Inheritance Pattern and Clinical Response to Splenectomy as a Reflection of Erythrocyte Spectrin Deficiency in Hereditary Spherocytosis

To determine how various inheritance patterns and responses to splenectomy relate to erythrocyte spectrin deficiencies in hereditary spherocytosis, we measured the spectrin content of erythrocytes by radioimmunoassay in 33 patients with this disease. Patients with the dominant form of hereditary spherocytosis generally had mild anemia, with spectrin at 63 to 81 percent of normal levels. Patients with the nondominant form of the disease had anemia ranging from severe to mild, with corresponding spectrin levels of 30 to 74 percent; their siblings were affected similarly. Distantly related homozygotes had different clinical severities with correspondingly different spectrin levels. The parents and offspring of patients with the nondominant form were clinically normal but consistently had subtle erythrocyte abnormalities. Spectrin levels in all patients were inversely related to osmotic fragility (P<0.0001), and they were also correlated with the clinical response to splenectomy: patients with spectrin levels above 70 percent achieved normal blood counts, those with levels of 40 to 70 percent had compensated hemolysis, and those with levels below 40 percent improved but remained anemic (P<0.0001). We conclude that the inheritance pattern and response to splenectomy in hereditary spherocytosis reflect erythrocyte spectrin deficiencies as determined by radioimmunoassay. (N Engl J Med 1986; 315:1579–83.), Hereditary spherocytosis is the most common inherited anemia affecting persons of northern European ancestry, and it has intrigued clinicians and investigators for decades.¹ The increased sensitivity of the erythrocytes in spherocytosis to hypotonic lysis suggests that a simple but variable defect in the membrane skeleton leads to a reduction in the surface area of the membrane relative to its volume, which is responsible for the clinical problems and abnormal shape and fragility of the erythrocytes. Defects have recently been identified in the red-cell membranes of patients with spherocytosis. Recessively inherited spherocytosis in severely anemic mice is associated with gross deficiencies…