Congenital Nonspherocytic Hemolytic Anemia, Associated with Glutathione Deficiency of the Erythrocytes : Hematologic, Biochemical and Genetic Studies

1. A new biochemical defect of erythrocytes is described: glutathione deficiency (reduced glutathione less than 10 per cent of the amount of reduced glutathione in normal erythrocytes).

2. The defect is associated with a clinical picture of congenital nonspherocytic hemolytic anemia which is fairly well compensated.

3. The results of a family study are consistent with an autosomal recessive pattern of inheritance.

4. Labeling with Na₂Cr⁵¹O₄ has a damaging effect on glutathione-deficient erythrocytes. The erythrocyte life span, as estimated by a serological method (Ashby), was markedly shortened (30 days instead of 100-120 days).

5. Red cell destruction could be increased by the administration of primaquine.

6. Secondary to the glutathione deficiency, low glyoxalase activity was observed. The glutathione-reducing capacity, glycolytic activity, and the ATP level of the abnormal red cells were found to be within the normal range.

7. On incubation of the glutathione-deficient erythrocytes in vitro with glycine-C¹⁴ and glutamine-C¹⁴, no formation of labeled glutathione could be demonstrated.