The New York pilot newborn screening program for lysosomal storage diseases: Report of the First 65,000 Infants

Abstract

Our results suggest that NBS for LSDs is much more likely to detect individuals at risk for late-onset disease, similar to results from other NBS programs. This work has demonstrated the feasibility of using a novel consented pilot NBS study design that can be modified to include other disorders under consideration for public health implementation as a means to gather critical evidence for evidence-based NBS practices.

Development of a newborn screening tool for mucopolysaccharidosis type I based on bivariate normal limits: Using glycosaminoglycan and alpha‐L‐iduronidase determinations on dried blood spots to predict symptoms

“…4,30 In terms of the bivariate elliptical plots presented here for MPSI ( Figure 1) and earlier for KD, 13 the choice of a low threshold for enzyme level determined as a first tier NBS test would result in an extremely sensitive screening tool; a univariate test with a low threshold would presumably ensure the absence of false negative screens at the possible expense of increased false positive screens. Eliminating false negative results is a critical goal of NBS, and low-threshold univariate tests are indeed the standard practice among screening programs, consistent with the urgent, ethically motivated need to identify every infant with a potentially treatable illness 19,29,31,32 .…”

“…The PPV suggested by this study is considerably higher than those reported in earlier pilot studies. 1,16,17,19 This PPV was estimated from a previously reported prevalence rate, the observed sensitivity, and a target false positive rate. The Monte Carlo simulation verified that this target false positive rate was achieved by the BVNL tool and suggests that these results could indeed be duplicated in a prospective study.…”

“…The MPSI cases being at the limit of enzyme detection (Figure 1) very likely relates to the need to cautiously define thresholds for NBS biomarkers. This need has been described in general with lysosomal storage disorders (LSDs) 19,29 and more specifically with GAG levels in MPS disorders. 4,30 In terms of the bivariate elliptical plots presented here for MPSI ( Figure 1) and earlier for KD, 13 the choice of a low threshold for enzyme level determined as a first tier NBS test would result in an extremely sensitive screening tool; a univariate test with a low threshold would presumably ensure the absence of false negative screens at the possible expense of increased false positive screens.…”

“…However, the choice of low (and therefore sensitive) enzyme thresholds is partially responsible for the lack of an acceptable balance between false positive and negative screens in NBS, as reported for the two disorders to which BVNL diagnostic tools have now been applied: KD 13,33 and MPSI. [14][15][16][17][18][19] There is also ethically motivated urgency to reduce high false positive rates. 32 Using more aggressive thresholds to reduce false positive screens in a univariate test may, however, increase false negative screens.…”

“…This would represent a remarkable improvement in NBS for MPSI. [14][15][16][17][18][19] No new case was identified among the 5000 prospective screens from the Gifu prefecture. New York State recently reported the results of 65 000 LSDs newborn screens.…”