Cytosolic phosphoenolpyruvate carboxykinase deficiency presenting with acute liver failure following gastroenteritis

Mol Genet Metab. 2016 May;118(1):21-7. doi: 10.1016/j.ymgme.2016.03.001. Epub 2016 Mar 4.


We report a patient from a consanguineous family who presented with transient acute liver failure and biochemical patterns suggestive of disturbed urea cycle and mitochondrial function, for whom conventional genetic and metabolic investigations for acute liver failure failed to yield a diagnosis. Whole exome sequencing revealed a homozygous 12-bp deletion in PCK1 (MIM 614168) encoding cytosolic phosphoenolpyruvate carboxykinase (PEPCK); enzymatic studies subsequently confirmed its pathogenic nature. We propose that PEPCK deficiency should be considered in the young child with unexplained liver failure, especially where there are marked, accumulations of TCA cycle metabolites on urine organic acid analysis and/or an amino acid profile with hyperammonaemia suggestive of a proximal urea cycle defect during the acute episode. If suspected, intravenous administration of dextrose should be initiated. Long-term management comprising avoidance of fasting with the provision of a glucose polymer emergency regimen for illness management may be sufficient to prevent future episodes of liver failure. This case report provides further insights into the (patho-)physiology of energy metabolism, confirming the power of genomic analysis of unexplained biochemical phenotypes.

Keywords: Hepatopathy; Hyperammonaemia; Lactic acidosis; PCK1; PEPCK; Treatment.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence*
  • Carbohydrate Metabolism, Inborn Errors / diagnosis*
  • Carbohydrate Metabolism, Inborn Errors / drug therapy
  • Carbohydrate Metabolism, Inborn Errors / genetics
  • Consanguinity
  • Exome
  • Gastroenteritis / etiology*
  • Gastroenteritis / genetics
  • Glucose / administration & dosage
  • Glucose / therapeutic use
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Infant
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Liver Diseases / diagnosis*
  • Liver Diseases / drug therapy
  • Liver Diseases / genetics
  • Liver Failure, Acute / etiology*
  • Liver Failure, Acute / genetics
  • Male
  • Pedigree
  • Phosphoenolpyruvate Carboxykinase (GTP) / deficiency*
  • Phosphoenolpyruvate Carboxykinase (GTP) / genetics
  • Sequence Deletion*


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

Supplementary concepts

  • Phosphoenolpyruvate carboxykinase deficiency