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Hypothesis: proposals for the management of a neonate at risk of hyperammonaemia due to a urea cycle disorder

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Abstract

It is difficult to prevent hyperammonaemia in patients with urea cycle disorders that present in the newborn period. This is true, even if treatment is started prospectively because of an affected relative. We propose several additional measures that could be used in conjunction with conventional therapy to improve the metabolic control. Catabolism could be reduced by delivering the babies by elective caesarean section, by starting intravenous glucose immediately after delivery and, possibly, by using β-blockers or octreotide and insulin. The effectiveness of sodium benzoate and sodium phenylbutyrate might be increased by giving phenobarbital to the mother before delivery and subsequently to the baby to induce the enzymes for conjugation. We would expect the proposed measures to reduce the risk of hyperammonaemia and to improve the outcome for these patients. They have not, however, previously been used in this context, so families would need to be counselled carefully and controlled studies should be undertaken.

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Fig. 1

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Abbreviations

ACTH:

Adrenocorticotrophic hormone

CPS:

Carbamyl phosphate synthetase

ECMO:

Extracorporeal membrane oxygenation

NAG:

N-aceylglutamate

OTC:

Ornithine transcarbamylase

References

  1. Ali A, Qureshi IA (1992) Benzoyl-CoA ligase activity in the liver and kidney cortex of weanling guinea pigs treated with various inducers: relationship with hippurate synthesis and carnitine levels. Dev Pharmacol Ther 18:55–64

    PubMed  CAS  Google Scholar 

  2. Arnold J, Campbell IT, Hipkin LJ et al (1995) Manipulation of substrate utilization with somatostatin in patients with secondary multiple organ dysfunction syndrome. Crit Care Med 23:71–77

    Article  PubMed  CAS  Google Scholar 

  3. Bachmann C (2003) Long-term outcome of patients with urea cycle disorders and the question of neonatal screening. Eur J Pediatr 162(Suppl 1):S29–S33

    Article  PubMed  CAS  Google Scholar 

  4. Falconer AD, Poyser LM (1986) Fetal sympatho-adrenal mediated metabolic responses to parturition. Br J Obstet Gynaecol 93:747–753

    PubMed  CAS  Google Scholar 

  5. Gebhardt B, Dittrich S, Parbel S, Vlaho S, Matsika O, Bohles H (2005) N-carbamylglutamate protects patients with decompensated propionic aciduria from hyperammonaemia. J Inherit Metab Dis 28:241–244

    Article  PubMed  CAS  Google Scholar 

  6. Gropman AL, Batshaw ML (2004) Cognitive outcome in urea cycle disorders. Mol Genet Metab 81(Suppl 1):S58–S62

    Article  PubMed  CAS  Google Scholar 

  7. Haller M, Henzler-Le Boulanger A, Sass JO, Brandis M, Zimmerhackl LB (2005) Successful extracorporeal treatment of a male with hyperammonaemic coma. Nephrol Dial Transplant 20:453–455

    Article  PubMed  Google Scholar 

  8. Herndon DN, Hart DW, Wolf SE, Chinkes DL, Wolfe RR (2001) Reversal of catabolism by beta-blockade after severe burns. N Engl J Med 345:1223–1229

    Article  PubMed  CAS  Google Scholar 

  9. Hiroma T, Nakamura T, Tamura M, Kaneko T, Komiyama A (2002) Continuous venovenous hemodiafiltration in neonatal onset hyperammonemia. Am J Perinatol 19:221–224

    Article  PubMed  Google Scholar 

  10. Hussain K (2005) Congenital hyperinsulinism. Semin Fetal Neonatal Med 10:369–376

    Article  PubMed  CAS  Google Scholar 

  11. Kern RM, Yang Z, Kim PS, Grody WW, Iyer RK, Cederbaum SD (2007) Arginase induction by sodium phenylbutyrate in mouse tissues and human cell lines. Mol Genet Metab 90:37–41

    Article  PubMed  CAS  Google Scholar 

  12. Ktorza A, Bihoreau MT, Nurjhan N, Picon L, Girard J (1985) Insulin and glucagon during the perinatal period: secretion and metabolic effects on the liver. Biol Neonate 48:204–220

    Article  PubMed  CAS  Google Scholar 

  13. Kuchler G, Rabier D, Poggi-Travert F et al (1996) Therapeutic use of carbamylglutamate in the case of carbamoyl-phosphate synthetase deficiency. J Inherit Metab Dis 19:220–222

