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In addition, a NBS pilot study in Southwest Germany identifies individuals with propionic acidemia (PA), methylmalonic acidemia (MMA), combined and isolated remethylation disorders (e.g., cobalamin [cbl] C and methylenetetrahydrofolate reductase [MTHFR] deficiency), cystathionine \u03b2\u2010synthase (CBS) deficiency, and neonatal cbl deficiency through one multiple\u2010tier algorithm. The long\u2010term health benefits of screened individuals are evaluated in a multicenter observational study. Twenty seven screened individuals with IMDs (PA [<jats:italic>N<\/jats:italic>\u2009=\u200913], MMA [<jats:italic>N<\/jats:italic>\u2009=\u20096], cblC deficiency [<jats:italic>N<\/jats:italic>\u2009=\u20095], MTHFR deficiency [<jats:italic>N<\/jats:italic>\u2009=\u20092] and CBS deficiency [<jats:italic>N<\/jats:italic>\u2009=\u20091]), and 42 with neonatal cbl deficiency were followed for a median of 3.6\u2009years. Seventeen screened IMD patients (63%) experienced at least one metabolic decompensation, 14 of them neonatally and six even before the NBS report (PA, cbl\u2010nonresponsive MMA). Three PA patients died despite NBS and immediate treatment. Fifteen individuals (79%) with PA or MMA and all with cblC deficiency developed permanent, mostly neurological symptoms, while individuals with MTHFR, CBS, and neonatal cbl deficiency had a favorable clinical outcome. Utilizing a combined multiple\u2010tier algorithm, we demonstrate that NBS and specialized metabolic care result in substantial benefits for individuals with MTHFR deficiency, CBS deficiency, neonatal cbl deficiency, and to some extent, cbl\u2010responsive MMA and cblC deficiency. However, its advantage is less evident for individuals with PA and cbl\u2010nonresponsive MMA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Synopsis<\/jats:title><jats:p>Early detection through newborn screening and subsequent specialized metabolic care improve clinical outcomes and survival in individuals with MTHFR deficiency and cystathionine\u2010\u03b2\u2010synthase deficiency, and to some extent in cobalamin\u2010responsive methylmalonic acidemia (MMA) and cblC deficiency while the benefit for individuals with propionic acidemia and cobalamin\u2010nonresponsive MMA is less evident due to the high (neonatal) decompensation rate, mortality, and long\u2010term complications.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jimd.12731","type":"journal-article","created":{"date-parts":[[2024,4,2]],"date-time":"2024-04-02T15:39:32Z","timestamp":1712072372000},"page":"674-689","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Outcomes after newborn screening for propionic and methylmalonic acidemia and homocystinurias"],"prefix":"10.1002","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7766-4847","authenticated-orcid":false,"given":"Anna T.","family":"Reischl\u2010Hajiabadi","sequence":"first","affiliation":[{"name":"Heidelberg University, Medical Faculty of Heidelberg, Center for Child and Adolescent Medicine, Division of Child Neurology and Metabolic Medicine  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Schnabel","sequence":"additional","affiliation":[{"name":"Heidelberg University, Medical Faculty of Heidelberg, Center for Child and Adolescent Medicine, Division of Child Neurology and Metabolic Medicine  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Gleich","sequence":"additional","affiliation":[{"name":"Heidelberg University, Medical Faculty of Heidelberg, Center for Child and Adolescent Medicine, Division of Child Neurology and Metabolic Medicine  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Mengler","sequence":"additional","affiliation":[{"name":"Heidelberg University, Medical Faculty of Heidelberg, Center for Child and Adolescent Medicine, Division of Child Neurology and Metabolic Medicine  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Lindner","sequence":"additional","affiliation":[{"name":"University Children's Hospital  Frankfurt 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Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah C.","family":"Gr\u00fcnert","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Adolescent Medicine and Neonatology Medical Center, University of Freiburg, Faculty of Medicine  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Thimm","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Neonatology, and Pediatric Cardiology University Children's Hospital, Heinrich Heine University D\u00fcsseldorf  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Freisinger","sequence":"additional","affiliation":[{"name":"Children's Hospital Reutlingen Klinikum am Steinenberg Reutlingen  Reutlingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia B.","family":"Hennermann","sequence":"additional","affiliation":[{"name":"Villa Metabolica, 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