PRACTICAL METHODS TO ESTIMATE WHOLE-BODY LEUCINE OXIDATION IN MAPLE SYRUP URINE DISEASE

We report the comparison of noninvasive methods to estimate whole body leucine oxidation in patients who have maple syrup urine disease. We used both an i.v. and an oral bolus of L-[1-C-13]leucine and quantitat ed (CO2)-C-13 in expired air. Both methods differentiated patients wit h maple syrup urine disease from heterozygous and control subjects. Ei ght patients, whose disease differed in clinical severity, were select ed for study and had a range of impaired values for whole body leucine oxidation. Six h after an i.v. bolus dose of L-[1-C-13]-L-leucine, (C O2)-C-13 recoveries ranged from 0.8 to 19.7%. Three of the eight patie nts had significant increases in (CO2)-C-13 production after supraphys iologic thiamine therapy. After the oral dose of L-[1-C-13]leucine, ho mozygous affected children produced less (CO2)-C-13 than normal, age-m atched, childhood controls. In addition, the oxidation of orally admin istered L-[1-C-13] leucine was reduced significantly in adult heterozy gotes compared with adult controls. The proportion of whole body leuci ne oxidation by affected children was comparatively greater than that by their cultured cells, but cellular oxidation correlated significant ly with whole body oxidation of leucine among affected patients. We co nclude that these simplified analyses of whole body leucine oxidation define the degree of impaired branched-chain alpha-ketoacid dehydrogen ase activity in patients with differing types of maple syrup urine dis ease and distinguish the subpopulation who might benefit from thiamine supplementation.