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

Rochelle Hirschhorn, Howard Ratech, Arye Rubinstein, Photini Papageorgiou, Hernant Kesarwala, Erwin Gelfand, Vivien Roegner-Maniscalco

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

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 N<sup>8</sup>- 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, N<sup>6</sup>, 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 N<sup>6</sup>, 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.

Original languageEnglish (US)
Pages (from-to)362-369
Number of pages8
JournalPediatric Research
Volume16
Issue number5
StatePublished - 1982

Fingerprint

Adenosine Deaminase
Adenine
Nucleosides
Adenosine
B-Lymphocytes
Urine
Severe combined immunodeficiency due to adenosine deaminase deficiency
Creatinine

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Hirschhorn, R., Ratech, H., Rubinstein, A., Papageorgiou, P., Kesarwala, H., Gelfand, E., & Roegner-Maniscalco, V. (1982). Increased excretion of modified adenine nucleosides by children with adenosine deaminase deficiency. Pediatric Research, 16(5), 362-369.

Increased excretion of modified adenine nucleosides by children with adenosine deaminase deficiency. / Hirschhorn, Rochelle; Ratech, Howard; Rubinstein, Arye; Papageorgiou, Photini; Kesarwala, Hernant; Gelfand, Erwin; Roegner-Maniscalco, Vivien.

In: Pediatric Research, Vol. 16, No. 5, 1982, p. 362-369.

Research output: Contribution to journalArticle

Hirschhorn, R, Ratech, H, Rubinstein, A, Papageorgiou, P, Kesarwala, H, Gelfand, E & Roegner-Maniscalco, V 1982, 'Increased excretion of modified adenine nucleosides by children with adenosine deaminase deficiency', Pediatric Research, vol. 16, no. 5, pp. 362-369.
Hirschhorn R, Ratech H, Rubinstein A, Papageorgiou P, Kesarwala H, Gelfand E et al. Increased excretion of modified adenine nucleosides by children with adenosine deaminase deficiency. Pediatric Research. 1982;16(5):362-369.
Hirschhorn, Rochelle ; Ratech, Howard ; Rubinstein, Arye ; Papageorgiou, Photini ; Kesarwala, Hernant ; Gelfand, Erwin ; Roegner-Maniscalco, Vivien. / Increased excretion of modified adenine nucleosides by children with adenosine deaminase deficiency. In: Pediatric Research. 1982 ; Vol. 16, No. 5. pp. 362-369.
@article{49764b0f855a44e7abad583a2a9c0d4c,
title = "Increased excretion of modified adenine nucleosides by children with adenosine deaminase deficiency",
abstract = "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.",
author = "Rochelle Hirschhorn and Howard Ratech and Arye Rubinstein and Photini Papageorgiou and Hernant Kesarwala and Erwin Gelfand and Vivien Roegner-Maniscalco",
year = "1982",
language = "English (US)",
volume = "16",
pages = "362--369",
journal = "Pediatric Research",
issn = "0031-3998",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

TY - JOUR

T1 - Increased excretion of modified adenine nucleosides by children with adenosine deaminase deficiency

AU - Hirschhorn, Rochelle

AU - Ratech, Howard

AU - Rubinstein, Arye

AU - Papageorgiou, Photini

AU - Kesarwala, Hernant

AU - Gelfand, Erwin

AU - Roegner-Maniscalco, Vivien

PY - 1982

Y1 - 1982

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0020024890&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0020024890&partnerID=8YFLogxK

M3 - Article

C2 - 6980397

AN - SCOPUS:0020024890

VL - 16

SP - 362

EP - 369

JO - Pediatric Research

JF - Pediatric Research

SN - 0031-3998

IS - 5

ER -