HEMOLYTIC ANEMIA AND LOW RED CELL ATP/dATP RATIO IN GENETIC ADENOSINE DEAMINASE DEFICIENCY: 86

Abstract

Marked depletion of ATP and hemolysis have been reported to accompany dATP accumulation in erythrocytes of patients undergoing treatment with the ADA inhibitor deoxycoformycin (dCF), but not in patients with inherited ADA deficiency. It has therefore been unclear whether ATP depletion and hemolysis were caused by ADA inhibition per se, or by unrelated effects of phosphorylated derivatives of dCF. We have studied a 9 month old ADA deficient girl who at diagnosis had a heinz body positive hemolytic anemia as well as immune deficiency. Her RBC's underwent spontaneous lysis in vitro, which was not corrected by glucose or enhanced by osmotic or pH stress. Known causes of anemia were excluded. ATP, measured on 4 occasions, was 0.69 +/- 0.14 umol/ml RBC's (range=0.5-0.8) (controls=1.4 +/- 0.3). dATP was 1.24 +/- 0.22 umol/ml RBC's (normally <0.002); the ratio of ATP:dATP was 0.46-0.67. We have previously described a mechanism by which dATP accumulation can Induce marked ATP catabolism (Bagnara and Hershfield, PNAS 79:2637, 1982). Thus, ADA deficiency, like pyruvate kinase deficiency and massively Increased erthrocyte ADA activity, may be an inborn error of metabolism that can lead to hemolysis by causing ATP depletion. However, in most cases some compensatory mechanism must operate to prevent ATP depletion as marked as in the patient we have described.