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<0.01), while mean plasma propionate was reduced from 45.0 μmol/l to 25.1 μmol/l (P<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.
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Abbreviations
- GC:
-
gas chromatographic
- MMA:
-
methylmalonic acidaemia
- PA:
-
propionic acidaemia
References
Anil MH, Forbes JM (1980) Feeding in sheep during intraportal infusions of short-chain fatty acids and the effect of liver denervation. J Physiol 298:407–414
Armitage P, Berry G (1987) Statistical methods in medical research, 2nd edn. Blackwell, Oxford
Bain MD, Jones M, Borrielo SP, Reed PJ, Tracey BM, Chalmers RA, Stacey TE (1988) Contribution of gut bacterial metabolism to human metabolic disease. Lancet I:1078–1079
Chalmers RA, Lawson AM (1982) Organic acids in man. Chapman and Hall, London
Harig JM, Soergel KH, Komorowski RA, Wood CM (1989) Treatment of diversion colitis with short-chain-fatty-acid irrigation. N Eng J Med 320:23–28
Holdeman LV, Cato EP, Moore WEC (1977) Anaerobe laboratory manual, 4th edn. Polytechnic Institute and State University, Blacksburg, Virginia
Hoverstad T, Carlstedt-Duke B, Lingaas E, Midtvedt T, Norin KE, Saxerholt H, Steinbakk M (1986) Influence of ampicillin, clindamycin and metronidazole on faecal excretion of shortchain fatty acids in healthy subjects. Scand J Gastroenterol 21:621–626
Hoverstad T, Carlstedt-Duke B, Lingaas E, Norin KE, Saxerholt H, Steinbakk M, Midtvedt T (1986) Influence of oral intake of seven different antibiotics on faecal short-chain fatty acid excretion in healthy subjects. Scand J Gastroenterol 21: 997–1003
Oberholzer VG, Levin B, Burgess EA, Young WF (1967) Methylmalonic aciduria. A new inborn error of metabolism leading to chronic metabolic acidosis. Arch Dis Child 42:492–504
Roediger WE (1980) Role of anaerobic bacteria in the metabolic welfare of the colonic mucosa in man. Gut 21:793–798
Rosenberg LE (1983) Disorders of propionate and methylmalonate metabolism. In: Stanbury JB, Wyngaarden JB, Frederickson DS, Goldstein JL, Brown MS (eds) The metabolic basis of inherited disease, 5th edn. McGraw-Hill, New York, pp 474–497
Snyderman SE, Sansaricq C, Norton P Phansalkar SV (1972) The use of neomycin in the treatment of methylmalonic acidaemia. Pediatrics 50:925–927
Stevenson DK, Cohen RS, Ostrander CR, Shahin SM, Kerner JA, Wetmore DL, Werner SB, Tomczyk M, Johnson JD (1982) A sensitive analytical apparatus for measuring hydrogen production rates. II. Application to studies in human infants. J Pediatr Gastroenterol Nutr 1:233–237
Thompson GN, Christodoulou J, Danks DM (1989) Metabolic stroke in methylmalonic acidaemia: a reason for tighter metabolic control? J Pediatr 115:499–500
Walter JH, Leonard JV, Thompson GN, Halliday D, Bartlett K (1988) Propionate production from the gut in propionic acidaemia. Lancet II:226
Walter JH, Michalski A, Wilson WM, Leonard JB, Barratt TM, Dillon MJ (1989) Chronic renal failure in methylmatlonic acidaemia. Eur J Pediatr 148:344–348
Walter JH, Thompson GN, Leonard JV, Hetherington CS, Bartlett K (1989) Measurement of propionate turnover in vivo using sodium2H5 − and13C-propionate. Clin Chim Acta 182:141–150
Walter JH, Thompson GN, Leonard JV, Bartlett K, Halliday D (1989) Contribution of aminoacid catabolism to propionate production in methylmalonic acidaemia. Lancet I:1298–1299
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Thompson, G.N., Chalmers, R.A., Walter, J.H. et al. The use of metronidazole in management of methylmalonic and propionic acidaemias. Eur J Pediatr 149, 792–796 (1990). https://doi.org/10.1007/BF01957284
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DOI: https://doi.org/10.1007/BF01957284