Abstract
Suitability of a recently proposed noninvasive L-[13C]leucine breath test for assessment of whole body leucine oxidation in maple syrup urine disease (MSUD) was examined. Oral L-[1-13C]leucine loads (38 μmol/kg body weight) were performed in overnight fasted MSUD patients (n = 6, classical form), obligate heterozygote parents (n = 6), and control subjects (n = 10). Three-hour 13CO2 exhalation kinetics were evaluated using curve fitting procedures. Venous blood was obtained in most cases and analyzed for 13C-labeled plasma metabolites. In control subjects, maximal 13CO2 exhalation was reached at tmax = 55 ± 18 min. Cumulative 13CO2 output at 3 h amounted to 4.7 ± 0.7 μmol × (kg body weight)-1. Estimated total 13CO2 exhalation was 7.2± 1.4 μmol × (kg body weight)-1 (19.0 ± 3.6% of the dose). Half of this amount was expired at t1/2 = 130± 18 min. The data show a considerable degree of intersubject variability. Intraindividual variability was comparable, however, when checked in two volunteers. In obligate heterozygotes, 13CO2 kinetics were similar to controls (tmax = 35 ± 8 min,t1/2 = 95 ± 16 min). Total 13CO2 output[5.7 ± 1.4 μmol × (kg body weight)-1] tended to be in the lower control range. None of the MSUD patients under study exhibited a significant increase in 13CO2 output after load. Maximal increase of label in plasma 4-methyl-2-oxopentanoate, the physiologic precursor of 13CO2, was 16.1 ± 3.5 MPE in control subjects. In MSUD, label dilution was increased and correlated with the patients' leucine/4-methyl-2-oxopentanoate plasma levels. Considering the generally high variability of 13CO2 output and the unstable substrate pools in MSUD, we discuss the limitations of whole body leucine oxidation measurements by noninvasive approaches.
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Abbreviations
- APE:
-
atom percent 13C-label enrichment
- BCAA:
-
branched chain L-amino acids
- BCOA:
-
branched chain 2-oxo acids
- BCOA-DH:
-
branched-chain 2-oxo acid dehydrogenase complex
- KIC:
-
4-methyl-2-oxopentanoate
- MPE:
-
mole percent13 C-label enrichment
- MSUD:
-
maple syrup urine disease
- WBLO:
-
whole body leucine oxidation
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Acknowledgements
We thank all the subjects who participated in the study and Dr. U. Matthiesen (Düsseldorf) for performing GC-MS analyses. We are indebted to Dr. D. Leupold (Ulm) and to Dr. E. Mönch(Berlin) for allowing us to investigate their MSUD patients.
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Supported in part by Grants We 614/9-1 and 614/9-2 from the Deutsche Forschungs-gemeinschaft.
Some preliminary results have been presented at the 1994 Annual Meeting of the Arbeitsgemeinschaft Stabile Isotope, Kiel, Germany. This communication contains parts of the doctoral thesis of A.B.
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Schadewaldt, P., Bodner, A., Brösicke, H. et al. Assessment of Whole Body L-Leucine Oxidation by Noninvasive L-[1-13C]Leucine Breath Tests: A Reappraisal in Patients with Maple Syrup Urine Disease, Obligate Heterozygotes, and Healthy Subjects. Pediatr Res 43, 592–600 (1998). https://doi.org/10.1203/00006450-199805000-00006
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DOI: https://doi.org/10.1203/00006450-199805000-00006
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