Alloisoleucine reference values in plasma were established in healthy adults [1.9 +/- 0.6 micromol/L (mean +/- SD); n = 35], children 3-11 years (1.6 +/- 0.4 micromol/L; n = 17), and infants <3 years (1.3 +/- 0.5 micromol/L; n = 37). The effect of dietary
isoleucine was assessed in oral loading tests. In controls receiving 38 micromol (n = 6; low dose) and 1527 micromol (n = 3; high dose) of
L-isoleucine per kilogram of
body weight, peak increases of plasma
isoleucine were 78 +/- 24 and 1763 +/- 133 micromol/L, respectively; the peak increase of
alloisoleucine, however, was negligible for low-dose (<0.3 micromol/L) and minor for high-dose (5. 5 +/- 2.1 micromol/L) load. In patients with
diabetes mellitus, ketotic
hypoglycemia,
phenylketonuria, and obligate heterozygous parents of MSUD patients,
alloisoleucine was not significantly different from healthy subjects. Therefore, a plasma concentration of 5 micromol/L was used as a cutoff value. In patients with classical MSUD (n = 7),
alloisoleucine was beyond the cutoff value in 2451 of 2453 unselected samples. In patients with variant MSUD (n = 9),
alloisoleucine was >5 micromol/L in all samples taken for establishment of diagnosis and in 94% of the samples taken for treatment control (n = 624). With the other
branched-chain amino acids, the frequency of diagnostically significant increases was <45%.
CONCLUSIONS: