Déficit en phosphoénolpyruvate carboxykinase

Introduction

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

Épidémiologie¹²

• 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.

Présentation

• Hypoglycaemia - difficulty keeping blood sugars high.

• Drowsiness due to hypoglycaemia.

• Échec de croissance.

• 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

Enquêtes

• Fasting provokes lactic acidosis.

• LFTs are abnormal and liver biopsy shows giant cell hepatitis.

• Culture of skin fibroblasts shows reduced activity of phosphoenolpyruvate carboxykinase.

Diagnostic différentiel

Other causes of neonatal hypoglycaemia - for example:

• Glucose-6-phosphatase deficiency

• Fructose-1,6,-diphosphatase deficiency

• Déficit en pyruvate carboxylase

Management and prognosis

• 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).¹²

• 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.