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Pyruvate carboxylase deficiency
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Condition

Pyruvate carboxylase deficiency

Pyruvate carboxylase deficiency is an inherited metabolic disorder that leads to the buildup of lactic acid and other toxins, causing damage to the nervous system and other organs.

Overview

This condition is caused by a deficiency in the enzyme pyruvate carboxylase. There are three recognized types based on severity:

  • Type A: Characterized by severe developmental delay and lactic acidosis. Symptoms often include vomiting, abdominal pain, fatigue, and muscle weakness. Survival is typically limited to infancy or early childhood.
  • Type B: A severe, life-threatening form appearing shortly after birth. It involves extreme lactic acidosis, hyperammonemia (high ammonia levels), liver failure, and neurological issues like seizures and coma. Survival is usually less than 3 months.
  • Type C: A milder form with slightly increased lactic acid levels and minimal neurological symptoms.

Causes

The condition is caused by mutations in the PC gene. This gene provides instructions for the pyruvate carboxylase enzyme, which is active in the mitochondria. The enzyme is essential for:

  • Generating glucose, the body's primary energy source.
  • Forming the protective myelin sheath around nerve cells.
  • Producing neurotransmitters that allow nerve cells to communicate.

When the enzyme is missing or altered, the body cannot efficiently produce energy, and toxic compounds like lactic acid and ammonia accumulate, damaging tissues and organs.

Inheritance

Pyruvate carboxylase deficiency is inherited in an autosomal recessive pattern. This means that both copies of the PC gene in each cell must have mutations for the condition to manifest. Parents of an affected individual each carry one copy of the mutated gene but typically do not show symptoms.

Frequently Asked Questions

Each pregnancy carries a 25 % risk of an affected child, a 50 % chance of a carrier, and a 25 % chance of an unaffected non‑carrier. Prenatal diagnosis can be performed via chorionic villus sampling (10‑12 weeks) or amniocentesis (15‑18 weeks) with targeted PC‑gene sequencing. Pre‑implantation genetic testing for monogenic disorders (PGT‑M) is also an option for couples undergoing IVF.
Diagnosis combines biochemical and molecular studies. First, obtain plasma lactate, ammonia, and pyruvate levels; an elevated lactate‑to‑pyruvate ratio suggests a mitochondrial defect. Then, perform a fibroblast or lymphocyte enzyme assay to measure pyruvate carboxylase activity. Finally, confirm with sequencing of the PC gene to identify pathogenic variants.
high‑protein, low‑carbohydrate diet reduces glycolytic flux that generates pyruvate. Supplementation with triheptanoin (a medium‑chain triglyceride) provides anaplerotic substrates that bypass the enzyme block. Frequent small meals and avoidance of fasting are also important, as prolonged fasting worsens lactic acidosis.
Research is ongoing on gene‑replacement strategies using adeno‑associated viral vectors and on enzyme‑replacement via liver transplantation. A few international centers are recruiting patients for trials of triheptanoin and for mitochondrial biogenesis enhancers such as bezafibrate. Families should consult a metabolic specialist and check registries like ClinicalTrials.gov for the latest eligibility criteria.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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