Liver transplant in ethylmalonic encephalopathy: a new treatment for an otherwise fatal disease

Brain. 2016 Apr;139(Pt 4):1045-51. doi: 10.1093/brain/aww013. Epub 2016 Feb 25.


Ethylmalonic encephalopathy is a fatal, rapidly progressive mitochondrial disorder caused by ETHE1 mutations, whose peculiar clinical and biochemical features are due to the toxic accumulation of hydrogen sulphide and of its metabolites, including thiosulphate. In mice with ethylmalonic encephalopathy, liver-targeted adeno-associated virus-mediated ETHE1 gene transfer dramatically improved both clinical course and metabolic abnormalities. Reasoning that the same achievement could be accomplished by liver transplantation, we performed living donor-liver transplantation in an infant with ethylmalonic encephalopathy. Unlike the invariably progressive deterioration of the disease, 8 months after liver transplantation, we observed striking neurological improvement with remarkable achievements in psychomotor development, along with dramatic reversion of biochemical abnormalities. These results clearly indicate that liver transplantation is a viable therapeutic option for ETHE1 disease.

Keywords: ethylmalonic encephalopathy; liver transplant; mitochondrial disorders treatment.

Publication types

  • Case Reports

MeSH terms

  • Brain Diseases, Metabolic, Inborn / diagnosis*
  • Brain Diseases, Metabolic, Inborn / genetics
  • Brain Diseases, Metabolic, Inborn / surgery*
  • Female
  • Follow-Up Studies
  • Humans
  • Infant
  • Liver Transplantation / methods*
  • Mitochondrial Proteins / genetics
  • Mutation / genetics
  • Nucleocytoplasmic Transport Proteins / genetics
  • Purpura / diagnosis*
  • Purpura / genetics
  • Purpura / surgery*
  • Treatment Outcome


  • ETHE1 protein, human
  • Mitochondrial Proteins
  • Nucleocytoplasmic Transport Proteins

Supplementary concepts

  • Ethylmalonic encephalopathy