Phosphoenolpyruvate carboxykinase deficiency

Phosphoenolpyruvate carboxykinase (PEPCK) deficiency is an extremely rare inherited disorder of gluconeogenesis. PEPCK is a critical enzyme in the gluconeogenic pathway, responsible for converting oxaloacetate to phosphoenolpyruvate, a key step in the production of glucose from non-carbohydrate precursors. Deficiency of this enzyme impairs the body's ability to maintain blood glucose levels during fasting and disrupts normal energy metabolism. The condition primarily affects the liver, kidneys, and other tissues involved in gluconeogenesis. There are two forms of PEPCK: a cytosolic form (PEPCK1, encoded by the PCK1 gene) and a mitochondrial form (PEPCK2, encoded by the PCK2 gene), and deficiency can involve either or both isoforms. Key clinical features typically present in infancy or early childhood and include hypoglycemia (low blood sugar), lactic acidosis, hepatomegaly (enlarged liver), hypotonia (decreased muscle tone), and failure to thrive. Some patients may also exhibit developmental delay, seizures, and metabolic acidosis. Laboratory findings often reveal elevated lactate, and there may be associated abnormalities in liver function. Due to the extreme rarity of this condition, with very few confirmed cases reported in the medical literature, the clinical spectrum and natural history remain incompletely characterized. Treatment is primarily supportive and focuses on preventing hypoglycemia through frequent feeding, avoidance of prolonged fasting, and dietary management including adequate carbohydrate intake. During acute metabolic crises, intravenous glucose administration may be necessary. There is currently no specific curative therapy available. Long-term prognosis varies depending on the severity of the enzymatic deficiency and the effectiveness of metabolic management.

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