biotin and transport to the fetus have been demonstrated and appear to be specific for biotin (Hu et al., 1994; Karl and Fisher, 1992; Schenker et al., 1993); however, because the fetus does not concentrate biotin, placental transfer appears to be passive.
Isolation and chemical identification of more than a dozen metabolites of biotin have established the main features of utilization in microbes and mammals (McCormick, 1976; McCormick and Wright, 1971). About half of the biotin undergoes metabolism to bisnorbiotin and biotin sulfoxide before excretion. Biotin, bisnorbiotin, and biotin sulfoxide are present in molar proportions of approximately 3:2:1 in human urine and plasma (Mock, 1996). Two additional minor metabolites, bisnorbiotin methyl ketone and biotin sulfone, were recently identified in human urine (Zempleni et al., 1997). The urinary excretion and serum concentrations of biotin and its metabolites increase roughly in the same proportion in response to either intravenous or oral administration of large doses of biotin (Mock and Heird, 1997; Zempleni et al., 1997).
Signs of biotin deficiency in humans have been demonstrated conclusively in individuals who consume raw egg white over long periods (Baugh et al., 1968) and in total parenteral nutrition (TPN) before biotin supplementation in patients with malabsorption, including short-gut syndrome (Mock et al., 1981). The clinical findings of biotin deficiency include dermatitis, conjunctivitis, alopecia, and central nervous system abnormalities (Mock, 1996).
In adults fed raw egg white or receiving biotin-free TPN for months to years, thinning of hair, frequently with loss of hair color, was reported. Most adults with the deficiency demonstrated a red, scaly, skin rash, frequently around the eyes, nose, and mouth. Most of the adults had neurological symptoms, including depression, lethargy, hallucinations, and paresthesia of the extremities.
In infants on biotin-free TPN, symptoms of biotin deficiency begin to appear within 3 to 6 months after initiation of the TPN regimen, which is earlier than that seen in adults, probably because of the increased biotin requirement related to growth (Mock, 1996). The associated rash appears first around the mouth, eyes, and nose. The rash and the unusual distribution of facial fat observed in these infants together are called biotin deficiency facies. As the rash progresses,