AUTHOR=Li Ruotong , Tian Liping , Gao Qing , Guo Yuanfang , Li Gaijie , Li Yulin , Sun Meng , Yan Yan , Li Qing , Nie Wenying , Zou Hui 

TITLE=Establishment of Cutoff Values for Newborn Screening of Six Lysosomal Storage Disorders by Tandem Mass Spectrometry

JOURNAL=Frontiers in Pediatrics

VOLUME=Volume 10 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2022.814461

DOI=10.3389/fped.2022.814461

ISSN=2296-2360

ABSTRACT=Objective Lysosomal storage disorders (LSDs) are becoming increasingly important in newborn screening, and tandem mass spectrometry (MS/MS) has been widely used in newborn screening for LSDs through measurement of enzymatic activities in dried blood spots (DBSs). Overall, the determination of the cutoff value is important in such screening, and different laboratories have different methods of determining this value; most do not use a fixed cutoff value but rather calculate the corresponding batch cutoff value based on each batch of experimental data. In this study, we used MS/MS to screen for LSDs and sought to find a appropriate method to establish the cutoff value for LSD screening.
Methods A total of 38,945 samples from newborn blood tablets collected from various maternity hospitals in six cities in Shandong province, including Jinan, Dezhou, Heze, Linyi, Weifang, Zibo, were tested using a Waters Xevo TQD tandem mass spectrometer; the experimental data were analyzed with MassLynx V4.1. The laboratory used 30% of the median GLA enzyme activity and 20% of the median ABG, ASM, GALC, IDUA and GAA enzyme activities in every test as the cutoff values for that batch of experiments.
Results There were 254 suspicious positives in the initial screening test, including 1 case of Gaucher disease, 1 of Niemann-Pick disease, 47 of Krabbe disease, 4 of MPS-I, 21 of Fabry disease and 180 of Pompe disease. After genetic screening, 11 children were diagnosed, including 3 with Pompe disease, 3 with Fabry disease and 5 with Krabbe disease. In addition, the enzyme activity cutoff value of this experiment showed seasonal variation, which was initially believed to be related to the ambient temperature, such as the effect of ambient temperature on the human body or the temperature when the blood tablets dried naturally.
Conclusion Overall, MS/MS can be used in LSD screening, and using different cutoff values in each batch of experiments is feasible. The ambient temperature might be a reason why the enzyme activity cutoff value has seasonal variation. More samples are needed to develop a method of determining cutoff values in laboratories.