Hereditary, X-Linked, Sideroachrestic Anemia. The Isolation of Two Erythrocyte Populations Differing in Xga Blood Type and Porphyrin Content

1. Two morphologically distinct populations of erythrocytes were found in a mother and in two of her daughters, one of whom (the proband) was anemic. One erythrocyte population was morphologically normal; the other was hypochromic and microcytic. 2. The X-linked blood group antigen, Xga, was present in erythrocytes from the mother and the two daughters, but not in erythrocytes from the father. The daughters were, therefore, heterozygous for the gene controlling this antigen. 3. Separation of the two populations of erythrocytes was accomplished by centrifugation in layered gum acacia solutions of different specific gravity. 4. The microcytic cells from the three affected individuals were Xga-positive. Isolated normal cells were Xga-positive in the mother, but negative in both daughters. These data suggest that the erythrocyte defect is X-linked and that the phenomenon of X-inactivation applies to genes controlling both the morphologic defect and the Xga antigen. 5. The free protoporphyrin content of the isolated microcytes was lower than that of the normal cells. The capacity of the microcytes to convert delta-aminolevulinic acid to protoporphyrin was unimpaired. On these bases it is suggested that the hereditary defect lies either at or before the step in which delta-aminolevulinic acid is synthesized.