Inborn errors of purine metabolism: clinical update and therapies

Balasubramaniam, Shanti, Duley, John A. and Christodoulou, John (2014) Inborn errors of purine metabolism: clinical update and therapies. Journal of Inherited Metabolic Disease, 37 5: 669-686. doi:10.1007/s10545-014-9731-6

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Author Balasubramaniam, Shanti
Duley, John A.
Christodoulou, John
Title Inborn errors of purine metabolism: clinical update and therapies
Journal name Journal of Inherited Metabolic Disease   Check publisher's open access policy
ISSN 0141-8955
Publication date 2014-06-28
Year available 2014
Sub-type Article (original research)
DOI 10.1007/s10545-014-9731-6
Open Access Status
Volume 37
Issue 5
Start page 669
End page 686
Total pages 18
Place of publication Dordrecht, Netherlands
Publisher Springer Netherlands
Language eng
Formatted abstract
Inborn errors of purine metabolism exhibit broad neurological, immunological, haematological and renal manifestations. Limited awareness of the phenotypic spectrum, the recent descriptions of newer disorders and considerable genetic heterogeneity, have contributed to long diagnostic odysseys for affected individuals. These enzymes are widely but not ubiquitously distributed in human tissues and are crucial for synthesis of essential nucleotides, such as ATP, which form the basis of DNA and RNA, oxidative phosphorylation, signal transduction and a range of molecular synthetic processes. Depletion of nucleotides or accumulation of toxic intermediates contributes to the pathogenesis of these disorders. Maintenance of cellular nucleotides depends on the three aspects of metabolism of purines (and related pyrimidines): de novo synthesis, catabolism and recycling of these metabolites. At present, treatments for the clinically significant defects of the purine pathway are restricted: purine 5′-nucleotidase deficiency with uridine; familial juvenile hyperuricaemic nephropathy (FJHN), adenine phosphoribosyl transferase (APRT) deficiency, hypoxanthine phosphoribosyl transferase (HPRT) deficiency and phosphoribosyl-pyrophosphate synthetase superactivity (PRPS) with allopurinol; adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) deficiencies have been treated by bone marrow transplantation (BMT), and ADA deficiency with enzyme replacement with polyethylene glycol (PEG)-ADA, or erythrocyte-encapsulated ADA; myeloadenylate deaminase (MADA) and adenylosuccinate lyase (ADSL) deficiencies have had trials of oral ribose; PRPS, HPRT and adenosine kinase (ADK) deficiencies with S-adenosylmethionine; and molybdenum cofactor deficiency of complementation group A (MOCODA) with cyclic pyranopterin monophosphate (cPMP). In this review we describe the known inborn errors of purine metabolism, their phenotypic presentations, established diagnostic methodology and recognised treatment options.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online: 28 June 2014 Presented at the 12th International Congress of Inborn Errors of Metabolism, Barcelona, Spain, September 3-6, 2013.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Mater Research Institute-UQ (MRI-UQ)
Official 2015 Collection
School of Pharmacy Publications
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Citation counts: TR Web of Science Citation Count  Cited 8 times in Thomson Reuters Web of Science Article | Citations
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Created: Wed, 27 Aug 2014, 11:39:56 EST by Dr John Duley on behalf of School of Pharmacy