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Acute and Chronic Management in an Atypical Case of Ethylmalonic Encephalopathy

  • Research Report
  • Chapter
  • First Online:
JIMD Reports, Volume 45

Part of the book series: JIMD Reports ((JIMD,volume 45))

Abstract

Ethylmalonic encephalopathy (EE) is caused by mutations in the ETHE1 gene. ETHE1 is vital for the catabolism of hydrogen sulfide (H2S). Patients with pathogenic mutations in ETHE1 have markedly increased thiosulfate, which is a reliable index of H2S levels. Accumulation of H2S is thought to cause the characteristic metabolic derangement found in EE. Recently introduced treatment strategies in EE, such as combined use of metronidazole (MNZ) and N-acetylcysteine (NAC), are aimed at lowering chronic H2S load. Experience with treatment strategies directed against acute episodes of metabolic decompensation (e.g., hemodialysis) is limited. Here we present an unusually mild, molecularly confirmed, case of EE in a 19-year-old male on chronic treatment with MNZ and NAC. During an acute episode of metabolic decompensation, we employed continuous renal replacement therapy (CRRT) to regain metabolic control. On continuous treatment with NAC and MNZ during the months preceding the acute event, plasma thiosulfate levels ranged from 1.6 to 4 μg/mL (reference range up to 2 μg/mL) and had a mean value of 2.5 μg/mL. During the acute decompensation, thiosulfate levels were 6.7 μg/mL, with hyperlactatemia and perturbed organic acid, acylglycine, and acylcarnitine profiles. CRRT decreased thiosulfate within 24 h to 1.4 μg/mL. Following discontinuation of CRRT, mean thiosulfate levels were 3.2 μg/mL (range, 2.4–3.7 μg/mL) accompanied by clinical improvement with metabolic stabilization of blood gas, acylcarnitine, organic acid, and acylglycine profiles. In conclusion, CRRT may help to regain metabolic control in patients with EE who have an acute metabolic decompensation on chronic treatment with NAC and MNZ.

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Acknowledgments

We would like to thank the patient and his family for giving us permission to publish this case report. We also thank Patrick Bherer (of the CHUS biochemical genetics laboratory) for analysis of urine acylglycine profiles and Dr. Massimo Zeviani for his advice during the second acute decompensation.

Author information

Authors and Affiliations

  1. Department of Medical Genetics, McGill University Health Centre, Montreal, QC, Canada

    Thomas M. Kitzler, Yannis Trakadis & Daniela C. Buhas

  2. Department of Pediatrics, Division of Nephrology, McGill University Health Centre, Montreal, QC, Canada

    Indra R. Gupta

  3. Department of Pediatric Neurology, Centre Hospitalier de l’Université Laval (CHUL), Quebec City, QC, Canada

    Bradley Osterman

  4. Department of Pediatrics, Division of Neurology, McGill University Health Centre, Montreal, QC, Canada

    Chantal Poulin

  5. Medical Genetics Service, Department of Pediatrics, University of Sherbrooke Hospital Centre (CHUS), Sherbrooke, QC, Canada

    Paula J. Waters

Authors
  1. Thomas M. Kitzler
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  2. Indra R. Gupta
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  3. Bradley Osterman
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  4. Chantal Poulin
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  5. Yannis Trakadis
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  6. Paula J. Waters
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  7. Daniela C. Buhas
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Corresponding author

Correspondence to Thomas M. Kitzler .

Editor information

Editors and Affiliations

  1. Tulane University Medical School, New Orleans, LA, USA

    Eva Morava

  2. Division of Metabolism & Children’s Research Centre, University Children’s Hospital Zürich, Zürich, Switzerland

    Matthias Baumgartner

  3. Division of Child and Adolescent Neurology, Mayo Clinic, Rochester, MN, USA

    Marc Patterson

  4. Clinical and Molecular Genetics Unit, UCL Institute of Child Health, London, UK

    Shamima Rahman

  5. Division of Human Genetics, Medical University Innsbruck, Innsbruck, Austria

    Johannes Zschocke

  6. Center for Child and Adolescent Medicine, Heidelberg University Hospital, Heidelberg, Germany

    Verena Peters

Additional information

Communicated by: Ivo Barić, M.D., PhD, Professor of Pediatrics

Electronic Supplementary Material

Supplementary Table 1

Sequential results for urinary ethylmalonic acid, other organic acids, and acylglycines (DOCX 21 kb)

Appendices

Take-Home Message

By reading this case report on a patient with an unusually mild form of ethylmalonic encephalopathy (EE), readers will learn about the acute and chronic management of this rare condition and about the importance of keeping metabolic causes, such as EE, in mind in patients presenting with a purely neurological phenotype. Finally, our report illustrates the importance of identifying all possible triggers of a metabolic decompensation in patients with inborn errors of metabolism.

Author Contributions

TMK::

Data analysis and interpretation and planning and drafting most of the article.

IRG::

Article contribution and revision.

BO::

Article contribution and revision.

CP::

Article contribution and revision.

YT::

Data analysis and interpretation and article contribution and revision.

PJW::

Data analysis and interpretation and article contribution and revision.

DCB::

Data analysis and interpretation and planning and drafting of article.

Competing Interests

The authors have no competing interests to declare.

Funding

This work has not received any funding.

Patient Consent

The patient and his parents provided informed consent for publication of this case report.

Ethical Standards

The authors declare that the experiments comply with the current laws of Canada, the country in which they were performed.

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© 2018 Society for the Study of Inborn Errors of Metabolism (SSIEM)

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Kitzler, T.M. et al. (2018). Acute and Chronic Management in an Atypical Case of Ethylmalonic Encephalopathy. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 45. JIMD Reports, vol 45. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2018_136

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  • DOI: https://doi.org/10.1007/8904_2018_136

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  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-58646-4

  • Online ISBN: 978-3-662-58647-1

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