Biochemical Genetics

, Volume 17, Issue 7–8, pp 709–713 | Cite as

Evaluation of biotin responsiveness in cultured fibroblasts from patients with propionic acidemia: Absence of response by structurally altered carboxylases

  • Barry Wolf


We have demonstrated that, although propionyl CoA carboxylase (PCC) activity is deficient in fibroblast extracts from PCC-deficient patients belonging to the two major and two minor genetic complementation groups, the activity of another biotin-dependent carboxylase, β-methylcrotonyl CoA carboxylase (βMCC), is normal. Moreover, βMCC activity is stimulated when the fibroblasts are cultured in high concentrations of biotin, in the same way that it is in normal fibroblasts, whereas the depressed PCC activity remains essentially unchanged. Because these results are parallel with the in vivo failure of high-dose biotin to stimulate PCC activity in peripheral blood leukocytes, we conclude that the biotin responsiveness of PCC in cultured fibroblasts from patients with PCC deficiency may be used to predict or confirm biotin responsiveness in vivo.

Key words

propionic acidemia propionyl CoA carboxylase deficiency biotin 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Barnes, N. D., Hull, D., Balgabin, L., and Gompertz, D. (1970). Biotin responsive propionic acidemia. Lancet 2244.Google Scholar
  2. Bartlett, K., and Gompertz, D. (1976). Combined carboxylase defect: Biotin responsiveness in cultured firbroblasts. Lancet 2804.Google Scholar
  3. Gravel, R. A., Lam, K.-F., Scully, K. J., and Hsia, Y. E. (1977). Genetic complementation of propionyl CoA carboxylase deficiency in cultured fibroblasts. Am. J. Hum. Genet. 29378.Google Scholar
  4. Hillman, R. E., Keating, J. P., and Williams, J. C. (1978). Biotin responsive propionic acidemia presenting as the rumination syndrome. J. Pediat. 92439.Google Scholar
  5. Hsia, Y. E., Scully, K., and Rosenberg, L. E. (1971). Inherited propionyl CoA carboxylase deficiency in “ketotic hyperglycinemia.” J. Clin. Invest. 50127.Google Scholar
  6. Weyler, W., Sweetman, L., Maggio, D. C., and Nyhan, W. L. (1977). Deficiency of propionyl CoA carboxylase and β-methylcrotonyl CoA carboxylase in a patient with methylcrotonylglycinuria. Clin. Clim. Acta 76321.Google Scholar
  7. Wolf, B. (1979). Biochemical characterization of mutant propionyl CoA carboxylases from two minor genetic complementation groups. Biochem. Genet. 17703.Google Scholar
  8. Wolf, B., and Hsia, Y. E. (1978). Biotin responsiveness in propionic acidemia. Lancet 2901.Google Scholar
  9. Wolf, B., and Rosenberg, L. E. (1978). Heterozygote expression in propionyl CoA carboxylase deficiency: Differences between major complementation groups. J. Clin. Invest. 62931.Google Scholar
  10. Wolf, B., and Rosenberg, L. E. (1979). Stimulation of propionyl CoA and β-methylcrotonyl CoA carboxylase activities in human leukocytes and cultured fibroblasts by biotin. Pediat. Res. (in press).Google Scholar
  11. Wolf, B., Hsia, Y. E., and Rosenberg, L. E. (1978). Biochemical differences between mutant propionyl CoA carboxylases from two complementation groups. Am. J. Hum. Genet. 30455.Google Scholar

Copyright information

© Plenum Publishing Corporation 1979

Authors and Affiliations

  • Barry Wolf
    • 1
  1. 1.Departments of Human Genetics and PediatricsMedical College of VirginiaRichmond

Personalised recommendations