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The use of metronidazole in management of methylmalonic and propionic acidaemias
G N Thompson1, R A Chalmers, J H Walter
1Nutrition Research Group, Clinical Research Centre, Harrow, UK.
Abstract:
Gut bacteria have been implicated as an important source of propionate in children with inborn errors of propionate metabolism. We have investigated the value of oral metronidazole (10-20 mg/kg per day) in five children with methylmalonic acidaemia (MMA) and four with propionic acidaemia (PA). Urinary excretion of propionate metabolites fell significantly during the treatment in all subjects, the mean decrease being 41% (range 12-76, P less than 0.01), while mean plasma propionate was reduced from 45.0 mumol/l to 25.1 mumol/l (P less than 0.05). Substantial reduction of the gut bacterial population was confirmed by lactulose breath hydrogen tests and by stool culture, and stool propionate concentration was reduced in most subjects. Clinical improvement was noted in three children. These results suggest that long-term antimicrobial therapy may offer significant clinical benefit to children with inborn errors of propionate metabolism.
Insights
Oral metronidazole reduced harmful propionate levels in children with inborn errors of propionate metabolism. This antimicrobial therapy showed potential for clinical benefit in methylmalonic acidaemia and propionic acidaemia.
Area of Science:
- Biochemistry
- Microbiology
- Pediatric Medicine
Background:
- Inborn errors of propionate metabolism are linked to gut bacteria producing propionate.
- Methylmalonic acidaemia (MMA) and propionic acidaemia (PA) are key examples.
Purpose of the Study:
- To evaluate the efficacy of oral metronidazole in treating children with MMA and PA.
- To assess the impact of metronidazole on propionate levels and gut bacterial populations.
Main Methods:
- Administered oral metronidazole (10-20 mg/kg/day) to nine children (five with MMA, four with PA).
- Monitored urinary propionate metabolites, plasma propionate levels, and gut bacterial activity using lactulose breath hydrogen tests and stool cultures.
Main Results:
- Significant reduction in urinary propionate metabolites (mean 41% decrease) and plasma propionate levels (45.0 to 25.1 mumol/l).
- Confirmed substantial reduction in gut bacterial population and stool propionate concentration.
- Observed clinical improvement in three children.
Conclusions:
- Long-term antimicrobial therapy with metronidazole may be beneficial for children with inborn errors of propionate metabolism.
- Targeting gut bacteria offers a potential therapeutic strategy for these metabolic disorders.