sicklecell

Sickle cell disease (SCD) is a group of inherited red blood cell disorders caused by a mutation in the beta-globin gene (HBB) that leads to hemoglobin S (HbS). Most commonly two HbS alleles (HbSS) cause disease, but other genotypes include HbSC and HbS beta-thalassemia. SCD is inherited in an autosomal recessive pattern; individuals with one HbS allele have sickle cell trait and typically do not have severe disease.

Sickled HbS polymerizes when deoxygenated, producing rigid, crescent-shaped red blood cells. These cells are prone to hemolysis and to obstructing small vessels, resulting in pain crises, organ ischemia, and chronic anemia. Complications can include acute painful crises, acute chest syndrome, stroke, splenic sequestration, infections (due to functional asplenia), priapism, and leg ulcers.

Diagnosis relies on newborn screening and confirmatory testing such as hemoglobin electrophoresis or high-performance liquid chromatography, with genetic testing available for definitive typing. Management focuses on preventing complications and treating symptoms. In children, penicillin prophylaxis and vaccination are standard; folic acid is commonly given. Disease-modifying therapies include hydroxyurea, L-glutamine, voxelotor, and crizanlizumab. Regular transfusions may be used to treat severe anemia or prevent stroke, with iron chelation required for long-term transfusion programs. Curative options such as stem cell transplantation and experimental gene therapies aim to address the underlying defect.

Epidemiology and prognosis: SCD is most common in people of African descent but occurs in other populations. The course and life expectancy vary by genotype and quality of care; with modern management, survival into adulthood has improved significantly.