Summary about Disease
Pyruvate carboxylase deficiency (PCD) is a rare inherited metabolic disorder that affects the body's ability to convert pyruvate (a product of glucose metabolism) into oxaloacetate, an essential component of the citric acid cycle (Krebs cycle) and gluconeogenesis. This deficiency disrupts energy production and the synthesis of glucose from non-carbohydrate sources, leading to a buildup of toxic substances in the body and a shortage of glucose. PCD presents with a range of severities, from a lethal neonatal form to milder, later-onset forms.
Symptoms
Symptoms vary depending on the severity of the deficiency. Common symptoms include:
Severe (Type A/Infantile): Intellectual disability, Seizures, Developmental delay, Hypotonia (floppy muscle tone), Lactic acidosis, Failure to thrive, Breathing problems, Liver dysfunction, Vomiting, lethargy, coma. Often fatal in early infancy.
Intermediate (Type B): Similar to type A, but symptoms may be less severe and develop later. Neurological problems, developmental delays, seizures, and metabolic crises are common.
Mild (Type C/Benign): Developmental delay, Recurrent lactic acidosis during illness/stress, Normal or near-normal intelligence. Fewer and less severe symptoms.
Causes
PCD is caused by mutations in the PC gene, which provides instructions for making the pyruvate carboxylase enzyme. These mutations are inherited in an autosomal recessive pattern, meaning that both parents must carry a copy of the mutated gene for a child to be affected. Individuals carrying only one copy of the mutated gene are carriers and usually do not show symptoms.
Medicine Used
There is no cure for PCD, and treatment focuses on managing symptoms and preventing complications. Medical management often includes:
Dietary modifications: A ketogenic diet (high fat, low carbohydrate) to provide alternative energy sources. Restriction of protein intake may also be considered.
Supplements: Biotin supplementation (as pyruvate carboxylase requires biotin as a cofactor) and citrulline supplementation.
Sodium Bicarbonate or other Alkalinizing Agents: To treat lactic acidosis.
Medications: Anti-seizure medications to control seizures.
L-Carnitine: To facilitate removal of excess organic acids
Is Communicable
No, Pyruvate carboxylase deficiency is not communicable. It is a genetic disorder caused by inherited gene mutations.
Precautions
For individuals with PCD:
Strict adherence to the prescribed diet and medication regimen.
Avoidance of prolonged fasting.
Prompt medical attention during illnesses to prevent metabolic crises.
Genetic counseling for families with a history of PCD. For carriers:
Genetic counseling to understand the risk of having an affected child.
How long does an outbreak last?
PCD is not an outbreak-related illness. It is a chronic, lifelong condition. Individual metabolic crises can occur and may last from days to weeks, requiring hospitalization.
How is it diagnosed?
Diagnosis of PCD typically involves:
Clinical evaluation: Assessment of symptoms and medical history.
Blood tests: Measurement of lactate, pyruvate, ammonia, and other metabolites. Increased levels of these substances can suggest PCD.
Urine tests: Analysis of organic acids.
Enzyme assay: Measurement of pyruvate carboxylase enzyme activity in liver, fibroblasts, or white blood cells.
Genetic testing: Sequencing of the PC gene to identify mutations.
Newborn Screening: In some regions, PCD is included in newborn screening programs.
Timeline of Symptoms
Type A (Infantile): Symptoms typically appear within the first few days or weeks of life.
Type B (Intermediate): Symptoms may appear later in infancy or early childhood.
Type C (Benign): Symptoms may not appear until later in childhood or even adulthood, often triggered by illness or stress.
Important Considerations
Early diagnosis and management are crucial for improving outcomes.
The severity of PCD can vary widely, even among individuals with the same genetic mutations.
Long-term monitoring and support are essential for individuals with PCD and their families.
Consultation with a metabolic specialist or geneticist is recommended for diagnosis and management.
Research is ongoing to develop new therapies for PCD.