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Disorders of Purine and Pyrimidine Metabolism

  • Chapter
Inborn Metabolic Diseases

Zusammenfassung

Inborn errors of purine metabolism comprise defects or superactivities of purine nucleotide synthesis and interconversions: phosphoribosyl pyrophosphate synthetase (PRS) superactivity and deficiency, adenylosuccinase (ADSL) deficiency, AICA-ribosiduria caused by ATIC deficiency; purine catabolism: the deficiencies of muscle AMP deaminase (AMPD, also termed myoadenylate deaminase), adenylate kinase (AK), adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), and xanthine oxidase (XO); purine salvage: the deficiencies of hypoxanthine-guanine phosphoribosyltransferase (HPRT), adenine phosphoribosyltransferase (APRT) and adenosine kinase (ADK). The deficiency of deoxyguanosine kinase (DGUOK) causes mitochondrial DNA depletion. Deficiency of thiopurine S-methyltransferase (TPMT) results in less efficient methylation and hence in enhanced toxicity of pharmacologic thiopurine analogs. Deficiency of inosine triphosphate pyrophosphatase (ITPase) also increases the toxicity of thiopurines. With the exception of the deficiencies of muscle AMPD and TPMT, all these inborn errors are very rare. Inborn errors of pyrimidine metabolism comprise defects of: pyrimidine synthesis: CAD, UMP synthase deficiency and Miller syndrome; pyrimidine catabolism: deficiencies of dihydropyrimidine dehydrogenase (DPD) dihydropyrimidinase (DHP), ureidopropionase, thymidine phosphorylase (a mitochondrial disorder), pyrimidine 5‘-nucleotidase and cytidine deaminase, and superactivity of cytosolic 5‘-nucleotidase; pyrimidine salvage: thymidine kinase 2 deficiency (a mitochondrial disease).

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Authors and Affiliations

  1. Laboratory for Inherited Metabolic Diseases, Saint-Luc University Hospital, University of Louvain Medical School, Avenue Hippocrate 10, 1200, Brussels, Belgium

    Sandrine Marie

  2. Laboratory of Physiological Chemistry, de Duve Institute, University of Louvain Medical School, Avenue Hippocrate 75/39, 1200, Brussels, Belgium

    Georges van den Berghe

  3. Laboratory for Inherited Metabolic Diseases, Saint-Luc University Hospital, University of Louvain Medical School, Avenue Hippocrate 10, 1200, Brussels, France

    Marie-Françoise Vincent

Authors
  1. Sandrine Marie
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  2. Georges van den Berghe
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  3. Marie-Françoise Vincent
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Correspondence to Sandrine Marie , Georges van den Berghe or Marie-Françoise Vincent .

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Editors and Affiliations

  1. Department of Neurology, Neurometabolic Unit, Hôpital Pitié Salpêtrière, Paris, France

    Jean-Marie Saudubray

  2. Division of Metabolism, University Children’s Hospital, Zurich, Switzerland

    Matthias R. Baumgartner

  3. Willink Biochemical Genetics Unit Manchester Centre for Genomic Medicine, University of Manchester, Manchester, UK

    John Walter

  4. Central Manchester University Hospitals NHS Foundation Trust, St Mary‘s Hospital, Manchester, UK

    John Walter

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Marie, S., van den Berghe, G., Vincent, MF. (2016). Disorders of Purine and Pyrimidine Metabolism. In: Saudubray, JM., Baumgartner, M., Walter, J. (eds) Inborn Metabolic Diseases. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-49771-5_35

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  • DOI: https://doi.org/10.1007/978-3-662-49771-5_35

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