Three Cases of Hereditary Nonspherocytic Hemolytic Anemia Associated With Red Blood Cell Glutathione Deficiency

Three unrelated Japanese patients with chronic nonspherocytic hemolytic anemia were found to have marked deficiency of red blood cell (RBC) reduced glutathione (GSH) (4.4%, 13.1%, and 6.9% of normal, respectively). A panel of RBC enzyme assays showed that one patient had decreased glutathione synthetase activity and the other two were moderately deficient in γ-glutamylcysteine synthetase. Some family members of each patient showed mild deficiency of the respective enzymes. RBCs of these patients also showed a decreased level of glutathione-S-transferase as in previously described GSH-deficient cases. Hemolytic anemia was their only manifestation, and neither 5-oxoproli-nemia nor 5-oxoprolinuria, which are usually associated with the generalized type of glutathione synthetase deficiency, was noted in our patients.