Hereditary spherocytosis. I. Clinical,hematologic and genetic features in 28 cases,with particular reference to the osmotic and mechanical fragility of incubated erythrocytes

Clinical, hematologic and genetic data on 28 cases of hereditary spherocytosisare presented for the purpose of characterizing this disorder as completely aspossible. On the basis of this experience it is recommended that the followingtypical laboratory findings be sought in establishing a diagnosis in suspectedcases: (1) Presence of spherocytes or abnormally thick red cells in peripheralblood; (2) greater than normal osmotic fragility of the red cells; in cases in whichthe fragility of fresh cells is not significantly increased, determinations should bemade 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 cellsduring sterile incubation at body temperature for 48 hours; and (6) presence ofsimilar abnormalities in relatives.

Abnormality of the erythrocyte persisted in all of the 11 patients in this seriesfollowed one or more years after splenectomy. An unusual case of chronic hemolytic anemia is described but not included in the numbered series because (1) bothparents were hematologically normal and (2) spherocytosis and abnormally greatosmotic and mechanical fragility and autohemolysis could not be demonstratedafter the fifth postoperative month. Classification of this case is deferred pendingfurther 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 withoutpositive findings, low gene expressivity, gene mutation and illegitimacy may beconsidered as explanations. Evidence is cited to suggest the possibility of a lowdegree of penetrance or expression in some cases and to illustrate the need forstill more sensitive laboratory tests that might aid in diagnosis of the mildestforms of this disease. The lower incidence of spherocytosis in siblings of propositithan in offspring of propositi is cited as evidence bearing on the theory of genemutation in some propositi.

A simplified "qualitative" test of osmotic fragility of incubated red cells isdescribed.

Submitted on April 16, 1951 Accepted on May 10, 1951