Hereditary Spherocytosis (HS) is a common hemolytic anemia characterized by a chronic hemolysis with a broad spectrum of clinical severity. The red cells present a varying degree of surface area deficiency resulting in a spherocytic phenotype and increased osmotic fragility. It is now recognized that this disorders is associated with defects of the erythrocyte membrane skeleton. Spectrin, the most abundant skeletal protein, consistes in two chains, α and β, intertwined in an antiparallele manner to form heterodimers which associate at their head region to form tetramers. This skeletal network plays an essential role in determining the shape and deformability of the red cell.
We describe a 12 yrs. old HS child with a moderate, dominantly inherited, hemolytic anemia. His peripheral blood smear showed marked spherocytosis with some spiculated erythrocytes. Analysis of the red cell membrane proteins by 3.5-17% exponential gradient SDS-PAGE revealed an overall moderate spectrin deficiency (16%). Moreover an additional band migrating between ankyrin (band 2.1) and protein 2.2 was observed. Western blot analysis using polyclonal antibodies raised against β spectrin -NH2 extremity revealed the β spectrin origin of this extra band. The estimated molecular weight of this truncated protein was 202 kD. It constitute approximately 8% of the totalβ spectrin present on the membrane. Interestingly differing from the great majority of the other truncated β spectrins, in this case non-denaturing gel electrophoresis of spectrin extracts performed at 4 °C showed a normal spectrin dimers to tetramers ratio (9%) suggesting the integrity of the β spectrin -COOH tail.
