Abstract
Whole-body l-leucine oxidation was assessed in patients with maple syrup urine disease of different severity using oral l-[1-13C]leucine bolus tests (38 μmol/kg body weight). Residual whole-body l-leucine oxidation was estimated on the basis of the 3-h kinetics of 13CO2 exhalation and 13C-isotopic enrichment in plasma 4-methyl-2-oxopentanoate using a noncompartmental mathematical approach. In four patients with classical maple syrup urine disease (two females and two males; mean age, 13 ± 5 y; range, 7–17 y), l-leucine oxidation was too low to be measurable. In two females (aged 11 and 15 y) with a severe variant form of the disease, whole-body l-leucine oxidation was reduced to about 4% of control. In six milder variants (two females and four males; mean age ± SD, 15 ± 10 y; range, 6–34 y), the estimates for residual whole-body l-leucine oxidation ranged from 19 to 86% (59 ± 24%) of control and were substantially higher than the residual branched-chain 2-oxo acid dehydrogenase complex activities in the patients’ fibroblasts (10–25% of control). Possible mechanisms are considered that might contribute to a comparatively high residual in vivo l-leucine oxidation in (mild) variant maple syrup urine disease.
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Abbreviations
- APE:
-
atom percent 13C-label enrichment
- BCAA:
-
branched-chain l-aminoacids
- BCOA:
-
branched-chain 2-oxo acids
- BCOA-DH:
-
branched-chain 2-oxo acid dehydrogenase complex
- KIC:
-
4-methyl-2-oxopentanoate (α-ketoisocaproate)
- MPE:
-
mole percent 13C-label enrichment
- MSUD:
-
maple syrup urine disease
- WBLO:
-
whole-body l-leucine oxidation
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Acknowledgements
This study was generously supported by the following colleagues: Herbert Brösicke and Eberhardt Mönch, Berlin, Germany; Dorothea Leupold, Ulm, Germany; Rudolf Mallmann, Essen, Germany; Klaus Mohnike and Irmgard Starke, Magdeburg, Germany; Helmut Niederhoff, Freiburg, Germany; Barbara Pleçko, Graz, Austria; Jean-Marie Saudubray, Paris, France; and Jörg Seidel, Jena, Germany.
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This work was supported in part by Grant We 614/9-3 from Deutsche Forschungsgemeinscheft.
Some preliminary results have been presented at the 1999 annual meetings of the Arbeitsgemeinschaft Pädiatrische Stoffwechselstörungen (APS), Fulda, Germany, and of the Society for the Study of Inborn Errors of Metabolism (SSIEM), Genoa, Italy.
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Schadewaldt, P., Bodner-Leidecker, A., Hammen, HW. et al. Whole-Body l-Leucine Oxidation in Patients with Variant Form of Maple Syrup Urine Disease. Pediatr Res 49, 627–635 (2001). https://doi.org/10.1203/00006450-200105000-00004
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DOI: https://doi.org/10.1203/00006450-200105000-00004
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