Newborn screening for lysosomal storage diseases (LSDs) is increasingly being considered as an option. The development of analytical screening methods, of second-tier methods, and of therapeutic possibilities, are paving the way for routine screening for LSDs in the coming years. Here, we give a brief description of the current status quo, what screening methods are currently available or are in the pipeline, what is the current status of therapeutic possibilities for LSDs, what LSDs are the most obvious candidates for introduction in screening programs, and what LSDs are already part of regional or national pilot or routine screening programs worldwide.

The implementation of newborn screening for severe combined immunodeficiency (SCID) in the Netherlands is a multifaceted process in which several parties are involved. The Dutch Ministry of Health adopted the advice of the Dutch Health Council to include SCID in the Dutch newborn screening program in 2015. As newborn screening for SCID is executed with a new, relatively expensive assay for the Dutch screening laboratory, an implementation pilot study is deemed instrumental for successful implementation. A feasibility study was performed in which the practicalities and preconditions of expanding the newborn screening program were defined. Cost-effectiveness analysis (CEA) indicated that SCID screening in the Netherlands might be cost-effective, recognizing that there are still many uncertainties in the variables underlying the CEA. Data and experience of the pilot study should provide better estimates of these parameters, thus enabling the actualization of CEA results. Prior to the implementation pilot study, a comparison study of two commercially available SCID screening assays was performed. A prospective implementation pilot study or so-called SONNET study (SCID screening research in the Netherlands with TRECs) started in April 2018 and allows the screening for SCID of all newborns in three provinces of the Netherlands for one year. Based on the results of the SONNET study, the Dutch Ministry of Health will make a final decision about national implementation of newborn screening for SCID in the Netherlands.

Currently, Dutch newborns are screened for tyrosinemia type 1 (TT1) using succinylacetone (SA) as the biomarker. Although the sensitivity of the test is high, a high number of false positives is observed. Here, the aim is to evaluate the current Dutch newborn-screening protocol and to assess alternatives, specifically the use of biomarkers that are already being measured, to increase the positive predictive value (PPV). TT1 screening was performed with the Revvity NeoBase assay between 2008 and 2017, and since 2018, the Revvity NeoBase 2 assay has been used. Data from 2018 to 2021 were used for evaluation. To simulate alternative screening protocols, these data were enriched with results of referrals from other periods and a false negative (FN) from 2010. In 2018–2021, 693,821 newborns were screened, resulting in 23 referrals, of whom two were TT1 patients. For this period, to date, no FN have been reported, resulting in a provisional sensitivity of 100%, a specificity of 99.997%, and a PPV and negative predictive value of 9% and 100%, respectively. To improve the PPV, we combined SA, tyrosine (tyr), tyr × SA and tyr/phenylalanine and achieved a PPV of 72% for this dataset without introducing FN in the original dataset. This illustrates that future screening for TT1 may benefit from the addition of these biomarkers.