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

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

Author information

1
Division of Metabolism, Department of Paediatric Medicine, Bambino Gesù Children's Research Hospital IRCCS, Rome, Italy carlo.dionisivici@opbg.net.
2
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.
3
Division of Hepatology and Gastroenterology, Bambino Gesù Children's Research Hospital IRCCS, Rome, Italy.
4
Division of Nephrology and Dialysis, Bambino Gesù Children's Research Hospital IRCCS, Rome, Italy.
5
Division of Intensive Care and Anaesthesia, Bambino Gesù Children's Research Hospital IRCCS, Rome, Italy.
6
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.
7
Division of Metabolism, Department of Paediatric Medicine, Bambino Gesù Children's Research Hospital IRCCS, Rome, Italy.
8
MRC-Mitochondrial Biology Unit, Cambridge, UK.
9
Department of Surgery and Transplantation, Bambino Gesù Children's Research Hospital IRCCS, Rome, Italy.

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

PMID:
26917598
DOI:
10.1093/brain/aww013
[Indexed for MEDLINE]

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