HEREDITARY SPHEROCYTOSIS - FROM CLINICAL TO MOLECULAR DEFECTS

Resistance and elastic deformability of red cells are due to a protein network (cytoskeleton) that laminates the lipid bilayer and to protei ns that span the latter. All proteins are interconnected. Their struct ure as well as the structure of the corresponding genes are now well k nown. Hereditary spherocytosis (HS) is the most common hemolytic anemi a due to a red cell membrane defect. It derives from alterations of th e following genes: ANK1, EPB3, ELB42, SPTA1 and SPTB. This condition i s clinically, biochemically and genetically heterogeneous. The osmotic ally fragile spherocytes are selectively trapped in the spleen and des troyed. Increased red blood cell destruction causes the three main cli nical signs of HS: anemia, jaundice and splenomegaly. In this review w e analyze the most recent advances concerning the molecular basis and the clinical course of HS. In particular, we examine the major individ ual proteins that constitute the skeleton, which are now known to play an essential role in the pathogenesis of HS. This paper also includes a review of the therapeutical approach to HS. Concerning the diagnosi s we provide a flow chart from the clinical aspects to the molecular d iagnosis. (C) 1998, Ferrata Storti Foundation.