Recently numerous defects of erythrocyte membrane
proteins have been described in
hereditary hemolytic anemias. An exact biochemical characterization of some different types of
hereditary spherocytosis,
hereditary elliptocytosis,
hereditary pyropoikilocytosis and the hemolytic
anemias with increased
cation permeability (hereditary stomatocytosis) is possible after analysis of
membrane proteins with SDS-
polyacrylamide gel electrophoresis, quantitative determination of
spectrin, the relation of dimeric to tetrameric
spectrin, and partial tryptic digestion of the
spectrins. The known clinical heterogeneity of the mentioned disorders is now partially explained by the different biochemical defects of the erythrocyte membrane. In classical
hereditary spherocytosis a close relationship between erythrocyte
spectrin content and clinical severity has been found. The clinical manifestation in
hereditary elliptocytosis and
hereditary pyropoikilocytosis mainly depends on the functional disturbance of variant
spectrins, especially their ability to form tetramers, i.e. their ability for self-association of the
spectrin chains. In the hydrocytic form of stomatocytosis a deficiency of the integral
protein band 7.2b has been documented. Besides the analysis of erythrocyte membrane
proteins the classical methods used in the study of
congenital hemolytic anemias cannot be missed. Signs of increased
hemolysis, erythrocyte morphology, osmotic fragility, autohemolysis, heat and mechanical stability of the erythrocyte membrane, intracellular
cation concentration and studies of other family members, are indispensable prerequisites for classification, prognosis, and indication of therapeutic efforts, especially
splenectomy.