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Disorders of the Urea Cycle and Related Enzymes

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Inborn Metabolic Diseases

Abstract

Six inherited enzyme defects of the urea cycle are known. These are the deficiencies of carbamoylphosphate synthetase (CPS), ornithine transcarbamoylase (OTC), argininosuccinate synthetase (ASS), argininosuccinate lyase (ASL), arginase and N-acetylglutamate synthetase (NAGS).

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References

  1. Spronsen FJ, Reijngoud DJ, Verhoeven NM et al. (2006) High cerebral guanidinoacetate and variable creatine concentrations in argininosuccinate synthase and lyase deficiency: implications for treatment? Mol Genet Metab 89:274–276

    Article  PubMed  Google Scholar 

  2. Nagasaka H, Tsukahara H, Yorifuji T et al. (2009) Evaluation of endogenous nitric oxide synthesis in congenital urea cycle enzyme defects. Metbolism 58:278–282

    Article  CAS  Google Scholar 

  3. Saheki T, Inoue K, Tushima A, Mutoh K, Kobayashi K (2010) Citrin deficiency and current treatment concepts. Mol Genet Metab 100:S59-S64

    Article  PubMed  CAS  Google Scholar 

  4. Mercimek-Mahmutoglu S, Moeslinger D, Häberle J et al. (2010) Long-term outcome of patients with argininosuccinatelyase deficiency diagnosed by newborn screening in Austria. Mol Genet Metab 100:24–28

    Article  PubMed  CAS  Google Scholar 

  5. Nakagawa T, Lomb DJ, Haigis MC, Guarente L (2009) SIRT5 Deacetylatescarbamoyl phosphate synthetase 1 and regulates the urea cycle. Cell 137:560–570

    Article  PubMed  CAS  Google Scholar 

  6. Hallows WC, Smith BC, Lee S, Denu JM (2009) Ure(k)a! Sirtuins regulate mitochondria. Cell 137:404–406

    Article  PubMed  CAS  Google Scholar 

  7. Pappas PA, Saudubray JM, Tzakis AG et al. (2002) Serum citrulline as a marker of acute cellular rejection for intestinal transplantation. Transplant Proc 34:915–917

    Article  PubMed  CAS  Google Scholar 

  8. Crenn P, Coudray-Lucas C, Thuillier F, Cynober L, Messing B (2000) Postabsorptive plasma citrulline concentration is a marker of absorptive enterocyte mass and intestinal failure in humans. Gastroenterology 119:1496–1505

    Article  PubMed  CAS  Google Scholar 

  9. Ceballos I, Chauveau P, Guerin V et al. (1990) Early alteration of plasma amino acids in chronic renal failure. Clin Chim Acta 188:101–108

    Article  PubMed  CAS  Google Scholar 

  10. Rabier D, NarcyC,Bardet J et al. (1991) Arginine remains an essential amino acid after liver transplantation in urea cycle enzyme deficiencies. J Inherit Metab Dis 327:24–27

    Google Scholar 

  11. Braissant O (2010) Current concepts in the pathogenesis of urea cycle disorders. Mol Genet Metab 100:S3-S12

    Article  PubMed  CAS  Google Scholar 

  12. Gropman A (2010) Brain imaging in urea cycle disorders. Mol Genet Metab 100:S20-S30

    Article  PubMed  CAS  Google Scholar 

  13. Luksan O, Jirsa M, Eberova J et al. (2010) Disruption of OTC promoter-enhancer interaction in a patient with symptoms of ornithine carbamoyltransferase deficiency. Hum Mutat 4:E1294-E1303

    Article  Google Scholar 

  14. Grünewald S, Fairbanks L, Genet S et al. (2004) How reliable is the allopurinol load in detecting carriers for ornithine transcarbamoylase deficiency? J Inherit Metab Dis 27:179–186

    Article  PubMed  Google Scholar 

  15. Rowe PC, Newman SL, Brusilow SW (1986) Natural history of symptomatic partial ornithine transcarbamoylase deficiency. N Engl J Med 314:541–547

    Article  PubMed  CAS  Google Scholar 

  16. Ray PF, Gigarel N, Bonnefont JP et al. (2000) First specific preimplantation genetic diagnosis for ornithine transcarbamoylase deficiency. Prenat Diagn 20:1048–1054

