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Hereditary spherocytosis: Clinical features, diagnosis, and treatment

William C Mentzer, MD
Section Editor
Stanley L Schrier, MD
Deputy Editor
Jennifer S Tirnauer, MD


Hereditary spherocytosis (HS) is the most common hemolytic anemia due to a red cell membrane defect. It is a result of heterogeneous alterations in one of six genes (most often the ankyrin gene) that encode for proteins involved in vertical associations that tie the membrane skeleton to the lipid bilayer. (See "Hereditary spherocytosis: Mechanism of hemolysis and pathogenesis".)

The clinical features, diagnosis, and treatment of HS will be reviewed here. Red blood cell membrane function is discussed separately. (See "Red blood cell membrane dynamics and organization" and "Red blood cell mechanics".)


The incidence of hereditary spherocytosis (HS) is approximately 200 to 300 per million in northern European populations, but this is likely to be an underestimate as mild cases are often not diagnosed [1]. In other parts of the world, the disease is thought to be less common although comprehensive population survey data are unavailable. Family studies indicate autosomal dominant inheritance in approximately 75 percent of patients, with recessive inheritance occurring in most of the remaining patients. However, a significant number of patients with hematologically normal parents and presumed recessive disease prove to harbor de novo mutations that will exhibit dominant inheritance in subsequent generations [2-4].


Spectrum of severity — Anemia, jaundice, and splenomegaly are the common clinical features of hereditary spherocytosis (HS). The degree of anemia is extremely variable and may be absent, mild, moderate, or severe to the point of threatening life [5-7]. HS is generally classified into three forms based upon the severity of the disease process [8].

Mild HS occurs in 20 to 30 percent of cases. These patients have no anemia, modest reticulocytosis, little in the way of splenomegaly or jaundice, and the disorder may not be detected until adolescence or adult life. Subjects with mild HS maintain normal hemoglobin levels in the face of accelerated erythrocyte destruction via an erythropoietin-driven increase in erythropoiesis [9]. The stimulus for increased production of erythropoietin is not known but does not appear to be due to hypoxia [10]. (See "Regulation of erythropoiesis".)


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Literature review current through: Sep 2016. | This topic last updated: May 3, 2016.
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