Sickle cell anemia is caused by a mutation in the HBB gene, which provides instructions for making a protein called beta-globin. Beta-globin is one of the components of hemoglobin, the molecule that carries oxygen in red blood cells. The mutation changes one of the amino acids (the building blocks of proteins) in beta-globin from glutamic acid to valine. This alters the structure and behavior of hemoglobin, leading to the formation of sickle cells.

Sickle cell anemia is inherited in an autosomal recessive pattern, which means that both copies of the HBB gene in each cell have the mutation. A person with two copies of the mutated gene has sickle cell anemia. A person with one copy of the mutated gene and one normal copy is called a carrier or has sickle cell trait. Carriers usually do not have any symptoms of the disease, but they can pass the mutation to their children. The chance of inheriting sickle cell anemia depends on the genetic status of the parents. If both parents have sickle cell anemia, all of their children will have the disease. If both parents are carriers, each child has a 25% chance of having the disease, a 50% chance of being a carrier, and a 25% chance of being unaffected. If one parent has sickle cell anemia and the other is a carrier, each child has a 50% chance of having the disease and a 50% chance of being a carrier. If one parent has sickle cell anemia and the other is unaffected, all of their children will be carriers. If one parent is a carrier and the other is unaffected, each child has a 50% chance of being a carrier and a 50% chance of being unaffected.

The symptoms of sickle cell anemia vary from person to person and may change over time. Some of the common symptoms include:

• Anemia: Sickle cells die faster than normal red blood cells, resulting in a low number of red blood cells and a reduced amount of oxygen in the body. This causes fatigue, weakness, pale skin, and shortness of breath.
• Pain crises: Sickle cells can block blood vessels and reduce blood flow to various parts of the body, causing sudden and severe pain. The pain can affect the chest, abdomen, joints, bones, or any other organ. The frequency and duration of pain crises vary among individuals. Some people may have only a few pain crises a year, while others may have more than a dozen. Pain crises can be triggered by factors such as infection, dehydration, stress, cold weather, or high altitude.
• Swelling of hands and feet: Sickle cells can obstruct blood flow to the hands and feet, causing them to swell and become painful. This is more common in infants and young children with sickle cell anemia.
• Infections: Sickle cells can damage the spleen, an organ that helps fight infections. People with sickle cell anemia are more prone to infections, especially by bacteria that cause pneumonia, meningitis, and sepsis. Infections can be life-threatening and require prompt medical attention.
• Delayed growth and puberty: Sickle cell anemia can affect the growth and development of children and adolescents. The lack of oxygen and nutrients can slow down the growth of bones and muscles, and delay the onset of puberty.
• Vision problems: Sickle cells can block the blood vessels in the eyes, causing damage to the retina, the layer of tissue that senses light and sends signals to the brain. This can lead to vision loss or blindness. Regular eye exams are recommended for people with sickle cell anemia to detect and treat any eye problems.

Sickle cell anemia can be diagnosed before or after birth. Prenatal testing can be done by analyzing a sample of the amniotic fluid or the placenta to check for the presence of the HBB mutation. Newborn screening can be done by testing a blood sample from the baby’s heel to measure the amount and type of hemoglobin. If the screening test is positive, a confirmatory test called hemoglobin electrophoresis can be done to determine the exact type of sickle cell disease. Genetic testing can also be done to identify the HBB mutation in people who have a family history of sickle cell anemia or who are at risk of being carriers.

There is no cure for sickle cell anemia, but treatments are available to manage the symptoms and prevent complications. Some of the treatments include:

• Medications: Painkillers can be used to relieve pain during crises. Antibiotics can be used to prevent or treat infections. Hydroxyurea is a drug that can reduce the frequency of pain crises and the need for blood transfusions by increasing the production of fetal hemoglobin, a type of hemoglobin that does not sickle. Folic acid supplements can help the body make new red blood cells. Other drugs that are being developed or tested include voxelotor, which can improve the oxygen-carrying capacity of hemoglobin, and crizanlizumab, which can prevent the sickle cells from sticking to the blood vessels.
• Blood transfusions: Blood transfusions can be used to increase the number of normal red blood cells and improve the oxygen level in the body. They can also help prevent or treat complications such as stroke, acute chest syndrome, or severe anemia. Blood transfusions can be given regularly or as needed, depending on the severity of the disease. People who receive frequent blood transfusions need to be monitored for iron overload, a condition that can damage the liver, heart, and other organs. Iron chelation therapy can be used to remove excess iron from the body.
• Bone marrow transplant: Bone marrow transplant is a procedure that can potentially cure sickle cell anemia by replacing the defective bone marrow with healthy bone marrow from a donor. Bone marrow is the soft tissue inside the bones that produces blood cells. The donor’s bone marrow must match the recipient’s tissue type to avoid rejection. Bone marrow transplant is a risky and complex procedure that can cause serious side effects and complications. It is usually reserved for people who have severe sickle cell anemia and who have a suitable donor, such as a sibling or a close relative.

Sickle cell anemia cannot be prevented, but it can be detected early and managed effectively. People who have sickle cell trait or who have a family history of sickle cell anemia can consult a genetic counselor to understand the risk of passing the disease to their children and to explore the options of prenatal testing or preimplantation genetic diagnosis. People who have sickle cell anemia can take steps to reduce the frequency and severity of pain crises and complications, such as:

• Drinking plenty of fluids to stay hydrated
• Avoiding extreme temperatures, high altitudes, and strenuous activities that can trigger sickling
• Getting regular check-ups and vaccinations to prevent infections
• Taking medications as prescribed by the doctor
• Seeking medical help promptly if any signs of infection, pain, or other problems occur

There are many organizations and resources that provide information and support for people with sickle cell anemia and their families, such as:

• Sickle Cell Disease Association of America: A national organization that advocates for people with sickle cell disease and promotes awareness, education, research, and quality care.
• Sickle Cell Information Center: A website that provides comprehensive information on sickle cell disease, including news, events, publications, and links to other resources.
• Sickle Cell Society: A UK-based charity that supports and represents people with sickle cell disease and their families, and works to improve their quality of life.
• Sickle Cell Foundation of Nigeria: A non-governmental organization that provides care and support for people with sickle cell disease and their families, and promotes awareness, prevention, and research in Nigeria.
• [World Sickle Cell Day]: An annual event that is celebrated on June 19 to raise awareness and understanding of sickle cell disease and its impact on individuals and communities.