Identification of the hereditary pyropoikilocytosis carrier state.
We evaluated the hematologic, rheologic, and biochemical features of erythrocytes obtained from 10 relatives of a 5-yr-old black female with hereditary pyropoikilocytosis (HPP) and severe hemolytic anemia. Erythrocyte morphology was normal in the father and five other relatives, but ghost mechanical fragility and drug-induced red cell endocytosis were increased, as was the percentage of spectrin dimers noted on 3.2% nondenaturing PAGE of spectrin extracts. Identical changes were also noted in the mother and her sister, whose erythrocytes were elliptocytic and exhibited morphological changes upon heating to 45 degrees-48 degrees C (normal 49 degrees). The two other family members were normal in every respect. SDS-PAGE analysis of membrane proteins demonstrated diminished amounts of spectrin in HPP erythrocytes, but was normal in other family members. A diffuse band (mol wt 575,000-665,000), composed entirely of spectrin, was apparent adjacent to the dimer region on nondenaturing PAGE of spectrin extracts from the propositus, mother, and aunt. In this family, HPP appears to have resulted from compound heterozygosity for two distinct genetic abnormalities (reflected by the differences between elliptocytic and nonelliptocytic carriers). Although the membrane abnormalities in carriers did not result in hemolytic anemia, they were of sufficient magnitude to allow the detection of the carrier state.
D000328:Adult; D000745:Anemia, Hemolytic, Congenital / Q000175:diagnosis*; D002675:Child, Preschool; D004705:Endocytosis / Q000187:drug effects; D004910:Erythrocyte Membrane / Q000032:analysis; D004913:Erythrocytes, Abnormal; D005260:Female; D006580:Genetic Carrier Screening; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000032:analysis; D009994:Osmolar Concentration; D009996:Osmotic Fragility; D010375:Pedigree; D011319:Primaquine / Q000494:pharmacology; D013049:Spectrin / Q000032:analysis; D014747:Vinblastine / Q000494:pharmacology
D008565:Membrane Proteins; D013049:Spectrin; D014747:Vinblastine; D011319:Primaquine