Sickle cell disease (SCD) is a genetic disorder characterised by the presence of abnormal haemoglobin, the protein responsible for carrying oxygen in red blood cells.
This hereditary condition primarily affects individuals of African, Mediterranean, Middle Eastern, and Indian descent, but it can occur in any ethnic group. SCD is caused by a mutation in the HBB gene, which encodes the beta-globin subunit of haemoglobin. Individuals with SCD inherit two copies of the mutated gene, one from each parent, resulting in the production of abnormal haemoglobin known as haemoglobin S (HbS). When oxygen levels are low, HbS molecules can cause red blood cells to take on a characteristic sickle shape. This altered shape leads to increased fragility and decreased flexibility of the red blood cells, contributing to various complications associated with the disease.
The hallmark of SCD is the sickling of red blood cells, which can lead to a cascade of events causing vascular occlusion, inflammation, and tissue damage. The abnormal cells can become trapped in small blood vessels, leading to reduced blood flow and oxygen delivery to tissues and organs. This process, known as vaso-occlusion, is responsible for the painful crises that are a common feature of SCD. Additionally, the shortened lifespan of sickle cells contributes to chronic anaemia, further complicating the disease’s clinical course.
Sickle Cell Disease affects around 20 million people worldwide.
Symptoms
Sickle cell disease is a multisystem disorder, affecting various organs and tissues throughout the body. Common clinical manifestations include:
- Painful Crises: Sudden and severe episodes of pain, often affecting the bones, joints, lungs (acute chest syndrome) and abdomen, are a hallmark of SCD. These crises result from vaso-occlusion and can last for hours to days.
- Anemia: The destruction of sickle cells leads to chronic anaemia, causing fatigue, weakness, and pallor.
- Organ Damage: Over time, vaso-occlusive events can damage organs such as the spleen, kidneys, lungs, and brain, leading to complications like stroke, pulmonary hypertension, and renal dysfunction.
- Infections: Individuals with SCD are at an increased risk of infections, particularly those caused by encapsulated bacteria, due to functional asplenia resulting from spleen damage.
Diagnosis
SCD is diagnosed at birth with a simple blood test that forms part of routine newborn screening tests in some countries. It can also be diagnosed during pregnancy. In many countries where SCD is not part of the national screening program, patients are often first diagnosed at time of their first vaso-occlusive crisis requiring hospitalisation. On diagnosis, healthcare professionals may test for complications; patients are typically referred to a genetic counsellor.
Treatment
There is currently no cure for Sickle Cell Disease. Management of the disease involves a multidisciplinary approach to address both acute complications and long-term consequences. Treatment options include pain management; regular blood transfusions, and stem cell transplantation. A number of medications can reduce vaso-occlusive episodes, improve blood flow and thus reduce pain. It may also be necessary to take penicillin as a life-long treatment to prevent infection. Gene editing therapy provides hope for the future, although it is currently in its early stages.
Summary
Sickle cell disease is a complex genetic disorder that significantly impacts the lives of those affected. While advances in research and treatment have improved outcomes, ongoing efforts are crucial to further understand the disease and develop innovative therapies. Increased awareness, genetic counselling, and early intervention can contribute to better management and improved quality of life for individuals with sickle cell disease.
