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

Summary: We have identified seven adenine nucleosides in urines of untreated adenosine deaminase (ADA) deficient patients, four of which (adenosine, 2'-deoxyadenosine, 1-methyladenosine and N⁸- 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'-deox- yadenosine (582 ± 363 versus normal of < 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 other modified adenine nucleosides previously undetected in human urine. These three compounds are 2'-O-methyladenosine, N⁶, 2'-0-dimethyladenosine and an as yet incompletely characterized modified adenine nucleoside, R-aden- osine. Only ADA deficient patients excrete detectable amounts of 2'-0-methyladenosine (2.1 ± 1.1 versus normal of < 0.1 nmoles/ mg creatinine), whereas both normals and ADA deficient children excrete N⁶, 2'-0-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). Speculation: Accumulation in ADA deficient patients of two newly detected modified adenine nucleosides (2'-0-methyladenosine and R-adenosine) or their metabolites could play a role in explaining the profound abnormalities of B cell function seen in ADA deficiency but not in purine nucleoside phosphorylase deficiency. This differential involvement of B cell function is not easily explained by accumulation of deoxytrinucleotides, which occurs in both disorders.