Hyperammonemia Questions & Answers

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3. Meyburg J, Das AM, Hoerster F, Lindner M, Kriegbaum H, Engelmann G, et al. One liver for four children: first clinical series of liver cell transplantation for severe neonatal urea cycle defects. Transplantation. 2009 Mar 15. 87(5):636-41. [QxMD MEDLINE Link].

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6. Lichter-Konecki U, Mangin JM, Gordish-Dressman H, Hoffman EP, Gallo V. Gene expression profiling of astrocytes from hyperammonemic mice reveals altered pathways for water and potassium homeostasis in vivo. Glia. 2008 Mar. 56(4):365-77. [QxMD MEDLINE Link].

7. Panickar KS, Jayakumar AR, Rao KV, Norenberg MD. Ammonia-induced activation of p53 in cultured astrocytes: role in cell swelling and glutamate uptake. Neurochem Int. 2009 Jul-Aug. 55(1-3):98-105. [QxMD MEDLINE Link].

8. Llansola M, Rodrigo R, Monfort P, Montoliu C, Kosenko E, Cauli O, et al. NMDA receptors in hyperammonemia and hepatic encephalopathy. Metab Brain Dis. 2007 Dec. 22(3-4):321-35. [QxMD MEDLINE Link].

9. Monfort P, Cauli O, Montoliu C, Rodrigo R, Llansola M, Piedrafita B, et al. Mechanisms of cognitive alterations in hyperammonemia and hepatic encephalopathy: therapeutical implications. Neurochem Int. 2009 Jul-Aug. 55(1-3):106-12. [QxMD MEDLINE Link].

10. Schliess F, Görg B, Häussinger D. RNA oxidation and zinc in hepatic encephalopathy and hyperammonemia. Metab Brain Dis. 2009 Mar. 24(1):119-34. [QxMD MEDLINE Link].

11. Summar ML, Dobbelaere D, Brusilow S, Lee B. Diagnosis, symptoms, frequency and mortality of 260 patients with urea cycle disorders from a 21-year, multicentre study of acute hyperammonaemic episodes. Acta Paediatr. 2008 Oct. 97(10):1420-5. [QxMD MEDLINE Link]. [Full Text].

12. Ichikawa K, Gakumazawa M, Inaba A, Shiga K, Takeshita S, Mori M, et al. Acute encephalopathy of Bacillus cereus mimicking Reye syndrome. Brain Dev. 2009 Sep 29. [QxMD MEDLINE Link].

13. Lheureux PE, Hantson P. Carnitine in the treatment of valproic acid-induced toxicity. Clin Toxicol (Phila). 2009 Feb. 47(2):101-11. [QxMD MEDLINE Link].

14. DeWolfe JL, Knowlton RC, Beasley MT, Cofield S, Faught E, Limdi NA. Hyperammonemia following intravenous valproate loading. Epilepsy Res. 2009 Jul. 85(1):65-71. [QxMD MEDLINE Link].

15. Cheung E, Wong V, Fung CW. Topiramate-valproate-induced hyperammonemic encephalopathy syndrome: case report. J Child Neurol. 2005 Feb. 20(2):157-60. [QxMD MEDLINE Link].

16. Deutsch SI, Burket JA, Rosse RB. Valproate-induced hyperammonemic encephalopathy and normal liver functions: possible synergism with topiramate. Clin Neuropharmacol. 2009 Nov-Dec. 32(6):350-2. [QxMD MEDLINE Link].

17. Tantikittichaikul S, Johnson J, Laengvejkal P, DeToledo J. Topiramate-induced hyperammonemic encephalopathy in a patient with mental retardation: A case report and review of the literature. Epilepsy Behav Case Rep. 2015. 4:84-5. [QxMD MEDLINE Link]. [Full Text].

18. Adler LW, Regenold WT. Valproate-Related Hyperammonemia in Older Adult Psychiatric Inpatients. Prim Care Companion CNS Disord. 2015. 17 (2):[QxMD MEDLINE Link].

19. Adams EN, Marks A, Lizer MH. Carbamazepine-induced hyperammonemia. Am J Health Syst Pharm. 2009 Aug 15. 66(16):1468-70. [QxMD MEDLINE Link].

20. Yamamoto Y, Takahashi Y, Imai K, Mishima N, Yazawa R, Inoue K, et al. Risk factors for hyperammonemia in pediatric patients with epilepsy. Epilepsia. 2013 Feb 14. [QxMD MEDLINE Link].

21. Adatia S, Poladia B, Joshi SR, Panikar V, Chauhan V, Hastak SM. Hyperammonemic coma presenting as Hashimoto's encephalopathy. J Assoc Physicians India. 2008 Dec. 56:989-91. [QxMD MEDLINE Link].

