What best describes the primary mechanism underlying sickle cell disease?

The primary mechanism underlying sickle cell disease is the altered synthesis of hemoglobin due to a genetic mutation. In sickle cell disease, there is a specific mutation in the HBB gene, which encodes the beta-globin subunit of hemoglobin. This mutation results in the production of hemoglobin S (HbS) instead of normal hemoglobin A (HbA).

When oxygen levels are low, hemoglobin S polymerizes, causing red blood cells to become rigid, sticky, and distorted into a sickle shape. These sickle-shaped cells have a reduced lifespan compared to normal red blood cells and can lead to various complications, including vaso-occlusive crises where the sickle cells obstruct blood flow in small vessels. This fundamental issue with hemoglobin production is central to the pathophysiology of the disease, affecting oxygen delivery to tissues and leading to various clinical manifestations.

Understanding this genetic basis is essential, as it also explains why sickle cell disease is inherited in an autosomal recessive manner, affecting individuals who inherit two copies of the mutated gene. This mechanism differentiates sickle cell disease from other conditions that may involve blood cells or iron metabolism.