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Biotinidase

  • Chapter
Laboratory Guide to the Methods in Biochemical Genetics

Abstract

Biotinidase (EC 3.5.1.12) is required for the recycling of biotin and for the utilization of protein bound biotin from the diet. Biotinidase deficiency (MIM 253260) is inherited as an autosomal recessively trait. Patients become progressively biotin deficient which results in reduced activity of the 4 biotin-dependent carboxylases existing in man, and severe life-threatening illness. Oral biotin substitution effectively protects against disease or reverses symptoms. Delayed treatment may result in irreversible neurological damage. Time of onset and severity of illness depend on the level of residual enzyme activity necessitating early (preferably neonatal) assessment of biotinidase activity. Patients are classified as having profound (0-10% residual activity) or partial (residual activity >10-30%) deficiency, or a Km defect due to reduced affinity of biotinidase for its substrate biocytin. Heterozygous individuals show activities intermediate between the deficient and normal activity. The natural substrate of biotinidase is biocytin but it can also act on artificial biotinyl-derivatives. Biotinidase activity in plasma is usually assayed using biotinyl-p-aminobenzoic acid (biotinyl-PABA) as substrate. Liberated PABA is converted to a purple azo dye and quantitated spectrophotometrically. This simple, reproducible and easy to perform colorimetric assay for the diagnosis of patients with different forms of biotinidase deficiency, including those with a Km defect, is described.

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References

  1. Baker H, DeAngelis B, Frank O (1989) Plasma biotinidase assay using the protozoan Ochromonas danica. Nutr Rep Int 39:243–251

    CAS  Google Scholar 

  2. Baumgartner ER, Suormala T (1997) Multiple carboxylase deficiency: inherited and acquired disorders of biotin metabolism. Int J Vitam Nutr Res 67:377–384

    PubMed  CAS  Google Scholar 

  3. Baumgartner ER, Suormala T. Wick H, Bausch J, Bonjour JP (1985) Biotinidase deficiency associated with renal loss of biocytin and biotin. Ann N Y Acad Sci 447:272–287

    Article  Google Scholar 

  4. Baumgartner ER, Suormala TM, Wick H, Probst A, Blauenstein U, Bachmann C, Vest M (1989) Biotinidase deficiency: a cause of subacute necrotizing encephalomyelopathy (Leigh Syndrome) Report of a case with lethal outcome. Pediatr Res 26:260–266

    Article  PubMed  CAS  Google Scholar 

  5. Broda E, Baumgartner ER, Scholl S, Stopsack M, Horn A, Rhode H (2001) Biotinidase determination in serum and dried blood spots – high sensitivity fluorometric ultramicro-assay. Clin Chim Acta 314:175–185

    Article  PubMed  CAS  Google Scholar 

  6. Cole H, Reynolds TR, Lockyer JM, Buck GA, Denson T, Spence JE, Hymes J, Wolf B (1994) Human serum biotinidase. cDNA cloning, sequence, and characterization. J Biol Chem 269:6566–6570

    PubMed  CAS  Google Scholar 

  7. Craft DV, Goss NH, Chandramouli N, Wood HG (1985) Purification of biotinidase from human plasma and its activity on biotinyl peptides. Biochemistry 24:2471–2476

    Article  PubMed  CAS  Google Scholar 

  8. Grier RE, Heard GS, Watkins P, Wolf B (1989) Low biotinidase activities in the sera of patients with impaired liver function: evidence that the liver is the source of serum biotinidase. Clin Chim Acta 186:397–400

    Article  Google Scholar 

  9. Haagerup A, Andersen JB, Blichfeldt S, Christensen MF (1997) Biotinidase deficiency: two cases of very early presentation. Dev Med Child Neurol 39:832–835

    PubMed  CAS  Google Scholar 

  10. Hart PS, Hymes J, Wolf B (1991) Isoforms of human serum biotinidase. Clin Chim Acta 197:257–264

    Article  PubMed  CAS  Google Scholar 

  11. Heard GS, Secor McVoy JR, Wolf B (1984) A screening method for biotinidase deficiency in newborns. Clin Chem 30:125–127

