Sickle Cell Disease

Sickle cell disease (SCD) is a group of inherited blood disorders that affect the shape and function of red blood cells (RBCs). RBCs are responsible for carrying oxygen throughout the body, but in SCD, they become rigid and crescent-shaped, resembling a sickle. This causes them to block blood vessels, impair blood flow, and damage various organs. SCD is caused by a mutation in the HBB gene, which encodes the beta-globin subunit of hemoglobin, the protein that binds oxygen in RBCs. The mutation results in the production of abnormal hemoglobin, called hemoglobin S (HbS), which polymerizes under low oxygen conditions and deforms the RBCs. SCD is inherited in an autosomal recessive manner, meaning that both copies of the HBB gene must have the mutation for a person to have the disease. People who inherit only one copy of the mutation are called carriers or trait carriers and usually do not have symptoms but can pass the mutation to their offspring. SCD is one of the most common genetic diseases in the world, affecting millions of people, especially those of African, Mediterranean, Middle Eastern, and Indian origin. According to the World Health Organization (WHO), about 300,000 babies are born with SCD each year, and about 5% of the world's population carries the trait.

Molecular pathophysiology of sickle cell disease Fig.1 Molecular pathophysiology of sickle cell disease. (Sundd P, 2019)

Clinical Manifestations

SCD is characterized by a wide range of clinical manifestations that vary in severity, frequency, and duration among individuals. The major features of SCD are related to chronic hemolytic anemia and vaso-occlusion, leading to acute and chronic pain and tissue ischemia or infarction.

The most common and distinctive manifestation of SCD is the acute painful episode, also known as vaso-occlusive crisis or pain crisis. This occurs when sickle cells obstruct the blood flow in small vessels, causing hypoxia, inflammation, and tissue damage. The pain can affect any part of the body, but most often involves the chest, abdomen, and joints. The pain intensity can range from mild to severe, and the duration can vary from hours to days. The frequency of pain crises can also vary from person to person, from less than one to more than 10 per year. Pain crises can be triggered by various factors, such as temperature changes, stress, dehydration, and high altitude. Another common and serious manifestation of SCD is infection. Sickle cells can damage the spleen, an organ that filters the blood and fights bacteria. As a result, people with SCD are more susceptible to infections, especially by encapsulated organisms such as Streptococcus pneumoniae and Haemophilus influenzae. Infections can cause fever, chills, cough, sore throat, headache, and other symptoms. Infections can also precipitate or worsen pain crises and other complications of SCD. Therefore, people with SCD are recommended to receive vaccinations and antibiotics to prevent potentially life-threatening infections. Additionally, SCD can affect multiple organs and systems in the body, causing various complications that can impair the function and quality of life of individuals with SCD.

Moreover, there are many other manifestations that are less common or less severe but still affect the health and well-being of people with SCD, such as leg ulcers, priapism (prolonged erection), gallstones, liver problems, and heart problems. Therefore, people with SCD need regular medical care and monitoring to prevent or treat these complications.

Clinical Diagnosis and Treatment

SCD is diagnosed by detecting the presence of abnormal hemoglobin (HbS) in the blood, caused by a mutation in the HBB gene. Different methods diagnose SCD, such as blood tests, hemoglobin electrophoresis, cytogenetics, and prenatal testing. Blood tests measure the number, size, and shape of red blood cells, as well as the level of hemoglobin. People with SCD usually have low hemoglobin levels and sickle-shaped red blood cells. Hemoglobin electrophoresis separates different types of hemoglobin based on their electrical charge and movement in a gel. People with SCD have a high percentage of HbS in their blood. Cytogenetics analyze the chromosomes and genes in the cells. People with SCD have a mutation in both copies of the HBB gene. Prenatal testing diagnoses SCD in an unborn baby by obtaining a sample of cells from the placenta or amniotic fluid. The diagnosis of SCD is based on the combination of clinical symptoms and laboratory results, which can be challenging in some cases, such as heterozygous carriers, compound heterozygotes, or false-positive or false-negative results.

SCD is a chronic and incurable disease requiring lifelong management and care. Treatment methods can be divided into two categories: conventional and gene therapy. Conventional treatment methods include medications, blood transfusions, and bone marrow transplant. These methods help reduce the symptoms and complications of SCD, such as anemia, pain, infection, organ damage, and stroke. However, these methods also have risks, such as side effects, iron overload, immune reactions, and infections. Gene therapy is a new and promising treatment method aiming to correct or modify the genetic defect causing SCD. Different types of gene therapy, such as gene addition, gene editing, and gene silencing, can help restore normal hemoglobin function, preventing sickling. However, these methods are still experimental and face challenges such as safety, efficacy, accessibility, affordability, and ethical concerns.

Conclusion

Sickle cell disease (SCD) is a common and serious genetic disorder affecting the shape and function of red blood cells. SCD causes chronic hemolytic anemia, vaso-occlusion, pain, infection, and organ damage. SCD is a major public health problem affecting millions worldwide. More research and innovation are needed to improve the diagnosis and treatment of SCD, reducing the disease burden and mortality.

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