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J Clin Invest. Oct 1979; 64(4): 1130–1139.
PMCID: PMC372225
Erythrocyte Adenosine Deaminase Deficiency without Immunodeficiency
EVIDENCE FOR AN UNSTABLE MUTANT ENZYME
Rochelle Hirschhorn, Vivien Roegner, Trefor Jenkins, Carol Seaman, Sergio Piomelli, and William Borkowsky
Department of Medicine, New York University School of Medicine, New York 10016
Department of Pediatrics, New York University School of Medicine, New York 10016
Department of Human Genetics, School of Pathology, University of the Witwatersrand, Johannesburg, South Africa
The South African Institute for Medical Research, University of the Witwatersrand, Johannesburg, South Africa
Abstract
Inherited deficiency of the purine salvage enzyme adenosine deaminase (ADA) gives rise to a syndrome of severe combined immunodeficiency (SCID). We have studied a 2.5-yr-old immunologically normal child who had been found to lack ADA in his erythrocytes during New York State screening of normal newborns. His erythrocytes were not detectably less deficient in ADA than erythrocytes of ADA-SCID patients. In contrast, his lymphocytes and cultured long-term lymphoid cells contained appreciably greater ADA activity than those from patients with ADA-SCID. This residual ADA activity had a normal molecular weight and Km but was markedly unstable at 56°C. His residual erythrocytes-ADA activity also appeared to have diminished stability in vivo. ADA activity in lymphoid line cells of a previously reported erythrocyte-ADA-deficient!Kung tribesman was found to contain 50% of normal activity and to exhibit diminished stability at 56°C. ATP content of erythrocytes from both partially ADA-deficient individuals was detectably greater than normal (12.3 and 6.1 vs. normal of 2.6 nmol/ml packed erythrocytes). However, the dATP content was insignificant compared to that found in erythrocytes of ADA-SCID patients (400-1,000 nmol/ml packed erythrocytes). The New York patient, in contrast to normals, excreted detectable amounts of deoxyadenosine, but this was <2% of deoxyadenosine excreted by ADA-SCID patients. Thus, the residual enzyme in cells other than erythrocytes appears to be sufficient to almost totally prevent accumulation of toxic metabolites.
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