22. Rimar D, Kruzel-Davila E, Dori G, Baron E, Bitterman H. Hyperammonemic coma--barking up the wrong tree. J Gen Intern Med. 2007 Apr. 22(4):549-52. [QxMD MEDLINE Link].

23. Lora-Tamayo J, Palom X, Sarrá J, Gasch O, Isern V, Fernández de Sevilla A, et al. Multiple myeloma and hyperammonemic encephalopathy: review of 27 cases. Clin Lymphoma Myeloma. 2008 Dec. 8(6):363-9. [QxMD MEDLINE Link].

24. J.M. U-King-Im, E. Yu, E. Bartlett, R. Soobrah and W. Kucharczyk. Acute Hyperammonemic Encephalopathy in Adults: Imaging Findings. American Journal of Neuroradiology. 2011 FEB. [Full Text].

25. Rovira A, Alonso J, Córdoba J. MR imaging findings in hepatic encephalopathy. AJNR Am J Neuroradiol. 2008 Oct. 29(9):1612-21. [QxMD MEDLINE Link].

26. Zwingmann C. Nuclear magnetic resonance studies of energy metabolism and glutamine shunt in hepatic encephalopathy and hyperammonemia. J Neurosci Res. 2007 Nov 15. 85(15):3429-42. [QxMD MEDLINE Link].

27. Al-Hassnan ZN, Rashed MS, Al-Dirbashi OY, Patay Z, Rahbeeni Z, Abu-Amero KK. Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome with stroke-like imaging presentation: clinical, biochemical and molecular analysis. J Neurol Sci. 2008 Jan 15. 264(1-2):187-94. [QxMD MEDLINE Link].

28. Oldham MS, VanMeter JW, Shattuck KF, Cederbaum SD, Gropman AL. Diffusion tensor imaging in arginase deficiency reveals damage to corticospinal tracts. Pediatr Neurol. 2010 Jan. 42(1):49-52. [QxMD MEDLINE Link].

29. Arbeiter AK, Kranz B, Wingen AM, Bonzel KE, Dohna-Schwake C, Hanssler L, et al. Continuous venovenous haemodialysis (CVVHD) and continuous peritoneal dialysis (CPD) in the acute management of 21 children with inborn errors of metabolism. Nephrol Dial Transplant. 2009 Nov 23. [QxMD MEDLINE Link].

30. Cardenas JF, Bodensteiner JB. Osmotic Demyelination Syndrome as a Consequence of Treating Hyperammonemia in a Patient With Ornithine Transcarbamylase Deficiency. J Child Neurol. 2009 Feb 18. [QxMD MEDLINE Link].

31. Thompson CA. Carglumic acid approved to treat genetic hyperammonemia. Am J Health Syst Pharm. 2010 May 1. 67(9):690. [QxMD MEDLINE Link].

32. Albrecht J. Roles of neuroactive amino acids in ammonia neurotoxicity. J Neurosci Res. 1998 Jan 15. 51(2):133-8. [QxMD MEDLINE Link].

33. Albrecht J, Jones EA. Hepatic encephalopathy: molecular mechanisms underlying the clinical syndrome. J Neurol Sci. 1999 Nov 30. 170(2):138-46. [QxMD MEDLINE Link].

34. Batshaw ML. Hyperammonemia. Curr Probl Pediatr. 1984 Nov. 14(11):1-69. [QxMD MEDLINE Link].

35. Batshaw ML. Inborn errors of urea synthesis. Ann Neurol. 1994 Feb. 35(2):133-41. [QxMD MEDLINE Link].

36. Becker L, Prior T, Yates A. Metabolic diseases. Textbook of Neuropathology, Baltimore: Williams & Wilkins. 1997. 487.

37. Berlot G, Battaglia K, Ukmar M. [Hyperammoniemia and central pontine myelinolysis in a patient with Sjögren syndrome and chronic valproate use]. Recenti Prog Med. 2008 Oct. 99(10):502-4. [QxMD MEDLINE Link].

38. Bhoyar A, Short A. Congenital hypopituitarism associated with hyperammonemia. Indian J Pediatr. 2009 Mar. 76(3):327-8. [QxMD MEDLINE Link].

39. Bosoi CR, Rose CF. Identifying the direct effects of ammonia on the brain. Metab Brain Dis. 2009 Mar. 24(1):95-102. [QxMD MEDLINE Link].

40. Breningstall GN. Neurologic syndromes in hyperammonemic disorders. Pediatr Neurol. 1986 Sep-Oct. 2(5):253-62. [QxMD MEDLINE Link].

41. Brusilow SW, Horwich AL. Urea cycle disorders. The Metabolic and Molecular Bases of Inherited Disease, New York: McGraw-Hill. 1995. 1:1187-1232.

