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Current management often relies on a reactive approach, with treatment initiated after clinical manifestations. Glycerol phenylbutyrate (GPB) is widely used for ammonia control in UCD. However, its role in later-onset forms remains incompletely defined, particularly regarding timing of initiation. Available evidence suggests that hyperammonemia-related neurological injury may occur even in apparently stable patients, raising concerns about the adequacy of a wait-and-see strategy. This work provides a clinical perspective integrating current evidence together with personal experience to explore the potential role of pre-emptive GPB therapy in later-onset UCD. The limitations of current approaches are discussed, highlighting the discrepancy between apparent biochemical stability and ongoing neurological risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We suggest that a proactive treatment strategy may reduce the risk of neurological complications in selected patients with later-onset UCD. We propose a shift from reactive to pre-emptive management, positioning GPB as a potential tool in this context.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13023-026-04466-4","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T09:05:04Z","timestamp":1782378304000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pre-emptive treatment in later-onset urea cycle disorders: a clinical perspective on glycerol phenylbutyrate"],"prefix":"10.1186","volume":"21","author":[{"given":"Marco","family":"Spada","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3899-4867","authenticated-orcid":false,"given":"Francesco","family":"Porta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"key":"4466_CR1","doi-asserted-by":"publisher","unstructured":"Summar ML, Koelker S, Freedenberg D, Le Mons C, Haberle J, Lee HS, Kirmse B; European Registry and Network for Intoxication Type Metabolic Diseases (E-IMD); Members of the Urea Cycle Disorders Consortium (UCDC). 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