    PubMed  CAS  Google Scholar 

  12. Heard GS, Wolf B, Jefferson LG, Weissbecker KA, Nance WE, Secor McVoy JR, Napolitano A, Mitchell PL, Lambert FW, Linyear AS (1986) Neonatal screening for biotinidase deficiency: results of a 1-year pilot study. J Pediatr 108:40–46

    Article  PubMed  CAS  Google Scholar 

  13. Hymes J, Fleischhauer K, Wolf B (1995) Biotinylation of histones by human serum biotinidase: assessment of biotinyl-transferase activity in sera from normal individuals and children with biotinidase deficiency. Biochem Mol Med 56:76–83

    Article  PubMed  CAS  Google Scholar 

  14. Knappe J, Brümmer W, Biederbick K (1963) Reinigung und Eigenschaften der Biotinidase aus Schweinenieren und Lactobacillus casei. Biochem Z 338:599–613

    PubMed  CAS  Google Scholar 

  15. Kumasaka K, Muratsuga M, Fukui T, Kimura M, Takagi Y, Hashizume N (2001) A new quantitative analytical method of serum biotinidase activity using biocytin as a substrate and its clinical significance in Japan. Clin Chim Acta 306:71–77

    Article  PubMed  CAS  Google Scholar 

  16. Livaniou E, Evangelatos GP, Ithakissios DS (1987) Biotin radioligand assay with an 125I-labeled biotin derivative, avidin, and avidin double-antibody reagents. Clin Chem 33:1983–1988

    PubMed  CAS  Google Scholar 

  17. Möslinger D, Stöckler-Ipsiroglu S, Scheibenreiter S, Tiefenthaler M, Mühl A, Seidl R, Strobl W, Plecko B, Suormala T, Baumgather ER (2001) Clinical and neuropsychological outcome in 33 patients with biotinidase deficiency ascertained by nationwide newborn screening and family studies in Austria. Eur J Pediatr 160:277–282

    Article  PubMed  Google Scholar 

  18. Nagamine T, Saito S, Yamada S, Arai T, Takehara K, Fukui T (1993) Biotinidase activity in patients with liver disease. Scand J Gastroenterol 28:899–906

    Article  PubMed  CAS  Google Scholar 

  19. Pabuccuoglu A, Aydogdu S, Bas M (2002) Serum biotinidase activity in children with chronic liver disease and its clinical significance. J Pediatr Gastroenterol Nutr 34:59–62

    Article  PubMed  CAS  Google Scholar 

  20. Pispa J (1965) Animal biotinidase. Ann Med Exp Biol Fenn 43:1–39

    Article  PubMed  Google Scholar 

  21. Santer R, Gokcay G, Demirkol M, Gal A, Lukacs Z (2005) Hyperchylomicronaemia due to lipoprotein lipase deficiency as a cause of false-positive newborn screening for biotinidase deficiency. J Inherit Metab Dis 28:137–140

    Article  PubMed  CAS  Google Scholar 

  22. Schulpis KH, Gavrili S, Tjamouranis J, Karikas GA, Kapiki A, Costalos C ( 2003) The effect of neonatal jaundice on biotinidase activity. Early Hum Dev 72:15–24

    Article  PubMed  CAS  Google Scholar 

  23. Suormala T, Wick H, Baumgartner ER (1988) Low biotinidase activity in plasma of some preterm infants: possible source of false-positive screening results. Eur J Pediatr 147:478–480

    Article  PubMed  CAS  Google Scholar 

  24. Suormala TM, Baumgartner ER, Bausch J, Holick W, Wick H (1988) Quantitative determination of biocytin in urine of patients with biotinidase deficiency using high-performance liquid chromatography (HPLC). Clin Chim Acta 177:253–270

    Article  PubMed  CAS  Google Scholar 

  25. 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 13:76–92

    Article  PubMed  CAS  Google Scholar 

  26. Suormala T, Ramaekers VTH, Schweitzer S, Fowler B, Laub MC, Schwermer C, Bachmann J, Baumgartner ER (1995) Biotinidase K m-variants: detection and detailed biochemical investigations. J Inherit Metab Dis 18:689–700

