Adenosine Deaminase Deficiency with

Inmostinstances, markeddeficiency ofthepurine catabolic enzymeadenosine deaminase results inlymphopenia andsevere combined immu- nodeficiency disease. Overa2-yrperiod, westudied awhite malechild withmarkedly deficient erythro- cyteandlymphocyte adenosine deaminase activity andnormal immunefunction. We havedocumented that(a)adenosine deaminase activity andimmuno- reactive protein areundetectable inerythrocytes, 0.9% ofnormal inlymphocytes, 4% incultured lympho- blasts, and14%inskin fibroblasts; (b) plasma adenosine anddeoxyadenosine levels areundetectable anddeoxy ATPlevels areonlyslightly elevated inlymphocytes andinerythrocytes; (c)nodefect indeoxyadenosine metabolism ispresent intheproband's cultured lym- phoblasts; (d)lymphoblast adenosine deaminase has normal enzymekinetics, absolute specific activity, S20,w, pHoptimum, andheatstability; and(e)thepro- band's adenosine deaminase exhibits anormal appar- entsubunit molecular weight butanabnormal iso- electric pH.Incontrast tothethree other adenosine deaminase-deficient healthy subjects whohavebeen described, theproband isunique indemonstrating an acidic, heat-stable protein mutation oftheenzymethat isassociated with<1%lymphocyte adenosine deam- inase activity. Residual adenosine deaminase activity intissues other thanlymphocytes maysuffice tome- tabolize theotherwise lymphotoxic enzymesub- strate(s) andaccount forthepreservation ofnormal immunefunction.