{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T16:24:06Z","timestamp":1783009446131,"version":"3.54.5"},"reference-count":20,"publisher":"Walter de Gruyter GmbH","issue":"6","license":[{"start":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T00:00:00Z","timestamp":1779840000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_jpem-2025-0722_abs_001\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      Citrullinemia type I (CTLN1), caused by variants in the\n                      <jats:italic>ASS1<\/jats:italic>\n                      gene, is characterized by life-threatening neonatal hyperammonemia. The severity of CTLN1 correlates with residual enzyme function: nearly absent activity leads to severe neonatal presentations, while partial function results in milder forms. The increasing identification of patients with mild citrullinemia highlights the need for a deeper understanding of its natural history, genotype\u2013phenotype correlations, and long-term management strategies. This study aims to characterize the clinical and molecular features of mild citrullinemia and explore its implications for long-term management.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jpem-2025-0722_abs_002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective analysis of six pediatric patients diagnosed with mild CTLN1, examining their clinical presentations, biochemical parameters, and long-term outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jpem-2025-0722_abs_003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We present a case series of six patients (three males, three females; median age at presentation 0.5 years, median follow-up 8.5 years) identified through newborn screening (66.7\u202f%), cascade testing (16.7\u202f%), or symptomatic presentation (16.7\u202f%). Consanguinity was present in half of the patients, including one sibling pair. None experienced metabolic decompensation. Baseline citrulline levels were mildly elevated (median 294\u202f\u03bcmol\/L) and ammonia levels ranged from mild to moderate (median 101\u202f\u03bcmol\/L; range 51\u2013154\u202f\u03bcmol\/L). Arginine supplementation was administered to all patients at various stages without dietary protein restriction. Ammonia scavengers were used in three cases\u00a0\u2013\u00a0two during the neonatal period and one at age 14 following neurological symptoms. Despite biochemical stability, half of patients had neurocognitive or psychiatric symptoms, including learning disabilities, obsessive compulsive disorder, attention deficit and hyperactivity disorder, and global developmental\u00a0delay.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jpem-2025-0722_abs_004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings indicate that, despite its classification as \u201cmild\u201d, citrullinemia may involve underrecognized neurological risks, reflecting an incompletely understood pathophysiology. This underscores the importance of individualized treatment and long-term\u00a0care.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/jpem-2025-0722","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T12:58:26Z","timestamp":1779800306000},"page":"594-603","source":"Crossref","is-referenced-by-count":0,"title":["Is mild citrullinemia type I truly benign? a study of long-term clinical outcomes"],"prefix":"10.1515","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-4754-7607","authenticated-orcid":false,"given":"Elif","family":"\u0130\u015fler-Soylu","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Nutrition and Metabolism , \u0130stanbul University-Cerrahpa\u015fa, Cerrahpa\u015fa Medical Faculty, \u0130stanbul , T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5781-1168","authenticated-orcid":false,"given":"Tu\u011f\u00e7e","family":"Aras-\u00c7\u00f6l","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Nutrition and Metabolism , \u0130stanbul University-Cerrahpa\u015fa, Cerrahpa\u015fa Medical Faculty, \u0130stanbul , T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0734-4415","authenticated-orcid":false,"given":"Han\u0131m","family":"Babazade Aghakishili","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Nutrition and Metabolism , \u0130stanbul University-Cerrahpa\u015fa, Cerrahpa\u015fa Medical Faculty, \u0130stanbul , T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8645-5975","authenticated-orcid":false,"given":"Ka\u011fan","family":"\u00c7al\u0131\u015fgan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Nutrition and Metabolism , \u0130stanbul University-Cerrahpa\u015fa, Cerrahpa\u015fa Medical Faculty, \u0130stanbul , T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7159-4008","authenticated-orcid":false,"given":"Tanyel","family":"Zubarioglu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Nutrition and Metabolism , \u0130stanbul University-Cerrahpa\u015fa, Cerrahpa\u015fa Medical Faculty, \u0130stanbul , T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5170-5594","authenticated-orcid":false,"given":"Ertu\u011frul","family":"K\u0131yk\u0131m","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Nutrition and Metabolism , \u0130stanbul University-Cerrahpa\u015fa, Cerrahpa\u015fa Medical Faculty, \u0130stanbul , T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3315-5124","authenticated-orcid":false,"given":"Mehmet \u015eerif","family":"Cansever","sequence":"additional","affiliation":[{"name":"Department of Medical Services and Techniques, Medical Laboratory Techniques Programme , Vocational School of Health Services, \u0130stanbul University-Cerrahpa\u015fa , \u0130stanbul , T\u00fcrkiye"},{"name":"Department of Pediatrics, Metabolic Diseases Research Laboratory, \u0130 stanbul University-Cerrahpa\u015fa , Cerrahpa\u015fa Medical Faculty , \u0130stanbul , T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7256-0750","authenticated-orcid":false,"given":"Ay\u015fe \u00c7i\u011fdem","family":"Aktu\u011flu-Zeybek","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Nutrition and Metabolism , \u0130stanbul University-Cerrahpa\u015fa, Cerrahpa\u015fa Medical Faculty, \u0130stanbul , T\u00fcrkiye"},{"name":"Department of Pediatrics, Metabolic Diseases Research Laboratory, \u0130 stanbul University-Cerrahpa\u015fa , Cerrahpa\u015fa Medical Faculty , \u0130stanbul , T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2026,5,27]]},"reference":[{"key":"2026070215583360713_j_jpem-2025-0722_ref_001","doi-asserted-by":"crossref","unstructured":"H\u00e4berle, J, Boddaert, N, Burlina, A, Chakrapani, A, Dixon, M, Huemer, M, et al.. 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