Researchers established cutoff values for newborn screening of 6 lysosomal storage disorders (LSDs), including Pompe disease (PD), and published their results in Frontiers in Pediatrics.

Tandem mass spectrometry resulted as an appropriate method to screen for LSDs, detecting that PD had the highest initial screening positive rate among the other diseases.

Li and colleagues obtained a total of 38,945 samples from newborn dry blood spots collected from different maternity hospitals in 6 cities of the Shandong province. These dry blood spots were useful to determine the activity of 6 lysosomal enzymes (coded by IDUA, GLA, ABG, GALC, ASM, and GAA) in newborns, hence assessing the risk of 6 LSDs.


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In this study, 254 cases were suspicious positives in the initial screening test, including 180 of PD, 1 case of Gaucher disease, 1 of Niemann-Pick disease, 47 of Krabbe disease, 4 of mucopolysaccharidosis type 1, and 21 of Fabry disease. After the genetic screening, 11 children were diagnosed, including 3 with PD, 3 with Fabry disease, and 5 with Krabbe disease.

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“The total incidence of LSDs was nearly 1/3,000, though some research shows that the rate of these diseases is 1/6,000–7,000. This discrepancy might be due to the inclusion of carriers in screen-positive specimens, and the enzyme activity of carriers would also be reduced,” the authors wrote.

The laboratory used 30% of the median GLA enzyme activity and 20% of the median ABG, ASM, GALC, IDUA, and GAA (present in PD) enzyme activities as the cutoff values in every test for that batch of experiments. Interestingly, this method showed seasonal variation, suggesting an association with the effect of ambient temperature on the human body or the temperature when the dry blood spots occur naturally. 

The lysosomal enzyme activity cutoff values were lowest in July and August, and highest in December and January, possibly because a relatively low ambient temperature could provide low-temperature storage conditions for lysosomal enzymes, which would better retain the enzyme activity.

LSDs are becoming increasingly necessary in newborn screening, and tandem mass spectrometry is widely used for PD through the measurement of enzymatic activities in dry blood spots. Determining a fixed cutoff value is essential since each laboratory has different methods of determining this value by calculating it on each batch of experimental data, the authors concluded.

Reference

Li R, Tian L, Gao Q, et al. Establishment of cutoff values for newborn screening of six lysosomal storage disorders by tandem mass spectrometry. Front Pediatr. Published March 28, 2022. doi:10.3389/fped.2022.814461