Abstract
The chance observation that a patient with methylmalonic acidaemia (MMA) improved clinically and biochemically with amoxycillin given for a chest infection led to speculation about the contributory role of volatile fatty acids (VFA) produced by faecal bacteria. Response to amoxycillin was not sustained, and metronidazole was selected for further study, being active against anaerobes, which are the major producers of VFA's. Urinary methylmalonic acid (MM) and stool propionate, a precursor of MM were estimated over a period of 40 days before and 90 days during metronidazole treatment (11 mg/kg). Urinary MM fell from 12.8 mole/mole creatinine (SD 4.21 n=17) to 3.5 (SD 1.5 n=15), p < 0.001. Stool propionate fell from 101 μmole/ml stool (SD 5.3 n =13), to 2.1 (SD 6.8 n=23), p < 0.001. Neomycin had previously been shown to improve metabolic control in MMA.
This is the first study correlating stool propionate and urine methylmalonate excretion in response to antibiotics in MMA. The faecal flora may contribute up to 70% of the substrate for propionate metabolism. This suggests a previously largely unexplored metabolic role for the intestinal flora and a novel avenue of therapy for MMA.
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Bain, M., Borriello, S., Reed, P. et al. THERAPEUTIC POTENTIAL OF ANTIBIOTICS IN METHYLMALONIC ACIDAEMIA. Pediatr Res 19, 1083 (1985). https://doi.org/10.1203/00006450-198510000-00089
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DOI: https://doi.org/10.1203/00006450-198510000-00089