Increased excretion of modified adenine nucleosides by children with adenosine deaminase deficiency

We have identified seven adenine nucleosides in urines of untreated adenosine deaminase (ADA) deficient patients, four of which (adenosine, 2'-deoxyadenosine, 1-methyladenosine and N6-methyladenosine) have been previously identified in urines of normals and/or ADA deficient patients. We confirm that ADA deficient patients excrete markedly increased amounts of 2'-deoxyadenosine (582 +/- 363 versus normal of less than 0.1 nmoles/mg creatinine) and increased amounts of adenosine (29.4 +/- 5.7 versus normal of 4.12 +/- 1.0 nmoles/mg creatinine). We have found three modified adenine nucleosides previously undetected in human urine. These three compounds are 2'-O-methyladenosine, N6, 2'-O-dimethyladenosine and an as yet incompletely characterized modified adenine nucleoside, R-adenosine. Only ADA deficient patients excrete detectable amounts of 2'-O-methyladenosine (2.1 +/- 1.1 versus normal of less than 0.1 nmoles/ mg creatinine), whereas both normals and ADA deficient children excrete N6, 2'-O-dimethyladenosine and R-adenosine. However, ADA deficient patients do excrete increased amounts of R-adenosine (5.5 +/- 1.0 versus normal of 1.4 +/- 0.4 nmoles/mg creatinine).