Sickle cell disease is a group of inherited disorders that affect red blood cells. The condition affects hemoglobin, the protein that carries oxygen throughout the body. In individuals with this disease, the hemoglobin is abnormal, causing red blood cells to become misshapen. Instead of being flexible and disc-shaped, the cells become rigid and take on a crescent or “sickle” form, which can obstruct blood flow and lead to various health issues.
Genetic Basis and Inheritance
Sickle cell disease originates from a variation in the HBB gene, which provides instructions for making a component of hemoglobin called beta-globin. This genetic change results in the production of an abnormal version of hemoglobin known as hemoglobin S. The inheritance pattern is autosomal recessive, meaning the gene is not on a sex chromosome and affects males and females equally. To have the disease, an individual must inherit two copies of the altered gene, one from each parent.
If both parents have the sickle cell trait, they each carry one altered and one normal copy of the gene. For each pregnancy, there is a 25% chance that their child will inherit two altered genes and have sickle cell disease. There is a 50% chance the child will inherit one altered gene and have the sickle cell trait, and a 25% chance the child will inherit two normal genes.
People with sickle cell trait have one copy of the gene and usually do not experience symptoms of the disease. However, they can pass the gene on to their children. In rare instances, individuals with the trait may encounter health problems, particularly under conditions of extreme physical stress or dehydration.
Physical Manifestations and Symptoms
A primary symptom resulting from blood flow blockage is intense pain, known as a vaso-occlusive crisis or pain crisis. These episodes can occur suddenly and affect almost any part of the body, but they are most common in the chest, arms, and legs. The pain is often described as sharp, stabbing, or throbbing and can last for days or weeks.
Chronic anemia is another common manifestation, as sickle cells have a much shorter lifespan than healthy red blood cells. This shortage leads to symptoms like fatigue, dizziness, and shortness of breath. The rapid breakdown of these cells also releases a substance called bilirubin, which can cause a yellowish discoloration of the skin and eyes, known as jaundice. In young children, a frequent early sign is dactylitis, a painful swelling of the hands and feet caused by blocked blood flow.
Diagnosis and Health Complications
Sickle cell disease is most often identified at birth through routine newborn screening programs. A blood sample is analyzed to detect abnormal hemoglobin, which allows for medical intervention before symptoms become severe. The diagnosis is confirmed with a blood test called hemoglobin electrophoresis, which can distinguish between sickle cell disease and sickle cell trait.
The chronic obstruction of blood flow can lead to long-term health complications. A stroke is one of the most serious and can occur if blood vessels in the brain become blocked. Signs include seizures, weakness on one side of the body, or sudden difficulty with speech, and prompt medical attention is necessary to prevent lasting brain damage.
Acute chest syndrome is another life-threatening complication. It happens when sickle cells block blood vessels in the lungs, often following an infection or a pain crisis. Symptoms resemble pneumonia and include chest pain, fever, and difficulty breathing, requiring immediate hospitalization and treatment.
Over time, the disease can cause damage to major organs, including the kidneys, liver, and spleen. The spleen is particularly vulnerable and can become nonfunctional, a state known as autosplenectomy, which increases the risk of severe infections. Other potential complications include pulmonary hypertension, vision problems due to blocked blood vessels in the eyes, and gallstones.
Management and Therapeutic Approaches
Managing sickle cell disease focuses on preventing complications and alleviating symptoms. A primary medication is hydroxyurea, which can reduce the frequency of painful crises and the need for blood transfusions by helping to prevent the formation of sickle-shaped red blood cells. It is often prescribed for both adults and children as young as nine months old.
Blood transfusions are another component of treatment. They are used for severe anemia and can help prevent strokes by increasing the number of normal red blood cells, which improves oxygen delivery. Because repeated transfusions can lead to iron overload, which can damage organs, patients may also require iron chelation therapy to remove excess iron.
Pain management is a central part of care. Treatment can range from over-the-counter pain relievers for mild pain to stronger medications administered in a hospital for severe pain episodes. Staying hydrated and avoiding triggers like extreme temperatures can also help reduce the frequency of these crises.
Curative therapies are an option for some individuals. A stem cell or bone marrow transplant from a closely matched relative can cure the disease by replacing the patient’s bone marrow with healthy marrow that produces normal red blood cells. Newer gene therapies, which involve modifying a patient’s own stem cells to produce healthy hemoglobin, have also been approved and offer another potential cure, though these procedures carry significant risks.