GeneHealth - Your precision medicine

Pyruvate Carboxylase Deficiency Disease

Disease Details

Family Health Simplified

Buy Membership

Description: Pyruvate carboxylase deficiency is a rare metabolic disorder characterized by the inability of the body to convert pyruvate to oxaloacetate, disrupting gluconeogenesis and energy production.
Type: Pyruvate carboxylase deficiency is an inherited metabolic disorder. It follows an autosomal recessive pattern of genetic transmission.
Signs And Symptoms: Pyruvate carboxylase deficiency causes lactic acidosis and hyperammonaemia. Lactic acidosis may then lead to liver failure, hepatomegaly, reduced ketone body synthesis, and demyelination of neurons.
Prognosis: The prognosis of pyruvate carboxylase deficiency disease varies depending on the form and severity of the condition. Generally, the prognosis is poor for the severe forms, especially if onset occurs in infancy, due to significant metabolic disturbances and neurologic impairment. Survival beyond early childhood is uncommon without aggressive management. Milder forms may have a better prognosis with early detection and proper metabolic management, though affected individuals may still experience developmental delays and other complications.
Onset: Pyruvate carboxylase deficiency typically presents in infancy or early childhood. Symptoms can appear shortly after birth or within the first few months of life.
Prevalence: The prevalence of pyruvate carboxylase deficiency is very rare, estimated to be less than 1 in 250,000 live births.
Epidemiology: Pyruvate carboxylase deficiency is very rare, and is estimated to affect around 1 in 250,000 people.
Intractability: Pyruvate carboxylase deficiency is considered a challenging condition to manage, often described as intractable. This metabolic disorder can lead to severe and persistent symptoms, including developmental delay, lactic acidosis, and other neurological issues. Treatment focuses on managing symptoms and metabolic crises, but there is currently no cure for the underlying enzyme deficiency.
Disease Severity: Pyruvate carboxylase deficiency (PCD) is a rare genetic disorder affecting the body's ability to convert pyruvate to oxaloacetate, leading to lactic acidosis and a range of symptoms.

Disease severity: The severity of pyruvate carboxylase deficiency can vary widely among individuals. There are three main types:
1. **Type A (Infantile form)**: Typically presents in infancy with developmental delays, failure to thrive, and recurrent metabolic acidosis. It is moderately severe.
2. **Type B (Severe neonatal form)**: Presents soon after birth with severe lactic acidosis, hyperammonemia, and life-threatening symptoms. It is the most severe form and is often fatal in early life.
3. **Type C (Mild or intermittent form)**: Characterized by mild or intermittent symptoms that may include developmental delays and episodes of metabolic acidosis. It is the least severe of the three types.

The course of the disease and life expectancy can be highly variable depending on the type and the effectiveness of the management of metabolic crises.
Healthcare Professionals: Disease Ontology ID - DOID:3651
Pathophysiology: Pyruvate carboxylase deficiency is a rare metabolic disorder characterized by an insufficient activity of the enzyme pyruvate carboxylase. This enzyme is crucial for gluconeogenesis, the metabolic pathway that results in the generation of glucose from non-carbohydrate sources, and plays an important role in the citric acid cycle. The deficiency disrupts these metabolic pathways, leading to a buildup of lactic acid (lactic acidosis) and other metabolic intermediates, resulting in symptoms such as developmental delay, seizures, and failure to thrive. This disorder is inherited in an autosomal recessive pattern.
Carrier Status: Carrier status for pyruvate carboxylase deficiency disease: Pyruvate carboxylase deficiency is an autosomal recessive disorder. This means that carriers of the disease have one normal allele and one mutated allele of the gene responsible, and do not typically exhibit symptoms. Carriers can pass the mutated gene to their offspring. If two carriers have a child, there is a 25% chance that the child will inherit two mutated alleles (one from each parent) and will have pyruvate carboxylase deficiency.
Mechanism: Pyruvate carboxylase is active in mitochondria in cells. It is involved in the generation of glucose through gluconeogenesis. By generating oxaloacetate, it catalyses an important anaplerotic reaction that maintains the citric acid cycle to generate energy by aerobic respiration. Pyruvate carboxylase also plays a role in the formation of the myelin sheath that surrounds certain nerve cells, and the production of neurotransmitters for communication between neurons.
Mutations in the PC gene reduce the amount of pyruvate carboxylase in cells or disrupt the enzyme's activity. The missing or altered enzyme cannot carry out its essential role in generating glucose, which impairs the body's ability to make energy in mitochondria. Additionally, a loss of pyruvate carboxylase allows potentially toxic compounds, such as lactic acid and ammonia, to build up and damage organs and tissues. Loss of pyruvate carboxylase function in the nervous system, particularly the role of the enzyme in myelin formation and neurotransmitter production, may contribute to the neurological features of pyruvate carboxylase deficiency.
Treatment: Pyruvate carboxylase deficiency treatment typically consists of providing the body with alternate sources of energy (anaplerotic therapy). This may include a diet rich in proteins and carbohydrates but not lipids.
Acutely, triheptanoin may be administered as a source of acetyl-CoA.
Compassionate Use Treatment: Pyruvate carboxylase deficiency (PCD) is a rare metabolic disorder that disrupts the body's ability to generate energy. As for compassionate use treatment and off-label or experimental treatments for PCD:

1. **Compassionate Use Treatment:**
- **Triheptanoin (UX007):** This is being investigated for use in several inborn errors of metabolism. It is a synthetic triglyceride that can provide an alternative energy source.
- **Sodium phenylbutyrate:** Typically used in urea cycle disorders, this compound may help manage hyperammonemia, a potential complication of PCD.

