3. Phosphoenolpyruvate Carboxykinase Deficiency

Phosphoenolpyruvate Carboxykinase Deficiency

This PatientPlus article is written for healthcare professionals so the language may be more technical than the condition leaflets. You may find the abbreviations list helpful.

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Phosphoenolpyruvate carboxykinase is an important enzyme in gluconeogenesis. It is found in both the cytosol and mitochondria of the liver cells. The enzyme is regulated by insulin, glucocorticoids, cyclic adenosine monophosphate (cAMP) and diet to maintain glucose homeostasis.

Two types of phosphoenolpyruvate carboxykinase exist:

  • PCK1, PEPCK1 - soluble in the cytosol[1]
  • PCK2, PEPCK2 - soluble in the mitochondria[2]
  • Both conditions are extremely rare.
  • They have been reported in siblings.
  • Both are autosomal recessive inheritance.
  • The enzyme mutation in PCK1 is at gene map locus 20q13.31, and in PCK2 at 14q11.2-q12.
  • Hypoglycaemia - difficulty keeping blood sugars high.
  • Drowsiness due to hypoglycaemia.
  • Failure to thrive.
  • Metabolic acidosis from accumulation of lactic acid.
  • Mild icterus with hepatomegaly.[3]
  • Generalised muscle weakness.

Deficiency of the enzyme can cause persistent neonatal hypoglycaemia but failure of downregulation has also been linked with type 2 diabetes mellitus and, especially, maturity-onset diabetes in the young (MODY).[4][5]

  • Fasting provokes lactic acidosis.
  • LFTs are abnormal and liver biopsy shows giant cell hepatitis.
  • Culture of skin fibroblasts shows reduced activity of phosphoenolpyruvate carboxykinase.[3]

Other causes of neonatal hypoglycaemia, for example:

  • Glucose-6-phosphate deficiency
  • Fructose-1,6,-diphosphatase deficiency
  • Pyruvate carboxylase deficiency
  • Presumably regular feeding would prevent or reduce hypoglycaemia but the impression is of a relentless disease that causes early death(within first 6 months).
  • Autopsy shows considerable fatty infiltration of both the liver and the kidneys.[6] Fatty infiltration of other tissues also occurs but is less marked.
  • Genetic counselling may be given as for any other autosomal recessive disorder. There is no literature about antenatal detection.
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Further reading & references

  • CLIMB, Children Living with Inherited Metabolic Diseases
  1. Phosphoenolpyruvate carboxykinase 1, Soluble; PCK1, Online Mendelian Inheritance in Man (OMIM)
  2. Phosphoenolpyruvate carboxykinase 2, Mitochondrial; PCK2, Online Mendelian Inheritance in Man (OMIM)
  3. Clayton PT, Hyland K, Brand M, et al; Mitochondrial phosphoenolpyruvate carboxykinase deficiency. Eur J Pediatr. 1986 Apr;145(1-2):46-50.
  4. Cao H, van der Veer E, Ban MR, et al; Promoter polymorphism in PCK1 (phosphoenolpyruvate carboxykinase gene) associated with type 2 diabetes mellitus. J Clin Endocrinol Metab. 2004 Feb;89(2):898-903.
  5. Ting CN, Burgess DL, Chamberlain JS, et al; Phosphoenolpyruvate carboxykinase (GTP): characterization of the human PCK1 gene and localization distal to MODY on chromosome 20. Genomics. 1993 Jun;16(3):698-706.
  6. Hommes FA, Bendien K, Elema JD, et al; Two cases of phosphoenolpyruvate carboxykinase deficiency. Acta Paediatr Scand. 1976 Mar;65(2):233-40.
Original Author: Dr Gurvinder Rull Current Version:
Last Checked: 16/07/2010 Document ID: 2606  Version: 21 © EMIS

Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.

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