Abstract

Objective: Biotinidase deficiency (BD) is an autosomal recessive inherited metabolic disorder. Biotin plays an important role as a cofactor of carboxylases. BD is categorized into two groups as profound and partial deficiency based on serum quantitative biotinidase enzyme activity (BA). Clinical manifestations are highly variable, ranging from severe metabolic acidosis to asymptomatic.

Methods: Patients who were referred to the pediatric metabolism department due to the suspicion of BD are retrospectively retrieved. This study was conducted between 2019 to 2021 at Cengiz Gökçek Children’s Hospital. The values of quantitative BA, below 30% were defined as deficiency, 10-30% were defined as partial deficiency (PBD), and below 10% were defined as profound deficiency (PFBD). Molecular analysis was performed on the patients. Quantitative analysis of the BA and BTD genes supported the diagnosis. Patients who were misdiagnosed with BD were classified as a false-positive group.

Results: A total of 255 patient files were retrospectively evaluated. 211 patients were included. The median age at presentation of the patients was 27±26,2 days (range: 10-240). 48.3% (n=102) patients in the BD group, and 51.7 % (n=109) patients in the false-positive group. Consanguinity was significantly higher in the BD group (p=0.002). The rate of patients with normal quantitative BA was 54.5% (n=115), PBD was 36.5% (n=77) and PFBD was 9% (n=19). For a variety of reasons, BTD gene analysis was carried out in 79.6% (n=168) of patients. 35.1% (n=59) of them were homozygous mutations, 13.1% (n=22) were compound heterozygous mutations, 40.5% were (n=68) heterozygous mutations, and 11.3% (n=19) were normal. Genetic analysis was consistent with BD in 26.8% (n=25/93) of patients with normal quantitative BA.

Conclusion: BA measurement may be affected by technical reasons. Because sensitivity and specificity of quantitative BA measurement methods are still controversial and inconsistent, confirmation of results by molecular analysis may reduce the risk of misdiagnosis.

Keywords: Biotinidase deficiency, biotin, newborn screening

Copyright and license

Copyright © 2023 The author(s). This is an open-access article published by Aydın Pediatric Society under the terms of the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium or format, provided the original work is properly cited.

How to cite

1.
Göksoy E. Evaluation of newborn screening for biotinidase deficiency from southeastern region of Türkiye. Trends in Pediatrics. 2023;4(4):247-52. https://doi.org/10.59213/TP.2023.07769

