Inborn Error of Metabolism (IEM) screening in Singapore by electrospray ionization-tandem mass spectrometry (ESI/MS/MS): An 8 year journey from pilot to current program

摘要

IEM screening by ESI/MS/MS was introduced in Singapore in 2006. There were two phases; a pilot study followed by implementation of the current program. The pilot study was over a 4 year period. During the pilot study, a total of 61,313 newborns were screened, and 20 cases of IEM were diagnosed (detection rate of 1:3065; positive predictive value (PPV) of 11%). Regular self-review, participation in external quality assessment and the Region 4 Genetic collaborative programs (http://www.region4genetics.org/) had led to the robust development of our current NBS MS/MS program. Overall, from July 2006 to April 2014, we screened a total of 177,267 newborns. The mean age at the time of sampling was 47.9 h. Transportation of samples to the testing laboratory averaged 0.92 day. Upon receipt of sample, the NBS result was available within 1.64 days and within 3.8 days if a second tier test was required. Using absolute cut-off values in place of the initial 99th percentile reference range for the analyte markers and the introduction of two 2nd tier tests (MMA and Succinylacetone) had significantly reduced the high recall rate from an initial 1.5% during the period 2006-07 to 0.12% in 2013. The NBS MS/MS program was supported by a centralized confirmatory/diagnostic testing laboratory and a rapid response team of metabolic specialists. The detection rate was 1: 3165 (1:2727 if maternal conditions were also included). There were 23 newborns affected with organic acidemias (incidence: 1:6565), 23 with fatty acid oxidation disorders (incidence: 1:6565), and 10 with amino acidopathies (incidence 1:17,726). The performance metrics for the screening test were acceptable (sensitivity: 95.59%, specificity: 99.85%, PPV: 20%, FPR: 0.15). Participation in the NBS MS/MS program by hospitals was voluntary, and in 2013, the uptake rate was 71% of the annual births. We hope that newborn screening by MS/MS will become a standard of care for all babies in Singapore. (C) 2014 Elsevier Inc. All rights reserved.