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Cytosolic phosphoenolpyruvate carboxykinase deficiency presenting with acute liver failure following gastroenteritis
- Source :
- Molecular Genetics and Metabolism, 118, 21-7, Molecular genetics and metabolism, 118(1), 21-27. Academic Press Inc., Molecular Genetics and Metabolism, 118, 1, pp. 21-7
- Publication Year :
- 2016
-
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. (C) 2016 Elsevier Inc. All rights reserved
- Subjects :
- Male
0301 basic medicine
medicine.medical_specialty
Endocrinology, Diabetes and Metabolism
Biology
Biochemistry
Consanguinity
03 medical and health sciences
Endocrinology
PCK1
Internal medicine
Genetics
medicine
Humans
Exome
Molecular Biology
Exome sequencing
Sequence Deletion
Base Sequence
Liver Diseases
Intracellular Signaling Peptides and Proteins
High-Throughput Nucleotide Sequencing
Infant
Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6]
Liver Failure, Acute
Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3]
medicine.disease
Gastroenteritis
Pedigree
Citric acid cycle
Glucose
030104 developmental biology
Lactic acidosis
Urea cycle
Phosphoenolpyruvate Carboxykinase (GTP)
Phosphoenolpyruvate carboxykinase
Carbohydrate Metabolism, Inborn Errors
Urine organic acids
Subjects
Details
- ISSN :
- 10967192
- Database :
- OpenAIRE
- Journal :
- Molecular Genetics and Metabolism, 118, 21-7, Molecular genetics and metabolism, 118(1), 21-27. Academic Press Inc., Molecular Genetics and Metabolism, 118, 1, pp. 21-7
- Accession number :
- edsair.doi.dedup.....95f822334253bbd6b9d405444f00df6c