{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T08:02:42Z","timestamp":1779782562488,"version":"3.53.1"},"reference-count":30,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T00:00:00Z","timestamp":1768780800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T00:00:00Z","timestamp":1768780800000},"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":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Cytosolic phosphoenoylpyruvate carboxykinase (PEPCK\u2010C) is an essential, rate\u2010limiting enzyme in the gluconeogenesis pathway. PEPCK\u2010C deficiency presents with hypoglycaemia, hyperlactataemia and hepatopathy, and was first reported in association with bi\u2010allelic\n                    <jats:italic>PCK1<\/jats:italic>\n                    variants in 2014. A Finnish cohort with a common homozygous variant (c.925G&gt;A, p.(Gly309Arg)) is well\u2010described, but few other genotypes are reported. Five non\u2010Finnish probands with PEPCK\u2010C deficiency with novel genotypes are presented. All five presented with hypoglycaemia (hypoketotic in three), lactic acidosis, and elevated transaminases. Age at presentation was newborn to 3\u2009years. Two presented with hypoglycaemic seizures after overnight fasting during intercurrent infection. Prominent renal manifestations were noted in two, including proximal tubulopathy with bicarbonate wasting, and acute renal failure, respectively, with markedly elevated plasma glutamine in both. Urine organic acid analysis identified elevated lactate, dicarboxylic aciduria, and tricarboxylic acid cycle metabolites, especially fumarate which was detected in 3\/5.\n                    <jats:italic>PCK1<\/jats:italic>\n                    genotypes included homozygous missense variants c.1211C&gt;T, p.(Ser404Leu) and c.265G&gt;A, p.(Glu89Lys), or compound heterozygous variants including c.824del, p.(Gly275Valfs21); c.496G&gt;A, p.(Val166Met); c.961\u2009+\u20092\u2009T&gt;C; c.204del, p.(Leu69), and c.728A&gt;G p.(Lys243Arg). A severe phenotype with failure to thrive, short fasting tolerance, liver dysfunction, and tubulopathy was noted in one individual harboring compound heterozygous splicing and nonsense variants. Evidence from in silico analyses and the specific phenotype supported the pathogenicity of novel missense variants. These patients reinforce the recognizable presentation of PEPCK\u2010C deficiency while highlighting renal manifestations and expanding the genotypic spectrum.\n                  <\/jats:p>","DOI":"10.1002\/ajmga.70063","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T09:56:23Z","timestamp":1768816583000},"page":"1192-1203","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cytosolic Phosphoenoylpyruvate Carboxykinase Deficiency: Clinical, Biochemical, and Genetic Features of Five Non\u2010Finnish Patients"],"prefix":"10.1002","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9368-9887","authenticated-orcid":false,"given":"Isaac","family":"Bernhardt","sequence":"first","affiliation":[{"name":"National Metabolic Service, Te Toka Tumai, Te Whatu Ora Health New Zealand  Auckland New Zealand"},{"name":"University of Auckland  Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9436-5857","authenticated-orcid":false,"given":"Polona Le Quesne","family":"Stabej","sequence":"additional","affiliation":[{"name":"Molecular Medicine and Pathology, Faculty of Medical and Health Sciences University of Auckland  Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6863-2341","authenticated-orcid":false,"given":"Claire","family":"Hart","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Newborn Screening Sheffield Children's Hospital, South Yorkshire and Bassetlaw Pathology  Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"De Hora","sequence":"additional","affiliation":[{"name":"Specialist Biochemistry Labplus Auckland  Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Hulley","sequence":"additional","affiliation":[{"name":"Inherited Metabolic Disease Service Sheffield Children's Hospital, Sheffield Children's NHS Foundation Trust  Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Anderson","sequence":"additional","affiliation":[{"name":"Great North Children's Hospital, Royal Victoria Infirmary  Newcastle UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry G.","family":"Leitch","sequence":"additional","affiliation":[{"name":"Genetics &amp; Genomic Medicine Department UCL Great Ormond Street Institute of Child Health  London UK"},{"name":"North East Thames Regional Genetics Service, Great Ormond Street Hospital for Children NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugh","family":"Lemonde","sequence":"additional","affiliation":[{"name":"Department of Inherited Metabolic Disease Evelina Children's Hospital, Guys &amp; St Thomas' NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryony","family":"Ryder","sequence":"additional","affiliation":[{"name":"National Metabolic Service, Te Toka Tumai, Te Whatu Ora Health New Zealand  Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9009-5538","authenticated-orcid":false,"given":"James","family":"Davison","sequence":"additional","affiliation":[{"name":"Metabolic Medicine Department Great Ormond Street Hospital for Children NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,19]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2014.04.001"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-023-02946-5"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-197901000-00009"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0040-1722685"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2023.11.009"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41594-021-00714-2"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgmr.2024.101175"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010023\u201006045\u20100"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.adg7492"},{"key":"e_1_2_11_11_1","unstructured":"ClinGen Variant Classification Guidance.2019.ClinGen Sequence Variant Interpretation Recommendation for In Trans Criterion (PM3)\u2014Version 1.0 Working Group Page.https:\/\/clinicalgenome.org\/working\u2010groups\/sequence\u2010variant\u2010interpretation\/."},{"key":"e_1_2_11_12_1","unstructured":"Durkie M. 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