Disorders of the red blood cell (RBC) membrane comprise an important group of inherited hemolytic anemias where there is decreased RBC deformability and permeability resulting in reduced half-life of RBC with premature removal.
These syndromes are characterized by marked clinical and genetic heterogeneity. Significant advances have been made in our understanding of the structural basis for altered cell function in various inherited RBC membrane disorders. These syndromes arise from mutations in genes encoding the cytoskeletal proteins of RBC and the transmembrane transporters.
The clinical definition of patients is often difficult since there are overlapping phenotypes. For some conditions, the great phenotypic variability is partially explained by the high genetic heterogeneity. Thus, it is sometimes complicated to distinguish one form from the others since the signs can be masked in symptom-free carriers or in mildly affected patients. Moreover, some subtypes of RBC membrane disorders can be easily confused with other clinically-related hereditary haemolytic conditions.
Specialized tests provide additional evidence in supporting the diagnosis to facilitate the management of these patients. In the case of a patient's clinical phenotype being more severe than the affected members within the immediate family, molecular testing of all family members is useful for confirming the diagnosis and allows an insight into the molecular basis of the abnormality.
Additionally, the development of new methods in molecular biology has led to individualized molecular diagnosis towards targeted therapeutic schemes.