    Article  PubMed  CAS  Google Scholar 

  17. Arbeiter AK, Kranz B, Wingen AM et al. (2010) Continuous venovenous haemodialysis (CVVHD) and continuous peritoneal dialysis (CPD) in the acute management of 21 children with inborn errors of metabolism. Nephrol Dial Transplant 25:1257–1265

    Article  PubMed  Google Scholar 

  18. McBryde KD, Kudelka TL, Kershaw DB et al. (2004) Clearance of amino acids by hemodialysis in argininosuccinatesynthetase deficiency. J Pediatr 144:536–540

    Article  PubMed  CAS  Google Scholar 

  19. Bunchman TE, Barletta GM, Winters JW et al. (2007) Phenylacetate and benzoate clearance in a hyperammonemic infant on sequential hemodialysis and hemofiltration. Pediatr Nephrol 22:1062–1065

    Article  PubMed  Google Scholar 

  20. Lai YC, Huang HP, Tsai IJ, Tsau YK (2007) High-volume continuous venovenous hemofiltration as an effective therapy for acute management of inborn errors of metabolism in young children. Blood Purif 25;303–308

    Article  PubMed  Google Scholar 

  21. Westrope C, Morris K, Burford D, Morrison G (2010) Continuous hemofiltration in the control of neonatal hyperammonemia: a 10-year experience. Pediatr Nephrol 25:1725–30

    Article  PubMed  Google Scholar 

  22. Brusilow SW, Danney M, Waber LJ et al. (1984) Treatment of episodic hyperammonemia in children with inborn errors of urea synthesis. N Engl J Med 310:1630–1634

    Article  PubMed  CAS  Google Scholar 

  23. Enns GM (2010) Nitrogen sparing therapy revisited. Mol Genet Metab 100:S65-S71

    Article  PubMed  CAS  Google Scholar 

  24. Scaglia F (2010) New insights in nutritional management and amino acid supplementation in urea cycle disorders. Mol Genet Metab 100:S72-S76

    Article  PubMed  CAS  Google Scholar 

  25. Morris AAM, Richmond SWJ, Oddie SJ et al. (1998) N-Acetylglutamatesynthetase deficiency: favourable experience with carbamoylglutamate. J Inherit Metab Dis 21:867–868

    Article  PubMed  CAS  Google Scholar 

  26. Gessler P, Buchal P, Schwenk HU, Wermuth B (2010) Favourable long-term outcome after immediate treatment of neonatal hyperammonemia due to N-acetylglutamate synthase deficiency. Eur J Pediatr 169:197–199

    Article  PubMed  Google Scholar 

  27. Lee B, Singh RH, Rhead WJ et al. (2005) Considerations in the difficult-to-manage urea cycle disorder patient. Crit Care Clin 21:S19-S25

    Article  PubMed  Google Scholar 

  28. Leonard JV (2001) The nutritional management of urea cycle disorders. J Pediatr 138:S40-S45

    Article  PubMed  CAS  Google Scholar 

  29. Singh RH, Rhead WJ, Smith W et al. (2005) Nutritional management of urea cycle disorders. Crit Care Clin 21:S27-S35

    Article  PubMed  Google Scholar 

  30. Avitsland TL, Kristensen C, Emblem R et al. (2006) Percutaneous endoscopic gastrostomy in children: a safe technique with major symptom relief and high parental satisfaction. J Pediatr Gastroenterol Nutr 43:624–628

    Article  PubMed  Google Scholar 

  31. Kuchler G, Rabier D, Poggi-Travert F et al. (1996) Therapeutic use of carbamoylglutamate in the case of carbamoyl-phosphate synthetase deficiency 19:220–222

    Google Scholar 

  32. Maestri NE, McGowan KD, Brusilow SW (1992) Plasma glutamine concentration: a guide to the management of urea cycle disorders. J Pediatr 121:259–261

    Article  PubMed  CAS  Google Scholar 

  33. Schmidt J, Kroeber S, Irouschek A et al. (2006) Anesthetic management of patients with ornithine transcarbamoylase deficiency. Paediatr Anaesth 16:333–337

    Article  PubMed  Google Scholar 

  34. Oechsner M, Steen C, Sturenburg HJ et al. (1998) Hyperammonaemic encephalopathy after initiation of valproate therapy in unrecognised ornithine transcarbamoylase deficiency. J Neurol Neurosurg Psychiatry 64:680–682

    Article  PubMed  CAS  Google Scholar 

  35. Cederbaum JA, LeMons C, Rosen M et al. (2001) Psychosocial issues and coping strategies in families affected by urea cycle disorders. J Pediatr 138 [Suppl 1]:S72-S80

