Inborn errors of pyrimidine metabolism: clinical update and therapy

Balasubramaniam, Shanti, Duley, John A. and Christodoulou, John (2014) Inborn errors of pyrimidine metabolism: clinical update and therapy. Journal of Inherited Metabolic Disease, 37 5: 687-698. doi:10.1007/s10545-014-9742-3

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Author Balasubramaniam, Shanti
Duley, John A.
Christodoulou, John
Title Inborn errors of pyrimidine metabolism: clinical update and therapy
Journal name Journal of Inherited Metabolic Disease   Check publisher's open access policy
ISSN 0141-8955
Publication date 2014-07-17
Year available 2014
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1007/s10545-014-9742-3
Open Access Status
Volume 37
Issue 5
Start page 687
End page 698
Total pages 12
Place of publication Dordrecht, Netherlands
Publisher Springer Netherlands
Collection year 2015
Language eng
Formatted abstract
Inborn errors involving enzymes essential for pyrimidine nucleotide metabolism have provided new insights into their fundamental physiological roles as vital constituents of nucleic acids as well as substrates of lipid and carbohydrate metabolism and in oxidative phosphorylation. Genetic aberrations of pyrimidine pathways lead to diverse clinical manifestations including neurological, immunological, haematological, renal impairments, adverse reactions to analogue therapy and association with malignancies. Maintenance of cellular nucleotides depends on the three aspects of metabolism of pyrimidines: de novo synthesis, catabolism and recycling of these metabolites. Of the ten recognised disorders of pyrimidine metabolism treatment is currently restricted to only two disorders: hereditary orotic aciduria (oral uridine therapy) and mitochondrial neurogastrointestinal encephalomyopathy (MNGIE; allogeneic hematopoetic stem cell transplant and enzyme replacement). The ubiquitous role that pyrimidine metabolism plays in human life highlights the importance of improving diagnostic evaluation in suggestive clinical settings, which will contribute to the elucidation of new defects, future development of novel drugs and therapeutic strategies. Limited awareness of the expanding phenotypic spectrum, with relatively recent descriptions of newer disorders, compounded by considerable genetic heterogeneity has often contributed to the delays in the diagnosis of this group of disorders. The lack of an easily recognisable, easily measurable end product, akin to uric acid in purine metabolism, has contributed to the under-recognition of these disorders.This review describes the currently known inborn errors of pyrimidine metabolism, their variable 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: 17 July 2014. Presented at the 12th International Congress of Inborn Errors of Metabolism, Barcelona, Spain, September 3-6, 2013.

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
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 6 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 6 times in Scopus Article | Citations
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Created: Wed, 27 Aug 2014, 11:35:55 EST by Dr John Duley on behalf of School of Pharmacy