Related Experiment Video
Updated: May 31, 2026
Characterization of Neuronal Lysosome Interactome with Proximity Labeling Proteomics
Published on: June 23, 2022
Insights from the LysoNeo prospective cohort study to improve newborn screening of lysosomal diseases
Abdellah Tebani1, David Guenet2, Stéphanie Torre3
1Department of Metabolic Biochemistry, UNIROUEN, AIMS, SysMedLab, CHU Rouen, Referral Center for Lysosomal Diseases, Filière G2M, Normandie University, Rouen, France.
Insights
Newborn screening for 13 lysosomal diseases is feasible, identifying 8 confirmed cases in 100,000 infants. This pilot study informs policy for early detection and intervention in rare genetic disorders.
Area of Science:
- Genetics
- Metabolic Disorders
- Public Health
Background:
- Newborn screening (NBS) enables early detection of genetic conditions.
- Lysosomal diseases are rare inherited metabolic disorders increasingly considered for NBS.
- Early identification of lysosomal diseases improves neurodevelopmental outcomes.
Purpose of the Study:
- Evaluate the feasibility of high-throughput, multi-tiered newborn screening for 13 lysosomal diseases.
- Assess screening cascade dynamics and actionability in a pilot study.
- Provide evidence to inform national policy on expanded NBS.
Main Methods:
- Approached 106,609 families, with 100,212 consenting to screen 100,000 newborns.
- Employed a multi-tier screening process: biochemical testing, reassessment, multidisciplinary review, and confirmatory investigations.
- Utilized dried blood spots collected shortly after birth.
Main Results:
- Identified 75 newborns with abnormal first-tier results (0.075% screen-positive rate).
- Recalled 14 newborns (0.014% recall rate) for further investigation.
- Confirmed 8 cases of lysosomal disease (0.008% confirmed case rate), with 2 initiating therapy.
Conclusions:
- The LysoNeo pilot study demonstrates the feasibility of expanded newborn screening for lysosomal diseases.
- Real-world evidence on screening cascade dynamics and governance was provided.
- Findings can inform national policy for implementing lysosomal disease newborn screening.
Background:
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.
Methods:
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.
Results:
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.
Conclusion:
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.
