Improved Identification of Partial Biotinidase Deficiency by Newborn Screening Using Age-Related Enzyme Activity Cutoffs: Reduction of the False-Positive Rate

International Journal of Neonatal Screening

Nicole VanVleck²  Barry Wolf¹  Mary Seeterlin²  Kristin G. Monaghan³  Eleanor Stanley²  Harry Hawkins²  Bonita Taffe² 

[1] Genetics Research Laboratory of Research Administration, Henry Ford Hospital, Detroit, MI 48202, USA;Michigan Department of Community Health, Bureau of Laboratories/Division of Chemistry and Toxicology/Newborn Screening Section, Lansing, MI 48906, USA; E-Mails:;Department of Pathology, Henry Ford Hospital, Detroit, MI 48202, USA; E-Mail:

关键词: biotinidase deficiency;    partial biotinidase deficiency;    newborn screening;    biotinidase;    Fluorometric assay;    cutoffs;    age-related;   

DOI  :  10.3390/ijns1010045

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.