Abstract
Ethylmalonic encephalopathy is caused by mutations in ETHE1, a mitochondrial matrix sulfur dioxygenase, leading to failure to detoxify sulfide, a product of intestinal anaerobes and, in trace amounts, tissues. Metronidazole, a bactericide, or N-acetylcysteine, a precursor of sulfide-buffering glutathione, substantially prolonged the lifespan of Ethe1-deficient mice, with the combined treatment being additive. The same dual treatment caused marked clinical improvement in five affected children, with hardly any adverse or side effects.
Publication types
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Case Reports
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylcysteine / administration & dosage*
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Acetylcysteine / adverse effects
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Administration, Oral
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Animals
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Anti-Infective Agents / administration & dosage
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Anti-Infective Agents / adverse effects
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Brain Diseases, Metabolic, Inborn / drug therapy*
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Brain Diseases, Metabolic, Inborn / genetics
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Brain Diseases, Metabolic, Inborn / metabolism
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Brain Diseases, Metabolic, Inborn / mortality
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Child, Preschool
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Dioxygenases / genetics
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Drug Combinations
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Drug Evaluation, Preclinical
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Female
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Humans
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Infant
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Male
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Malonates / metabolism
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Metronidazole / administration & dosage*
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Metronidazole / adverse effects
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Mice
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Mice, Knockout
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Mitochondrial Proteins / genetics
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Treatment Outcome
Substances
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Anti-Infective Agents
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Drug Combinations
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Malonates
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Mitochondrial Proteins
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Metronidazole
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ethylmalonic acid
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Dioxygenases
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ETHE1 protein, mouse
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Acetylcysteine