Newborn screening enables early detection and treatment of serious genetic conditions before symptom onset. Lysosomal diseases, a group of more than 70 rare inherited metabolic disorders, are increasingly considered for inclusion in NBS owing to advances in pathophysiological understanding and therapy development. Early, pre-symptomatic identification offers a critical window for intervention that can improve neurodevelopmental outcomes and quality of life. To evaluate the feasibility of high-throughput, multi-tiered newborn screening for 13 lysosomal diseases, in the LysoNeo pilot study, families of 106,609 newborns were approached between March 2021 and November 2024; 100,212 consented, and 100,000 newborns were successfully screened. Dried blood spots collected shortly after birth underwent a multi-tier screening process combining first-tier biochemical testing, repeat testing of abnormal samples, second-tier reassessment, multidisciplinary review and confirmatory biochemical and molecular investigations for recalled newborns. Among 106,609 families approached, consent is obtained for 100,212 (94.0%), and screening is successfully completed for 100,000 newborns. First-tier screening identifies 75 newborns with abnormal results (screen-positive rate: 0.075%). Following second-tier reassessment and multidisciplinary review, 14 newborns are recalled (recall rate: 0.014%). Eight newborns have concordant biochemical and molecular findings consistent with lysosomal disease (confirmed case rate: 0.008%; Predictive Positive Value among recalled: 57.1% 8/14; Predictive Positive Value among first-tier positives: 10.6% 8/75). Two newborns initiate disease-specific therapy and six remain under structured follow-up. LysoNeo demonstrates the feasibility of implementing expanded lysosomal diseases newborn screening within a regional healthcare system and provides real-world evidence on screening cascade dynamics and actionability-based governance to inform national policy. Newborn screening tests babies shortly after birth to find serious diseases before symptoms appear. Some rare genetic conditions, called lysosomal diseases, can cause severe health problems but may benefit from early treatment. We carried out a large pilot study in the Normandy region of France to assess whether screening for 13 of these diseases could be added safely and effectively to routine newborn screening. Between 2021 and 2024, more than 100,000 newborns were tested using a step-by-step process that combined blood tests and genetic analysis. Eight babies were confirmed to have a lysosomal disease. Two started treatments early, and six are being closely monitored. Our results show that large-scale screening for these rare diseases is possible and can identify affected children early, helping guide future decisions about expanding newborn screening programs. Tebani et al. evaluate the feasibility of high-throughput, multi-tier newborn screening for 13 lysosomal diseases in 100,000 newborns using biochemical, molecular and multidisciplinary assessment. It shows feasible implementation with low recall rates and moderate predictive value, identifying confirmed cases and enabling early treatment in some infants.
Tebani et al. (Fri,) studied this question.