Newborn Screening and Beyond: Diagnosis, Clinical Management, and Treatment of Inherited Disorders of Intermediary Metabolism and Lysosomal Storage Diseases

Newborn screening (NBS) represents one of the most successful strategies for the early identification of inherited metabolic disorders, enabling diagnosis and treatment before the onset of irreversible clinical manifestations. The progressive expansion of NBS programs, together with advances in tandem mass spectrometry, enzymatic assays, second-tier testing, and molecular technologies, has substantially broadened the spectrum of detectable conditions. This evolution increasingly includes not only disorders of intermediary metabolism, such as amino acid, fatty acid oxidation, urea cycle, and carbohydrate metabolism disorders, but also lysosomal storage diseases. At the same time, expanded screening has generated new clinical challenges, including the interpretation of borderline or uncertain results, identification of attenuated or late-onset phenotypes, and definition of appropriate strategies for confirmation, treatment initiation, and long-term follow-up.This Research Topic aims to provide a clinically oriented overview of the evolving continuum from newborn screening to diagnosis, treatment, and long-term management of inherited metabolic disorders. Particular attention will be given to translating advances in screening technologies into meaningful improvements in clinical practice and patient outcomes. It will explore how biochemical, enzymatic, molecular, and genomic approaches can improve screening accuracy, diagnostic confirmation, and phenotypic characterization, while addressing the challenges associated with false-positive, borderline, and uncertain screening results. It will also examine how early diagnosis influences therapeutic decision-making, including the optimal timing of treatment initiation and the management of presymptomatic, mild, or late-onset phenotypes, and address longitudinal care from the neonatal period through childhood and adolescence.This Research Topic welcomes contributions addressing inherited metabolic disorders included in, or potentially relevant to, newborn screening programs, including amino acid disorders, fatty acid oxidation disorders, urea cycle disorders, disorders of carbohydrate metabolism, and lysosomal storage diseases. To gather further insights into this scope, we welcome articles addressing, but not limited to, the following themes:• Newborn screening strategies and biomarkers• Tandem mass spectrometry and enzymatic assays• Second-tier testing• Molecular and genomic approaches• Diagnostic algorithms and false-positive, borderline, or uncertain results• Genotype–phenotype correlations, natural history, and phenotypic variability• Acute metabolic decompensations and long-term complications• Biochemical and clinical monitoring and multidisciplinary follow-up• Dietary and pharmacological management• Enzyme replacement and other disease-specific therapies• Emerging therapeutic approaches• The effects of newborn screening and presymptomatic diagnosis on treatment initiation, clinical outcomes, and long-term disease trajectoriesWe welcome Original Research, Reviews, Systematic Reviews, and other clinically relevant article types within the journal's scope. Topic editors: Egidio Candela, Diego Martinelli, Vincenza Gragnaniello, Francesco Tagliaferri, Francesco Baldo Source: https://www.frontiersin.org/research-topics/86935/newborn-screening-and-beyond-diagnosis-clinical-management-and-treatment-of-inherited-disorders-of-intermediary-metabolism-and-lysosomal-storage-diseases