Increased Cell Membrane Permeability in the Pathogenesis of Hereditary Spherocytosis.

The hemolytic process in hereditary spherocytosis (HS) is presumed to involve an intrinsic defect in the structure or metabolism of the red cell (1-3). The nature of the basic cellular defect remains enigmatic, although its manifestations are well characterized. Distinctive features of the HS red cell are its more spheroidal shape, small surface area, and high hemoglobin concentration and its exceptional proclivity toward splenic sequestration. However, the most singular feature of these cells is their abnormally rapid spheroidal change and increase in osmotic fragility on sterile incubation in vitro (4-6). This characteristic response of HS red cells has provided the most reliable method for diagnosis of the disorder (7). Efforts to identify a presumed biochemical lesion in HS red cells have had little success. A reported diminution in turnover of organic phosphate esters (8) has not been confirmed (9, 10), nor have abnormalities been found in the concentrations or kinetics of glycolytic intermediates or in glucose consumption of HS red cells (6, 11, 12). More recently, evidence has been presented (13, 14), but later denied (15, 16), that an abnormality exists in the phospholipids of the red cell membrane in this disease. With incubation, increased loss in lipids from spherocytic membranes has also been reported (17, 18). The general presumption in studies of HS red cells has been that a deficit existed in their energy metabolism. This presumption is difficult to reconcile with the findings by Harris and Prankerd (19) and Bertles (20) that the sodium efflux and influx, respectively, across HS cell membranes are