Whole-body L-leucine oxidation in patients with variant form of maple syrup urine disease.
Whole-body L-leucine oxidation was assessed in patients with maple syrup urine disease of different severity using oral L-[1-(13)C]leucine bolus tests (38 micromol/kg body weight). Residual whole-body L-leucine oxidation was estimated on the basis of the 3-h kinetics of (13)CO(2) exhalation and (13)C-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.
Schadewaldt
P
P
Deutsches Diabetes Forschungsinstitut, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany. schadewa@uni-duesseldorf.de
Bodner-Leidecker
A
A
Hammen
H W
HW
Wendel
U
U
D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D005260:Female; D005502:Food; D006801:Humans; D007930:Leucine / Q000097:blood / Q000378:metabolism*; D008297:Male; D008375:Maple Syrup Urine Disease / Q000378:metabolism*; D010084:Oxidation-Reduction
D007930:Leucine