Erythrocyte membrane skeleton abnormalities in hereditary spherocytosis.

Erythrocyte ghosts from eight individuals with hereditary spherocytosis have been compared with respect to their protein compositions as judged by SDS gel electrophoresis, their ease of spectrin extractability, and their freeze-etch electron microscopic appearance after incubation in condition designed to promote aggregation of the intramembrane particles. Four of these HS cases were unrelated, while the other four represented two generations from a single family, including a pair of identical twins, one of whom had not undergone splenectomy when this investigation was initiated. Of the four unrelated cases, one showed no departures from normal under the conditions of this investigation, whereas the other three exhibited features which suggested a membrane skeleton lesion. In one of these there was a reduced proportion of spectrin tetramers relative to dimers in 4 degrees C extracts, while the two remaining cases exhibited abnormal intramembrane particle aggregation. The four related cases had almost identical variations from normal. Spectrin was not extractable from their ghost membranes during a mild extraction incubation which removed spectrin from normal control ghosts. However, the intramembrane particle aggregation subsequently induced in these ghosts was of a degree unobtainable in normal ghosts without such spectrin extraction. In addition the ghosts from one twin, the only one of these patients who had not undergone splenectomy at the start of this investigation, showed a reduced amount of band 4.2. However, when this patient's blood was re-tested after splenectomy, this protein was found to be at normal levels. Our results support the view that hereditary spherocytosis is not a single disease, but is rather a term used to describe a variety of different molecular lesions of the erythrocyte membrane skeleton with similar clinical manifestations.