Liver transplant in ethylmalonic encephalopathy

A new treatment for an otherwise fatal disease

Carlo Dionisi Vici, Daria Diodato, Giuliano Torre, Stefano Picca, Rosanna Pariante, Sergio Giuseppe Picardo, Ivano Di Meo, C. Rizzo, Valeria Sonia Tiranti, Massimo Zeviani, Jean De Ville De Goyet

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)1045-1051
Number of pages7
JournalBrain
Volume139
Issue number4
DOIs
Publication statusPublished - Apr 1 2016

Fingerprint

Liver Transplantation
Transplants
Liver
Thiosulfates
Mitochondrial Diseases
Dependovirus
Hydrogen Sulfide
Living Donors
Poisons
Therapeutics
Mutation
Ethylmalonic encephalopathy
Genes

Keywords

  • ethylmalonic encephalopathy
  • liver transplant
  • mitochondrial disorders treatment

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Liver transplant in ethylmalonic encephalopathy : A new treatment for an otherwise fatal disease. / Dionisi Vici, Carlo; Diodato, Daria; Torre, Giuliano; Picca, Stefano; Pariante, Rosanna; Giuseppe Picardo, Sergio; Di Meo, Ivano; Rizzo, C.; Tiranti, Valeria Sonia; Zeviani, Massimo; De Goyet, Jean De Ville.

In: Brain, Vol. 139, No. 4, 01.04.2016, p. 1045-1051.

Research output: Contribution to journalArticle

Dionisi Vici, Carlo ; Diodato, Daria ; Torre, Giuliano ; Picca, Stefano ; Pariante, Rosanna ; Giuseppe Picardo, Sergio ; Di Meo, Ivano ; Rizzo, C. ; Tiranti, Valeria Sonia ; Zeviani, Massimo ; De Goyet, Jean De Ville. / Liver transplant in ethylmalonic encephalopathy : A new treatment for an otherwise fatal disease. In: Brain. 2016 ; Vol. 139, No. 4. pp. 1045-1051.
@article{f1b0c5a36c7f44c6be2eea06c3f32ac9,
title = "Liver transplant in ethylmalonic encephalopathy: A new treatment for an otherwise fatal disease",
abstract = "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",
author = "{Dionisi Vici}, Carlo and Daria Diodato and Giuliano Torre and Stefano Picca and Rosanna Pariante and {Giuseppe Picardo}, Sergio and {Di Meo}, Ivano and C. Rizzo and Tiranti, {Valeria Sonia} and Massimo Zeviani and {De Goyet}, {Jean De Ville}",
year = "2016",
month = "4",
day = "1",
doi = "10.1093/brain/aww013",
language = "English",
volume = "139",
pages = "1045--1051",
journal = "Brain",
issn = "0006-8950",
publisher = "Oxford University Press",
number = "4",

}

TY - JOUR

T1 - Liver transplant in ethylmalonic encephalopathy

T2 - A new treatment for an otherwise fatal disease

AU - Dionisi Vici, Carlo

AU - Diodato, Daria

AU - Torre, Giuliano

AU - Picca, Stefano

AU - Pariante, Rosanna

AU - Giuseppe Picardo, Sergio

AU - Di Meo, Ivano

AU - Rizzo, C.

AU - Tiranti, Valeria Sonia

AU - Zeviani, Massimo

AU - De Goyet, Jean De Ville

PY - 2016/4/1

Y1 - 2016/4/1

N2 - 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.

AB - 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.

KW - ethylmalonic encephalopathy

KW - liver transplant

KW - mitochondrial disorders treatment

UR - http://www.scopus.com/inward/record.url?scp=84964496558&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84964496558&partnerID=8YFLogxK

U2 - 10.1093/brain/aww013

DO - 10.1093/brain/aww013

M3 - Article

VL - 139

SP - 1045

EP - 1051

JO - Brain

JF - Brain

SN - 0006-8950

IS - 4

ER -