2025/07/01 by Mirjam Langeveld, Sandra Sirrs, Daphne H. Schoenmakers +7 · 1 voice
Biochemistry, Genetics and Molecular Biology · Medicine · #Biochemical and Molecular Research #Folate and B Vitamins Research #Metabolism and Genetic Disorders
paper · pdf · doi:10.1002/jimd.70057
openalex publication_date 2025/07/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/25
The number of inherited metabolic diseases (IMDs) in newborn screening (NBS) programs has increased significantly in the past decades. For some of the IMDs included in NBS (e.g., tyrosinemia type I), there are clear and substantial health benefits of NBS, while for others (e.g., very long chain acyl CoA dehydrogenase deficiency and 3-methylcrotonyl CoA carboxylase 1 deficiency), this is less clear as NBS identifies individuals who are asymptomatic or have milder forms of the disease. Therefore, knowledge of the full disease spectrum (including later onset forms) is needed when setting diagnostic metabolite cut-offs for NBS. Insights into the clinical, genetic and biochemical characteristics of different patient subsets can be used to redefine NBS protocols to identify patients with more severe forms of the disease who are most likely to benefit from identification in the newborn period. These insights require life-long monitoring of individuals identified based on symptoms versus those identified by NBS to determine long-term health outcomes and quantify the benefits of NBS. Adult metabolic specialists should be included in the development of NBS programs to provide data from this long-term monitoring and to contribute specific knowledge about later onset phenotypes of the IMDs included in NBS programs. The goal should be to develop NBS programs that identify newborns that benefit from early disease detection and treatment, without increasing psychological, social and management burden for individuals who may develop disease in adulthood with milder phenotype or potentially even not at all.