Improved identification of partial biotinidase deficiency by newborn screening using age-related enzyme activity cutoffs: Reduction of the false-positive rate

Nicole VanVleck, Barry Wolf*, Mary Seeterlin, Kristin G. Monaghan, Eleanor Stanley, Harry Hawkins, Bonita Taffe

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Background: Biotinidase deficiency is an inherited metabolic disorder that if untreated can result in neurological and cutaneous features. Profound biotinidase deficiency presents in early childhood with severe symptoms, whereas partial biotinidase deficiency can also present with symptoms under times of stress. Symptoms can be prevented by administering biotin. Newborn screening for the disorder is performed using dried blood spots. We examined the relationship between biotinidase activity and age at collection to determine how best to identify infants with partial biotinidase deficiency. Methods: Biotinidase activity in dried blood spots is determined using a quantitative fluorometric assay. Subsequent specimens with biotinidase activity .100 U were analyzed by mutation analysis to determine the range of activities expressed in infants with partial biotinidase deficiency. Results: Enzyme activity increased with age, beginning at about three days of age, and rose until plateauing at about 11 days of age. An increase of about 47.6% was observed. A total of 54 specimens had mutation analysis performed identifying 20 affected infants who would not have been identified using the original cutoff activity of 50 U. Conclusion: Biotinidase activity in infants increases with age. Age-related cutoffs assist in selectively identifying infants with partial biotinidase deficiency.

Original languageEnglish (US)
Pages (from-to)45-56
Number of pages12
JournalInternational Journal of Neonatal Screening
Volume1
Issue number1
DOIs
StatePublished - Jun 2015

Keywords

  • Age-related
  • Biotinidase deficiency
  • Biotinidase; Fluorometric assay
  • Cutoffs
  • Newborn screening
  • Partial biotinidase deficiency

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Immunology and Microbiology (miscellaneous)
  • Obstetrics and Gynecology

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