Which genetic condition is characterized by a defect in spectrin, causing hemolysis?

Hereditary spherocytosis is characterized by defects in proteins that are crucial for maintaining the integrity and stability of the red blood cell membrane, particularly spectrin, which is a vital cytoskeletal protein. In this condition, the abnormality in spectrin leads to a more rigid and spherical shape of the red blood cells, as opposed to the normal biconcave shape. This altered morphology makes the cells more prone to destruction as they navigate through the spleen and other parts of the microvascular system, resulting in hemolysis.

The hemolysis seen in hereditary spherocytosis is often associated with anemia, jaundice, and splenomegaly. The inability of spectrin to properly anchor the membrane leads to instability and fragility, causing these cells to rupture more easily than typical red blood cells.

In contrast, conditions like acute intermittent porphyria, Gilbert's disease, and Crigler-Najjar syndrome primarily involve metabolic pathways and do not directly impact the structural integrity of red blood cells in the same way. They are associated with issues such as bilirubin metabolism or heme synthesis, rather than defects in erythrocyte membrane proteins like spectrin.