    Article  PubMed  CAS  Google Scholar 

  27. Thuy LP, Zielinska B, Sweetman L, Nyhan WL (1985) Determination of biotinidase activity in human plasma using (14C)-biocytin as substrate. Ann N Y Acad Sci 447:434

    Article  Google Scholar 

  28. Wastell H, Dale G, Bartlett K (1984) A sensitive rate assay for biotinidase using a new derivative of biotin, biotinyl-6-aminoquinoline. Anal Biochem 140:69–73

    Article  PubMed  CAS  Google Scholar 

  29. Weiner DL, Grier RE, Wolf B (1985) A bioassay for determining biotinidase activity and for discriminating biocytin from biotin using holocarboxylase synthetase-deficient cultured fibroblasts. J Inherit Metab Dis 8:101–102

    Article  PubMed  CAS  Google Scholar 

  30. Wolf B (2001) Disorders of biotin metabolism. In: Scriver CR, Beaudet AL, Sly VS, Valle D (eds) The Metabolic and Molecular Basis of Inherited Disease. McGraw-Hill, New York, pp 3935–3962

    Google Scholar 

  31. Wolf B, Freehaus CL, Thomas JA, Gordon PL, Greene CL, Ward JC (2003) Markedly elevated serum biotinidase activity may indicate glycogen storage disease type 1a. J Inherit Metab Dis 26:805–809

    Article  PubMed  CAS  Google Scholar 

  32. Wolf B, Grier RE, Allen RJ, Goodman SI, Kien CL (1983) Biotinidase deficiency: the enzymatic defect in late-onset multiple carboxylase deficiency. Clin Chim Acta 131:273–281

    Article  PubMed  CAS  Google Scholar 

  33. Wolf B, Norrgard KJ, Pomponio RJ, Mock DM, McVoy JRS, Fleischhauer K, Shapiro S, Blitzer MG, Hymes J (1997) Profound biotinidase deficiency in two asymptomatic adults. Am J Med Genet 73:5–9

    Article  PubMed  CAS  Google Scholar 

  34. Wolf B, Secor McVoy J (1983) A sensitive radioassay for biotinidase activity: deficient activity in tissues of serum biotinidase-deficient individuals. Clin Chim Acta 135:275–281

    Article  PubMed  CAS  Google Scholar 

  35. Wright LD, Driscoll CA, Boger WP (1954) Biocytinase, an enzyme concerned with hydrolytic cleavage of biocytin. Proc Soc Exp Biol Med 86:335–337

    PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Stoffwechsellabor, UKBB Kinderspital, Römergasse 8, 4005, Basel, Switzerland

    Terttu Suormala

  2. Division of Metabolism and Molecular Pediatrics, University Children’s Hospital, Steinwiesstrasse 75, 8032 , Zurich, Switzerland

    Matthias Baumgartner

  3. Stoffwechsellabor, UKBB Kinderspital, Römergasse 8, 4005, Basel, Switzerland

    Brian Fowler

Authors
  1. Terttu Suormala
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  2. Matthias Baumgartner
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  3. Brian Fowler
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Editor information

Editors and Affiliations

  1. Division of Clinical Chemistry and Biochemistry, University Children’s Hospital, Steinwiesstrasse 75, 8032, Zurich, Switzerland

    Nenad Blau

  2. Academic Medical Centre, Lab. Genetic Metabolic; Diseases Fo-224, University Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, Netherlands

    Marinius Duran

  3. Dept. of Molecular and Medical Genetics, Oregon Health & Science University, 3rd Avenue 2525, 97201, Portland, USA

    K. Michael Gibson

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© 2008 Springer-Verlag Berlin Heidelberg

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Suormala, T., Baumgartner, M., Fowler, B. (2008). Biotinidase. In: Blau, N., Duran, M., Gibson, K. (eds) Laboratory Guide to the Methods in Biochemical Genetics. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-76698-8_15

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  • DOI: https://doi.org/10.1007/978-3-540-76698-8_15

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-76697-1

  • Online ISBN: 978-3-540-76698-8

  • eBook Packages: MedicineMedicine (R0)

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