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

Cytosolic phosphoenolpyruvate carboxykinase deficiency presenting with acute liver failure following gastroenteritis.

Author information

1
Birmingham Children's Hospital, Birmingham, UK. Electronic address: saikat.santra@bch.nhs.uk.
2
Genetics and Genome Biology Program, Peter Gilgan Centre for Research and Learning, Toronto, Canada.
3
Centre for Molecular Medicine, Child & Family Research Institute, Vancouver, Canada.
4
Centre for Molecular Medicine, Child & Family Research Institute, Vancouver, Canada; Department of Pediatrics, University of British Columbia, Canada.
5
Department of Medical Genetics, University of British Columbia, Vancouver, Canada.
6
Department of Medical Genetics, University of British Columbia, Vancouver, Canada; Centre for Molecular Medicine, Child & Family Research Institute, Vancouver, Canada; Department of Pediatrics, University of British Columbia, Canada.
7
Department of Medical Genetics, University of British Columbia, Vancouver, Canada; Centre for Molecular Medicine, Child & Family Research Institute, Vancouver, Canada.
8
Department of Laboratory Medicine - Translational Metabolic Laboratory, Radboudumc, Nijmegen, The Netherlands.
9
Nijmegen Center for Mitochondrial Disorders, Department of Pediatrics, Translational Metabolic Laboratory, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
10
Birmingham Children's Hospital, Birmingham, UK.
11
Centre for Molecular Medicine, Child & Family Research Institute, Vancouver, Canada; Department of Pediatrics, University of British Columbia, Canada. Electronic address: cvankarnebeek@cw.bc.ca.

Abstract

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

PMID:
26971250
DOI:
10.1016/j.ymgme.2016.03.001
[Indexed for MEDLINE]

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