Sickle Cell Disease

What is sickle cell disease?

Sickle cell disease is an inherited blood disorder. Normal red blood cells are smooth and flexible discs, like the letter O, enabling them to move easily through your child’s blood vessels. In contrast, sickle cells are stiff, sticky and often shaped like the letter C. Sickle cells tend to cluster together and to the lining of blood vessels, making it difficult for them to move through small blood vessels. These clusters can create blockages in your child’s small blood vessels, stopping the movement of healthy, oxygen-carrying blood. This blockage decreases oxygen delivery to the tissues which can cause pain and organ dysfunction and is what causes the majority of the complications of the disease.

The spleen, which helps filter bacterial infections from the blood and acts as the recycle center for old red blood cells, tends to destroy the misshapen sickle cells faster than normal red blood cells. Sickle cells only live for about 14 days, while normal red blood cells can live up to 120 days. This leads to a chronic lack of oxygen-carrying red cells in the blood, called anemia. Sickle cells can also damage your child’s spleen, increasing the risk of certain potentially life-threatening bacterial infections.

Gene therapy shows early promise against sickle cell

Manny Johnson is the first to participate in a clinical trial that is testing a novel gene therapy approach for treating SCD.

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Doctor examining a patient who was treated using a gene therapy for sickle cell disease,

Millions worldwide suffer complications from sickle cell disease and nearly 300,000 infants with sickle cell disease are born each year. Approximately two million African-Americans, or 1 in 12, are "carriers" of the sickle mutation (called sickle cell trait). About 100,000 people in the United States have sickle cell disease. It mostly affects children of African descent, Hispanics and Caribbean ancestry, but also is found in those with Middle Eastern, Indian, Latin American, and Mediterranean heritage. The Global Health Initiative at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center is working to improve survival for children with sickle cell disease around the world, including programs to establish newborn screening for sickle cell disease and developing research partnerships in Liberia and Haiti.

What are the different types of sickle cell disease?

All children with sickle cell disease have inherited sickle cell trait (HbAS) from at least one parent. People with sickle cell trait have one copy of the HbS gene and one copy of the normal hemoglobin A gene (HbA). Sickle cell trait is not a form of sickle cell disease, although in rare circumstances, sickle cell trait can become symptomatic. People with sickle cell trait may pass on the HbS gene to their children.

There are several different types of sickle cell disease that differ in symptoms and severity. The type of sickle cell disease depends on the specific gene variant that your child has inherited.

Sickle cell anemia (HbSS)

  • The child has two copies of the HbS gene, one inherited from each parent.
  • This is the most common and most severe form of sickle cell disease.
  • A variety of symptoms and complications of sickle cell disease occur.
  • Severe, chronic anemia is present.

Sickle cell with hemoglobin C disease (HbSC)

  • The child has one HbS gene and one defective hemoglobin C gene (HbC).
  • A more mild to moderate anemia is typical.
  • All complications of sickle cell disease may occur but tend to be a milder degree.

Hemoglobin S-β-thalassemia

  • This comes in two forms: HbSβ0 and Hbβ+ thalassemia.
  • The child has one HbS gene and one β thalassemia gene.
  • The degree of anemia is varied depending on the specific genetic type.
  • Children may experience a broad range of sickle cell symptoms and disease severity. HbSβ0 thalassemia is very similar to HbSS. Hbβ+ thalassemia severity is varied but usually mild.

Other forms of sickle cell disease (compound heterozygotes), including HbSE, HbSO, and HbSD

  • The child has one HbS gene and another abnormal hemoglobin gene.
  • Symptoms vary depending on the specific genetic defect.

How we care for sickle cell disease

Dana-Farber/Boston Children's Cancer and Blood Disorders Center is an international leader in improving treatment and quality of life for children affected by sickle cell disease. We treat sickle cell anemia (HbSS), sickle cell with hemoglobin C disease (HbSC), hemoglobin S-beta-thalassemia (HbSβ0 and Hbβ+thalassemia), and less common compound forms, including HbSD, HbSO and HbSE.

Through our Sickle Cell Disease Program, children with sickle cell disease have access to world-renown pediatric hematologists, top-rated nursing care, and the latest treatment options including hydroxyurea and stem cell transplantation. We are also one of the few centers in the nation using a new type of technology, called PreciseType, to precisely match blood donors to sickle cell patients who need blood transfusions. PreciseType allows our doctors to more precisely type the patient’s blood groups and decreases the risk of developing antibodies to the transfused donor blood.

Gene therapy for sickle cell

The sickle cell gene therapy clinical trial focuses on newborn hemoglobin. Newborns have a different hemoglobin called fetal hemoglobin that doesn't sickle. The goal of this clinical trial is to flip the switch in SCD red cells back to fetal hemoglobin to prevent sickling from occurring.

Dana Farber/Boston Children's researchers identified that variations in the expression of a gene known as BCL11A can affect levels of fetal hemoglobin and spent several years devising a way to prevent BCL11A production, resulting in a clinical trial. The treatment process is similar to a stem cell transplant. A patient's blood stem cells are removed, and then undergo months of gene modification to reduce BCL11A expression and induce production of healthy fetal hemoglobin. The gene-modified cells are then given back to the patient via an intravenous infusion to silence the sickle-producing adult hemoglobin.

Learn more about the Gene Therapy Program.