Renal clearance of branched-chain L-amino and 2-oxo acids in maple syrup urine disease

In maple syrup urine disease (MSUD), branched-chain L-amino (BCAA) and 2-ox o acids (BCOA) accumulate in body fluids owing to an inherited deficiency o f branched-chain 2-oxo acid dehydrogenase complex activity. In MSUD, little information is available on the significance of urinary disposal of branch ed-chain compounds. We examined the renal clearance of leucine, valine, iso leucine and alloisoleucine, and their corresponding 2-oxo acids 4-methyl-2- oxopentanoate (KIC), 3-methyl-2-oxobutanoate (KIV), (S)- (S-KMV), and (R)-3 -methyl-2-oxopentanoate (R-KMV), using pairs of plasma and urine samples (n =63) from 10 patients with classical MSUD. The fractional renal excretion o f free BCAA was in the normal range (< 0.5%) and independent of the plasma concentrations. The excretion of bound (N-acylated) BCAA was normal and not significantly dependent on the BCAA plasma concentrations. The fractional renal excretion of BCOA was in the order KIC<<KIV < R-KMV less than or equa l to S-KMV (range (%): KIC 0.1-25; KIV 0.14-21.3; S-KMV 0.26-24.6; R-KMV 0. 1-35.9), significantly correlated with the KIC plasma concentrations, and g enerally higher than that of the related BCAA. The results show that the re nal excretion of free BCAA as well as of the acylated derivatives is neglig ible. The renal excretion of BCOA, however, to some extent counteracts incr eases in BCAA concentrations and thus contributes to the lowering of total BCAA pools in MSUD.