Agre et al. (1982) reported 2 daughters, of related but normal parents, who had nearly fatal hemolytic anemia requiring early splenectomy. Both improved strikingly thereafter but spherocytosis persisted. Red cell membranes were at least 50% deficient in spectrin, ... Agre et al. (1982) reported 2 daughters, of related but normal parents, who had nearly fatal hemolytic anemia requiring early splenectomy. Both improved strikingly thereafter but spherocytosis persisted. Red cell membranes were at least 50% deficient in spectrin, with band 1 reduced more than band 2. No defect was found in membrane binding of spectrin or in membrane binding sites (ankyrin). The parents were fourth cousins. Parentage was confirmed by HLA typing. Extensive hematologic studies showed no abnormality in the parents and other close relatives. Agre et al. (1986) found that distally related homozygotes showed different clinical severities and different spectrin levels as determined by radioimmunoassay. Agre et al. (1985) demonstrated deficiency of red cell spectrin in cases of several different types of spherocytosis. A number of observations indicated that deficiency of spectrin is a primary factor in the pathogenesis of spherocytosis. Studies in both mice and men indicated that a variety of mutations affecting spectrin synthesis or stability can underlie spherocytosis. Agre et al. (1986) found that spectrin levels in all patients with spherocytosis were inversely related to osmotic fragility and were also correlated with the clinical response to splenectomy.
In the kindred with autosomal recessive spherocytosis reported by Agre et al. (1986), Marchesi et al. (1989, 1989) identified a missense mutation in the alpha-II domain of the SPTA gene (182860.0005).
In a patient with severe ... In the kindred with autosomal recessive spherocytosis reported by Agre et al. (1986), Marchesi et al. (1989, 1989) identified a missense mutation in the alpha-II domain of the SPTA gene (182860.0005). In a patient with severe spherocytic hemolytic anemia, Wichterle et al. (1996) identified compound heterozygosity for 2 mutations in the SPTA gene (182860.0022; 182860.0023).