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The clinical development programme of pegzilarginase, a recombinant human ARG1 enzyme therapy, provides an opportunity to study the largest ARG1\u2010D cohort to date. The analysis included 48 paediatric and adult subjects (\u2265\u20092\u2009years) enrolled in the pegzilarginase trials. Baseline data collected before treatment included demographics, genotypes, red blood cell arginase activity, biochemical measures, age of symptom onset, neuromotor and neurological characteristics, growth indicators, quality of life, and use of treatments and assistive devices. The mean (SD) age of onset was 2.2 (3.6) years, which preceded diagnosis at 3.7 (5.0) years. Clinical features included motor impairment (48\/48, 100%), spasticity (33\/48, 69%), cognitive deficits (31\/48, 65%), intellectual disability (23\/36, 64%), speech and language deficits (26\/48, 54%), and seizures (18\/48, 38%), with symptom\u2010onset data consistent with a progressive phenotype. Median GMFCS Level II indicated moderate mobility limitation; two\u2010thirds scored &lt;\u200969 on FSIQ, and mean PedsQL total proxy scores were around 20% lower than typically developing peers. All subjects followed a protein\u2010restricted diet, and 90% used ammonia scavengers. ARG1\u2010D presents with a heterogeneous array of progressive and debilitating neurologic symptoms. These findings reflect the progressive impact of the disease and offer insights into its burden and natural history based on a large cohort, assessed using standardised neuromotor, cognitive, and quality\u2010of\u2010life instruments across international sites.<\/jats:p>","DOI":"10.1002\/jimd.70156","type":"journal-article","created":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T01:54:16Z","timestamp":1770429256000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Clinical Characteristics of Arginase 1 Deficiency: Natural History Insights From International Clinical Trials"],"prefix":"10.1002","volume":"49","author":[{"given":"Mattias","family":"Rudebeck","sequence":"first","affiliation":[{"name":"Immedica Pharma AB  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Braverman","sequence":"additional","affiliation":[{"name":"Research Institute of the McGill 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