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.
authors.affiliation: Division of Metabolism, Department of Paediatric Medicine, Bambino Gesù Children's Research Hospital IRCCS, Rome, Italy carlo.dionisivici@opbg.net.
authors.forename: Carlo
authors.initials: C
authors.lastname: Dionisi-Vici
authors.affiliation: Division of Metabolism, Department of Paediatric Medicine, Bambino Gesù Children's Research Hospital IRCCS, Rome, Italy Neuromuscular and Neurodegenerative Diseases Unit, Bambino Gesù Children's Research Hospital IRCCS, Rome, Italy.
authors.forename: Daria
authors.initials: D
authors.lastname: Diodato
authors.affiliation: Division of Hepatology and Gastroenterology, Bambino Gesù Children's Research Hospital IRCCS, Rome, Italy.
authors.forename: Giuliano
authors.initials: G
authors.lastname: Torre
authors.affiliation: Division of Nephrology and Dialysis, Bambino Gesù Children's Research Hospital IRCCS, Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Picca
authors.affiliation: Division of Intensive Care and Anaesthesia, Bambino Gesù Children's Research Hospital IRCCS, Rome, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Pariante
authors.affiliation: Division of Intensive Care and Anaesthesia, Bambino Gesù Children's Research Hospital IRCCS, Rome, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Giuseppe Picardo
authors.affiliation: Unit of Molecular Neurogenetics-Pierfranco and Luisa Mariani Centre for the Study of Mitochondrial Disorders in Children, Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy.
authors.forename: Ivano
authors.initials: I
authors.lastname: Di Meo
authors.affiliation: Division of Metabolism, Department of Paediatric Medicine, Bambino Gesù Children's Research Hospital IRCCS, Rome, Italy.
authors.forename: Cristiano
authors.initials: C
authors.lastname: Rizzo
authors.affiliation: Unit of Molecular Neurogenetics-Pierfranco and Luisa Mariani Centre for the Study of Mitochondrial Disorders in Children, Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Tiranti
authors.affiliation: MRC-Mitochondrial Biology Unit, Cambridge, UK.
authors.forename: Massimo
authors.initials: M
authors.lastname: Zeviani
authors.affiliation: Department of Surgery and Transplantation, Bambino Gesù Children's Research Hospital IRCCS, Rome, Italy.
authors.forename: Jean
authors.initials: J
authors.lastname: De Ville De Goyet
mesh_terms: D020739:Brain Diseases, Metabolic, Inborn / Q000175:diagnosis* / Q000235:genetics / Q000601:surgery*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D016031:Liver Transplantation / Q000379:methods*; D024101:Mitochondrial Proteins / Q000235:genetics; D009154:Mutation / Q000235:genetics; D029543:Nucleocytoplasmic Transport Proteins / Q000235:genetics; D011693:Purpura / Q000175:diagnosis* / Q000235:genetics / Q000601:surgery*; D016896:Treatment Outcome
chemical_list: C483228:ETHE1 protein, human; D024101:Mitochondrial Proteins; D029543:Nucleocytoplasmic Transport Proteins
keywords: ethylmalonic encephalopathy; liver transplant; mitochondrial disorders treatment