Urinary excretion of 3‐hydroxyisovaleryl carnitine (3HIAC) in response to a leucine load increases in marginal biotin deficiency

Marginal biotin deficiency occurs in about half of all normal human pregnancies and may cause birth defects. Urinary excretion of 3HIAC increases in response to decreased activity of the biotin‐dependent enzyme 3‐methylcrotonyl‐CoA carboxylase, which catalyzes an essential step in the leucine catabolic pathway. In 7 healthy adults (3 women) rendered marginally biotin deficient by feeding a diet high in uncooked egg‐white for 28 days, we sought to determine whether urinary 3HIAC excretion increases in response to a leucine load. Marginal asymptomatic biotin deficiency was successfully induced as judged by established indicators of biotin status. By day 7 of the egg‐white diet, mean 3HIAC had increased 83% (P=0.014). By day 14, 3HIAC had increased to above the upper limit in all subjects. This study provides evidence that urinary 3HIAC in response to leucine challenge is as sensitive as the best‐known indicators (lymphocyte propionyl‐CoA carboxylase activity, urinary 3‐hydroxyisovaleric acid excretion) in identifying marginal biotin deficiency in humans. Supported by NIH R37 DK 36823 and ‐26S1; CDC 200‐2007‐21729 and U90/CCU616974‐07; NCRR UL1RR029884.