{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T10:57:13Z","timestamp":1784631433717,"version":"3.55.0"},"reference-count":39,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,11,22]],"date-time":"2022-11-22T00:00:00Z","timestamp":1669075200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012235","name":"Aeglea BioTherapeutics","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012235","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disord Clin Pract"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Arginase 1 Deficiency (ARG1\u2010D) is a rare autosomal recessive urea cycle disorder (UCD) characterized by pathologic elevation of plasma arginine and debilitating manifestations. Based on clinical commonalities and low disease awareness, ARG1\u2010D can be diagnosed as hereditary spastic paraplegia (HSP), leading to treatment delays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Cases<\/jats:title><jats:p>A Hispanic woman with unremarkable medical history experienced progressive lower\u2010limb spasticity in her 20s and received a diagnosis of HSP. She developed significant gait abnormalities and is unable to walk without assistance. More recently, two Hispanic brothers with childhood\u2010onset manifestations including lower\u2010limb spasticity, developmental delays, and seizures presented with suspected HSP. All three patients were ultimately diagnosed with ARG1\u2010D based on plasma arginine several\u2010fold above normal levels and loss\u2010of\u2010function <jats:italic>ARG1<\/jats:italic> variants. Disease progression occurred before ARG1\u2010D was correctly diagnosed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Literature Review<\/jats:title><jats:p>Retrospective analyses demonstrate that diagnostic delays in ARG1\u2010D are common and can be lengthy. Because of clinical similarities between ARG1\u2010D and HSP, such as insidious onset and progressive spasticity, accurate diagnosis of ARG1\u2010D is challenging. Timely ARG1\u2010D diagnosis is critical because this UCD is a treatable genetic cause of progressive lower\u2010limb spasticity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Arginase 1 Deficiency should be considered in HSP differential diagnosis until biochemically\/genetically excluded, and should be routinely included in HSP gene panels.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mdc3.13612","type":"journal-article","created":{"date-parts":[[2022,11,7]],"date-time":"2022-11-07T06:58:41Z","timestamp":1667804321000},"page":"109-114","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Arginase 1 Deficiency in Patients Initially Diagnosed with Hereditary Spastic Paraplegia"],"prefix":"10.1002","volume":"10","author":[{"given":"Markey C.","family":"McNutt","sequence":"first","affiliation":[{"name":"UT Southwestern Medical Center  Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Foreman","sequence":"additional","affiliation":[{"name":"RehabMetrics  Colleyville Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garrett","family":"Gotway","sequence":"additional","affiliation":[{"name":"UT Southwestern Medical Center  Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,11,22]]},"reference":[{"key":"e_1_2_8_2_1","volume-title":"GeneReviews(R) [updated 2021]","author":"Sun A","year":"2000"},{"key":"e_1_2_8_3_1","volume-title":"StatPearls","author":"Stone WL","year":"2021"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12100"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2010.02.020"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-015-9861-5"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.12488"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2010.01.012"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23545"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv352"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-015-2032-z"},{"key":"e_1_2_8_12_1","first-page":"S137","article-title":"Delays in diagnosis are associated with poor clinical outcomes in patients with arginase 1 deficiency","volume":"86","author":"Diaz GA","year":"2019","journal-title":"Ann Neurol"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-016-9928-y"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.4103\/JPN.JPN_1_19"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27655"},{"key":"e_1_2_8_16_1","article-title":"Childhood\u2010onset hereditary spastic paraplegia and its treatable mimics","author":"Ebrahimi\u2010Fakhari D","year":"2021","journal-title":"Mol Genet Metab"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.21037\/tp-21-112"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.spen.2017.03.016"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2019.00131"},{"key":"e_1_2_8_20_1","volume-title":"GeneReviews\u00ae [updated 2021]","author":"Hedera P","year":"2000"},{"issue":"10","key":"e_1_2_8_21_1","first-page":"2929","article-title":"Defining the clinical, molecular and imaging spectrum of adaptor protein complex 4\u2010associated hereditary spastic paraplegia","volume":"143","author":"Ebrahimi\u2010Fakhari D","year":"2020","journal-title":"Brain"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1177\/088307389701200502"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-7-32"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-022-02226-8"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2014.08.001"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2012.03.016"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11910-021-01099-x"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2012.06.012"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2009.07.017"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181bacf59"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1980"},{"key":"e_1_2_8_32_1","unstructured":"National Organization for Rare Disorders.AP\u20104\u2010associated hereditary spastic paraplegia (AP\u20104\u2010HSP). 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