beta-Ureidopropionase deficiency: an inborn error of pyrimidine degradation associated with neurological abnormalities

Human Molecular Genetics
A B Van KuilenburgA H Van Gennip

Abstract

beta-Ureidopropionase deficiency is an inborn error of the pyrimidine degradation pathway, affecting the cleavage of N-carbamyl-beta-alanine and N-carbamyl-beta-aminoisobutyric acid. In this study, we report the elucidation of the genetic basis underlying a beta-ureidopropionase deficiency in four patients presenting with neurological abnormalities and strongly elevated levels of N-carbamyl-beta-alanine and N-carbamyl-beta-aminoisobutyric acid in plasma, cerebrospinal fluid and urine. No beta-ureidopropionase activity could be detected in a liver biopsy obtained from one of the patients, which reflected the complete absence of the beta-ureidopropionase protein. Analysis of the beta-ureidopropionase gene (UPB1) of these patients revealed the presence of two splice-site mutations (IVS1-2A>G and IVS8-1G>A) and one missense mutation (A85E). Heterologous expression of the mutant enzyme in Escherichia coli showed that the A85E mutation resulted in a mutant beta-ureidopropionase enzyme without residual activity. Our results demonstrate that the N-carbamyl-beta-amino aciduria in these patients is due to a deficiency of beta-ureidopropionase, which is caused by mutations in the UPB1 gene. Furthermore, an altered homeostasis of beta-amin...Continue Reading

References

Jan 1, 1991·Clinical Immunology and Immunopathology·P C de LaatG B Stoelinga
May 1, 1989·European Journal of Biochemistry·J Kautz, K D Schnackerz
Oct 1, 1985·Analytical Biochemistry·P K SmithD C Klenk
Jan 15, 1994·European Journal of Biochemistry·M KikugawaN Tamaki
Mar 1, 1996·Trends in Pharmacological Sciences·G P ConnollyJ A Duley
Jun 1, 1997·Journal of Inherited Metabolic Disease·A H van GennipA B van Kuilenburg
Mar 10, 1999·Human Genetics·A B Van KuilenburgA H Van Gennip
Aug 18, 2001·Journal of Nutritional Science and Vitaminology·T SakamotoN Tamaki
Oct 25, 2001·Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine·S H MoolenaarR A Wevers
Jan 11, 2002·Advances in Experimental Medicine and Biology·A H van Gennip, A B van Kuilenburg
Jan 11, 2002·Advances in Experimental Medicine and Biology·A B van KuilenburgA H van Gennip
Oct 4, 2002·Free Radical Biology & Medicine·Yoke W Kow
Apr 8, 2003·Cellular and Molecular Life Sciences : CMLS·M Huang, L M Graves
Sep 2, 2003·Molecular Genetics and Metabolism·Sacha FerdinandusseRonald J A Wanders
Jan 7, 2004·The Biochemical Journal·André B P Van KuilenburgAlbert H Van Gennip
Jan 8, 2004·Clinical Chemistry·André B P van KuilenburgWillem Kulik
Mar 24, 2004·The Journal of Biological Chemistry·Tokuyuki ShinoharaShuji Hinuma
Apr 20, 2004·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·André B P van Kuilenburg

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Citations

Mar 18, 2009·Journal of Inherited Metabolic Disease·A Jurecka
May 17, 2011·Nature Genetics·Karsten SuhreMatthias Nauck
Oct 27, 2006·Nucleosides, Nucleotides & Nucleic Acids·A B P van KuilenburgA H van Gennip
Jul 5, 2008·Nucleosides, Nucleotides & Nucleic Acids·A B P van KuilenburgM Duran
Jan 25, 2008·Pharmacogenetics and Genomics·Holly R ThomasRobert B Diasio
Oct 3, 2007·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Stina LundgrenDoreen Dobritzsch
Jan 19, 2006·Epilepsia·Birgit E AssmannErtan Mayatepek
Jul 6, 2010·Statistical Applications in Genetics and Molecular Biology·Zhu Wang, C Y Wang
Apr 1, 2011·Pharmacogenomics·Filipe A MuhaleHoward L McLeod
Dec 18, 2013·Nucleosides, Nucleotides & Nucleic Acids·J MeijerA B P Van Kuilenburg
Sep 23, 2014·Child's Nervous System : ChNS : Official Journal of the International Society for Pediatric Neurosurgery·Jianbo ShuLi Song
Oct 30, 2007·Molecular Genetics and Metabolism·J Yaplito-LeeA B P van Kuilenburg
Oct 15, 2008·Journal of Mass Spectrometry : JMS·T KuharaT Shinka
Oct 13, 2006·Angewandte Chemie·Katherine T Barglow, Benjamin F Cravatt
Apr 25, 2012·Biochimica Et Biophysica Acta·André B P van KuilenburgRaoul C M Hennekam
Apr 7, 2010·Biochimica Et Biophysica Acta·André B P van KuilenburgRaoul C M Hennekam
Aug 16, 2005·Trends in Molecular Medicine·Monika LöfflerH Anne Simmonds
Feb 27, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Hany H Ezzeldin, Robert B Diasio
Jun 1, 2017·PLoS Genetics·Mark A Charlton-PerkinsTiffany A Cook
Oct 27, 2006·Nucleosides, Nucleotides & Nucleic Acids·A B P van KuilenburgA H van Gennip
Jul 28, 2016·Nature Communications·Eugene P RheeRobert E Gerszten
Sep 29, 2007·Nature Methods·Katherine T Barglow, Benjamin F Cravatt
Jan 1, 2013·G3 : Genes - Genomes - Genetics·Aparna PrasadStephen W Scherer
Dec 1, 2009·Journal of Breath Research·Hany H EzzeldinRobert B Diasio
Jan 2, 2018·Translational Research : the Journal of Laboratory and Clinical Medicine·Ayse L MindikogluCristian Coarfa
Oct 16, 2021·Current Biology : CB·Brendan T KeenanAllan I Pack

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