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Biotin-Responsive Multiple Carboxylase Deficiency

  • E. Regula Baumgartner
  • Terttu Suormala

Abstract

Two inherited defects in biotin metabolism are known: holocarboxylase synthetase (HCS) deficiency and biotinidase deficiency. Both lead to multiple carboxylase deficiency (MCD). In HCS deficiency, the formation of holocarboxylases is impaired. In biotinidase deficiency, biotin depletion ensues from the inability to recycle endogenous biotin and to utilize protein-bound biotin from the diet. As the carboxylases play an important role in the catabolism of several amino acids, in gluconeogenesis and in fatty-acid synthesis, their deficiency provokes multiple, life-threatening metabolic derangements, eliciting characteristic organicaciduria and neurologic symptoms. The clinical presentation is extremely variable in both disorders. Characteristic manifestations of MCD are metabolic acidosis, hypotonia, seizures, ataxia, impaired consciousness and cutaneous symptoms, such as skin rash and alopecia. Both disorders respond dramatically to oral therapy with pharmacological doses of biotin. Acquired biotin deficiency, which also causes MCD, is extremely rare.

Keywords

Organic Aciduria Amniotic Fluid Cell Biotinidase Deficiency Biotinidase Activity Biotin Deficiency 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Wolf B (1995) Disorders of biotin metabolism. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic and molecular bases of inherited disease, 7th edn. McGraw-Hill, New York, pp 3151–3177Google Scholar
  2. 2.
    Wolf B, Heard GS, Jefferson LG et al. (1986) Newborn screening for biotinidase deficiency. In Carter TP, Willey AM (eds) Genetic disease: screening and management. Liss, New York, pp 175–182Google Scholar
  3. 3.
    Suormala T, Fowler B, Duran M et al. (1997) Five patients with a biotin-responsive defect in holocarboxylase formation: evaluation of responsiveness to biotin therapy in vivo and comparative studies in vitro. Pediatr Res 41: 666–673PubMedCrossRefGoogle Scholar
  4. 4.
    Sherwood WG, Saunders M, Robinson BH, Brewster T, Gravel RA (1982) Lactic acidosis in biotin-responsive multiple carboxylase deficiency caused by holocarboxylase synthetase deficiency of early and late onset. J Pediatr 101: 546–550PubMedCrossRefGoogle Scholar
  5. 5.
    Suormala T, Fowler B, Jakobs C et al. (1998) Late-onset holocarboxylase synthetase-deficiency: pre-and post-natal diagnosis and evaluation of effectiveness of antenatal biotin therapy. Eur J Pediatr 157: 570–575PubMedCrossRefGoogle Scholar
  6. 6.
    Baumgartner ER, Suormala TM, Wick H, Bausch J, Bonjour JP (1985) Biotinidase deficiency associated with renal loss of biocytin and biotin. Ann NY Acad Sci 447: 272–286PubMedCrossRefGoogle Scholar
  7. 7.
    Baumgartner ER, Suormala TM, Wick H et al. (1989) Biotinidase deficiency: a cause of subacute necrotizing encephalomyelopathy (Leigh syndrome). Report of a case with lethal outcome. Pediatr Res 26: 260–266PubMedCrossRefGoogle Scholar
  8. 8.
    Wolf B, Heard GS, Weissbecker KA et al. (1985) Biotinidase deficiency: initial clinical features and rapid diagnosis. Ann Neurol 18: 614–617PubMedCrossRefGoogle Scholar
  9. 9.
    Wastell HJ, Bartlett K, Dale G, Shein A (1988) Biotinidase deficiency: a survey of so cases. Arch Dis Child 63: 1244–1249PubMedCrossRefGoogle Scholar
  10. 10.
