Altered spectrin association and membrane fragility without abnormal spectrin heat sensitivity in a case of congenital hemolytic anemia

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Abstract
In hereditary pyropoikilocytosis (HPP) and one type of hereditary elliptocytosis (HE), spectrin self-association is abnormal [5,7]. Spectrin extracted from normal erythro-cyte membranes at 0°C is nearly all tetrameric, while in HPP and HE (type 1) a substantial amount of the extracted spectrin is dimeric. Abnormal reassociation of spectrin dimers to tetramers can also be demonstrated. We here report the case of a family in which the child has moderately severe hemolysis, with extreme microcytosis and poikilocytosis. The spectrin extracted at 0°C was predominately dimer. Parents had levels of dimer intermediate between patient and control values. The temperature dependence was normal for (a) erythrocyte fragmentation; (b) spectrin extractability; and (c) circular dichroism of purified spectrin. Neither the patient nor either parent had elliptocytic red cells as judged from smears and scanning electron microscopy. The presence of substantial amounts of dimeric spectrin in the parents is consistent with a model in which each parent is heterozygous for a different nonassociating mutant spectrin, while the child has inherited a nonassociating molecule from each parent. In each individual, the degree of mechanical stability of the erythrocyte membrane, determined by ektacytometry, was proportional to the amount of tetramer found in the membrane. The description of this case is consistent with either HPP or a form of homozygous HE which is asymptomatic in the carrier state.