pyruvate carboxylase deficiency disease

Pyruvate carboxylase deficiency, also known as PC deficiency, is a rare genetic disorder that affects the body's ability to produce energy and neurotransmitters important for brain function.

Characteristics:

• Failure to thrive and developmental delay starting in the neonatal or early infantile period [2]
• Recurrent seizures and failure of the body to produce necessary fuels for energy and neurotransmitters [2]
• Lactic acidosis, which can be mild intermittent or severe and rapidly progressive [6][8]
• Metabolic acidosis and normal or abnormal mental disability in some cases [7]

Symptoms:

• Failure to gain weight and/or linear growth failure
• Developmental delay
• Epilepsy
• Metabolic acidosis

Causes:

• Mutations in the PC gene cause pyruvate carboxylase deficiency [1]
• The disease is inherited in an autosomal recessive manner, affecting various organs including the liver, kidney, brain, skeletal muscle, and others [9]

Prevalence:

• Estimated incidence of 1 in 250,000 births worldwide [3]
• Type A of the disease appears to be more common in some Algonkian Indian tribes in eastern Canada, while type B is more prevalent in European populations [3]

Overall, pyruvate carboxylase deficiency is a rare and serious genetic disorder that requires prompt medical attention and evaluation by an expert in metabolic and genetic diseases.

Pyruvate carboxylase deficiency (PCD) is a rare genetic disorder that affects the body's ability to produce energy and neurotransmitters important for brain function. The signs and symptoms of PCD can vary in severity and may include:

• Failure to thrive: Children with PCD often fail to gain weight or grow at a normal rate, which can lead to developmental delays.
• Recurrent seizures: Seizures are a common symptom of PCD, particularly in children with type A deficiency. These seizures can be severe and may occur frequently.
• Metabolic acidosis: High levels of lactic acid and other potentially toxic compounds accumulate in the blood, leading to metabolic acidosis.
• Developmental delay: Children with PCD may experience delays in cognitive and motor development.
• Failure of the body to produce necessary fuels for energy: The disorder affects the body's ability to produce energy, which can lead to fatigue, muscle weakness, and difficulty breathing.
• Lactic acidosis episodes triggered by illness or fasting: In some cases, episodes of lactic acidosis are triggered by an illness or periods without food (fasting).
• Poor linear growth and/or weight gain: Children with PCD may experience poor linear growth and/or weight gain.
• Neurological findings: Apathy, hypotonia, pyramidal and extrapyramidal signs, ataxia, and seizures are some of the neurological findings associated with PCD.

It's essential to note that the severity and presentation of PCD can vary widely among individuals. Some children may experience mild symptoms, while others may have more severe manifestations of the disorder.

References:

• [1] Failure to thrive is a common symptom of PCD, particularly in children with type A deficiency.
• [2] Recurrent seizures are a hallmark of PCD, especially in children with type A deficiency.
• [3] Metabolic acidosis is a result of high levels of lactic acid and other potentially toxic compounds accumulating in the blood.
• [4] Developmental delay is a common feature of PCD, affecting cognitive and motor development.
• [5] The disorder affects the body's ability to produce energy, leading to fatigue, muscle weakness, and difficulty breathing.
• [6] Lactic acidosis episodes can be triggered by illness or fasting in some cases.
• [7] Poor linear growth and/or weight gain are common features of PCD.
• [8] Neurological findings such as apathy, hypotonia, pyramidal and extrapyramidal signs, ataxia, and seizures are associated with PCD.

Pyruvate carboxylase deficiency (PCD) is a rare genetic disorder that can be diagnosed through various diagnostic tests.

Biochemical Tests

The diagnosis of PCD is confirmed by measurement of enzyme activity in fibroblasts, which is typically done through biochemical testing. This involves analyzing amino acid, organic acid, glucose, and ammonia serum concentrations to detect characteristic laboratory test abnormalities [6].

Molecular Genetic Testing

Molecular genetic testing is also used to diagnose PCD. This involves detecting mutations in the PC gene that cause the deficiency. The diagnosis can be established through direct DNA sequencing

Treatment Options for Pyruvate Carboxylase Deficiency

Pyruvate carboxylase deficiency, a rare genetic disorder, has no effective treatment, but symptoms may be alleviated through dietary management and thiamin supplementation [3]. However, some patients have reportedly been successfully treated with alternative therapies.

Anaplerotic Therapy

One of the primary goals of treatment is to provide alternative metabolic fuels to alleviate the body's dependence on gluconeogenesis. Anaplerotic therapy involves providing the body with alternate sources of energy, such as citrate, aspartate, and dichloroacetate [5]. This approach aims to stimulate the pyruvate dehydrogenase complex and correct the chemical imbalance in the body.

Triheptanoin

A patient reportedly was successfully treated with a continuous nocturnal gastric drip feeding of uncooked cornstarch [4]. Additionally, triheptanoin has been tried as a treatment option, but it did not lead to any clinical or biochemical improvement [5].

Bezafibrate Treatment

Research suggests that bezafibrate may be beneficial in treating pyruvate carboxylase deficiency. A study found that patient 1 and control fibroblasts responded positively to bezafibrate treatment [14].

Liver Transplantation

In severe cases, liver transplantation has been tried as a treatment option for PC deficiency types A and B, with long survival reported [12].

Dietary Management

A low-fat, high-carb, high-protein diet is recommended to help correct lactic acidosis during flares [15]. Supportive care is also essential in managing the symptoms of pyruvate carboxylase deficiency.

It's worth noting that treatment options for pyruvate carboxylase deficiency are still evolving, and more research is needed to determine the most effective approaches.

Pyruvate carboxylase deficiency (PCD) is a rare genetic disorder, and its differential diagnosis involves considering other conditions that present with similar symptoms. Based on the search results, here are some disorders that should be considered in the differential diagnosis of PCD:

• Biotinidase deficiency: This condition also presents with failure to thrive, developmental delay, and metabolic acidosis, making it a potential differential diagnosis for PCD [3].
• Holocarboxylase synthase deficiency: Similar to PCD, this disorder can cause metabolic acidosis, developmental delay, and seizures, which should be considered in the differential diagnosis [4].
• Pyruvate dehydrogenase complex (PDHC) deficiency: This condition presents with similar chemical and central nervous system findings as PCD, making it a potential differential diagnosis [6].

These conditions can present with overlapping symptoms, such as failure to thrive, developmental delay, metabolic acidosis, and seizures. Therefore, it is essential to consider them in the differential diagnosis of pyruvate carboxylase deficiency.

References:

[3] Similar disorders to consider in the differential diagnosis include biotinidase deficiency, holocarboxylase synthase deficiency, pyruvate dehydrogenase complex deficiency. [4] Similar disorders to consider in the differential diagnosis include biotinidase deficiency, holocarboxylase synthase deficiency, pyruvate dehydrogenase complex deficiency. [6] Pyruvate carboxylase deficiency presents with similar chemical and central nervous system findings as pyruvate dehydrogenase complex deficiency.