{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:07:42Z","timestamp":1769645262588,"version":"3.49.0"},"reference-count":9,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T00:00:00Z","timestamp":1769385600000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JIMD Reports"],"published-print":{"date-parts":[[2026,1]]},"abstract":"ABSTRACT<\/jats:title>\n \n Cytosolic phosphoenolpyruvate carboxykinase (PEPCK\u2010C) deficiency is a rare autosomal recessive gluconeogenesis disorder caused by variants in the\n PCK1<\/jats:italic>\n gene. Clinically, PEPCK\u2010C deficiency is characterized by recurrent episodes of fasting\u2010induced hypoglycemia, liver dysfunction, and seizures, with the first hypoglycemic episode typically occurring in the neonatal period or in early childhood. We report a case of PEPCK\u2010C deficiency in an 8\u2010year\u2010old who presented with transient severe acute liver and kidney failure, accompanied by markedly elevated glutamine levels as the initial manifestation of the disease. The acute liver failure was reversible following continuous glucose infusion. Next\u2010generation sequencing identified two variants in the\n PCK1<\/jats:italic>\n gene: one previously known pathogenic variant, c.925G>A p.(Gly309Arg), and a second previously unreported variant, c.1833_1834del p.(Glu611AspfsTer16). These variants were confirmed to be in a compound heterozygous state. Based on the patient's clinical presentation, the second variant was classified as likely pathogenic. Subsequent genetic testing of family members revealed that the patient's 12\u2010year\u2010old sister has the same\n PCK1<\/jats:italic>\n variants but remains asymptomatic to date. Given the clinical findings, we propose that the c.1833_1834del p.(Glu611AspfsTer16) variant in the\n PCK1<\/jats:italic>\n gene should be classified as likely pathogenic. We recommend considering molecular diagnostics for PEPCK\u2010C deficiency in patients presenting with severe acute liver failure and elevated glutamine levels, as early diagnosis and intervention may lead to a reversible outcome.\n <\/jats:p>","DOI":"10.1002\/jmd2.70065","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T04:41:13Z","timestamp":1769488873000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Novel\n PCK1<\/i>\n Gene Variant Associated With Cytosolic Phosphoenolpyruvate Carboxykinase Deficiency: Two Siblings With Different Clinical Presentations"],"prefix":"10.1002","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5813-826X","authenticated-orcid":false,"given":"Lauma","family":"Vasi\u013cevska","sequence":"first","affiliation":[{"name":"Clinic of Medical Genetics and Prenatal Diagnostics Children's Clinical University Hospital Riga Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3318-2555","authenticated-orcid":false,"given":"Ieva","family":"Pu\u0137\u012bte","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology Children's Clinical University Hospital Riga Latvia"},{"name":"Riga Stradi\u0146\u0161 University Riga Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9925-2376","authenticated-orcid":false,"given":"Madara","family":"Auzenbaha","sequence":"additional","affiliation":[{"name":"Clinic of Medical Genetics and Prenatal Diagnostics Children's Clinical University Hospital Riga Latvia"},{"name":"Riga Stradi\u0146\u0161 University Riga Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4890-9147","authenticated-orcid":false,"given":"Dmitrijs","family":"Rots","sequence":"additional","affiliation":[{"name":"Riga Stradi\u0146\u0161 University Riga Latvia"},{"name":"Genetics Laboratory Children's Clinical University Hospital Riga Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1391-1220","authenticated-orcid":false,"given":"Ieva","family":"Gr\u012bnfelde","sequence":"additional","affiliation":[{"name":"Clinic of Medical Genetics and Prenatal Diagnostics Children's Clinical University Hospital Riga Latvia"},{"name":"Riga Stradi\u0146\u0161 University Riga Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"And\u017eela","family":"Lazd\u0101ne","sequence":"additional","affiliation":[{"name":"Genetics Laboratory Children's Clinical University Hospital Riga Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian","family":"Schulz\u2010J\u00fcrgensen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University Medical Center Eppendorf Hamburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,1,26]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"Orphanet \u201cOrphanet: Phosphoenolpyruvate Carboxykinase Deficiency \u201d2024 https:\/\/www.orpha.net\/en\/disease\/detail\/2880."},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.YMGME.2022.07.007"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.12659\/AJCR.943118"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010023\u201002946\u20105"},{"key":"e_1_2_11_6_1","volume-title":"PCK1 Phosphoenolpyruvate Carboxykinase 1 [Homo Sapiens (Human)]\u2014Gene","author":"National Center for Biotechnology Information (NCBI)","year":"2024"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1542\/PEDS.2021\u2010052888I"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.YMGME.2016.03.001"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2018.07.031"},{"key":"e_1_2_11_10_1","volume-title":"PEPCK Deficiency\u2014Symptoms, Causes, Treatment","author":"NORD","year":"2024"}],"container-title":["JIMD Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmd2.70065","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jmd2.70065","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmd2.70065","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T12:01:11Z","timestamp":1769601671000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jmd2.70065"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":9,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1002\/jmd2.70065"],"URL":"https:\/\/doi.org\/10.1002\/jmd2.70065","archive":["Portico"],"relation":{},"ISSN":["2192-8312","2192-8312"],"issn-type":[{"value":"2192-8312","type":"print"},{"value":"2192-8312","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"2025-02-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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