Advertisement

Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Biotin dependent multiple carboxylase deficiency presenting as a congenital lactic acidosis

Abstract

Two patients presented in early childhood with (i) alopecia, skin rashs, and candida dermatitis, (ii) severe hypotonia, ataxia and motor retardation, (iii) frequent episodes of ketoacidosis with hyperlactacidemia. Propionic and methylcrotonic aciduria only appeared on high protein diet. Mitochondrial biotin-dependent carboxylase activities were decreased in the liver and leukocytes, but were similar to control values in fibroblasts cultured in a biotin-free medium. In addition, the plasma biotin was found to be significantly lower than in control subjects. These disorders responded to biotin administration, pointing to biotin-dependent multiple carboxylase deficiencies (MCD). Our report stresses the polymorphism of MCD and suggests that MCD could be of two types: impaired vitamin metabolism (absorption, plasma transport), might result in low plasma biotin with generalized MCD involving acetyl CoA carboxylase. Defective mitochondrial holocarboxylase synthetase might lead to a pure mitochondrial MCD, with fibroblastic deficiency and presumably normal biotin metabolism.

This is a preview of subscription content, log in to check access.

References

  1. 1.

    Bonjour JP (1977) Biotin in man's nutrition and therapy: a review. Internat J Vit Nutr Res 46:314–325

  2. 2.

    Charles BM, Hosking G, Green A, Pollitt R, Bartlett K, Taitz LS (1979) Biotin responsive alopecia and developmental regression. Lancet 2:118–120

  3. 3.

    Cowan MJ, Wara DW, Packman S, Ammann AJ, Yoshino M, Sweetman L, Nyhan W (1979) Multiple biotin-dependent carboxylase deficiencies associated with defects in T-cell and B-cell immunity. Lancet 2:115–118

  4. 4.

    Frigg M, Brubacher G (1976) Biotin deficiency in chicks fed a wheat-based diet. Internat J Vit Nutr Res 46:8314–8321

  5. 5.

    Gompertz D, Draffan GH, Watts JL, Hull D (1971) Biotin responsive β methylcrotonylglycinuria. Lancet 2:22–24

  6. 6.

    Kamerling JP, Duran M, Bruinvis L, Ketting D, Wadman SK, De Groot CJ, Hommes FA (1977) (2-ethoxy ethoxy) acetic acid: an unusual compound found in the gaz chromatographic analysis of urinary organic acids. Clin Chim Acta 77:397–405

  7. 7.

    Lehnert W, Niederhoff H, Junker A, Saule H, Frasch W (1979) A case of biotin responsive 3-methylcrotonylglycin-and 3-hydroxyvaleric aciduria. Eur J Pediatr 132:107–114

  8. 8.

    Majerus PW, Kilburne E (1969) Acetyl coenzyme A carboxylase: the roles of synthesis and degradation in regulation of enzyme levels in rat liver. J Biol Chem 244:6254–6262

  9. 9.

    Munnich A, Saudubray JM, Coude FX, Charpentier C, Saurat JH, Frézal J (1980) Fatty acid responsive alopecia in multiple carboxylase deficiency. Lancet 1:1080–1081

  10. 10.

    Roth KS, Yang W, Foreman JW, Rothman R, Segal S (1980) Holocarboxylase synthetase deficiency: a biotin responsive organic acidemia. J Pediat 96:845–849

  11. 11.

    Saunders M, Sweetman L, Robinson B, Roth K, Cohn R, Gravel RA (1979) Biotin responsive organicaciduria: multiple carboxylase defects and complementation studies with propionicacidemia in cultured fibroblasts. J Clin Invest 64: 1695–1702

  12. 12.

    Sweetman L (1980) Two forms of biotin responsive multiple carboxylase deficiency. International Symposium on inborn errors of metabolism. Interlaken

Download references

Author information

Correspondence to A. Munnich.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Munnich, A., Saudubray, J.M., Cotisson, A. et al. Biotin dependent multiple carboxylase deficiency presenting as a congenital lactic acidosis. Eur J Pediatr 137, 203–206 (1981). https://doi.org/10.1007/BF00441318

Download citation

Key words

  • Biotin
  • Carboxylase
  • Lactic acidosis
  • Organicaciduria
  • Inborn errors of metabolism