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Limited evidence-based studies hamper our knowledge on the long-term effects of the proposed medical management in individuals with UCDs. We studied the impact of medical management on growth and weight development in 307 individuals longitudinally followed by the Urea Cycle Disorders Consortium (UCDC) and the European registry and network for Intoxication type Metabolic Diseases (E-IMD). Intrauterine growth of all investigated UCDs and postnatal linear growth of asymptomatic individuals remained unaffected. Symptomatic individuals were at risk of progressive growth retardation independent from the underlying disease and the degree of natural protein restriction. Growth impairment was determined by disease severity and associated with reduced or borderline plasma branched-chain amino acid (BCAA) concentrations. Liver transplantation appeared to have a beneficial effect on growth. Weight development remained unaffected both in asymptomatic and symptomatic individuals. Progressive growth impairment depends on disease severity and plasma BCAA concentrations, but cannot be predicted by the amount of natural protein intake alone. Future clinical trials are necessary to evaluate whether supplementation with BCAAs might improve growth in UCDs.<\/jats:p>","DOI":"10.1038\/s41598-020-67496-3","type":"journal-article","created":{"date-parts":[[2020,7,20]],"date-time":"2020-07-20T10:04:16Z","timestamp":1595239456000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Long-term effects of medical management on growth and weight in individuals with urea cycle disorders"],"prefix":"10.1038","volume":"10","author":[{"given":"Roland","family":"Posset","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven F.","family":"Garbade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Gleich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea L.","family":"Gropman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascale","family":"de Lonlay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg F.","family":"Hoffmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angeles","family":"Garcia-Cazorla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandesh C. 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SK receives funding from Horizon Pharma Ireland Limited for the European Post-Authorization Registry for Ravicti (glycerol phenylbutyrate) oral liquid in partnership with the E-IMD (RRPE) (EU PAS Register No. EUPAS17267; ). AB has received speaker honoraria and travel support from Sanofi Genzyme, Biomarin, Takeda, PIAM, and Nutricia Danone. CPG has received lecture fees from Nutricia, Mead Johnson and Vitaflo-Nestl\u00e9 Espa\u00f1a and travel reimbursement from Biomarin, Nutricia, Vitaflo-Nestl\u00e9 Espa\u00f1a, and SOBI. The sponsors have in no way influenced the design, conductance, analysis and report of the present study. All other authors declare that they have no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"11948"}}