Abstract
Inability to recycle biotin from endogenous biocytin in congenital biotinidase deficiency is associated with increased requirement of exogenous free biotin. We have observed that severe biotin depletion with clinical and biochemical consequences occurs within 12 days after birth in a newborn patient and within 15–20 days after withdrawal of biotin supplementation in four other patients. Our studies have shown that:
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(1)
Urinary loss of biotin and biocytin are major causes for this rapid biotin depletion.
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(2)
Intestinal absorption of biotin seems to be normal at least at the loading dose of 1.5 µg/kg.
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(3)
At normal or subnormal plasma biotin concentrations biocytin is found in low concentrations (below 1 nmoll−1) in plasma of patients but at much higher concentrations in urine (100–600 nmoll−1).
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(4)
An oral load of biocytin results in patients in unchanged biotin levels but in a marked rise of biocytin in plasma followed by rapid renal excretion of biocytin whereas in controls biotin levels in plasma increase rapidly and biocytin remains below detection levels.
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Baumgartner, E. R., Suormala, T., Wick, H. and Bonjour, J. P. Biotin-responsive multiple carboxylase deficiency (MCD): deficient biotinidase activity associated with renal loss of biotin.J. Inher. Metab. Dis. 7, Suppl. 2 (1984) 123–125
Baumgartner, E. R., Suormala, T., Wick, H., Geisert, J. and Lehnert, W. Infantile multiple carboxylase deficiency: evidence for normal intestinal absorption but renal loss of biotin.Helv. Pediatr. Acta 37 (1982) 499–502
Baumgartner, E. R., Suormala, T., Wick, H., Bausch, J. and Bonjour, J. P. Biotinidase deficiency associated with renal loss of biocytin and biotin.Ann. N.Y. Acad. Sci. (In press) (1985)
Baumgartner, E. R., Suormala, T., Wick, H., Bachmann, C. and Jaggi, K. H. Biotin dependency causing multiple carboxy-lase deficiencyin vivo.Pediatr. Res. 15 (1981) 1189
Bonjour, J. P., Bausch, J., Suormala, T. and Baumgartner, E. R. Detection of biocytin in urine of children with congenital biotinidase deficiency.Int. J. Vit. Nutr. Res. 54 (1984) 223–231
Burri, B. J., Sweetman, L. and Nyhan, W. L. Mutant holocarboxylase synthetase. Evidence for the enzyme defect in early infantile biotin-responsive multiple carboxylase deficiency.J. Clin. Invest. 68 (1981) 1491–1495
Craft, D. V., Goss, N. H., Chandramouli, N. and Wood, H. G. Purification of biotinidase from human serum and its activity on biotinyl peptides.Biochemistry (In press) (1984)
Frigg, M. and Brubacher, G. Biotin deficiency in chicks fed a wheat-based diet.Int. J. Vit. Nutr. Res. 46 (1976) 314–321
Ghneim, H. K. and Bartlett, K. Mechanism of biotin-responsive combined carboxylase deficiency.Lancet i (1982) 1187–1188
Munnich, A., Saudubray, J. M., Carré, G., Coudé, F. X., Ogier, H., Charpentier, C. and Frézal, J. Defective biotin absorption in multiple carboxylase deficiency.Lancet ii (1983) 263
Stirk, J. H., George, K., Alberti, M. M. and Bartlett, K. The effect of large dose of biotin on leukocyte carboxylases in humans.Biochem. Soc. Trans. 11 (1983) 185–186
Suormala, T., Wick, H., Bonjour, J. P. and Baumgartner, E. R. Rapid differential diagnosis of carboxylase deficiencies and evaluation for biotin-responsiveness in a single blood sample,Clin. Chim. Acta 145 (1985a) 151–162
Suormala, T., Wick, H., Bonjour, J. P. and Baumgartner, E. R. Intestinal absorption and renal excretion of biotin in patients with biotinidase deficiency.Eur. J. Pediatr. (In press) (1985b)
Taitz, L. S., Green, A., Strachan, I., Bartlett, K. and Bennet, M. Biotinidase deficiency and the eye and ear.Lancet ii (1983) 918
Thoene, J., Lemons, R. and Baker, H. Impaired intestinal absorption of biotin in juvenile multiple carboxylase deficiency,N. Engl. J. Med. 308 (1983a) 639–642
Thoene, J. and Wolf, B. Biotinidase deficiency in juvenile multiple carboxylase deficiency.Lancet ii (1983b) 398
Wolf, B., Grier, R. E., Allen, R. J., Goodman, S. I. and Kien, C.L. Biotinidase deficiency: the enzymatic defect in late-onset multiple carboxylase deficiency.Clin. Chim. Acta 131 (1983a) 273–281
Wolf, B., Grier, R. E., Allen, R. J., Goodman, S. I., Kien, G. L. Parker, W. D., Howell, D. M. and Hurst, D. L. Phenotypic variation in biotinidase deficiency.J. Pediatr. 103 (1983b) 233
Wolf, B., Grier, R. E. and Heard, G. S. Hearing loss in biotinidase deficiency.Lancet ii (1983c) 1365–1366
Wolf, B., Grier, R. E., Parker, W. D., Goodman, S. I. and Allen, R. J. Deficient biotinidase activity in late-onset multiple carboxylase deficiency.N. Engl. J. Med. 308 (1983d) 161
Wolf, B., Heard, G. S., Secor McVoy, J. R. and Raetz, H. M. Biotinidase deficiency: the possible role of biotinidase in the processing of dietary protein-bound biotin.J. Inher. Metab. Dis. 7, Suppl. 2 (1984) 121–122
Wolf, B. and Rosenberg, L. E. Stimulation of propionyl-CoA and beta-methylcrotonyl-CoA carboxylase activities in human leukocytes and cultured fibroblasts by biotin.Pediatr. Res. 13 (1979) 1275–1279
Wright, L. D., Driscoll, C. A. and Boger, W. P. Biocytinase, an enzyme concerned with hydrolytic cleavage of biocytin.Proc. Soc. Exp. Biol. Med. 86 (1954) 335–337
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Baumgartner, E.R., Suormala, T., Wick, H. et al. Biotinidase deficiency: Factors responsible for the increased biotin requirement. J Inherit Metab Dis 8 (Suppl 1), 59–64 (1985). https://doi.org/10.1007/BF01800661
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DOI: https://doi.org/10.1007/BF01800661