PC deficiency

Overview

Pyruvate Carboxylase (PC) Deficiency is a rare metabolic disorder characterized by a deficiency in the enzyme pyruvate carboxylase. This enzyme is crucial for gluconeogenesis, the process by which glucose is synthesized from non-carbohydrate precursors. PC deficiency leads to a buildup of lactic acid and other metabolic intermediates, causing a range of symptoms.

Pathophysiology

Pyruvate carboxylase is an enzyme that catalyzes the conversion of pyruvate to oxaloacetate, a critical step in the Citric Acid Cycle and gluconeogenesis. In PC deficiency, this conversion is impaired, leading to:

• Accumulation of pyruvate and lactic acid, resulting in Lactic Acidosis.
• Decreased production of glucose, leading to Hypoglycemia.
• Impaired synthesis of neurotransmitters and fatty acids, affecting brain function and development.

Clinical Presentation

The symptoms of PC deficiency can vary widely but often include:

• Developmental delay and neurological deficits.
• Hypotonia (reduced muscle tone).
• Seizures.
• Failure to thrive.
• Episodes of metabolic crisis, especially during illness or fasting.

Diagnosis

Diagnosis of PC deficiency typically involves:

• Measurement of enzyme activity in fibroblasts or leukocytes.
• Genetic testing to identify mutations in the PC gene.
• Metabolic testing showing elevated lactate and other metabolites.

Treatment

There is no cure for PC deficiency, but treatment focuses on managing symptoms and preventing metabolic crises:

• Dietary management with a high-carbohydrate, low-fat diet.
• Supplementation with biotin, a cofactor for pyruvate carboxylase.
• Avoidance of fasting and prompt treatment of infections.

Prognosis

The prognosis for individuals with PC deficiency varies depending on the severity of the enzyme deficiency. Some individuals may have a mild form with manageable symptoms, while others may experience severe neurological impairment and early mortality.

Research and Future Directions

Research is ongoing to better understand the genetic basis of PC deficiency and to develop potential therapies, such as gene therapy or enzyme replacement therapy.

See Also

• Metabolic Disorders
• Gluconeogenesis
• Lactic Acidosis

,

 Pyruvate Carboxylase Deficiency: A Review, 
 Journal of Metabolic Disorders, 
 2020, 
 Vol. 15(Issue: 3), 
 pp. 123-130,

R,

 Inherited Metabolic Diseases, 
  
 Academic Press, 
 2018,

NIH genetic and rare disease info

• NIH info on PC deficiency

PC deficiency is a rare disease.