Etiology. The biochemical basis of hereditary spherocytosis and hereditary elliptocytosis are similar. Both conditions appear to have a defect in the protein lattice (spectrin, ankyrin, protein 4.2, band 3) that underlies the RBC lipid bilayer and provides stability of the membrane shape. In hereditary spherocytosis, pieces of membrane bud off as microvesicles because of abnormal vertical interaction of the cytoskeletal proteins and uncoupling of the lipid bilayer from the cytoskeleton. When the RBC loses membrane, cell shape changes from a biconcave disk to a spherocyte. The RBC is less deformable when passing through narrow passages in the spleen. Hereditary elliptocytosis is a disorder of spectrin dimer interactions that occurs primarily in individuals of African descent. The transmission of the two variants is usually autosomal dominant, but spontaneous mutations causing hereditary spherocytosis are common. Hereditary pyropoikilocytosis (unusual instability of the erythrocytes when they are exposed to heat at 45°C) is the result of a structural abnormality of spectrin.
Clinical Manifestations. Hereditary spherocytosis varies greatly in clinical severity, ranging from an asymptomatic, well-compensated, mild hemolytic anemia that may be discovered incidentally to a severe hemolytic anemia with growth failure, splenomegaly, and chronic transfusion requirements in infancy necessitating early splenectomy. The most common variant of hereditary elliptocytosis is a clinically insignificant morphologic abnormality without shortened RBC survival. The less common variant is associated with spherocytes, ovalocytes, and elliptocytes with a moderate, usually compensated, hemolysis. Far more significant hemolysis occurs in hereditary pyropoikilocytosis. The peripheral blood smear in hereditary pyropoikilocytosis often includes elliptocytes, spherocytes, fragmented RBCs, and striking microcytosis. Such patients may have bizarre blood smears in the newborn period with small, fragmented RBCs.
Laboratory Diagnosis. The clinical diagnosis of hereditaryspherocytosis should be suspected in patients with even a fewspherocytes found on the blood smear because the spleenpreferentially removes spherocytes. An incubated osmotic fragility test confirms the presence of spherocytes andincreases the likelihood of the diagnosis. The osmotic fragility test result is abnormal in any hemolytic disease in whichspherocytes are present—for example, in antibody-mediatedhemolysis.
Treatment. Splenectomy corrects the anemia and normalizes the RBC survival in patients with hereditaryspherocytosis, but the morphologic abnormalities persist.Splenectomy should be considered for any child with symptoms referable to anemia or growth failure, but should bedeferred until age 5 years, if possible, to minimize the risk ofoverwhelming postsplenectomy sepsis and to maximize theantibody response to the polyvalent pneumococcal vaccine.In several reports, partial splenectomy seems to improvethe hemolytic anemia and maintain splenic function in hostdefense.