OBJECTIVE: The aim of this study was to develop a newborn screening algorithm for Krabbe disease. DESIGN AND 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.
OBJECTIVE: The aim of this study was to develop a newborn screening algorithm for Krabbe disease. DESIGN AND 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: Brian J Wolfe; Sophie Blanchard; Martin Sadilek; C Ronald Scott; Frantisek Turecek; Michael H Gelb Journal: Anal Chem Date: 2010-12-30 Impact factor: 6.986
Authors: Thomas J Langan; Amy L Barcykowski; Jonathan Dare; Erin C Pannullo; Leah Muscarella; Randy L Carter Journal: J Neurosci Res Date: 2016-11 Impact factor: 4.164
Authors: Thomas P Mechtler; Thomas F Metz; Hannes G Müller; Katharina Ostermann; Rene Ratschmann; Victor R De Jesus; Bori Shushan; Joseph M Di Bussolo; Joseph L Herman; Kurt R Herkner; David C Kasper Journal: J Chromatogr B Analyt Technol Biomed Life Sci Date: 2012-09-24 Impact factor: 3.205