{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T09:29:53Z","timestamp":1792056593266,"version":"4.4.0"},"reference-count":27,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T00:00:00Z","timestamp":1780790400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T00:00:00Z","timestamp":1780790400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100032720","name":"Immedica Pharma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100032720","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":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Arginase 1 deficiency (ARG1\u2010D) is an ultra\u2010rare urea cycle disorder characterized by progressive spastic paraplegia, developmental delay, epilepsy, and episodic hyperammonemia. Evidence on prevalence and clinical presentation is scarce. Therefore, epidemiology and the phenotypical spectrum were assessed in Germany, Austria, and Switzerland (DACH region). We conducted a questionnaire\u2010based, cross\u2010sectional study of confirmed ARG1\u2010D patients in the DACH region. Patients were stratified into early\u2010diagnosed (newborn screening [NBS] or high\u2010risk family screening [HR]) and diagnosed after symptom onset. We evaluated clinical, biochemical, and therapeutic characteristics of individuals with confirmed ARG1\u2010D. Epidemiological prevalence estimates were derived using national population data. A total of 20 patients were identified (Germany: 12, Austria: 7, Switzerland: 1). Eight were diagnosed early (NBS: 4, HR: 4) and 12 after symptom onset. Symptomatically diagnosed patients (median age 11\u2009years) presented with a broad range of clinical manifestations, specifically progressive spastic paraplegia (67%), epilepsy (58%), dystonia (46%), developmental delay (58%), and hepatopathy (50%). Median age at diagnosis was 35\u2009months in symptomatic patients versus 1\u2009month in early\u2010diagnosed patients (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.03). Estimated pediatric prevalence was 1:1042080 in the DACH region, with high regional differences. Hyperammonemia was reported in 72%. Enzyme therapy had been initiated in 21%; 2 patients underwent liver transplantation. ARG1\u2010D is a rare disease with a prevalence of approximately 1:1000000 individuals, and a complex and progressive clinical phenotype. Detection via NBS or HR allows early diagnosis and treatment initiation, potentially altering the clinical outcome.\n                  <\/jats:p>","DOI":"10.1002\/jimd.70210","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T05:50:29Z","timestamp":1780897829000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Prevalence, Disease Onset and Clinical Outcome in Arginase 1 Deficiency: Cross\u2010Border Surveillance in Germany, Austria, and Switzerland"],"prefix":"10.1002","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2619-8727","authenticated-orcid":false,"given":"Svenja","family":"Scharre","sequence":"first","affiliation":[{"name":"Department I, Division of Pediatric Neurology and Metabolic Medicine Heidelberg University, Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette L.","family":"Hess","sequence":"additional","affiliation":[{"name":"Department I, Division of Pediatric Neurology and Metabolic Medicine Heidelberg University, Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Gleich","sequence":"additional","affiliation":[{"name":"Department I, Division of Pediatric Neurology and Metabolic Medicine Heidelberg University, Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7420-4757","authenticated-orcid":false,"given":"Sven F.","family":"Garbade","sequence":"additional","affiliation":[{"name":"Department I, Division of Pediatric Neurology and Metabolic Medicine Heidelberg University, Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrik","family":"Feyh","sequence":"additional","affiliation":[{"name":"Division of Metabolic Diagnostics and Newborn Screening Heidelberg University, Medical Faculty Heidelberg  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4846-1047","authenticated-orcid":false,"given":"Daniela","family":"Karall","sequence":"additional","affiliation":[{"name":"Department for Pediatric and Adolescent Medicine, Clinic for Pediatrics I Medical University of Innsbruck  Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Baghdasaryan","sequence":"additional","affiliation":[{"name":"Division of General Pediatrics, Department of Pediatrics and Adolescent Medicine Medical University of Graz  Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0590-678X","authenticated-orcid":false,"given":"Martina","family":"Huemer","sequence":"additional","affiliation":[{"name":"Division of Metabolism and Children's Research Centre University Children's Hospital Zurich, University of Zurich  Zurich Switzerland"},{"name":"Department of Paediatrics LKH Bregenz  Bregenz Austria"},{"name":"Competence Area Healthcare and Nursing Vorarlberg University of Applied Sciences  Dornbirn Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2639-1233","authenticated-orcid":false,"given":"Julia B.","family":"Hennermann","sequence":"additional","affiliation":[{"name":"Villa Metabolica, Center for Pediatric and Adolescent Medicine, University Medical Center Mainz  Mainz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Hahn","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology and Center for Rare Diseases University Hospital Giessen  Giessen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Lindner","sequence":"additional","affiliation":[{"name":"University Hospital Frankfurt, Center for Pediatric and Adolescent Medicine Department of Paediatric Neurology  Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7596-6529","authenticated-orcid":false,"given":"Gwendolyn","family":"Gramer","sequence":"additional","affiliation":[{"name":"Department for Inborn Metabolic Diseases University Children's Hospital, University Medical Center Hamburg\u2010Eppendorf  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Luecke","sequence":"additional","affiliation":[{"name":"Ruhr\u2010University Bochum, St. Josef\u2010Hospital, University Hospital of Pediatrics and Adolescent Medicine Department of Neuropediatrics and Social Pediatrics  Bochum Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nils","family":"Kleinelanghorst","sequence":"additional","affiliation":[{"name":"Health Center for Children, Adolescents, and Young Adults, Medical Practice Doctores Dietz\/Illerhaus, Focus Neuropediatrics  Drensteinfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0635-091X","authenticated-orcid":false,"given":"Johannes","family":"Haeberle","sequence":"additional","affiliation":[{"name":"Division of Metabolism and Children's Research Centre University Children's Hospital Zurich, University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelie S.","family":"Lotz\u2010Havla","sequence":"additional","affiliation":[{"name":"Dr. von Hauner Children's Hospital, LMU University Hospital, Ludwig Maximilian University Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg F.","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Department I, Division of Pediatric Neurology and Metabolic Medicine Heidelberg University, Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juergen G.","family":"Okun","sequence":"additional","affiliation":[{"name":"Division of Metabolic Diagnostics and Newborn Screening Heidelberg University, Medical Faculty Heidelberg  Heidelberg 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