    Ramaekers VTH, Suormala TM, Brab M et al. (1992) A biotinidase Km variant causing late onset bilateral optic neuropathy. Arch Dis Child 67: 115–119PubMedCrossRefGoogle Scholar
  11. 11.
    Duran M, Baumgartner ER, Suormala TM et al. (1993) Cerebrospinal fluid organic acids in biotinidase deficiency. J Inherit Metab Dis 16: 513–516PubMedCrossRefGoogle Scholar
  12. 12.
    Burri BJ, Sweetman L, Nyhan WL (1985) Heterogeneity in holocarboxylase synthetase in patients with biotin-responsive multiple carboxylase deficiency. Am J Hum Genet 37: 326–337PubMedGoogle Scholar
  13. 13.
    Aoki Y, Suzuki Y, Li X et al. (1997) Characterization of mutant holocarboxylase synthetase (HCS): a Km for biotin was not elevated in a patient with HCS deficiency. Pediatr Res 42: 849–854PubMedCrossRefGoogle Scholar
  14. 14.
    Suormala TM, Baumgartner ER, Bausch J, Holiock W, Wick H (1988) Quantitative determination of biocytin in urine of patients with biotinidase deficiency using highperformance liquid chromatography ( HPLC ). Clin Chim Acta 177: 253–270Google Scholar
  15. 15.
    Hymes J, Fleischhauer K, Wolf B (1995) Biotinylation of 28. histones by human serum biotinidase: assessment of biotinyltransferase activity in sera from normal individuals and children with biotinidase deficiency. Biochem Mol Med 56: 76–83PubMedCrossRefGoogle Scholar
  16. 16.
    Norrgard KJ, Pomponio RJ, Swango KL et al. (1997) Mutation (Q456H) is the most common cause of profound biotinidase deficiency in children ascertained by newborn screening in the United States. Biochem Mol Med 61: 22–27PubMedCrossRefGoogle Scholar
  17. 17.
    Pomponio RJ, Hymes J, Reynolds TR et al. (1997) Mutation in the human biotinidase gene that causes profound biotinidase deficiency in symptomatic children: molecular, biochemical, and clinical analysis. Pediatr Res 42: 840–848PubMedCrossRefGoogle Scholar
  18. 18.
    Wolf B, Pomponio RJ, Norrgard KJ et al. (1998) Delayedonset profound biotinidase deficiency. J Pediatr 132: 362–365PubMedCrossRefGoogle Scholar
  19. 19.
    Suormala TM, Baumgartner ER, Wick H, Scheibenreiter S, Schweitzer S (1990) Comparison of patients with complete and partial biotinidase deficiency: biochemical studies. J Inherit Metab Dis 13: 76–92PubMedCrossRefGoogle Scholar
  20. 20.
    Baumgartner ER, Suormala T (1997) Multiple carboxylase deficiency: inherited and acquired disorders of biotin metabolism. Int J Vit Nutr Res 67: 377–384Google Scholar
  21. 21.
    Suzuki Y, Aoki Y, Sakamoto O et al. (1996) Enzymatic diagnosis of holocarboxylase synthetase deficiency using apocarboxyl carrier protein as a substrate. Clin Chim Acta 251: 41–52PubMedCrossRefGoogle Scholar
  22. 22.
    Wolf B (1991) Worldwide survey of neonatal screening for biotinidase deficiency. J Inherit Metab Dis 14: 923–927PubMedCrossRefGoogle Scholar
  23. 23.
    Baur B, Suormala T, Bernoulli C, Baumgartner ER (1998) Biotin determination by three different methods: specificity and application to urine and plasma ultrafiltrates of patients with and without disorders in biotin metabolism. Int J Vit Nutr Res 68: 300–308Google Scholar
  24. 24.
    Aoki Y, Suzuki Y, Sakamoto O et al. (1995) Molecular analysis of holocarboxylase synthetase deficiency: a missense mutation and a single base deletion are predominant in Japanese patients. Biochim Biophys Acta 1272: 168–174PubMedCrossRefGoogle Scholar
  25. 25.
    Wolf B, Hsia YE, Sweetman L et al. (1981) Multiple carboxylase deficiency: clinical and biochemical improvement following neonatal biotin treatment. Pediatrics 68: 113–118PubMedGoogle Scholar
