Introduction to discussion of Heinz body anemias—Unstable hemoglobinopathies

Abstract

During the past 18 years, numerous cases of “congenital Heinz body anemia” have been reported. It is now clear that unstable, thermolabile hemoglobins are present in most or all such cases. Unstable hemoglobins Zurich. H. Koln, Hasharon and L Ferrara have been reported in more than one family. Most of the unstable hemoglobins may be attributed to point mutations in the genetic code, such as a change from guanine to adenine. Nearly 30 such unstable hemoglobinopathies have been characterized from the standpoint of the molecular pathology—that is, the change in structure of the globin chains of hemoglobin. The manner by which these molecular changes cause instability of the hemoglobin molecule seems to be variable, but very likely the effect in most is to loosen the bond between heme and globin, followed by formation of mixed disulfides and denaturation and precipitation of globin. Erythrocytes that contain unstable hemoglobins may exhibit accelerated glucose consumption, low glutathione concentration, decreased glutathione stability, and low concentrations of adenosine triphosphate. The rate of methemoglobin formation and of in vitro autohemolysis may be increased. Oxygen dissociation is abnormal in some of these disorders. The inheritance of these disorders is commonly autosomal dominant. Hemolysis may be mild to severe; it may occur only after sulfonamide ingestion or may not be demonstrable at all. Splenectomy has been beneficial in a few cases of severe hemolytic anemia due to unstable hemoglobinopathy.