ArticleOrphanet journal of rare diseases2025
Combined biochemical profiling and DNA sequencing in the expanded newborn screening for inherited metabolic diseases: the experience in an Italian reference center.
Article in Orphanet journal of rare diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Newborn screening and biobanking for preventable genetic disorders in Mongolia: A developing country perspective.Regenerative therapy · 2026Review
- Next-generation newborn screening: feasibility of combined genetic and biochemical testing for 95 treatable inherited metabolic disorders.Metabolomics : Official journal of the Metabolomic Society · 2026Review
- Insights from the LysoNeo prospective cohort study to improve newborn screening of lysosomal diseases.Communications medicine · 2026Article
- Incorporating Next-Generation Sequencing in Newborn Screening for Organic Acidemias.International journal of neonatal screening · 2026Article
- Integrating the Genomic Revolution into Newborn Screening: Current Challenges and Future Perspectives.Pediatric reports · 2026Review
- Integrating next-generation sequencing with biochemical screening to optimize first-tier newborn screening systems.Human genomics · 2026Article
- Expert consensus on the combined screening of genes and biomarkers for neonatal diseases.World journal of pediatrics : WJP · 2026Review
- Newborn Screening Program for Spinal Muscular Atrophy in the Campania Region (Italy): Current Limitations and Potential Perspectives.International journal of neonatal screening · 2025Article
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23 authors.
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Abstract
backgroundNewborn screening (NBS) programs have significantly improved the health and outcomes of patients with inherited metabolic disorders (IMDs). Methods based on liquid chromatography/mass spectrometry (LC-MS/MS) analysis are viewed worldwide as the gold standard procedure for the expanded NBS programs for these disorders. Advanced molecular technologies point to genomic sequencing as an alternative and feasible strategy for the screening of genetic diseases, including IMDs. However, each of the two approaches has potential limitations when used as a first-tier analysis. In this study, we tested a workflow-based parallel biochemical and sequencing analyses to determine whether this approach could improve the diagnostic outcome.
resultsFor each patient identified by LC-MS/MS as positive, we performed both the biochemical confirmatory tests and next-generation sequencing (NGS) procedures from the same Dried Blood Spot (DBS). NGS analysis was based on applying Exome Sequencing libraries, limiting the analysis to 105 actionable genes involved in IMDs. This allows overtaking the actual limitations of NBS on DBS, enhancing our capacity to identify variants that can drive a genetic disease. Through this approach, we could reach 100% of cases solved, with 37.9% of cases (41/108) for which the combination of the biochemical and NGS analysis was indispensable for a correct diagnosis. In total, we could identify 17 affected, 34 false positives, 12 individuals referred to us for maternal conditions. In 45 newborns the molecular analysis showed heterozygosity for mutations in one or more of the genes analyzed, with results compatible with the biochemical profile indicative of NBS positivity.
conclusionsIn this study, we validated the performance of the proposed workflow. The advantage of this approach is limiting molecular analysis only to positive newborns and using a restricted panel of 105 genes relevant for the expanded NBS, with a 100% rate of diagnosis and potential reduction of the costs related to NBS procedures and reduced impact on patients and families.
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