title: Implementation of newborn screening for Krabbe disease: population study and cutoff determination.
abstract: OBJECTIVE
  The aim of this study was to develop a newborn screening algorithm for Krabbe disease.
  
  
  METHODS
  We measured the galactocerebrosidase activity of 139,074 anonymous newborns, 56 known carriers, and 16 Krabbe patients using a tandem mass spectrometry method. The activities were converted to percentages of daily mean activity (%DMA), and the results from diseased and normal populations were used to establish cutoffs.
  
  
  RESULTS
  The absolute activities for the newborns ranged from 0.17 to 355 micromol/L h (N=139,074) and activities for Krabbe-positive controls ranged from 0.08 to 0.48 micromol/L h (N=16, n=91 measurements) while activities for carriers ranged from 0.28 to 2.71 micromol/L h (N=56, n=72 measurements). Cutoffs were set based on results from Krabbe-positive and carrier controls and the newborn population distribution.
  
  
  CONCLUSIONS
  The algorithm and cutoffs we propose provided 100% detection of all positive controls with 60/100,000 screen positive results predicted. In the course of this study, one anonymous newborn was predicted to have Krabbe disease based on enzyme activity and subsequent DNA analysis.
authors.affiliation: Newborn Screening Program, New York State Department of Health, Wadsworth Center, P.O. Box 509, Albany, NY 12201-0509, USA. jjo01@health.state.ny.us
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Orsini
authors.forename: Mark A
authors.initials: MA
authors.lastname: Morrissey
authors.forename: Laura N
authors.initials: LN
authors.lastname: Slavin
authors.forename: Matthew
authors.initials: M
authors.lastname: Wojcik
authors.forename: Chad
authors.initials: C
authors.lastname: Biski
authors.forename: Monica
authors.initials: M
authors.lastname: Martin
authors.forename: Joan
authors.initials: J
authors.lastname: Keutzer
authors.forename: X Kate
authors.initials: XK
authors.lastname: Zhang
authors.forename: Wei-Lien
authors.initials: WL
authors.lastname: Chuang
authors.forename: Carole
authors.initials: C
authors.lastname: Elbin
authors.forename: Michele
authors.initials: M
authors.lastname: Caggana