Hereditary spherocytosis: a review.

Hereditary spherocytosis (HS) is a condition of abnormal red cell morphology seen microscopically as erythrocytes that have lost the central pallor characteristic of the biconcave disc shape. The red cells are instead rounder, denser, more fragile, and susceptible to extravascular haemolysis in the spleen. HS is the most common of the haemolytic anaemias that are caused by a red cell membrane defect. It derives from alterations of the ANK1, EPB3, ELB42, SPTA1 or SPTB genes and is clinically, biochemically and genetically heterogeneous. The osmotically fragile spherocytes are selectively trapped in the spleen and destroyed by phagocytes, the increased red blood cell destruction causing the three main clinical signs associated with the disease of anaemia, jaundice and splenomegaly. In the late 1990s there were major advances in the understanding of the molecular basis of HS, in which mutational analysis has clarified many questions about the structure-function relationship of components of the red cell membrane. Some of those recent findings, such as the mutations associated with the structural proteins of the membrane skeleton, are the subject of this review. The diagnosis of HS is based on red cell morphology and other conventional tests such as osmotic fragility, autohaemolysis and acidified glycerol lysis. However, milder cases are at times difficult to diagnose. Recently, a flow cytometric method has been described for quantitating the fluorescence intensity of intact red cells after incubation with the dye eosin-5'-maleimide (EMA), which binds specifically to the anion transport protein (band 3). This has been shown to be an effective screening test for red cell membrane disorders, particularly hereditary spherocytosis.