Clinical, hematologic and genetic data on 28 cases of hereditary spherocytosis are presented for the purpose of characterizing this disorder as completely as possible. On the basis of this experience it is recommended that the following typical laboratory findings be sought in establishing a diagnosis in suspected cases: (1) Presence of spherocytes or abnormally thick red cells in peripheral blood; (2) greater than normal osmotic fragility of the red cells; in cases in which the fragility of fresh cells is not significantly increased, determinations should be made after sterile incubation of the blood at body temperature for 24 hours; (3) greater than normal mechanical fragility of freshly drawn red cells; (4) negative antiglobulin (Coombs) test; (5) greater than normal lysis of the red cells during sterile incubation at body temperature for 48 hours; and (6) presence of similar abnormalities in relatives.
Abnormality of the erythrocyte persisted in all of the 11 patients in this series followed one or more years after splenectomy. An unusual case of chronic hemolytic anemia is described but not included in the numbered series because (1) both parents were hematologically normal and (2) spherocytosis and abnormally great osmotic and mechanical fragility and autohemolysis could not be demonstrated after the fifth postoperative month. Classification of this case is deferred pending further experience.
Demonstration in a parent, sibling or offspring of red cells showing the afore-mentioned abnormalities is necessary for an unequivocal diagnosis, but this requirement cannot always be met because relatives may not be available for examination. Moreover, when parents and/or several siblings are examined without positive findings, low gene expressivity, gene mutation and illegitimacy may be considered as explanations. Evidence is cited to suggest the possibility of a low degree of penetrance or expression in some cases and to illustrate the need for still more sensitive laboratory tests that might aid in diagnosis of the mildest forms of this disease. The lower incidence of spherocytosis in siblings of propositi than in offspring of propositi is cited as evidence bearing on the theory of gene mutation in some propositi.
A simplified "qualitative" test of osmotic fragility of incubated red cells is described.