  26. 26.
    Velazquez A, von Raesfeld D, Gonzalez-Noriega A et al. (1986) Pyruvate carboxylase responsive to ketosis in a multiple carboxylase deficient patient. J Inherit Metab Dis 9 [suppl 2]: 300–302CrossRefGoogle Scholar
  27. 27.
    Michalski AJ, Berry GT, Segal S (1989) Holocarboxylase synthetase deficiency: 9-year follow-up of a patient on chronic biotin therapy and a review of the literature. J Inherit Metab Dis 12: 312–316PubMedCrossRefGoogle Scholar
  28. 28.
    Suormala T, Ramaekers VTH, Schweitzer S et al. (1995) Biotinidase Km-variants: detection and detailed biochemical investigations. J Inherit Metab Dis 18: 689–700PubMedCrossRefGoogle Scholar
  29. 29.
    Wolf B, Norrgard KJ, Pomponio RJ et al. (1997) Profound biotinidase deficiency in two asymptomatic adults. Am J Med Genet 73: 5–9PubMedCrossRefGoogle Scholar
  30. 30.
    Secor McVoy JR, Levy HL, Lawler M et al. (1990) Partial biotinidase deficiency: clinical and biochemical features. J Pediatr 116: 78–83CrossRefGoogle Scholar
  31. 31.
    Bernoulli C, Suormala T, Baur B, Baumgartner ER (1998) A sensitive method for the determination of biotin in plasma and CSF, and application to partial biotinidase deficiency. J Inherit Metab Dis 21 [suppl 2] 46: 92Google Scholar
  32. 32.
    Suzuki Y, Aoki Y, Ishida Y et al. (1994) Isolation and characterization of mutations in the human holocarboxylase synthetase cDNA. Nature Genet 8: 122–128PubMedCrossRefGoogle Scholar
  33. 33.
    Leon-Del-Rio A, Leclerc D, Akerman B, Wakamatsu N, Gravel RA (1995) Isolation of cDNA encoding human holocarboxylase synthetase by functional complementation of a biotin auxotroph of Escherichia coli. Proc Natl Acad Sci USA 92: 4626–4630PubMedCrossRefGoogle Scholar
  34. 34.
    Cole H, Reynolds TR, Lockyer JM et al. (1994) Human serum biotinidase. cDNA cloning, sequence, and characterization. J Biol Chem 269: 6566–6570PubMedGoogle Scholar
  35. 35.
    Cole H, Weremovicz S, Morton CC, Wolf B (1994) Localization of serum biotinidase (BTD) to human chromosome 3 in Band Genomics 22: 662–663Google Scholar
  36. 36.
    Dupuis L, Leon-Del-Rio A, Leclerc D et al. (1996) Clustering of mutations in the biotin-binding region of holocarboxylase synthetase in biotin-responsive multiple carboxylase deficiency. Hum Mol Genet 5: 1011–1016PubMedCrossRefGoogle Scholar
  37. 37.
    Norrgard KJ, Pomponio RJ, Swango KL et al. (1997) Double mutation (A171 T and D444H) is a common cause of profound biotinidase deficiency in children ascertained by newborn screening in United States. Hum Mutat, mutations in brief no. 128, on-lineGoogle Scholar
  38. 38.
    Swango KL, Demirkol M, Huner G et al. (1998) Partial biotinidase deficiency is usually due to the D444H mutation in the biotinidase gene. Hum Genet 102: 571–575PubMedCrossRefGoogle Scholar
  39. 39.
    Aoki Y, Li X, Sakamoto O et al. (1999) Identification and characterization of seven mutations in patients with holocarboxylase synthetase deficiency. Hum Genet 104: 143–148PubMedCrossRefGoogle Scholar
  40. 40.
    Sakamoto O, Suzuki Y, Li X et al. (1999) Relationship between kinetic properties of mutant enzyme and biochemical and clinical responsiveness to biotin in holocarboxylase synthetase deficiency. Pediatr Res 46: 671–676PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2000

Authors and Affiliations

  • E. Regula Baumgartner
  • Terttu Suormala

There are no affiliations available

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