Health Information: Sickle Cell Anemia (http://www.nhlbi.nih.gov/health/)
Sickle Cell Disease Association: About Sickle Cell Disease (http://www.sicklecelldisease.org/)
Genetics Home Reference: beta thalassemia (http://ghr.nlm.nih.gov/)
Kids Health: Beta Thalassemia (http://kidshealth.org/parent/medical/)
Cooley's Anemia Foundation (http://www.thalassemia.org/)

OMIM [Sickle Cell Disease:603903] (http://www.ncbi.nlm.nih.gov/omim)
Gene Reviews: Sickle Cell Disease (http://www.ncbi.nlm.nih.gov/books/NBK1377/)
OMIM [BETA-THALASSEMIA :613985] (http://www.ncbi.nlm.nih.gov/omim)
Gene Reviews: Beta-Thalassemia (http://www.ncbi.nlm.nih.gov/books/NBK1426/)

• Full gene sequencing
• Copy number analysis: intron 2 and exon 3