Double inheritance of an alpha I/65 spectrin variant in a child with homozygous elliptocytosis

Hemolytic anemia with red cell fragmentation, poikilocytosis, and elliptocytosis was discovered in a 6-week-old black infant. Both parents and a brother of the propositus had compensated mild Hereditary Elliptocytosis (HE). Elliptocytosis was prominent in the proband's father with the presence of numerous rod-shaped cells whereas, in the proband's mother, elliptocytosis was less marked and cells were less elongated than in the father. The proband's red cells fragmented at 45 degrees C instead of 49 degrees C for control cells. Both the parents' and brother's red cells fragmented at 47 degrees C. The deformability of the proband's red cells was markedly reduced when measured with the ektacytometer; the red cells of both the proband's parent and brother exhibited an intermediate decrease in red cell deformability. Spectrin self-association was defective in the propositus as well as in his parents and brother. Limited tryptic digestion of the proband's spectrin, followed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), revealed a complete absence of the normal 80,000 dalton alpha I domain and the presence of an abnormal 65,000 dalton peptide. Two-dimensional isoelectric focusing/SDS-PAGE of limited tryptic digests of spectrin from both the proband's parents and brother revealed a decrease in the normal 80,000 alpha I domain and the presence of the 65,000 peptide variant. On the basis of biochemic studies performed on the patients' spectrin, we concluded that the proband had homozygous HE, having inherited the structural defect of spectrin present in a heterozygous state in each of his parents. On a clinical and morphologic level, homozygous HE imitates two other forms of congenital hemolytic anemia associated with a spectrin self- association defect: HE with pycnocytosis in infancy and Hereditary Pyropoikilocytosis. This report emphasizes the importance of confronting clinical and rheological as well as biochemical investigations in studying and discussing different entities.