Red cell enzyme defects as nondiseases and as diseases.

F OR A MODEST SUM, Sigma Chemical Company will supply a diagnostic kit that will enable one to determine the glutathione reductase activity of the erythrocytes in a patient with hemolytic anemia. This kit or one or another assay procedure for glutathione reductase is used by conscientious physicians in the work-up of patients with chronic hemolysis. Unfortunately, the money and effort are wasted. Glutathione reductase deficiency does not produce chronic hemolytic anemia. Within the past two decades, recognition of clear-cut relationships between hemolytic disease and deficiencies of glucose-6-phosphate dehydrogenase, pyruvate kinase, glucose-phosphate isomerase, pyrimidine 5’-nucleotidase, and a number of other enzymes has greatly advanced our understanding of the origin of hemolytic disease and of certain basic aspects of red cell metabolism. Although the cause of hereditary nonspherocytic hemolytic anemia has thus been correctly identified in some patients with this disorder, the etiology of hemolysis in other patients has eluded the investigator of red cell biochemistry. Quite naturally, such patients are being investigated in research laboratories with ever-enlarging panels of red cell enzyme assays. When deficiencies have been found, it has often been assumed that a cause-and-effect relationship exists between enzyme deficiency on the one hand and chronic hemolysis on the other. Glutathione reductase is a case in point. Many articles and reviews, even quite recent ones, have listed a deficiency of this enzyme as one of the causes of chronic hemolytic anemiaJ3 However, we now recognize that in the vast majority of cases, partial glutathione reductase deficiency is due to suboptimal riboflavin nutrition. 8 Glutathione reductase is an enzyme that contains flavine-adenine dinucleotide (FAD). In red cells its activity is markedly influenced by riboflavin intake.7 Whether nutritional or hereditary in origin, one thing is quite clear: partial glutathione reductase deficiency has no known hematologic effect. Virtually