    Article  PubMed  CAS  Google Scholar 

  14. Maestri NE, Clissold D, Brusilow SW (1999) Neonatal onset ornithine transcarbamylase deficiency: a retrospective analysis. J Pediatr 134:268–272

    Article  PubMed  CAS  Google Scholar 

  15. Maestri NE, Hauser ER, Bartholomew D, Brusilow SW (1991) Prospective treatment of urea cycle disorders. J Pediatr 119:923–928

    Article  PubMed  CAS  Google Scholar 

  16. Msall M, Batshaw ML, Suss R, Brusilow SW, Mellits ED (1984) Neurologic outcome in children with inborn errors of urea synthesis. Outcome of urea-cycle enzymopathies. N Engl J Med 310:1500–1505

    Article  PubMed  CAS  Google Scholar 

  17. Nicolaides P, Liebsch D, Dale N, Leonard J, Surtees R (2002) Neurological outcome of patients with ornithine carbamoyltransferase deficiency. Arch Dis Child 86:54–56

    Article  PubMed  CAS  Google Scholar 

  18. Picca S, Dionisi-Vici C, Abeni D et al (2001) Extracorporeal dialysis in neonatal hyperammonemia: modalities and prognostic indicators. Pediatr Nephrol 16:862–867

    Article  PubMed  CAS  Google Scholar 

  19. Qureshi IA, Lebel S, Letarte J (1989) Development and inducibility of the hepatic and renal hippurate-synthesizing system in sparse-fur (spf) mutant mice with ornithine transcarbamylase deficiency. Biochem Int 19:657–666

    PubMed  CAS  Google Scholar 

  20. Ramboer C, Thompson RP, Williams R (1969) Controlled trials of phenobarbitone therapy of neonatal jaundice. Lancet 1:966–968

    Article  PubMed  CAS  Google Scholar 

  21. Schubiger G, Bachmann C, Barben P, Colombo JP, Tonz O, Schupbach D (1991) N-acetylglutamate synthetase deficiency: diagnosis, management and follow-up of a rare disorder of ammonia detoxication. Eur J Pediatr 150:353–356

    Article  PubMed  CAS  Google Scholar 

  22. Sperling MA, DeLamater PV, Phelps D, Fiser RH, Oh W, Fisher DA (1974) Spontaneous and amino acid-stimulated glucagon secretion in the immediate postnatal period. Relation to glucose and insulin. J Clin Invest 53:1159–1166

    Article  PubMed  CAS  Google Scholar 

  23. Summar M (2001) Current strategies for the management of neonatal urea cycle disorders. J Pediatr 138:S30–S39

    Article  PubMed  CAS  Google Scholar 

  24. Uchino T, Endo F, Matsuda I (1998) Neurodevelopmental outcome of long-term therapy of urea cycle disorders in Japan. J Inherit Metab Dis 21(Suppl 1):151–159

    Article  PubMed  Google Scholar 

  25. Vogels BA, Maas MA, Daalhuisen J, Quack G, Chamuleau RA (1997) Memantine, a noncompetitive NMDA receptor antagonist improves hyperammonemia-induced encephalopathy and acute hepatic encephalopathy in rats. Hepatology 25:820–827

    Article  PubMed  CAS  Google Scholar 

  26. Whitelaw A, Bridges S, Leaf A, Evans D (2001) Emergency treatment of neonatal hyperammonaemic coma with mild systemic hypothermia. Lancet 358:36–38

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

We would like to thank Dr Claude Bachmann for valuable discussion and particularly for permission to publish Fig. 1. We are also grateful to Dr Khalid Hussain for his help with this work.

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Authors and Affiliations

  1. Clinical and Molecular Genetics Unit, Institute of Child Health, University College London, London, UK

    James Vivian Leonard

  2. Neonatal Unit, Royal Victoria Infirmary, Newcastle-upon-Tyne, UK

    Martin Peter Ward Platt

  3. The Willink Biochemical Genetics Unit, Royal Manchester Children’s Hospital, Pendlebury, Manchester, M27 4HA, UK

    Andrew Alan Myles Morris

Authors
  1. James Vivian Leonard
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  2. Martin Peter Ward Platt
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  3. Andrew Alan Myles Morris
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Correspondence to Andrew Alan Myles Morris.

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Leonard, J.V., Ward Platt, M.P. & Morris, A.A.M. Hypothesis: proposals for the management of a neonate at risk of hyperammonaemia due to a urea cycle disorder. Eur J Pediatr 167, 305–309 (2008). https://doi.org/10.1007/s00431-007-0486-z

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