42. Chung MY, Chen CC, Huang LT, et al. Transient hyperammonemia in a neonate. Acta Paediatr Taiwan. 2005 Mar-Apr. 46(2):94-6. [QxMD MEDLINE Link].

43. Cohn RM, Roth KS. Hyperammonemia, bane of the brain. Clin Pediatr (Phila). 2004 Oct. 43(8):683-9. [QxMD MEDLINE Link].

44. Collins FS, Summer GK, Schwartz RP, Parke JC Jr. Neonatal argininosuccinic aciduria-survival after early diagnosis and dietary management. J Pediatr. 1980 Mar. 96(3 Pt 1):429-31. [QxMD MEDLINE Link].

45. del Rosario M, Werlin SL, Lauer SJ. Hyperammonemic encephalopathy after chemotherapy. Survival after treatment with sodium benzoate and sodium phenylacetate. J Clin Gastroenterol. 1997 Dec. 25(4):682-4. [QxMD MEDLINE Link].

46. Deodato F, Boenzi S, Rizzo C, et al. Inborn errors of metabolism: an update on epidemiology and on neonatal-onset hyperammonemia. Acta Paediatr Suppl. 2004 May. 93(445):18-21. [QxMD MEDLINE Link].

47. Diaz GA, Krivitzky LS, Mokhtarani M, Rhead W, Bartley J, Feigenbaum A, et al. Ammonia control and neurocognitive outcome among urea cycle disorder patients treated with glycerol phenylbutyrate. Hepatology. 2012 Sep 7. [QxMD MEDLINE Link]. [Full Text].

48. Feillet F, Leonard JV. Alternative pathway therapy for urea cycle disorders. J Inherit Metab Dis. 1998. 21 Suppl 1:101-11. [QxMD MEDLINE Link].

49. Felipo V, Kosenko E, Minana MD, et al. Molecular mechanism of acute ammonia toxicity and of its prevention by L-carnitine. Adv Exp Med Biol. 1994. 368:65-77. [QxMD MEDLINE Link].

50. Hamed SA, Abdella MM. The risk of asymptomatic hyperammonemia in children with idiopathic epilepsy treated with valproate: Relationship to blood carnitine status. Epilepsy Res. 2009 May 13. [QxMD MEDLINE Link].

51. Hauser ER, Finkelstein JE, Valle D, Brusilow SW. Allopurinol-induced orotidinuria. A test for mutations at the ornithine carbamoyltransferase locus in women. N Engl J Med. 1990 Jun 7. 322(23):1641-5. [QxMD MEDLINE Link].

52. Jalan R, Lee WM. Treatment of Hyperammonemia in Liver Failure: A Tale of Two Enzymes. Gastroenterology. 2009 Apr 28. [QxMD MEDLINE Link].

53. Kuntze JR, Weinberg AC, Ahlering TE. Hyperammonemic coma due to Proteus infection. J Urol. 1985 Nov. 134(5):972-3. [QxMD MEDLINE Link].

54. Logan W. Neonatal hyperammonemic encephalopathy. Topics in Neonatal Neurology, Orlando: Grune & Stratton. 1984. 137-157.

55. Maestri NE, McGowan KD, Brusilow SW. Plasma glutamine concentration: a guide in the management of urea cycle disorders. J Pediatr. 1992 Aug. 121(2):259-61. [QxMD MEDLINE Link].

56. McCall M, Bourgeois JA. Valproic acid-induced hyperammonemia: a case report. J Clin Psychopharmacol. 2004 Oct. 24(5):521-6. [QxMD MEDLINE Link].

57. McGuire PJ, Lee HS, Summar ML. Infectious Precipitants of Acute Hyperammonemia Are Associated with Indicators of Increased Morbidity in Patients with Urea Cycle Disorders. J Pediatr. 2013 Sep 28. [QxMD MEDLINE Link].

58. Msall M, Batshaw ML, Suss R, et al. Neurologic outcome in children with inborn errors of urea synthesis. Outcome of urea-cycle enzymopathies. N Engl J Med. 1984 Jun 7. 310(23):1500-5. [QxMD MEDLINE Link].

59. Prasad AN, Breen JC, Ampola MG, Rosman NP. Argininemia: a treatable genetic cause of progressive spastic diplegia simulating cerebral palsy: case reports and literature review. J Child Neurol. 1997 Aug. 12(5):301-9. [QxMD MEDLINE Link].

60. Rajpoot DK, Gargus JJ. Acute hemodialysis for hyperammonemia in small neonates. Pediatr Nephrol. 2004 Apr. 19(4):390-5. [QxMD MEDLINE Link].

61. Ratnaike RN, Schapel GJ, Purdie G, et al. Hyperammonaemia and hepatotoxicity during chronic valproate therapy: enhancement by combination with other antiepileptic drugs. Br J Clin Pharmacol. 1986 Jul. 22(1):100-3. [QxMD MEDLINE Link].

