Abstract
Objective: To assess the incidence of biotinidase deficiency among newborns and their clinical outcome up to one year of age in a large pilot screening study in Minas Gerais, Brazil.
Methods: A prospective cohort study was conducted from September 2007 to June 2008 with heel-prick blood samples collected on filter paper for the purpose of newborn screening. A qualitative colorimetric test was used as the primary screening method. Colorimetric-positive cases were further tested with a serum confirmatory assay. Gene sequencing was performed for eight children suspected with biotinidase deficiency and for some of their parents. Positive cases were daily supplemented with oral biotin and were followed up for approximately six years.
Results: Out of 182,891 newborns screened, 129 were suspected of having biotinidase deficiency. Partial deficiency was confirmed in seven children (one was homozygous for p.D543E) and profound deficiency in one child (homozygous p.H485Q). Thus the incidence was one in 22,861 live births (95% confidence interval 1:13,503 to 1:74,454) for profound and partial biotinidase deficiency combined. Two novel mutations were detected: p.A281V and p.E177K. In silico analysis and estimation of the enzyme activity in the children and their parents showed that p.A281V is pathogenic and p.E177K behaves like p.D444H.
Conclusion: The incidence of biotinidase deficiency in newborn screening in Minas Gerais was higher than several international studies. The sample size should be larger for final conclusions. Oral daily biotin apparently precluded clinical symptoms, but it may have been unnecessary in some newborns.
Competing interests: None declared
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Acknowledgments
The authors gratefully acknowledge the technical and scientific staff of the Center for Newborn Screening and Genetic Diagnostics (Nupad/UFMG) for their involvement and logistical support. The contribution of the technologist Daniela Magalhães Nolasco was essential for the standardization of the biotinidase serum analysis. Marcos Antunes Lopes, Lívia Uliana, and their teams collaborated for the successful recall of the families for confirmatory tests. The authors also wish to thank Nupad and Fapemig for their financial support. Marcos Borato Viana received a researcher grant from CNPq (Brazilian National Council for Research).
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Communicated by: Georg Hoffmann
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Synopsis
This extensive pilot study showed a high incidence (1:22,861) of biotinidase deficiency in Brazilian newborns through a three-phase laboratory procedure: a colorimetric screening test, confirmatory determination of serum biotinidase activity, and gene sequencing (two novel mutants were detected).
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The authors declare that they have no conflict of interest.
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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study.
Details of the Contributions of Individual Authors
Study concept and design: Januario, Gurgel-Giannetti, Lara; Acquisition of data: Lara, Ladeira; Analysis and interpretation of data: Lara, Januario, Viana, del Castillo; Drafting of the manuscript: Lara, Gurgel-Giannetti; Critical revision of the manuscript for important intellectual content: Januario, Viana, Gurgel-Giannetti, Aguiar; Molecular and Biochemical analysis: Ladeira, Carvalho, del Castillo; Final proofreading: Januario, Viana; Paper Guarantor: Januario
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Lara, M.T. et al. (2015). High Incidence of Biotinidase Deficiency from a Pilot Newborn Screening Study in Minas Gerais, Brazil. In: Zschocke, J., Baumgartner, M., Morava, E., Patterson, M., Rahman, S., Peters, V. (eds) JIMD Reports, Volume 24. JIMD Reports, vol 24. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2015_447
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DOI: https://doi.org/10.1007/8904_2015_447
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