{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T03:10:37Z","timestamp":1782789037161,"version":"3.54.5"},"reference-count":45,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T00:00:00Z","timestamp":1736121600000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016062","name":"Stichting Metakids","doi-asserted-by":"publisher","award":["2018\u2010080"],"award-info":[{"award-number":["2018\u2010080"]}],"id":[{"id":"10.13039\/100016062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Gyrate atrophy of the choroid and retina (GACR, OMIM #258870) is a rare inherited metabolic disorder characterized by progressive chorioretinal degeneration and hyperornithinemia. Current therapeutic modalities potentially slow disease progression but are not successful in preventing blindness. To allow for trial development, increased knowledge of the clinical phenotype and current therapeutic outcomes is required. In this study, we analyzed 27 patients with GACR. The median age at inclusion was 24\u2009years (range 8\u201358), with a median age at diagnosis of 14\u2009years (range 0\u201342). Symptoms began at a mean age of 9\u2009years (range 0\u201321). Mixed\u2010models analysis showed a significant association between dietary natural protein intake and plasma ornithine levels. Ornithine increased significantly with age, independent of dietary natural protein intake. We found no statistically significant association between ornithine levels and best\u2010corrected visual acuity over time. Patients who started a natural protein\u2010restricted diet below 10\u2009years of age had better VF outcomes compared to patients that started at a later age. MR spectroscopy was used to asses cerebral creatine deficiency, which was present in 15\/20 patients, of whom 10 were supplemented with creatine at the time. Finally, using the Michigan Retinal Degeneration Questionnaire, we provided a first insight into the vision\u2010related disability reported by patients with GACR and showed that higher foveal sensitivity was associated with less perceived disability. To conclude, this study provides insights into the phenotype, genotype, biochemistry, and treatment effects of GACR, which can be used for care pathways and clinical trial design.<\/jats:p>","DOI":"10.1002\/jimd.12842","type":"journal-article","created":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T19:04:07Z","timestamp":1736190247000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Novel Insights Into Gyrate Atrophy of the Choroid and Retina (<scp>GACR<\/scp>): A Cohort Study"],"prefix":"10.1002","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6999-044X","authenticated-orcid":false,"given":"Berith M.","family":"Balfoort","sequence":"first","affiliation":[{"name":"Department of Pediatrics Emma Children's Hospital, Amsterdam UMC, University of Amsterdam  Amsterdam The Netherlands"},{"name":"Laboratory Genetic Metabolic Diseases, Amsterdam UMC, University of Amsterdam  Amsterdam The Netherlands"},{"name":"Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam UMC, University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filip","family":"Van den Broeck","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Ghent University Hospital  Ghent Belgium"},{"name":"Department of Head &amp; Skin Ghent University  Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camiel J. F.","family":"Boon","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Amsterdam UMC, University of Amsterdam  Amsterdam The Netherlands"},{"name":"Department of Ophthalmology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martijn C. G. J.","family":"Brouwers","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Endocrinology and Metabolic Disease Maastricht University Medical Center  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roselie M. H.","family":"Diederen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Amsterdam UMC, University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Preet","family":"Dhillon","sequence":"additional","affiliation":[{"name":"Genetics and Genome Biology, Peter Gilgan Center for Research and Learning, The Hospital for Sick Children  Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"GACR \u201cBird's Eye View\u201d Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter M.","family":"van Hasselt","sequence":"additional","affiliation":[{"name":"Department of Metabolic Diseases Wilhelmina Children's Hospital, University Medical Center Utrecht  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bregje","family":"Jaeger","sequence":"additional","affiliation":[{"name":"Department of Child Neurology Emma Children's Hospital, Amsterdam UMC, University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica S.","family":"Karuntu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander J. M.","family":"Rennings","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francjan J.","family":"van Spronsen","sequence":"additional","affiliation":[{"name":"Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corrie","family":"Timmer","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Amsterdam UMC, University of Amsterdam  Amsterdam The Netherlands"},{"name":"Department of Nutrition and Dietetics Amsterdam UMC, University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margreet A. E. M.","family":"Wagenmakers","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Center for Lysosomal and Metabolic Diseases, Erasmus University Medical Center Rotterdam  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"De Zaeytijd","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Ghent University Hospital  Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart P.","family":"Leroy","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Ghent University Hospital  Ghent Belgium"},{"name":"Department of Head &amp; Skin Ghent University  Ghent Belgium"},{"name":"Center for Medical Genetics, Ghent University Hospital  Ghent Belgium"},{"name":"Division of Ophthalmology and Center for Cellular and Molecular Therapeutics Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Schulze","sequence":"additional","affiliation":[{"name":"Genetics and Genome Biology, Peter Gilgan Center for Research and Learning, The Hospital for Sick Children  Toronto Canada"},{"name":"Department of Pediatrics and Biochemistry University of Toronto  Toronto Canada"},{"name":"Clinical and Metabolic Genetics, the Hospital for Sick Children  Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara D.","family":"van Karnebeek","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Emma Children's Hospital, Amsterdam UMC, University of Amsterdam  Amsterdam The Netherlands"},{"name":"Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam UMC, University of Amsterdam  Amsterdam The Netherlands"},{"name":"Emma Center for Personalized Medicine, Amsterdam UMC  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2025-5997","authenticated-orcid":false,"given":"Marion M.","family":"Brands","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Emma Children's Hospital, Amsterdam UMC, University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,6]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2021.07.010"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/S00417\u2010024\u201006540\u20108"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbapap.2020.140555"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/biology6010018"},{"key":"e_1_2_11_6_1","volume-title":"The Online Metabolic and Molecular Bases of Inherited Disease","author":"Valle D.","year":"2019"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2744(80)90194-1"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2008.12.010"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.53.2.303"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2362.1999.00569.x"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.59.5.735"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1005602405349"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.120.2.146"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.1991.01080110075039"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.122.7.982"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejcn.2017.102"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1076\/opge.20.4.219.2271"},{"key":"e_1_2_11_18_1","first-page":"616","article-title":"Pyridoxine\u2010Responsive Gyrate Atrophy of the Choroid and Retina: Clinical and Biochemical Correlates of the Mutation A226V","volume":"56","author":"Michaud J.","year":"1995","journal-title":"American Journal of Human Genetics"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.YMGME.2024.108542"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1010545811361"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1005638004530"},{"key":"e_1_2_11_22_1","first-page":"113","article-title":"The Proline\/Citrulline Ratio as a Biomarker for OAT Deficiency in Early Infancy","volume":"4","author":"De Sain\u2010van der Velden M. 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