Molema F.Gleich F.Burgard P.van der Ploeg A.T.Summar M.L.Chapman K.A.Bari? I.Lund A.M.K?lker S.Williams M.H?rster F.Jelsig A.M.de Lonlay P.Wijburg F.A.Bosch A.Freisinger P.Posset R.Augoustides-Savvopoulou P.Avram P.Deleanu C.Baumgartner M.R.H?berle J.Blasco-Alonso J.Burlina A.B.Rubert L.Cazorla A.G.Saladelafont E.C.I.Dionisi-Vici C.Martinelli D.Dobbelaere D.Mention K.Gr?newald S.Chakrapani A.WUH-LIANG HWUYIN-HSIU CHIENNI-CHUNG LEEKarall D.Scholl-B?rgi S.Lachmann R.De Laet C.Matsumoto S.de Meirleir L.M?hlhausen C.Schiff M.Pe?a-Quintana L.Djordjevic M.Sarajlija A.Sykut-Cegielska J.Wisniewska A.Leao-Teles E.Alves S.Vara R.Vives-Pinera I.Ortega D.G.Morris A.Zeman J.Honzik T.Chabrol B.Arnaudo F.Cano A.Thompson N.Eyskens F.Lindner M.L?sebrink N.Jalan A.Sokal E.Legros V.Nassogne M.C.Additional individual contributors from E-IMD2020-12-092020-12-0920190141-8955https://www.scopus.com/inward/record.uri?eid=2-s2.0-85062221655&doi=10.1002%2fjimd.12066&partnerID=40&md5=c2af6b9b4e4caa560e66c9371c664e94https://scholars.lib.ntu.edu.tw/handle/123456789/525074Organic acidurias (OAD) and urea-cycle disorders (UCD) are rare inherited disorders affecting amino acid and protein metabolism. As dietary practice varies widely, we assessed their long-term prescribed dietary treatment against published guideline and studied plasma amino acids levels. We analyzed data from the first visit recorded in the European registry and network for intoxication type metabolic diseases (E-IMD, Chafea no. 2010 12 01). In total, 271 methylmalonic aciduria (MMA) and propionic aciduria (PA) and 361 UCD patients were included. Median natural protein prescription was consistent with the recommended daily allowance (RDA), plasma L-valine (57%), and L-isoleucine (55%) levels in MMA and PA lay below reference ranges. Plasma levels were particularly low in patients who received amino acid mixtures (AAMs-OAD) and L-isoleucine:L-leucine:L-valine (BCAA) ratio was 1.0:3.0:3.2. In UCD patients, plasma L-valine, L-isoleucine, and L-leucine levels lay below reference ranges in 18%, 30%, and 31%, respectively. In symptomatic UCD patients who received AAM-UCD, the median natural protein prescription lay below RDA, while their L-valine and L-isoleucine levels and plasma BCAA ratios were comparable to those in patients who did not receive AAM-UCD. Notably, in patients with ornithine transcarbamylase syndrome (OTC-D), carbamylphosphate synthetase 1 syndrome (CPS1-D) and hyperammonemia-hyperornithinemia-homocitrullinemia (HHH) syndrome selective L-citrulline supplementation resulted in higher plasma L-arginine levels than selective L-arginine supplementation. In conclusion, while MMA and PA patients who received AAMs-OAD had very low BCAA levels and disturbed plasma BCAA ratios, AAMs-UCD seemed to help UCD patients obtain normal BCAA levels. In patients with OTC-D, CPS1-D, and HHH syndrome, selective L-citrulline seemed preferable to selective L-arginine supplementation. ? 2019 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM[SDGs]SDG3amino acid; branched chain amino acid; carbamoyl phosphate synthase; citrulline; isoleucine; leucine; ornithine carbamoyltransferase; valine; amino acid; ornithine; amino acid blood level; Article; carbamylphosphate synthetase 1 syndrome; child; clinical evaluation; cohort analysis; comparative study; cross-sectional study; diet supplementation; diet therapy; disease registry; disorders of amino acid and protein metabolism; enzyme deficiency; Europe; female; human; hyperornithinemia hyperammonemia homocitrullinuria syndrome; major clinical study; male; methylmalonic aciduria; organic aciduria; ornithine transcarbamylase syndrome; practice guideline; propionic aciduria; school child; urea cycle disorder; adolescent; adult; clinical trial; dietary supplement; disorders of amino acid and protein metabolism; feasibility study; hyperammonemia; infant; multicenter study; preschool child; propionic acidemia; register; retrospective study; treatment outcome; urea cycle disorder; young adult; Adolescent; Adult; Amino Acid Metabolism, Inborn Errors; Amino Acids; Child; Child, Preschool; Cross-Sectional Studies; Dietary Supplements; Europe; Feasibility Studies; Female; Humans; Hyperammonemia; Infant; Male; Ornithine; Propionic Acidemia; Registries; Retrospective Studies; Treatment Outcome; Urea Cycle Disorders, Inborn; Young Adultjournal article10.1002/jimd.12066307349352-s2.0-85062221655