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Phosphoenolpyruvate Carboxykinase Deficiency

Authored by , Reviewed by Dr Adrian Bonsall | Last edited | Certified by The Information Standard

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Phosphoenolpyruvate Carboxykinase Deficiency

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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.
  • 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).[3]

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

Other causes of neonatal hypoglycaemia - for example:

  • Glucose-6-phosphatase 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 the first six months).[1, 2]
  • Autopsy shows considerable fatty infiltration of both the liver and the kidneys. 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.

Further reading and references

  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. 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 Feb89(2):898-903.

I have a feeling that when you take FBS test fasting 8 hours results more glucose in the sample than taking a test fasting 12 hours. Have you noticed this?

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Article Information
  • Last Reviewed 20 June 2014
  • Next Review 19 June 2019
  • Document ID 2606 (v22)
  • Author Dr Colin Tidy
  • Peer reviewer Dr Adrian Bonsall

The information on this page is written and peer reviewed by qualified clinicians.

Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. Patient Platform Limited 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.