European Journal of Pediatrics

, Volume 149, Issue 6, pp 408–411 | Cite as

In vivo propionate oxidation as a prognostic indicator in disorders of propionate metabolism

  • G. N. Thompson
  • J. H. Walter
  • J. -L. Bresson
  • J. -P. Bonnefont
  • J. -M. Saudubray
  • J. V. Leonard
  • D. Halliday
Metabolic Diseases


Biochemical markers such as plasma and urinary metabolite concentrations and in vitro enzyme activity are of limited prognostic value in the most common disorders of propionate metabolism, methylmalonic acidaemia (MMA) and propionic acidaemia (PA). In vivo propionate oxidation was compared with conventional prognostic measures as predictors of clinical severity in seven children with MMA and six with PA. Propionate oxidation was measured using a continuous infusion of [1-13C]propionate and was expressed as the rate of appearance of13CO2 as a percentage of the propionate infusion rate. Children with MMA (mean oxidation 51.2%, range 17.5–91.6,P<0.05) and with PA (mean oxidation 36.3%, range 3.0–91.1,P=NS) oxidised substantially less propionate than controls (mean oxidation 81.9%, range 69.4–101.0,n=5). Percentage oxidation was a better predictor of the clinical severity score (r=0.75,P<0.01) than was in vitro enzyme activity, plasma propionate or methylmalonate concentration or urinary metabolite excretion. Studies were repeated after an interval of 1–3 weeks in six of the subjects; the percentage oxidation in each subject was virtually unchanged between studies (coefficient of variation 8.6%). These results suggest that in vivo oxidation measurements using [13C]propionate are both reproducible and prognostically useful in disorders of propionate metabolism.

Key words

Propionate Stable isotope Oxidation Methylmalonic acidaemia Propionic acidaemia 



methylmalonic acidaemia


propionic acidaemia


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Allsop JR, Wolfe RR, Burke JF (1978) Tracer priming the bicarbonate pool. J Appl Physiol 45:137–139PubMedGoogle Scholar
  2. 2.
    Causey AG, Bartlett K (1984) A radio-HPLC assay for the measurement of methylmalonyl CoA mutase. Clin Chim Acta 139: 179–186CrossRefPubMedGoogle Scholar
  3. 3.
    Chadefaux B, Augereau C, Rabier D, Rocchiccioli F, Boué J, Oury JF, Kamoun P (1988) Prenatal diagnosis of propionic acidaemia in chrionic villi by direct assay of propionyl-CoA carboxylase. Prenat Diagn 8:161–164PubMedGoogle Scholar
  4. 4.
    Chalmers RA, Lawson AM (1982) Organic acids in man. Chapman and Hall, LondonGoogle Scholar
  5. 5.
    Garrow JS, Webster JD (1986) A computer-controlled indirect calorimeter for the measurement of energy expenditure in one or two subjects simultaneously. Hum Nutr Clin Nutr 40C:315–321Google Scholar
  6. 6.
    Goodey PA, Gomperz D (1972) Methylmalonyl CoA mutase — a radiochromatographic assay. Biochim Biophys Acta 42:119–123Google Scholar
  7. 7.
    Halliday D, Thompson GN (1988) The use of stable isotopes in medicinal chemistry. In: Jones JR (ed) Isotopes: essential chemistry and applications II. The Royal Society of Chemistry, London, pp 173–202Google Scholar
  8. 8.
    Leonard JV, Daish P, Naughten ER, Bartlett K (1984) The management and long-term outcome of organic acidaemias. J Inherited Metab Dis [Suppl 1] 7:13–17PubMedGoogle Scholar
  9. 9.
    Matthews DE, Motil KJ, Rohrbaugh DK, Burke JF, Young VR, Bier DM (1980) Measurement of leucine metabolism in man from a primed continuous infusion ofl-[1-13C]leucine. Am J Physiol 238:E473–479PubMedGoogle Scholar
  10. 10.
    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 474–497Google Scholar
  11. 11.
    Rumsby G, Belloque J, Ersser RS, Seakins JWT (1987) Effect of temperature and sample preparation on performance of ion-moderated partition chromatography of organic acids in biological fluids. Clin Chim Acta 163:171–183PubMedGoogle Scholar
  12. 12.
    Schoeller DA, Klein PD, Watkins JB, Heim T, MacLean WC Jr (1980)13C abundances of nutrients and the effect of variations in13C isotopic abundances of test meals formulated for13CO2 breath tests. Am J Clin Nutr 33:2375–2385PubMedGoogle Scholar
  13. 13.
    Stanbury JB, Wyngaarden JB, Frederickson DS, Goldstein JL, Brown MS (eds) (1983) The metabolic basis of inherited disease, 5th edn. McGraw-Hill, New YorkGoogle Scholar
  14. 14.
    Walter JH, Michalski A, Wilson WM, Leonard JV, Barratt TM, Dillon MJ (1989) Chronic renal failure in methylmalonic acidaemia. Eur J Pediatr 148:344–348CrossRefPubMedGoogle Scholar
  15. 15.
    Walter JH, Thompson GN, Leonard JV, Bartlett K, Halliday D (1989) Contribution of aminoacid catabolism to propionate production in methylmalonic acidaemia. Lancet I:1298–1299CrossRefGoogle Scholar
  16. 16.
    Walter JH, Thompson GN, Leonard JV, Hetherington CS, Bartlett K (1989) Measurement of propionate turnover in vivo using sodium2H5-and13C-propionate. Clin Chim Acta 182:141–150CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • G. N. Thompson
    • 1
  • J. H. Walter
    • 2
  • J. -L. Bresson
    • 3
  • J. -P. Bonnefont
    • 3
  • J. -M. Saudubray
    • 3
  • J. V. Leonard
    • 2
  • D. Halliday
    • 1
  1. 1.Nutrition Research GroupClinical Research CentreHarrowUK
  2. 2.Department of Child HealthInstitute of Child HealthLondonUK
  3. 3.Clinique Genetique MedicaleHôpital des Enfants MaladesParisFrance

Personalised recommendations