Lymphocyte propionyl-CoA carboxylase and accumulation of odd-chain fatty acid in plasma and erythrocytes are useful indicators of marginal biotin deficiency☆

Background: Recent studies indicate marginal biotin deficiency is more common than previously thought. That conclusion’s validity rests on two indicators of biotin status that depend on renal function. Objective: Assessing the validity of two indicators of biotin status that do not depend upon renal function: 1) activity of the biotin-dependent enzyme propionyl-CoA carboxylase (PCC) in lymphocytes and 2) accumulation of odd-chain fatty acids in the lipids of plasma and erythrocytes. Design: Marginal biotin deficiency was induced in 11 healthy adults by egg-white feeding for 28 days. Blood and 24-h urine samples were collected before commencing the diet and twice weekly thereafter. After depletion, biotin status was restored with a general diet with or without 80 μg/day or 328 nmol/day biotin supplement. Activity of PCC was determined by an optimized NaH 14CO3 incorporation assay. Fatty acid composition was determined by gas chromatography. Results: With time on the egg-white diet, lymphocyte PCC activity decreased significantly (P <0.0001); C15:0 and C17:0 content increased significantly in the lipids of plasma and erythrocytes (P <0.015). In eight of 11 subjects, lymphocyte PCC activity returned to normal within three weeks of resuming general diets with or without biotin supplement. With repletion, C15:0 and C17:0 in plasma lipids decreased (P <0.02), but odd-chain content of erythrocytes did not decrease significantly. Conclusions: Lymphocyte PCC activity is an early and sensitive indicator of marginal biotin deficiency. Odd-chain fatty acids accumulate in blood lipids more gradually during marginal deficiency and return to normal more gradually after biotin repletion.