    PubMed  CAS  Google Scholar 

  36. Arnon R, Kerkar N, Davis MK et al. (2010) Liver transplantation in children with metabolic diseases: the studies of pediatric liver transplantation experience. Pediatr Transplant 14:796–805

    Article  PubMed  Google Scholar 

  37. Chang IF, Barshes NR, Bristow LJ et al. (2005) Orthotopic liver transplantation (OLT) for urea cycle disorders (UCDs): the US experience. Am J Transplant 5:337

    Google Scholar 

  38. Leonard JV, McKiernan PJ (2004) The role of liver transplantation in urea cycle disorders. Mol Genet Metab 81 [Suppl 1]:S74-S78

    Article  PubMed  CAS  Google Scholar 

  39. Meyburg J, Hoffman GF (2010) Liver, liver cell and stem cell transplantation for the treatment of urea cycle defects. Mol Genet Metab 100:S77-S83

    Article  PubMed  CAS  Google Scholar 

  40. Bachmann (2003) Long-term outcome of patients with urea cycle disorders and the question of neonatal screening. Eur J Pediatr 162:S29-S33

    Article  PubMed  CAS  Google Scholar 

  41. Nassogne MC, Héron B, Touati G, Rabier D, Saudubray JM (2005) Urea cycle defects: management and outcome. J Inherit Metab Dis 28:407–414

    Article  PubMed  CAS  Google Scholar 

  42. Summar ML, Dobbelaere D, Brusilow S, Lee B (2008) Diagnosis, symptoms, frequency and mortality of 260 patients with urea cycle disorders from a 21-year, multicentre study of acute hyperammonaemic episodes. Acta Paediatr 97: 1420–1425

    Article  PubMed  Google Scholar 

  43. Enns GM, Berry GT, Rhead WJ, Brusilow SW, Hamosh A (2007) Survival after treatment with phenylacetate and benzoate for urea-cycle disorders. N Engl J Med 356:2282–2292

    Article  PubMed  CAS  Google Scholar 

  44. Mendez-Figueroa HM, Lamance K, Sutton R, Aagaard-Tillery K, Veyver v d I (2010) Management of ornithine transcarbamoylase deficiency in pregnancy. Am J Perinatol 27:775–784

    Article  PubMed  Google Scholar 

  45. Kotani Y, Shiota M, Umemoto M, Tsuritani M, Hoshiai H (2010) Carbamoyl phosphate synthetase deficiency and postpartum hyperammonemia. Am J Obstet Gynecol 203:e10-e11

    Article  PubMed  Google Scholar 

  46. Tihtonen, Uotila J, Lähde J, Salo M, Keskinen P (2010) Risk of hyperammonemic coma in the puerperium: two cases of women with diagnosed and undiagnosed deficiency of urea cycle enzymes. Acta Obstet Gynecol Scand 89:404–406

    Article  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Pediatrics, University of Amsterdam Academic Medical Centre, Meibergdreef 9, 1105, AZ, Amsterdam, The Netherlands

    Frits A. Wijburg

  2. Paediatric Neurology Unit, Saint-Luc University Hospital, University of Louvain Medical School, Avenue Hippocrate 10/1067, 1200, Brussels, Belgium

    Marie-Cécile Nassogne

Authors
  1. Frits A. Wijburg
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  2. Marie-Cécile Nassogne
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Editor information

Editors and Affiliations

  1. Department of Neurology Neurometabolic Unit, Hôpital Pitié Salpêtrière 47–83 Boulevard de l’Hôpital, Paris Cedex 13, 75651, Paris, France

    Jean-Marie Saudubray

  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. Biochemical Genetics Unit Manchester Academic Health Science Centre, Central Manchester University Hospitals St Mary’s Hospital, Oxford Road, M13 9WL, Manchester, UK

    John H. Walter

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© 2012 Springer-Verlag Berlin Heidelberg

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Wijburg, F., Nassogne, MC. (2012). Disorders of the Urea Cycle and Related Enzymes. In: Saudubray, JM., van den Berghe, G., Walter, J.H. (eds) Inborn Metabolic Diseases. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-15720-2_20

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  • DOI: https://doi.org/10.1007/978-3-642-15720-2_20

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-15719-6

  • Online ISBN: 978-3-642-15720-2

  • eBook Packages: MedicineMedicine (R0)

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