- Hereditary Spherocytosis (HS) refers to a family of autosomal dominant inherited defects of the erythrocyte membrane that render these cells spherical in shape and less deformable, yielding their splenic destruction and in turn a hemolytic anemia.
|Etiology and Pathogenesis|
- HS can be caused by a variety of mutations to proteins critical for maintaining the structural integrity of the erythrocyte membrane, such as ankyrin and spectrin. The loss of this structural support yields two major changes to the erythrocyte: 1) Loss of its normal, disc-like biconcave shape with transformation into a spherical shape, and 2) Reduced deformability of the erythrocyte membrane.
- Because of the reduced membrane structural integrity, small membrane fragments are lost from freshly-produced erythrocytes. Because little volume loss is accompanied by this loss of membrane, a spherical shape is required to maintain this higher volume-to-surface area ratio.
- Hemolytic Anemia
- The reduced deformability of erythrocytes yields increased destruction of these cells by the reticuloendothelial system within the spleen, and thus an extravascular hemolytic anemia.
- Erythrocytes of patients with HS do not display the classic central area of pallor indicative of a normal bi-concave shape.
- It is important to point out that the presence of spherocytosis on its own is not diagnostic of HS, as spherocytes are also present when any immune-mediated destruction of erythrocytes is occurring, such as AIHA. However, erythrocytes of HS characteristically display increased fragility when placed in a low-osmotic solution, a result of their reduced membrane structural integrity.
- Depending on the mutation, the clinical manifestation of HS can be widely variable from largely asymptomatic to transfusion-dependence. In most cases patients present in childhood with jaundice, splenomegaly, and the symptomology of anemia.