Biochemical Genetics

, Volume 20, Issue 1–2, pp 17–28 | Cite as

Biochemical evidence for diverse etiologies in biotin-responsive multiple carboxylase deficiency

  • Seymour Packman
  • Nancy M. Caswell
  • Herman Baker
Article

Abstract

Biotin-responsive multiple carboxylase deficiency can be categorized by clinical criteria into a neonatal-onset disorder and a distinct syndrome of infantile onset. Pedigrees in each instance are consistent with autosomal recessive inheritance. For a neonatal-onset proband, the sensitivity to relative biotin deprivation and the rapid clinical response to biotin supplementation are reflected by in vitro studies. Specific activities of biotin-dependent pyruvate carboxylase, propionyl CoA carboxylase, and 3-methylcrotonyl CoA carboxylase are 0.8 to 16% of mean control values after growth of fibroblasts in intermediate and very low biotin concentrations. Following relative biotin depletion, pyruvate carboxylase activity returns to normal after only 14 hr of growth in biotin-supplemented medium. In contrast, carboxylase activities in fibroblasts of an infantile-onset proband remain normal at very low biotin concentrations, even when avidin is added to the growth medium. The clinical heterogeneity, taken together with the distinct responses of cultured skin fibroblasts to biotin deprivation in vitro, probably reflect fundamentally different etiologies for the two categories of biotin-responsive multiple carboxylase deficiency.

Key words

biotin avidin pyruvate carboxylase propionyl CoA carboxylase 3-methylcrotonyl CoA carboxylase 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Atkin, B., Utter, M., and Weinberg, M. (1979). Pyruvate caboxylase and phosphoenolpyruvate carboxykinase activity in leukocytes and fibroblasts from a patient with pyruvate carboxylase deficiency. Ped. Res. 1338.Google Scholar
  2. Baker, H., Frank, O., Matovich, V., Pasher, I., Aaronson, S., Hunter, S., and Sabotka, H. (1962). A new assay method for biotin in blood, serum, urine and tissue. Anal. Biochem. 331.Google Scholar
  3. Bartlett, K., Ng, H., and Leonard, J. V. (1980). A combined defect of three mitochondrial carboxylases presenting as biotin-responsive 3-methylcrotonyl glycinuria and 3-hydroxyisovaleric aciduria. Clin. Chim. Acta 100183.Google Scholar
  4. Burri, B., Sweetman, L., and Nyhan, W. (1982). Mutant holocarboxylase synthetase: evidence for the enzyme defect in early infantile biotin-responsive multiple carboxylase deficiency. J. Clin. Investigation, (in press).Google Scholar
  5. Charles, B. M., Hosking, A., Green, A., Pollit, R., Bartlett, K., and Taitz, L. S. (1979). Biotin-responsive alopecia and developmental regression. Lancet 2118.Google Scholar
  6. Cowan, M. J., Packman, S., Wara, D., Ammann, A., Yoshino, M., Sweetman, L., and Nyhan, W. (1979). Multiple biotin-dependent carboxylase deficiencies associated with defects in T-cell and B-cell immunity. Lancet 2115.Google Scholar
  7. Gompertz, D., and Draffan, G. H. (1972). The identification of tiglyglycine in the urine of a child with β-methylcrotonylglycinuria. Clin. Chim. Acta 37405.Google Scholar
  8. Gompertz, D., Draffan, G. H., Watts, J. L., and Hull, D. (1971). Biotin-responsive B-methylcrotonylglycinuria. Lancet 222.Google Scholar
  9. Lehnert, W., Niederhoff, H., Junker, A., Saule, H., and Frasch, W. (1979). A case of biotin-responsive 3-methylcrotonylglycin-and 3-OH-isovalericaciduria. Eur. J. Pediat. 132107.Google Scholar
  10. Markwell, M., Haas, S., Bieber, L., and Tolbert, N. (1978). A modification of the Lowry procedure to simplify protein determination in membrane and lipoprotein samples. Anal. Biochem. 87206.Google Scholar
  11. Munnich, A., Saudubray, J., Carré, G., Coudé, F., Ogier, H., Charpentier, C., and Frézal, J. (1981). Defective biotin absorption in multiple carboxylase deficiency. Lancet 2263.Google Scholar
  12. Murthy, P. N. A., and Mistry, S. P. (1974). Some aspects of biotin binding to protein catalyzed by biotin-deficient chicken liver preparations. Proc. Soc. Exp. Biol. Med. 145565.Google Scholar
  13. Packman, S., Sweetman, L., Baker, H., and Wall, S. (1981a). The neonatal form of biotin responsive multiple carboxylase deficiency. J. Pediat. 99418.Google Scholar
  14. Packman, S., Sweetman, L., Yoshino, M., Baker, H., and Cowan, M. (1981b). Biotin responsive multiple carboxylase deficiency of infantile onset. J. Pediat. 99421.Google Scholar
  15. Pennington, R. J. (1961). Biochemistry of dystrophic muscle. Biochem. J. 80649.Google Scholar
  16. Roth, K., Cohn, R., Yandrasitz, J., Preti, F., Dodd, P., and Segal, S. (1976). β-Methycrotonic aciduria associated with lactic acidosis. J. Pediat. 88229.Google Scholar
  17. Roth, K., Yang, W., Foreman, J., Rothman, R., and Segal, S. (1980). Holocarboxylase synthetase deficiency: A biotin-responsive organic aciduria. J. Pediat. 96845.Google Scholar
  18. Sander, J., Malamud, N., Cowan, M., Packman, S., Ammann, A., and Wara, D. (1980). Intermittent ataxia and immunodeficiency, with multiple carboxylase deficiencies. Ann. Neurol. 8544.Google Scholar
  19. Saunders, M., Sherwood, W., Duthie, M., Suhr, L., and Gravel, R. (1982). Evidence for a defect of holocarboxylase synthetase activity in cultured lymphoblasts from a patient with biotin-responsive multiple carboxylase deficiency. Am. J. Hum. Gen., (in press).Google Scholar
  20. Saunders, M., Sweetman, L., Robinson, B., Roth, K., Cohn, R., and Gravel, R. (1979). Biotin-responsive organic aciduria: Multiple carboxylase defects and complementation studies with propionic aciduria in cultured fibroblasts. J. Clin. Invest. 641695.Google Scholar
  21. Snedecor, G. W., and Cochran, W. G. (1980). Statistical Methods Iowa State University Press, Ames.Google Scholar
  22. Thoene, J., Baker, H., Yoshino, M., and Sweetman, L. (1981). Biotin responsive carboxylase deficiency associated with subnormal plasma and urinary biotin. New Engl. J. Med. 304817.Google Scholar
  23. Weyler, W., Sweetman, L., Maggio, D., and Nyhan, W. (1977). Deficiency of propionyl CoA carboxylase in a patient with methycrotonylglycinuria. Clin. Chim. Acta 76321.Google Scholar

Copyright information

© Plenum Publishing Corporation 1982

Authors and Affiliations

  • Seymour Packman
    • 1
  • Nancy M. Caswell
    • 1
  • Herman Baker
    • 2
  1. 1.Department of Pediatrics, Division of GeneticsUniversity of CaliforniaSan Francisco
  2. 2.Departments of Medicine and Preventive MedicineNew Jersey Medical SchoolEast Orange

Personalised recommendations