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 ur ine disease of different severity using oral L-[1-C-13]leucine bolus tests (38 mu mol/kg body weight). Residual whole-body L-leucine oxidation was est imated on the basis of the 3-h kinetics of (CO2)-C-13 exhalation and C-13-i sotopic enrichment in plasma 4-methyl-2-oxopentanoate using a noncompartmen tal mathematical approach. In four patients with classical maple syrup urin e 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 o xidation was reduced to about 4% of control. In six milder variants (two fe males and four males; mean age +/- SD, 15 +/- 10 y; range, 6-34 y), the est imates for residual whole-body L-leucine oxidation ranged from 19 to 86% (5 9 +/- 24%) of control and were substantially higher than the residual branc hed-chain 2-oxo acid dehydrogenase complex activities in the patients' fibr oblasts (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.