Partial deficiency of erythrocyte spectrin in hereditary spherocytosis

Abstract

Hereditary spherocytosis (HS) is a common, clinically heterogeneous haemolytic anaemia1,2 in which the primary erythrocyte defect is believed to be some abnormality in the spectrin–actin membrane skeleton3,4, leading to loss of surface membrane5. Recessively inherited spectrin deficiency with extreme erythrocyte fragility and spherocytosis has been identified in certain mutant mice6,7 and two severely anaemic humans8. Although suspected, deficiency of spectrin has not been demonstrated in less severe forms of human HS9. We now report the quantitation of erythrocyte spectrin by radioimmunoassay. We found that normal erythrocytes contained 240,000 copies of spectrin heterodimer, whereas erythrocytes from 14 patients with a variety of types of HS were all partially deficient in spectrin (range 74,000–200,000 copies), the magnitude of the deficiency correlating with the severity of the disease. Spectrin deficiency of varying degrees is common in HS and probably represents the principal structural defect leading to loss of surface membrane.