Erythrocyte adenosine deaminase deficiency without immunodeficiency. Evidence for an unstable mutant enzyme

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 newb...

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Bibliographic Details
Published in:The Journal of clinical investigation 1979-10, Vol.64 (4), p.1130-1139
Main Authors: Hirschhorn, R, Roegner, V, Jenkins, T, Seaman, C, Piomelli, S, Borkowsky, W
Format: Article
Language:English
Subjects:
Adenosine
Adenosine Deaminase - deficiency
Chromatography, Gel
Erythrocytes - enzymology
Humans
Immunologic Deficiency Syndromes - enzymology
Infant, Newborn
Lymphocytes - enzymology
Male
Nucleoside Deaminases - deficiency
Structure-Activity Relationship
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Summary: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 K(m) but was markedly unstable at 56 degrees 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 degrees 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
ISSN:0021-9738
DOI:10.1172/JCI109552