Laboratory Findings of Biotin Deficiency

Although various indices have been used to assess biotin status, these have been validated in humans only twice during progressive biotin deficiency. In both studies, marginal biotin deficiency was induced in normal adults by feeding egg white. The urinary excretion of biotin declined dramatically with time on the egg-white diet, reaching frankly abnormal values in 17 of 21 subjects by day 20 of egg-white feeding. Bisnorbiotin excretion declined in parallel, providing evidence for regulated catabolism of biotin. In most subjects, urinary excretion of 3-hydro-xyisovaleric acid increased steadily. By day 14 of egg-white feeding, 3-hydroxyisovaleric acid excretion was abnormally increased in 18 of 21 subjects, providing evidence that biotin depletion decreases the activity of MCC and alters leucine metabolism early in progressive biotin deficiency. Based on a study of only 5 subjects, 3-hydroxyisovaleric acid excretion in response to a leucine challenge may be even more sensitive than 3-hydroxyisovaleric acid excretion. Urinary excretions of 3-methylcrotonyl-glycine, 3-hydroxypropionic acid, and 3-methylcitric acid are not sensitive indicators of biotin deficiency compared to 3-hydroxyisovaleric acid excretion.

In a single study, plasma concentrations of free biotin decreased to abnormal values in only half of the subjects. This observation provides confirmation of the impression that blood biotin concentration is not an early or sensitive indicator of marginal biotin deficiency.

Lymphocyte PCC activity is an early and sensitive indicator of marginal biotin deficiency. In 11 of 11 subjects, lymphocyte PCC activity decreased to abnormal values by day 28 of egg-white feeding and returned to normal in 8 of 11 within 3 weeks of resuming a general diet with or without biotin supplement.

Odd-chain fatty acid accumulation is also a marker of biotin deficiency. The accumulation of odd-chain fatty acid is thought to result from PCC deficiency (Figure 3); the accumulation of propionyl-CoA likely leads to the substitution of a propionyl-CoA moiety for acetyl-CoA in the ACC reaction and to the incorporation of a three- (rather than two-) carbon moiety during fatty acid elongation. However, in comparison to lymphocyte PCC activity and urinary excretion of 3-hydroxyisovaleric acid, odd-chain fatty acids accumulate in blood lipids more slowly during biotin deficiency and return to normal more gradually after biotin repletion.

Requirements and Allowances

Data providing an accurate estimate of the dietary and parenteral biotin requirements for infants, children, and adults are lacking. However, recommendations for biotin supplementation have been formulated for oral and parenteral intake for preterm infants, term infants, children, and adults (Table 2).

Table 2 Adequate intake of biotin

Life-stage group Adequate intake fag/day)

Infants (months)

Children (years)

Males and females (years)

9-13 20

14-18 25

Pregnancy 30

Lactation 35

3-methylglutaconyl CoA

Figure 3 Organic acids and odd-chain fatty acids accumulate because biotin deficiency causes reduced activity of biotin-dependent enzymes. Hatched bars denote metabolic blocks at deficient carboxylases; ovals denote accumulation of products from alternative pathways.

3-methylglutaconyl CoA

Figure 3 Organic acids and odd-chain fatty acids accumulate because biotin deficiency causes reduced activity of biotin-dependent enzymes. Hatched bars denote metabolic blocks at deficient carboxylases; ovals denote accumulation of products from alternative pathways.

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