Defective Globin Synthesis in Hypochromic

By PAUL HELLER, JOHN VAN STONE, DAVID APPLE AND RICHARD D. COLEMAN A RARE FORM of hereditary anemia characterized by hypochromia of the erythrocytes in tile presence of increased iron stores has been designated by Heilmeyer1’2 as “hereditary hypochromic sideroachrestic anemia.” Garby and his co-workers3 and Hei1meyer1’ ’ have suggested that in this disorder heme synthesis is disturbed possibly because of a genetically determined defect in the enzymatic conversion from coproporphyrin to protoporphyrin. Tills pathogenic mechanism has been considered responsible for the elevated erythrocyte coproporphyrin levels in patients with tins disorder. The similarity of the clinical and laboratory features with those of thalassemia minor has been recognized, but the absence of any stigmata of increased hemolysis, the normal proportion of fetal and A2 hemoglobin and tile marked increase of sideroblasts in the bone marrow have been considered distinctive characteristics of “hereditary hypocilromic sideroachrestic anemia.”2 Verloop and ills co-workers4 have recently emphasized the importance of the presence of a large number of “ringed” sideroblasts5 in bone marrow smears as a diagnostic criterion of this disorder for which they use the designation “hereditary hypochromic hypersideremic anemia.” In these cells tile perinuclear region of tile cytoplasm is densely filled with coarse iron granules. These investigators have also observed patients with llypocllromic hypersidercmic anemia without ringed sideroblasts and they have raised tile question whether the abnormality in such patients might not be a form of a-thalassemia. Tile patient, described in tile following report, was found to have an erythropoietic disorder which had several characteristics of hypersideremic anemia with the postulated (lefect in heme synthesis, including an abundance of ringed sideroblasts in the bone marrow. Studies of heme and globin production with glycine-2-C” indicated that it was the globin moiety which was synthesized in an abllornlal pattern suggesting tile effect of a thalassemia gene.