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HomePediatrics: Genetics and Metabolic DiseaseGenetics of Pyruvate Carboxylase Deficiency

Genetics of Pyruvate Carboxylase Deficiency


Pyruvate carboxylase deficiency (PCD) is a rare disorder that can cause developmental delay and failure to thrive starting in the neonatal or early infantile period. Pyruvate carboxylase deficiency results in malfunction of the citric acid cycle and gluconeogenesis, thereby depriving the body of energy; the former biochemical process derives energy from carbohydrates, whereas the latter produces carbohydrate fuel for the body when carbohydrate intake is low. See the image below.

This is a diagrammatic representation of the citri

This is a diagrammatic representation of the citric acid cycle and the abnormalities found in pyruvate carboxylase deficiency. The dotted line represents absent pathways. Pyruvate cannot produce oxaloacetate and is shunted to alternative pathways that produce lactic acid and alanine. The lack of oxaloacetate prevents gluconeogenesis and urea cycle function.

Metabolic acidosis caused by an abnormal lactate production is associated with nonspecific symptoms such as severe lethargy, poor feeding, vomiting, and seizures, especially during periods of illness and metabolic stress. In the most severe form, pyruvate carboxylase deficiency results in progressive neurologic symptoms, starting in the neonatal or early infantile period, include developmental delay, poor muscle tone, abnormal eye movements, or seizures. Therapies can ameliorate the biochemical abnormalities but cannot undo the progressive neurologic damage.

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