Combined treatment with oral metronidazole and N-acetylcysteine is effective in ethylmalonic encephalopathy.
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.
Viscomi
Carlo
C
The Foundation Carlo Besta Institute of Neurology, Milan, Italy.
Burlina
Alberto B
AB
Dweikat
Imad
I
Savoiardo
Mario
M
Lamperti
Costanza
C
Hildebrandt
Tatjana
T
Tiranti
Valeria
V
Zeviani
Massimo
M
D000111:Acetylcysteine / Q000008:administration & dosage* / Q000009:adverse effects; D000284:Administration, Oral; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000009:adverse effects; D020739:Brain Diseases, Metabolic, Inborn / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D002675:Child, Preschool; D049308:Dioxygenases / Q000235:genetics; D004338:Drug Combinations; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008314:Malonates / Q000378:metabolism; D008795:Metronidazole / Q000008:administration & dosage* / Q000009:adverse effects; D051379:Mice; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000235:genetics; D016896:Treatment Outcome
D000890:Anti-Infective Agents; D004338:Drug Combinations; D008314:Malonates; D024101:Mitochondrial Proteins; D008795:Metronidazole; C038080:ethylmalonic acid; D049308:Dioxygenases; C538757:ETHE1 protein, mouse; D000111:Acetylcysteine