Urinary excretion of 3-hydroxyisovaleryl carnitine is an early and sensitive indicator of marginal biotin deficiency in humans.

Mounting evidence indicates that marginal biotin deficiency is not rare, contrary to previous assumptions. Accordingly, robust indicators of biotin status would be useful. In a study of 10 healthy adults, we recently provided evidence that abnormally increased plasma concentration of 3-hydroxyisovaleryl carnitine (3HIA-carnitine) is a sensitive indicator of marginal biotin deficiency. We sought to determine whether urinary excretion of 3HIA-carnitine (expressed as the ratio to urinary creatinine) significantly increases in marginal biotin deficiency. Marginal, asymptomatic biotin deficiency was induced experimentally in the same 10 healthy adults (8 women) by feeding undenatured egg white with meals for 28 d. Biotin status was repleted by a mixed general diet plus biotin supplementation. Urinary excretion of 3HIA-carnitine was determined by liquid chromatography-tandem MS on d 0, 14, and 28 (depletion) and on d 35 and 50 (repletion). Mean urinary 3HIA-carnitine concentration increased with depletion (P < 0.0001; d 0 vs. 28) and decreased with repletion (P = 0.0002; d 28 vs. 50). Urinary 3HIA-carnitine excretion was greater than the upper limit of normal in 9 of 10 participants by d 14 and decreased to within normal limits by d 50 in all participants. This study provides evidence that urinary excretion of 3HIA-carnitine is an early and sensitive indicator of marginal biotin deficiency. The ease of collection of untimed urine samples and application of a new analytical method with simplified sample preparation suggest that urinary 3HIA-carnitine is likely to be a useful indicator for large population studies.

[1]  D. Mock,et al.  Plasma concentration of 3-hydroxyisovaleryl carnitine is an early and sensitive indicator of marginal biotin deficiency in humans. , 2010, The American journal of clinical nutrition.

[2]  D. Mock,et al.  Quantitative measurement of urinary excretion of 3-hydroxyisovaleryl carnitine by LC-MS/MS as an indicator of biotin status in humans. , 2010, Analytical chemistry.

[3]  D. Mock,et al.  Quantitative measurement of plasma 3-hydroxyisovaleryl carnitine by LC-MS/MS as a novel biomarker of biotin status in humans. , 2010, Analytical chemistry.

[4]  A. Arduini,et al.  Carnitine, mitochondrial function and therapy. , 2009, Advanced drug delivery reviews.

[5]  D. Mock,et al.  Evidence that biotin status is impaired in human pregnancy , 2009 .

[6]  D. Mock.  Marginal biotin deficiency is common in normal human pregnancy and is highly teratogenic in mice. , 2009, The Journal of nutrition.

[7]  J. V. Van Hove,et al.  Management of a patient with holocarboxylase synthetase deficiency. , 2008, Molecular genetics and metabolism.

[8]  Georg Heinze,et al.  Long-term stability of amino acids and acylcarnitines in dried blood spots. , 2007, Clinical chemistry.

[9]  D. Mock,et al.  Lymphocyte propionyl-CoA carboxylase and its activation by biotin are sensitive indicators of marginal biotin deficiency in humans. , 2006, The American journal of clinical nutrition.

[10]  N. Longo,et al.  Biochemical findings in common inborn errors of metabolism , 2006, American journal of medical genetics. Part C, Seminars in medical genetics.

[11]  D. Mock,et al.  Marginal maternal biotin deficiency in CD-1 mice reduces fetal mass of biotin-dependent carboxylases. , 2005, The Journal of nutrition.

[12]  D. Mock,et al.  Smoking accelerates biotin catabolism in women. , 2004, The American journal of clinical nutrition.

[13]  I. Bykov,et al.  Acylcarnitine profile in tissues and body fluids of biotin-deficient rats with and withoutl-carnitine supplementation , 1994, Journal of Inherited Metabolic Disease.

[14]  D. Mock,et al.  Indicators of marginal biotin deficiency and repletion in humans: validation of 3-hydroxyisovaleric acid excretion and a leucine challenge. , 2002, The American journal of clinical nutrition.

[15]  D. Mock,et al.  Lymphocyte propionyl-CoA carboxylase and accumulation of odd-chain fatty acid in plasma and erythrocytes are useful indicators of marginal biotin deficiency small star, filled. , 2002, The Journal of nutritional biochemistry.

[16]  D. Mock,et al.  Lymphocyte propionyl-CoA carboxylase is an early and sensitive indicator of biotin deficiency in rats, but urinary excretion of 3-hydroxypropionic acid is not. , 2002, The Journal of nutrition.

[17]  J. Saudubray,et al.  Branched-chain organic acidurias. , 2002, Seminars in neonatology : SN.

[18]  D. Mock,et al.  Marginal biotin deficiency during normal pregnancy. , 2002, The American journal of clinical nutrition.

[19]  C. Kuepper.  Dietary reference intakes , 2000 .

[20]  J. Zempleni,et al.  Marginal biotin deficiency is teratogenic. , 2000, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[21]  H. Said.  Biotin bioavailability and estimated average requirement: why bother? , 1999, The American journal of clinical nutrition.

[22]  R. Nelson,et al.  Disturbances in biotin metabolism in children undergoing long-term anticonvulsant therapy. , 1998, Journal of pediatric gastroenterology and nutrition.

[23]  M. Dyken,et al.  Biotin catabolism is accelerated in adults receiving long-term therapy with anticonvulsants , 1997, Neurology.

[24]  D. Stadler,et al.  Conflicting indicators of biotin status from a cross-sectional study of normal pregnancy. , 1997, Journal of the American College of Nutrition.

[25]  D. Stadler,et al.  Biotin status assessed longitudinally in pregnant women. , 1997, The Journal of nutrition.

[26]  D. Mock,et al.  Increased urinary excretion of 3-hydroxyisovaleric acid and decreased urinary excretion of biotin are sensitive early indicators of decreased biotin status in experimental biotin deficiency. , 1997, The American journal of clinical nutrition.

[27]  S. Packman,et al.  3-Hydroxyisovalerylcarnitine in patients with deficiency of 3-methylcrotonyl CoA carboxylase. , 1995, Clinica chimica acta; international journal of clinical chemistry.

[28]  R. Rodríguez,et al.  Biotin supplementation affects lymphocyte carboxylases and plasma biotin in severe protein-energy malnutrition. , 1995, The American journal of clinical nutrition.

[29]  重松 陽介.  Acylcarnitine profile in tissues and body fluids of biotin-deficient rats with and without L-carnitine supplementation , 1994 .

[30]  D. Mock.  Rayon balls and disposable-diaper material selectively adsorb creatinine. , 1992, The American journal of clinical nutrition.

[31]  S. Weintraub,et al.  Quantification of urinary 3-hydroxyisovaleric acid using deuterated 3-hydroxyisovaleric acid as internal standard. , 1989, Biomedical & environmental mass spectrometry.

[32]  E. Casanueva,et al.  Biotin deficiency in protein-energy malnutrition. , 1989, European journal of clinical nutrition.

[33]  P. Berlit,et al.  Excretion of organic acids associated with biotin deficiency in chronic anticonvulsant therapy. , 1984, International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition.

[34]  P. Berlit,et al.  Imparied biotin status in anticonvulsant therapy , 1982, Annals of neurology.

[35]  P. Berlit,et al.  Vitamin status in patients on chronic anticonvulsant therapy. , 1982, International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition.

[36]  S. Pande.  A mitochondrial carnitine acylcarnitine translocase system. , 1975, Proceedings of the National Academy of Sciences of the United States of America.