Skip to main content

Advertisement

SpringerLink
Log in

Hyperammonemic Encephalopathy Caused by Carnitine Deficiency

  • Case Reports/Clinical Vignettes
  • Published:
Journal of General Internal Medicine Aims and scope Submit manuscript

Abstract

Carnitine is an essential co-factor in fatty acid metabolism. Carnitine deficiency can impair fatty acid oxidation, rarely leading to hyperammonemia and encephalopathy. We present the case of a 35-year-old woman who developed acute mental status changes, asterixis, and diffuse muscle weakness. Her ammonia level was elevated at 276 μg/dL. Traditional ammonia-reducing therapies were initiated, but proved ineffective. Pharmacologic, microbial, and autoimmune causes for the hyperammonemia were excluded. The patient was severely malnourished and her carnitine level was found to be extremely low. After carnitine supplementation, ammonia levels normalized and the patient’s mental status returned to baseline. In the setting of refractory hyperammonemia, this case illustrates how careful investigation may reveal a treatable condition.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Koizumi A, Nozaki J, Ohura T, et al. Genetic epidemiology of the carnitine transporter OCTN2 gene in a Japanese population and phenotypic characterization in Japanese pedigrees with primary systemic carnitine deficiency. Hum Mol Genet. 1999;8:2247–54.

    Article  PubMed  CAS  Google Scholar 

  2. Pons R, Carrozzo R, Tein I, et al. Deficient muscle carnitine transport in primary carnitine deficiency. Pediatr Res. 1997;42:583–7.

    Article  PubMed  CAS  Google Scholar 

  3. Glasgow AM, Engel AG, Bier DM, et al. Hypoglycemia, hepatic dysfunction, muscle weakness, cardiomyopathy, free carnitine deficiency and long-chain acylcarnitine excess responsive to medium chain triglyceride diet. Pediatr Res. 1983;17:319–26.

    Article  PubMed  CAS  Google Scholar 

  4. Di Donato S, Pelucchetti D, Rimoldi M, et al. Systemic carnitine deficiency: clinical, biochemical, and morphological cure with L-carnitine. Neurology. 1984;34:157–62.

    PubMed  Google Scholar 

  5. Wilcken B, Wiley V, Sim KG, Carpenter K. Carnitine transporter defect diagnosed by newborn screening with electrospray tandem mass spectrometry. J Pediatr. 2001;138:581–4.

    Article  PubMed  CAS  Google Scholar 

  6. Tokatli A, Coskun T, Ozalp I. Fifteen years’ experience with 212 hyperammonaemic cases at a metabolic unit. J Inherit Metab Dis. 1991;14:698–706.

    Article  PubMed  CAS  Google Scholar 

  7. Samtoy B, DeBeukelaer MM. Ammonia encephalopathy secondary to urinary tract infection with Proteus mirabilis. Pediatrics. 1980;65:294–7.

    PubMed  CAS  Google Scholar 

  8. Mutchnick MG, Lerner E, Conn HO. Portal-systemic encephalopathy and portacaval anastomosis: a prospective, controlled investigation. Gastroenterology. 1974;66:1005–19.

    PubMed  CAS  Google Scholar 

  9. Planas R, Gomes-Vieira MC, Cabre E, et al. Prognostic factors of hepatic encephalopathy after portacaval anastomosis: a multivariate analysis in 50 patients. Am J Gastroenterol. 1992;87:1792–6.

    PubMed  CAS  Google Scholar 

  10. Seashore JH, Seashore MR, Riely C. Hyperammonemia during total parenteral nutrition in children. JPEN J Parenter Enteral Nutr. 1982;6:114–8.

    PubMed  CAS  Google Scholar 

  11. Hamer HM, Knake S, Schomburg U, Rosenow F. Valproate-induced hyperammonemic encephalopathy in the presence of topiramate. Neurology. 2000;54:230–2.

    Article  PubMed  CAS  Google Scholar 

  12. Verrotti A, Greco R, Morgese G, Chiarelli F. Carnitine deficiency and hyperammonemia in children receiving valproic acid with and without other anticonvulsant drugs. Int J Clin Lab Res. 1999;29:36–40.

    Article  PubMed  CAS  Google Scholar 

  13. Lokrantz CM, Eriksson B, Rosen I, Asztely F. Hyperammonemic encephalopathy induced by a combination of valproate and pivmecillinam. Acta Neurol Scand. 2004;109:297–301.

    Article  PubMed  Google Scholar 

  14. Ohtani Y, Endo F, Matsuda I. Carnitine deficiency and hyperammonemia associated with valproic acid therapy. J Pediatr. 1982;101:782–5.

    Article  PubMed  CAS  Google Scholar 

  15. Stillman A, Gitter H, Shillington D, et al. Reye’s syndrome in the adult: case report and review of the literature. Am J Gastroenterol. 1983;78:365–8.

    PubMed  CAS  Google Scholar 

  16. Glasgow AM, Eng G, Engel AG. Systemic carnitine deficiency simulating recurrent Reye syndrome. J Pediatr. 1980;96:889–91.

    Article  PubMed  CAS  Google Scholar 

  17. Duran M, de Klerk JB, Wadman SK, et al. Systemic carnitine deficiency: benefit of oral carnitine supplements vs. persisting biochemical abnormalities. Eur J Pediatr. 1984;142:224–8.

    Article  PubMed  CAS  Google Scholar 

  18. Matsubasa T, Ohtani Y, Miike T, et al. Carnitine prevents Reye-like syndrome in atypical carnitine deficiency. Pediatr Neurol. 1986;2:80–4.

