Hemoglobin Koln Disease Occurring as a Fresh Mutation: Erythrocyte Metabolism and Survival

Electrophoretic and fingerprinting studies in a patient with congenital hemolytic anemia revealed the presenceof the unstable hemoglobin Köln (^98valmet). Examination of parents and siblings gave normal results. Extensive bloodgroup and isozyme studies were consistent with the thesis that Hb Köln diseasein the propositus was the result of afresh mutation in one of his parent’sgametes. In the propositus, the activitiesof enzymes of the Embden-Meyerhof andpentose phosphate pathways were increased, but the level of ATP was decreased. Methemoglobin reduction wasdelayed when the NADPH-dependentsystem was utilized with added methylene blue and gave a false-positive resultin the glucose-6-phosphate dehydrogenase screening test. Methemoglobin reduction in the absence of methylene bluewas normal. Increased methemoglobinand Heinz body formation, decreasedosmotic fragility, decreased red cell deformability, and a disproportionatepotassium loss without sodium gain occurred with metabolic depletion. Therate of decline of glutathione in propositus’ cells paralleled that in normal cells.Autologous survival of Hb Köln cells wasdecreased but was not compromised further by oxidant drugs. Marked splenicsequestration of Hb Köln erythrocyteswas demonstrated, and an excellent response to splenectomy with improvederythrocyte survival was observed. Theintracellular precipitation of unstableglobin chains, intracellular dehydration,and increased membrane rigidity probably all contribute to the splenic entrapment of these erythrocytes.

Submitted on April 20, 1971 Revised on June 4, 1971 Accepted on June 29, 1971