2. **Off-label or Experimental Treatments:**
- **Biotin supplementation:** Although its efficacy is variable, biotin has been used in some cases given its role as a cofactor in carboxylation reactions.
- **Anaplerotic therapies:** These are treatments that aim to replenish intermediates of the tricarboxylic acid cycle (e.g., triheptanoin).
- **Gene therapy:** This is still in the experimental stage but holds potential for correcting the underlying genetic defect in PCD.

Each of these treatments is considered based on the individual's specific symptoms and severity, and managed by healthcare professionals specializing in metabolic disorders.
Lifestyle Recommendations: Lifestyle recommendations for pyruvate carboxylase deficiency (PCD) typically focus on managing symptoms and improving quality of life. Here are some potential recommendations:

1. **Dietary Management**: A high-fat, low-carbohydrate ketogenic diet may help some individuals by providing an alternative energy source (ketones) for the brain and other tissues.

2. **Regular Monitoring**: Regular medical check-ups to monitor metabolic levels and detect any complications early.

3. **Hydration**: Maintaining proper hydration can help manage metabolic stress.

4. **Avoiding Fasting**: Ensuring regular meals to avoid periods of fasting, which can exacerbate symptoms due to the body’s reliance on continuous glucose supply.

5. **Supplementation**: Potential benefits from supplements such as biotin, thiamine, or citrate, as directed by a healthcare provider.

6. **Physical Therapy**: Engaging in physical therapy to maintain muscle function and mobility if neurological symptoms are present.

7. **Genetic Counseling**: Families may benefit from genetic counseling to understand the inheritance patterns and risks for future children.

8. **Stress Management**: Techniques for managing stress, which can worsen metabolic conditions.

9. **Emergency Plan**: Having an emergency plan in place for metabolic crises, including quick access to medical care and specific interventions.

Following these recommendations can help manage symptoms and improve the overall quality of life for individuals with pyruvate carboxylase deficiency. Always consult with a healthcare professional for personalized advice.
Medication: Pyruvate carboxylase deficiency is a rare metabolic disorder and there is no specific medication that cures the condition. Treatment primarily focuses on managing symptoms and might include:

1. **Dietary modifications**: High-carbohydrate and high-protein diets to provide alternative energy sources.
2. **Biotin supplementation**: Since pyruvate carboxylase is biotin-dependent.
3. **Anaplerotic agents**: Such as triheptanoin, to replenish the tricarboxylic acid cycle intermediates.
4. **Avoidance of fasting**: To prevent energy crises.

Management often involves a multidisciplinary team approach, including specialists in metabolic disorders.
Repurposable Drugs: Pyruvate carboxylase deficiency is a rare metabolic disorder with limited specific treatments. However, some repurposable drugs and therapeutic approaches that have been explored for this condition include:

1. **Biotin**: Since pyruvate carboxylase is a biotin-dependent enzyme, biotin supplementation can sometimes help in improving enzyme function.
2. **Aspartic Acid**: This amino acid can be supplemented to help bypass the metabolic block caused by the enzyme deficiency.
3. **Dichloroacetate (DCA)**: DCA has been investigated as a means to reduce lactic acid levels by promoting the metabolism of pyruvate through alternative pathways.

These treatments focus on managing symptoms and improving metabolic balance rather than curing the disease.
Metabolites: Pyruvate carboxylase deficiency is a rare metabolic disorder affecting the enzyme pyruvate carboxylase, leading to impaired gluconeogenesis and an accumulation of specific metabolites. This results in elevated levels of lactic acid, pyruvate, and other intermediates of glycolysis in the blood and urine. Additionally, there can be an accumulation of ketone bodies, elevated alanine, and decreased citric acid cycle intermediates, such as oxaloacetate.
Nutraceuticals: There are no specific nutraceuticals known to treat Pyruvate Carboxylase Deficiency Disease (PCD). Treatment typically focuses on managing symptoms and may include dietary modifications, such as a high-fat, low-carbohydrate ketogenic diet, to mitigate metabolic complications. Medical management might involve the use of supplements like biotin, although their efficacy is limited. Always consult healthcare professionals for tailored advice and treatment options.
Peptides: Peptides are short chains of amino acids, and they do not have a direct role in diagnosing or treating pyruvate carboxylase deficiency (PCD). PCD is a rare metabolic disorder resulting from a deficiency of the enzyme pyruvate carboxylase, which is essential for gluconeogenesis and other metabolic pathways. The primary focus in PCD is usually on managing symptoms and metabolic abnormalities rather than peptides specifically.

If you need information on specific peptides related to metabolic functions or conditions, please provide more context.