    Article  PubMed  CAS  Google Scholar 

  19. Matsuda I, Ohtani Y. Carnitine status in Reye and Reye-like syndromes. Pediatr Neurol. 1986;2:90–4.

    Article  PubMed  CAS  Google Scholar 

  20. Matsuda I, Ohtani Y, Ninomiya N. Renal handling of carnitine in children with carnitine deficiency and hyperammonemia associated with valproate therapy. J Pediatr. 1986;109:131–4.

    Article  PubMed  CAS  Google Scholar 

  21. Laub MC, Paetzke-Brunner I, Jaeger G. Serum carnitine during valproic acid therapy. Epilepsia. 1986;27:559–62.

    Article  PubMed  CAS  Google Scholar 

  22. Tamai I, Ohashi R, Nezu J, et al. Molecular and functional identification of sodium ion-dependent, high affinity human carnitine transporter OCTN2. J Biol Chem. 1998;273:20378–82.

    Article  PubMed  CAS  Google Scholar 

  23. Nezu J, Tamai I, Oku A, et al. Primary systemic carnitine deficiency is caused by mutations in a gene encoding sodium ion-dependent carnitine transporter. Nat Genet. 1999;21:91–4.

    Article  PubMed  CAS  Google Scholar 

  24. Korman SH, Waterham HR, Gutman A, et al. Novel metabolic and molecular findings in hepatic carnitine palmitoyltransferase I deficiency. Mol Genet Metab. 2005;86:337–43.

    Article  PubMed  CAS  Google Scholar 

  25. Roschinger W, Muntau AC, Duran M, et al. Carnitine-acylcarnitine translocase deficiency: metabolic consequences of an impaired mitochondrial carnitine cycle. Clin Chim Acta. 2000;298:55–68.

    Article  PubMed  Google Scholar 

  26. Siciliano M, Annicchiarico BE, Lucchese F, Bombardieri G. Effects of a single, short intravenous dose of acetyl-L-carnitine on pattern-reversal visual-evoked potentials in cirrhotic patients with hepatic encephalopathy. Clin Exp Pharmacol Physiol. 2006;33:76–80.

    Article  PubMed  CAS  Google Scholar 

  27. Malaguarnera M, Pistone G, Elvira R, et al. Effects of L-carnitine in patients with hepatic encephalopathy. World J Gastroenterol. 2005;11:7197–202.

    PubMed  CAS  Google Scholar 

  28. Ramsay RR, Arduini A. The carnitine acyltransferases and their role in modulating acyl-CoA pools. Arch Biochem Biophys. 1993;302:307–14.

    Article  PubMed  CAS  Google Scholar 

  29. Corvi MM, Soltys CL, Berthiaume LG. Regulation of mitochondrial carbamoyl-phosphate synthetase 1 activity by active site fatty acylation. J Biol Chem. 2001;276:45704–12.

    Article  PubMed  CAS  Google Scholar 

  30. Corkey BE, Hale DE, Glennon MC, et al. Relationship between unusual hepatic acyl coenzyme A profiles and the pathogenesis of Reye syndrome. J Clin Invest. 1988;82:782–8.

    Article  PubMed  CAS  Google Scholar 

  31. Costell M, O’Connor JE, Miguez MP, Grisolia S. Effects of L-carnitine on urea synthesis following acute ammonia intoxication in mice. Biochem Biophys Res Commun. 1984;120:726–33.

    Article  PubMed  CAS  Google Scholar 

  32. Rebouche CJ. Kinetics, pharmacokinetics, and regulation of L-carnitine and acetyl-L-carnitine metabolism. Ann N Y Acad Sci. 2004;1033:30–41.

    Article  PubMed  CAS  Google Scholar 

  33. Krajcovicova-Kudlackova M, Simoncic R, Bederova A, et al. Correlation of carnitine levels to methionine and lysine intake. Physiol Res. 2000;49:399–402.

    PubMed  CAS  Google Scholar 

  34. Ingenbleek Y. The nutritional relationship linking sulfur to nitrogen in living organisms. J Nutr. 2006;136:1641S–1651S.

    PubMed  CAS  Google Scholar 

  35. Stipanuk MH. Sulfur amino acid metabolism: pathways for production and removal of homocysteine and cysteine. Annu Rev Nutr. 2004;24:539–77.

    Article  PubMed  CAS  Google Scholar 

  36. Tein I. Carnitine transport: pathophysiology and metabolism of known molecular defects. J Inherit Metab Dis. 2003;147–69.

Download references

Acknowledgments

Midwest SGIM Meeting (September 2006) – oral presentation

Ohio ACP Meeting (October 2006) – poster presentation

Internal Medicine 2007 (April 2007) – oral presentation

The authors did not receive any internal or external funding for this work.

Conflict of Interest

None disclosed.

Author information

Authors and Affiliations

  1. Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA

    Berkeley N. Limketkai M.D. & Stephen D. Zucker M.D.

  2. Division of Digestive Diseases, University of Cincinnati, Cincinnati, OH, USA

    Berkeley N. Limketkai M.D. & Stephen D. Zucker M.D.

Authors
  1. Berkeley N. Limketkai M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stephen D. Zucker M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Berkeley N. Limketkai M.D..

Rights and permissions

Reprints and permissions

About this article

Cite this article

Limketkai, B.N., Zucker, S.D. Hyperammonemic Encephalopathy Caused by Carnitine Deficiency. J GEN INTERN MED 23, 210–213 (2008). https://doi.org/10.1007/s11606-007-0473-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11606-007-0473-0

KEY WORDS

Search

Navigation