References

  1. Canda E, Uçar SK, Çoker M. Biotinidase Deficiency: Prevalence, Impact And Management Strategies. Pediatr Heal Med Ther. 2020;11:127-33.
  2. Hymes J, Wolf B. Biotinidase and its roles in biotin metabolism. Clin Chim Acta. 1996;255:1-11. https://doi.org/10.1016/0009-8981(96)06396-6
  3. Strovel ET, Cowan TM, Scott AI, Wolf B. Laboratory diagnosis of biotinidase deficiency, 2017 update: a technical standard and guideline of the American College of Medical Genetics and Genomics. Genet Med. 2017;19:10.1038/gim.2017.84. https://doi.org/10.1038/gim.2017.84
  4. Zempleni J, Hassan YI, Wijeratne SS. Biotin and biotinidase deficiency. Expert Rev Endocrinol Metab. 2008;3:715-24. https://doi.org/10.1586/17446651.3.6.715
  5. McVoy JR, Levy HL, Lawler M, et al. Partial biotinidase deficiency: clinical and biochemical features. J Pediatr. 1990;116:78-83. https://doi.org/10.1016/s0022-3476(05)81649-x
  6. Wolf B. Successful outcomes of older adolescents and adults with profound biotinidase deficiency identified by newborn screening. Genet Med. 2017;19:396-402. https://doi.org/10.1038/gim.2016.135
  7. Wolf B. Biotinidase deficiency: "if you have to have an inherited metabolic disease, this is the one to have". Genet Med. 2012;14:565-75. https://doi.org/10.1038/gim.2011.6
  8. Gürbüz BB. Yenidoğan Döneminde Metabolik Taramalar. Turkiye Klin J Fam Med-Special Top. 2017;8:324-30.
  9. Wiltink RC, Kruijshaar ME, van Minkelen R, et al. Neonatal screening for profound biotinidase deficiency in the Netherlands: consequences and considerations. Eur J Hum Genet. 2016;24:1424-9. https://doi.org/10.1038/ejhg.2016.65
  10. Wolf B, Grier RE, Allen RJ, Goodman SI, Kien CL. Biotinidase deficiency: the enzymatic defect in late-onset multiple carboxylase deficiency. Clin Chim Acta. 1983;131:273-81. https://doi.org/10.1016/0009-8981(83)90096-7
  11. Heard GS, Secor McVoy JR, Wolf B. A screening method for biotinidase deficiency in newborns. Clin Chem. 1984;30:125-7.
  12. Heard GS, Wolf B, Jefferson LG, et al. Neonatal screening for biotinidase deficiency: results of a 1-year pilot study. J Pediatr. 1986;108:40-6. https://doi.org/10.1016/s0022-3476(86)80766-1
  13. Wolf B. Worldwide survey of neonatal screening for biotinidase deficiency. J Inherit Metab Dis. 1991;14:923-7. https://doi.org/10.1007/BF01800475
  14. Porta F, Pagliardini V, Celestino I, et al. Neonatal screening for biotinidase deficiency: A 30-year single center experience. Mol Genet Metab Rep. 2017;13:80-2. https://doi.org/10.1016/j.ymgmr.2017.08.005
  15. Maguolo A, Rodella G, Dianin A, et al. Newborn Screening for Biotinidase Deficiency. The Experience of a Regional Center in Italy. Front Pediatr. 2021;9:661416. https://doi.org/10.3389/fped.2021.661416
  16. Baykal T, Hüner G, Sarbat G, Demirkol M. Incidence of biotinidase deficiency in Turkish newborns. Acta Paediatr. 1998;87:1102-3. https://doi.org/10.1080/080352598750031518
  17. Kazanasmaz H, Atas N, Karaca M. Specificity and sensitivity of biotinidase activity measured from dried blood spot by colorimetric method. Ann Med Res. 2019;26:2306-11. https://doi.org/10.5455/annalsmedres.2019.07.415
  18. Gökpinar GU. Yenidoğan tarama programı ile tanı konulmuş biotinidaz eksikliği olan hastalarımızın retrospektif değerlendirilmesi [dissertation]. Dokuz Eylül University, 2020.
  19. Canda E, Yazici H, Er E, et al. Single center experience of biotinidase deficiency: 259 patients and six novel mutations. J Pediatr Endocrinol Metab. 2018;31:917-26. https://doi.org/10.1515/jpem-2018-0148
  20. Özdemir AH. Biyotinidaz eksikliği tanılı 901 hastanin geriye dönük değerlendirilmesi: 30 yıllık deneyim [dissertation]. Hacettepe University, 2022.
  21. Seker Yilmaz B, Mungan NO, Kor D, et al. Twenty-seven mutations with three novel pathologenic variants causing biotinidase deficiency: a report of 203 patients from the southeastern part of Turkey. J Pediatr Endocrinol Metab. 2018;31:339-43. https://doi.org/10.1515/jpem-2017-0406
  22. Hacettepe Üniversitesi Nüfus Etütleri Enstitüsü. Türkiye Nüfus ve Sağlık Araştırması. Hacettepe Üniversitesi Nüfus Etütleri Enstitüsü, T.C. Cumhurbaşkanlığı, and TUBİTAK. Ankara, Türkiye; 2018:47-8.
  23. Işeri-Erten SÖ, Dikmen ZG, Ulusu NN. Comparison of Spectrophotometric and Fluorimetric Methods in Evaluation of Biotinidase Deficiency. J Med Biochem. 2016;35:123-9. https://doi.org/10.1515/jomb-2016-0004