HbSS

HbSS, or homozygous sickle cell disease, is a hereditary blood disorder caused by inheriting two sickle beta-globin (HbS) genes. Hemoglobin S polymerizes when deoxygenated, causing red blood cells to become rigid and sickle-shaped. The resulting chronic hemolytic anemia and episodic vascular occlusion produce pain and organ injury.

Genetics and inheritance: HbSS is autosomal recessive; individuals with two HbS alleles are affected, while those with one HbS allele are carriers (HbAS). Pathophysiology: sickled cells occlude microvasculature, leading to vaso-occlusive crises, acute chest syndrome, stroke risk, and progressive organ damage. Functional asplenia increases infection risk, and growth and development may be affected.

Diagnosis: newborn screening followed by hemoglobin electrophoresis or high-performance liquid chromatography showing predominant HbS with little to no HbA; HbF levels vary. Molecular testing can confirm HBB gene mutations.

Management: there is no universal cure, though hematopoietic stem cell transplantation can cure in selected cases. Treatment emphasizes preventing crises and infections and managing complications: hydroxyurea to increase fetal hemoglobin, analgesia and hydration for crises, penicillin prophylaxis and vaccines in early childhood, regular transfusions when needed, and management of complications such as acute chest syndrome and stroke. Emerging therapies and gene therapy are under investigation.

Prognosis and epidemiology: life expectancy has improved with newborn screening and comprehensive care but remains shorter than in the general population. The condition is most common among individuals of African descent and certain other populations, with carrier screening and counseling advised for at-risk groups.