62. Schaefer F, Straube E, Oh J, et al. Dialysis in neonates with inborn errors of metabolism. Nephrol Dial Transplant. 1999 Apr. 14(4):910-8. [QxMD MEDLINE Link].

63. Schutze GE, Edwards MS, Adham BI, Belmont JW. Hyperammonemia and neonatal herpes simplex pneumonitis. Pediatr Infect Dis J. 1990 Oct. 9(10):749-50. [QxMD MEDLINE Link].

64. Smith W, Diaz GA, Lichter-Konecki U, Berry SA, Harding CO, McCandless SE, et al. Ammonia Control in Children Ages 2 Months through 5 Years with Urea Cycle Disorders: Comparison of Sodium Phenylbutyrate and Glycerol Phenylbutyrate. J Pediatr. 2013 Jan 13. [QxMD MEDLINE Link].

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66. Summar ML, Barr F, Dawling S, et al. Unmasked adult-onset urea cycle disorders in the critical care setting. Crit Care Clin. 2005 Oct. 21(4 Suppl):S1-8. [QxMD MEDLINE Link].

67. Uchino T, Endo F, Matsuda I. Neurodevelopmental outcome of long-term therapy of urea cycle disorders in Japan. J Inherit Metab Dis. 1998. 21 Suppl 1:151-9. [QxMD MEDLINE Link].

68. Weng TI, Shih FF, Chen WJ. Unusual causes of hyperammonemia in the ED. Am J Emerg Med. 2004 Mar. 22(2):105-7. [QxMD MEDLINE Link].

69. Whitington PF, Alonso EM, Boyle JT, et al. Liver transplantation for the treatment of urea cycle disorders. J Inherit Metab Dis. 1998. 21 Suppl 1:112-8. [QxMD MEDLINE Link].

70. Williams CA, Tiefenbach S, McReynolds JW. Valproic acid-induced hyperammonemia in mentally retarded adults. Neurology. 1984 Apr. 34(4):550-3. [QxMD MEDLINE Link].

71. Ourlad Alzeus G Tantengco, Federico Cristobal C De Jesus 2nd, Eloina Faye S Gampoy, Eric David B Ornos, Manuel S Vidal Jr, Cybele Lara R Abad. Hyperammonemia syndrome associated with Ureaplasma spp. Infections in immunocompromised patients and transplant recipients: A systematic review and meta-analysis. The Journal of Clinical and Translational Research. 2021 APR 26. 1-10. [QxMD MEDLINE Link]. [Full Text].

Jasvinder Chawla, MD, MBA Chief of Neurology, Hines Veterans Affairs Hospital; Professor of Neurology, Loyola University Medical Center

Jasvinder Chawla, MD, MBA is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American Clinical Neurophysiology Society, American Medical Association

Disclosure: Nothing to disclose.

Gurjot Singh MD Candidate, Aureus University School of Medicine

Gurjot Singh is a member of the following medical societies: American Academy of Family Physicians

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Nicholas Lorenzo, MD, CPE, MHCM, FAAPL Co-Founder and Former Chief Publishing Officer, eMedicine and eMedicine Health, Founding Editor-in-Chief, eMedicine Neurology; Founder and Former Chairman and CEO, Pearlsreview; Founder and CEO/CMO, PHLT Consultants; Former Chief Medical Officer, MeMD Inc

Nicholas Lorenzo, MD, CPE, MHCM, FAAPL is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, American Association for Physician Leadership

Disclosure: Nothing to disclose.

Stephen L Nelson, Jr, MD, PhD, FAACPDM, FAAN, FAAP, FANA Professor of Pediatrics, Neurology, Neurosurgery, and Psychiatry, Medical Director, Tulane Center for Autism and Related Disorders, Tulane University School of Medicine; Pediatric Neurologist and Epileptologist, Ochsner Hospital for Children; Professor of Neurology, Louisiana State University School of Medicine

Stephen L Nelson, Jr, MD, PhD, FAACPDM, FAAN, FAAP, FANA is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Neurology, American Academy of Pediatrics, American Epilepsy Society, American Medical Association, American Neurological Association, Association of Military Surgeons of the US, Child Neurology Society, Southern Pediatric Neurology Society

Disclosure: Nothing to disclose.

J Stephen Huff, MD, FACEP Professor of Emergency Medicine and Neurology, Department of Emergency Medicine, University of Virginia School of Medicine

J Stephen Huff, MD, FACEP is a member of the following medical societies: American Academy of Neurology, American College of Emergency Physicians, Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Elena Crisan, MD Neurology Staff, Department of Neurology, Edwards Hines Veterans Affairs Hospital; Assistant Professor of Neurology, Loyola University Medical Center

Disclosure: Nothing to disclose.

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author Kazi Imran Majeed, MD to the development and writing of this article.

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