All newborn screening (NBS) for mucopolysaccharidosis-I (MPS-I) is carried out by the measurement of α-iduronidase (IDUA) enzymatic activity in dried blood spots (DBS). The majority of low enzyme results are due to pseudodeficiencies, and studies from the Mayo Clinic have shown that the false positive rate can be greatly reduced by including a second-tier analysis of glycosaminoglycans (GAGs) in DBS as part of NBS. In the present study, we obtained newborn DBS from 13 patients with severe MPS-I and 2 with attenuated phenotypes. These samples were submitted to four different GAG mass spectrometry analyses in a comparative study: (1) internal disaccharide; (2) endogenous disaccharide; (3) Sensi-Pro; (4) Sensi-Pro Lite (a variation of Sensi-Pro with a simplified workflow). Patients with attenuated MPS-I show less GAG elevation than those with severe disease, and all MPS-I patients were separated from the reference range using all four methods. The minimal differential factor (lowest GAG marker level in MPS-I samples divided by highest level in the reference range of 30 random newborns) was about two for internal disaccharide, Sensi-Pro, and Sensi-Pro Lite methods. The endogenous disaccharide was clearly the best method with a minimal differential of 16-fold. This study supports use of second-tier GAG analysis of newborn DBS, especially the endogenous disaccharide method, as part of NBS to reduce the false positive rate.

All newborn screening (NBS) for mucopolysaccharidosis-I and -II (MPS-I and MPS-II) is carried out via the measurement of α-iduronidase (IDUA) and iduronate-2-sulfatase (IDS) enzymatic activity, respectively, in dried blood spots (DBS). The majority of low enzyme results are due to pseudodeficiencies, and data from recent MPS-II population screenings and studies from the Mayo Clinic show that the false positive rate can be dramatically reduced by the inclusion of a second-tier analysis of glycosaminoglycans (GAGs) in DBS as part of NBS. In the present study, which focused on MPS-II, we obtained newborn DBS from 17 patients with severe MPS-II, 1 with attenuated MPS-II, and 6 patients with various IDS pseudodeficiencies. These samples were submitted to two different GAG mass spectrometry analyses in a comparative study: (1) internal disaccharide biomarkers and (2) endogenous biomarkers. For both of these methods, the biomarker levels in six patients with pseudodeficiencies were below the range measured in MPS-II patients. One patient with attenuated MPS-II was not distinguishable from severe disease patients, but all MPS-II patients were distinguishable from the reference range using both methods. The minimal differential factor (lowest GAG marker level in MPS-II samples divided by highest level in the reference range of 60 random newborns) was 3.01-fold for the internal disaccharide method. The endogenous biomarker method demonstrated an improved minimum differential of 5.41-fold. The minimum differential factors between MPS-II patients and patients with pseudodeficiencies for the internal disaccharide and endogenous biomarker methods were 3.77-fold and 2.06-fold, respectively. This study supports use of the second-tier GAG analysis of newborn DBS, especially the endogenous disaccharide method, as part of NBS to reduce the false positive rate.

BackgroundThe role of pre-school children as a source and distributor of SARS-CoV-2 infections is still unclear. Daycare facilities that care particularly for young children with limited hygiene measures may contribute to the infection dynamics during the pandemic. The aim of this study was to implement and evaluate a voluntary SARS-CoV-2 screening program in daycare facilities.MethodsThe study was conducted over a period of 4 weeks, from June 10th to July 7th 2020. The aim was to screen a representative group of 5000 individuals (children and staff at a ratio 3:1) attending daycare facilities in Düsseldorf, North Rhine-Westphalia. Tests were performed twice per week with oral rinsing water as sample material for the detection of SARS-CoV-2-RNA by molecular pool testing.ResultsA total number of 5210 participants (75.9% children and 24.1% staff) from 115 day care centers participated in the study. Of a total of 34,068 returned samples (81.7%) during the study period, only one SARS-CoV-2 infection of a child was detected in the study cohort with one likely secondary infection within the daycare facility. Of note, during the study phase, no increase of SARS- CoV-2 infections was observed in daycare center compared to the overall incidence in Düsseldorf.ConclusionsA voluntary screening program for SARS-CoV-2 infections could successfully be implemented in daycare facilities. Although the low overall incidence during the study period precludes firm conclusions, there was no evidence for increased transmission in children attending daycare facilities compared to the general population of Düsseldorf.SummarySARS-CoV-2 screening programs in daycare facilities may help to detect asymptomatic infections at an early stage and thereby support containment. Here, a large screening study was evaluated suggesting similar infection rates in daycare facilities compared to the general population.

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There have been significant advances allowing for the integration of mucopolysaccharidosis I into newborn screening programs. Initial experiences using a single-tier approach for this disorder have highlighted shortcomings that require immediate remediation. The recent evaluation of a second-tier biomarker integrated into the MPS I newborn screening protocol has been demonstrated to greatly improve the precision and predictive value of newborn screening for this disorder. This commentary urges newborn screening programs to learn from these experiences and improve newborn screening for mucopolysaccharidosis I and future mucopolysaccharidoses newborn screening programs by implementation of a second-tier biomarker analyte.