2. Academic Validation
  3. Novel homozygous PCK1 mutation causing cytosolic phosphoenolpyruvate carboxykinase deficiency presenting as childhood hypoglycemia, an abnormal pattern of urine metabolites and liver dysfunction

Novel homozygous PCK1 mutation causing cytosolic phosphoenolpyruvate carboxykinase deficiency presenting as childhood hypoglycemia, an abnormal pattern of urine metabolites and liver dysfunction

  • Mol Genet Metab. 2017 Apr;120(4):337-341. doi: 10.1016/j.ymgme.2017.02.003.
Päivi Vieira 1,  Jessie Cameron 2,  Elisa Rahikkala 3,  Riikka Keski-Filppula 3,  Lin-Hua Zhang 4,  Saikat Santra 5,  Allison Matthews 4,  Päivi Myllynen 6,  Matti Nuutinen 7,  Jukka S Moilanen 3,  Richard J Rodenburg 8,  Arndt Rolfs 9,  Johanna Uusimaa 10,  Clara D M van Karnebeek 11
Affiliations

Affiliations

  • 1 PEDEGO Research Unit, University of Oulu, Clinic for Children and Adolescents, Oulu University Hospital, Oulu, Finland. Electronic address: paivi.vieira@fimnet.fi.
  • 2 Genetics and Genome Biology, Peter Gilgan Center for Research and Learning, 686 Bay Street, Toronto, Ontario M5G0A4, Canada.
  • 3 PEDEGO Research Unit, Clinical Genetics, University of Oulu, Medical Research Center Oulu, Department of Clinical Genetics, Oulu University Hospital, Oulu, Finland.
  • 4 Department of Pediatrics, Centre for Molecular Medicine and Therapeutics, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, Canada.
  • 5 Department of Clinical Inherited Metabolic Disorders, Birmingham Children's Hospital, Steelhouse Lane, Birmingham B4 6NH, United Kingdom.
  • 6 Northern Finland Laboratory Centre Nordlab, Oulu University Hospital, Oulu, Finland.
  • 7 PEDEGO Research Unit, University of Oulu, Clinic for Children and Adolescents, Oulu University Hospital, Oulu, Finland.
  • 8 Radboud Center for Mitochondrial Medicine, Department of Pediatrics, Translational Metabolic Laboratory, Radboud University Medical Center, Nijmegen, The Netherlands.
  • 9 Centogene AG, The Rare Disease Company, Rostock, Germany; Albrecht Kossel Institute for Neuroregeneration, University of Rostock, Germany.
  • 10 PEDEGO Research Unit, University of Oulu, Clinic for Children and Adolescents, Oulu University Hospital, Oulu, Finland; Medical Research Center Oulu and Biocenter Oulu, University of Oulu, Finland.
  • 11 Department of Pediatrics, Centre for Molecular Medicine and Therapeutics, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, Canada; Department of Pediatrics, Emma Children's Hospital, Academic Medical Centre, Amsterdam, The Netherlands.
PMID: 28216384 DOI: 10.1016/j.ymgme.2017.02.003
Abstract

Clinical and laboratory data were collected from three Finnish patients including a sibling pair and another unrelated child with unexplained childhood hypoglycemia. Transient elevation of alanine transaminase, lactate and tricarboxylic acid cycle intermediates, especially fumarate, were noticed in urine organic acid analysis. Exome Sequencing was performed for the patients and their parents. A novel homozygous PCK1 c.925G>A (p.G309R) mutation was detected in all affected individuals. COS-1 cells transfected with mutant PCK1 transcripts were used to study the pathogenic nature of the detected variant. The COS-1 transfected cells showed the mutant gene to be incapable of producing a normally functioning cytosolic phosphoenolpyruvate carboxykinase (PEPCK) Enzyme. This report further delineates the clinical phenotype of isolated cytosolic PEPCK deficiency and offers a metabolic pattern helping to recognize these patients. Cytosolic PEPCK deficiency should be considered in the differential diagnosis of children presenting with hypoglycemia, hepatic dysfunction and elevated tricarboxylic acid intermediates in urinary organic acid analysis.

Keywords

Autosomal recessive; Child; Impaired gluconeogenesis; Recurrent hypoglycemia.

Figures