Implementation of newborn screening for Krabbe disease: Population study and cutoff determination

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 mu mol/L h (N=139,074) and activities for Krabbe-positive controls ranged from 0.08 to 0.48 mu mol/L h (N=16, n=91 measurements) while activities for carriers ranged from 0.28 to 2.71 mu mol/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. (C) 2009 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.