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. Epub 2017 Feb 6.


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.

MeSH terms

  • Animals
  • COS Cells
  • Carbohydrate Metabolism, Inborn Errors / diagnosis*
  • Carbohydrate Metabolism, Inborn Errors / physiopathology
  • Child
  • Chlorocebus aethiops
  • Exome
  • Female
  • Genetic Predisposition to Disease
  • Homozygote
  • Humans
  • Hypoglycemia / etiology*
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Liver / physiopathology*
  • Liver Diseases / diagnosis*
  • Liver Diseases / physiopathology
  • Male
  • Mutation, Missense*
  • Pedigree
  • Phosphoenolpyruvate Carboxykinase (GTP) / deficiency*
  • Phosphoenolpyruvate Carboxykinase (GTP) / genetics
  • Sequence Analysis, DNA / methods
  • Urine / chemistry*


  • Intracellular Signaling Peptides and Proteins
  • PCK1 protein, human
  • Phosphoenolpyruvate Carboxykinase (GTP)

Supplementary concepts

  • Phosphoenolpyruvate carboxykinase deficiency

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