{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T02:06:24Z","timestamp":1784685984158,"version":"3.55.0"},"reference-count":14,"publisher":"Georg Thieme Verlag KG","issue":"05","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropediatrics"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cytosolic phosphoenolpyruvate carboxykinase (PEPCK) deficiency (MIM 261680, EC 4.1.1.32, encoded by PCK1) is a rare disorder of gluconeogenesis presenting with recurrent hypoglycemia, hepatic dysfunction, and lactic acidosis. We report on a previously healthy 3-year-old boy who was initially admitted under the suspicion of a febrile seizure during an upper airway infection. Diagnostic workup revealed hypoglycemia as well as a cerebral edema and ruled out an infection. After a complicated course with difficult to treat symptomatic seizures, the child died on the 5th day of admission due to progressive cerebral edema. The metabolic screening showed elevated urinary lactate and Krebs cycle intermediates in line with a primary or secondary energy deficit. Due to the unclear and fatal course, trio exome sequencing was initiated postmortem (\u201cmolecular autopsy\u201d) and revealed the diagnosis of cytosolic PEPCK deficiency based on the compound heterozygosity of a known pathogenic (c.925G\u2009&gt;\u2009A, p.(Gly309Arg)) and a previously unreported (c.724G\u2009&gt;\u2009A, p.(Gly242Arg)) variant in PCK1 (NM_002591.3). Sanger sequencing ruled out the disease and carrier status in three older brothers. Molecular autopsy was performed due to the unclear and fatal course. The diagnosis of a cytosolic PEPCK deficiency not only helped the family to deal with the grief, but especially took away the fear that the siblings could be affected by an unknown disease in the same manner. In addition, this case increases the genetic and phenotypic spectrum of cytosolic PEPCK deficiency.<\/jats:p>","DOI":"10.1055\/s-0040-1722685","type":"journal-article","created":{"date-parts":[[2021,1,14]],"date-time":"2021-01-14T23:39:15Z","timestamp":1610667555000},"page":"398-402","source":"Crossref","is-referenced-by-count":10,"title":["Cytosolic Phosphoenolpyruvate Carboxykinase Deficiency: Cause of Hypoglycemia-Induced Seizure and Death"],"prefix":"10.1055","volume":"52","author":[{"given":"Johanna","family":"Becker","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology and Intensive Care, Klinikum der Universit\u00e4t M\u00fcnchen, LMU, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaus A.","family":"Haas","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology and Intensive Care, Klinikum der Universit\u00e4t M\u00fcnchen, LMU, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Vlaho","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Altoetting-Burghausen, Altoetting, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Heineking","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology and Intensive Care, Klinikum der Universit\u00e4t M\u00fcnchen, LMU, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saskia B.","family":"Wortmann","sequence":"additional","affiliation":[{"name":"University Children\u2019s Hospital, Paracelsus Medical University (PMU), Salzburg, Austria"},{"name":"Radboud Center for Mitochondrial Medicine, Department of Pediatrics, Amalia Children\u2019s Hospital, Radboud University Medical Center, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doroth\u00e9e","family":"Rabenhorst","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology and Intensive Care, Klinikum der Universit\u00e4t M\u00fcnchen, LMU, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Thomas","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology and Intensive Care, Klinikum der Universit\u00e4t M\u00fcnchen, LMU, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa","family":"Brunet","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Technical University Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2021,1,14]]},"reference":[{"key":"ref2","first-page":"Q4a. 1","volume-title":"Diagnostische Prinzipien bei Epilepsien im Kindesalter","author":"B Neubauer","year":"2015"},{"issue":"02","key":"ref3","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.pcl.2017.11.005","article-title":"Inborn errors of metabolism with hypoglycemia: glycogen storage diseases and inherited disorders of gluconeogenesis","volume":"65","author":"D A Weinstein","year":"2018","journal-title":"Pediatr Clin North Am"},{"key":"ref4","volume-title":"Pediatric endocrinology","author":"M A Sperling","year":"2014"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-15720-2","volume-title":"Inborn Metabolic Diseases: Diagnosis and Treatment","author":"J Fernandes","year":"1995"},{"key":"ref6","volume-title":"Inborn Errors of Metabolism: From Neonatal Screening to Metabolic Pathways","author":"B Lee","year":"2015"},{"issue":"03","key":"ref7","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.ymgme.2014.04.001","article-title":"Three rare diseases in one Sib pair: RAI1, PCK1, GRIN2B mutations associated with Smith-Magenis Syndrome, cytosolic PEPCK deficiency and NMDA receptor glutamate insensitivity","volume":"113","author":"D R Adams","year":"2014","journal-title":"Mol Genet Metab"},{"issue":"01","key":"ref8","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.ymgme.2016.03.001","article-title":"Cytosolic phosphoenolpyruvate carboxykinase deficiency presenting with acute liver failure following gastroenteritis","volume":"118","author":"S Santra","year":"2016","journal-title":"Mol Genet Metab"},{"issue":"01","key":"ref9","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.ejmg.2018.04.016","article-title":"Underdiagnoses resulting from variant misinterpretation: Time for systematic reanalysis of whole exome data?","volume":"62","author":"F Al-Murshedi","year":"2019","journal-title":"Eur J Med Genet"},{"issue":"04","key":"ref10","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.ymgme.2017.02.003","article-title":"Novel homozygous PCK1 mutation causing cytosolic phosphoenolpyruvate carboxykinase deficiency presenting as childhood hypoglycemia, an abnormal pattern of urine metabolites and liver dysfunction","volume":"120","author":"P Vieira","year":"2017","journal-title":"Mol Genet Metab"},{"issue":"04","key":"ref11","doi-asserted-by":"crossref","first-page":"e001738","DOI":"10.1161\/CIRCGENETICS.116.001738","article-title":"Investigating the genetic causes of sudden unexpected death in children through targeted next-generation sequencing analysis","volume":"10","author":"L J Dewar","year":"2017","journal-title":"Circ Cardiovasc Genet"},{"issue":"05","key":"ref12","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1002\/jimd.12109","article-title":"Mitochondrial DNA mutation analysis from exome sequencing: a more holistic approach in diagnostics of suspected mitochondrial disease","volume":"42","author":"M Wagner","year":"2019","journal-title":"J Inherit Metab Dis"},{"issue":"05","key":"ref13","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"S Richards","year":"2015","journal-title":"Genet Med"},{"key":"ref14","first-page":"531210","article-title":"Variation across 141,456 human exomes and genomes reveals the spectrum of loss-of-function intolerance across human protein-coding genes","author":"K J Karczewski","year":"2019","journal-title":"bioRxiv"},{"issue":"02","key":"ref15","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1007\/s10897-014-9773-9","article-title":"\u201cIs it going to hurt?\u201d: the impact of the diagnostic odyssey on children and their families","volume":"24","author":"N Carmichael","year":"2015","journal-title":"J Genet Couns"}],"container-title":["Neuropediatrics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0040-1722685.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,20]],"date-time":"2021-09-20T22:34:30Z","timestamp":1632177270000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0040-1722685"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,14]]},"references-count":14,"journal-issue":{"issue":"05","published-online":{"date-parts":[[2021,9,20]]},"published-print":{"date-parts":[[2021,10]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0040-1722685","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0174-304X","1439-1899"],"issn-type":[{"value":"0174-304X","type":"print"},{"value":"1439-1899","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,14]]}}}