Abnormal organic aciduria in biotin deficiency: the rat is similar to the human.

We sought to determine whether the biotin-deficient rat excretes the same constellation of abnormal organic acids in urine that has been reported for biotin deficiency in humans and, if so, to determine the variation of the abnormal organic aciduria with time during progressive biotin deficiency. Biotin deficiency was induced by a 30% egg white diet. Gas chromatography-mass spectrometry was used to identify and quantitate the trimethylsilyl derivatives of the organic acids extracted from urine. We detected a progressive increase in the urinary excretion of 3-hydroxyisovaleric acid that was highly significant (p less than 0.0001). Abnormal excretion of 3-hydroxyisovaleric acid was detectable in some biotin-deficient rats as early as week 1; by week 5, all biotin-deficient rats had abnormally increased excretion of 3-hydroxyisovaleric acid. We also detected a highly significant increase (p less than 0.0001) in the urinary excretion of 3-methylcrotonylglycine. We conclude that biotin deficiency in the rat causes abnormal organic aciduria similar but not identical to that caused by biotin deficiency in humans. We speculate that this abnormal organic aciduria may serve as a useful index of biotin deficiency at the tissue level.