Acute and Chronic Management in an Atypical Case of Ethylmalonic Encephalopathy

  • Thomas M. KitzlerEmail author
  • Indra R. Gupta
  • Bradley Osterman
  • Chantal Poulin
  • Yannis Trakadis
  • Paula J. Waters
  • Daniela C. Buhas
Research Report
Part of the JIMD Reports book series (JIMD, volume 45)


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.


Continuous renal replacement therapy Ethylmalonic encephalopathy Metronidazole N-acetylcysteine Thiosulfate 



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.

Supplementary material

477698_1_En_136_MOESM1_ESM.docx (18 kb)
Supplementary Table 1 Sequential results for urinary ethylmalonic acid, other organic acids, and acylglycines (DOCX 21 kb)


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Copyright information

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

Authors and Affiliations

  • Thomas M. Kitzler
    • 1
    Email author
  • Indra R. Gupta
    • 2
  • Bradley Osterman
    • 3
  • Chantal Poulin
    • 4
  • Yannis Trakadis
    • 1
  • Paula J. Waters
    • 5
  • Daniela C. Buhas
    • 1
  1. 1.Department of Medical GeneticsMcGill University Health CentreMontrealCanada
  2. 2.Department of Pediatrics, Division of NephrologyMcGill University Health CentreMontrealCanada
  3. 3.Department of Pediatric NeurologyCentre Hospitalier de l’Université Laval (CHUL)Quebec CityCanada
  4. 4.Department of Pediatrics, Division of NeurologyMcGill University Health CentreMontrealCanada
  5. 5.Medical Genetics Service, Department of PediatricsUniversity of Sherbrooke Hospital Centre (CHUS)SherbrookeCanada

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