Purine nucleoside metabolism in the erythrocytes of patients with adenosine deaminase deficiency and severe combined immunodeficiency

Deficiency of erythrocytic and lymphocytic adenosine deaminase (ADA) occurs in some patients with severe combined immunodeficiency disease (SCID). SCID with ADA deficiency is inherited as an autosomal recessive trait. ADA is markedly reduced or undetectable in affected patients (homozygotes), and ap...

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Bibliographic Details
Published in:The Journal of clinical investigation 1976-04, Vol.57 (4), p.1025-1035
Main Authors: Agarwal, R P, Crabtree, G W, Parks, Jr, R E, Nelson, J A, Keightley, R, Parkman, R, Rosen, F S, Stern, R C, Polmar, S H
Format: Article
Language:English
Subjects:
Adenosine Deaminase - blood
Adenosine Deaminase - deficiency
Adenosine Deaminase Inhibitors
Adenosine Diphosphate - metabolism
Adenosine Triphosphate - metabolism
Azepines - pharmacology
Child, Preschool
Erythrocytes - enzymology
Erythrocytes - metabolism
Female
Formycins - metabolism
Glycolysis
Guanosine - metabolism
Humans
Immunologic Deficiency Syndromes - blood
Infant
Inosine Monophosphate - metabolism
Inosine Nucleotides - metabolism
Male
Nucleoside Deaminases - deficiency
Purine Nucleosides - antagonists & inhibitors
Purine Nucleosides - metabolism
Ribonucleosides - pharmacology
Thioguanine
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Summary:Deficiency of erythrocytic and lymphocytic adenosine deaminase (ADA) occurs in some patients with severe combined immunodeficiency disease (SCID). SCID with ADA deficiency is inherited as an autosomal recessive trait. ADA is markedly reduced or undetectable in affected patients (homozygotes), and approximately one-half normal levels are found in individuals heterozygous for ADA deficiency. The metabolism of purine nucleosides was studied in erythrocytes from normal individuals, four ADA-deficiency patients, and two heterozygous individuals. ADA deficiency in intake erythrocytes was confirmed by a very sensitive ammonia-liberation technique. Erythrocytic ADA activity in three heterozygous individuals (0.07,0.08, and 0.14 mumolar units/ml of packed cells) was between that of the four normal controls (0.20-0.37 mumol/ml) and the ADA-deficient patients (no activity). In vitro, adenosine was incorporated principally into IMP in the heterozygous and normal individuals but into the adenosine nucleotides in the ADa-deficient patients. Coformycin (3-beta-D-ribofuranosyl-6,7,8-trihydroimidazo[4,5-4] [1,3] diazepin-8 (R)-ol), a potent inhibitor of ADA, made possible incorporation of adenosine nucleotides in the ADA-deficient patients...
ISSN:0021-9738
DOI:10.1172/JCI108344