Pyruvate Carboxylase Deficiency (PC) is an autosomal recessive disorder occurs due to mutations in pyruvate carboxylase gene.
PC is an important mitochondrial enzyme using biotin to convert pyruvate to oxaloacetate for energy production pathways.
Pyruvate carboxylase converts pyruvate to oxaloacetate which is essential for Krebs cycle.
Pyruvate is converted into oxaloacetate to generate glucose. Replenishes oxaloacetate in the Krebs cycle which is essential for the proper functioning.
Lipogenesis provides oxaloacetate for the synthesis of fatty acids.
Types of Pyruvate Carboxylase Deficiency are:
Type A (Mild or North American type)
Type B (Severe or French type)
Type C (Intermittent or benign)
Citric acid cycle uses carbs for energy in gluconeogenesis to create carbs when intake is low.
Metabolic acidosis due to lactate production has nonspecific symptoms in illness. Severe pyruvate carboxylase deficiency leads to progressive neurological symptoms in infancy.
Epidemiology
PC deficiency disrupts citrate production to impact the citric acid cycle and overall metabolism in significant ways.
Acetyl-CoA needs oxaloacetate to produce citrate and ketone bodies, while gluconeogenesis is required to prevent hypoglycemia.
Cells rely on glycolysis for energy production from glucose since citric acid cycle is inefficient. It reduced aspartic acid production increases serum ammonia levels in body.
PC creates citric acid cycle intermediates crucial for nervous system. Alpha-ketoglutarate is important for glutamate production.
Anatomy
Pathophysiology
PC deficiency disrupts citrate production to impact the citric acid cycle and overall metabolism in significant ways.
Acetyl-CoA needs oxaloacetate to produce citrate and ketone bodies, while gluconeogenesis is required to prevent hypoglycemia.
Cells rely on glycolysis for energy production from glucose since citric acid cycle is inefficient. It reduced aspartic acid production increases serum ammonia levels in body.
PC creates citric acid cycle intermediates crucial for nervous system. Alpha-ketoglutarate is important for glutamate production.
Etiology
The causes for PCD are:
Autosomal Recessive Inheritance
PC Gene Mutations
Pyruvate Carboxylase Dysfunction
Gluconeogenesis
Fatty Acid Synthesis
Accumulation of Pyruvate
Hyperammonemia
Genetics
Prognostic Factors
Dietary changes and supplements can improve some biochemical issues in type B PC deficiency, but patients usually die within 6 months.
Energy deficit in CNS causes neurologic symptoms and brain malformations during neurogenesis.
Neonates may have different outcomes such as hypomyelination, cystic lesions, and grey matter degeneration due to brain abnormalities.
Patients with type A pyruvate carboxylase deficiency live into adulthood with neurologic and cognitive dysfunction.
Clinical History
Collect details including presenting symptoms, episodes of metabolic acidosis, medical and family history to understand clinical history of patient.
Physical Examination
Neurological Examination
Musculoskeletal assessment
Abdominal Examination
Cardiovascular assessment
Age group
Associated comorbidity
Associated activity
Acuity of presentation
Type A symptoms are:
Failure to thrive, hypotonia, and developmental delay
Episodes of metabolic acidosis
Type B symptoms are:
Hypotonia, lethargy, seizures, episodes of vomiting, and refusal to feed,
hyperammonemia
Differential Diagnoses
Lactic acidosis
Leigh encephalopathy
Pyruvate dehydrogenase complex deficiency
Metabolic acidosis
Laboratory Studies
Imaging Studies
Procedures
Histologic Findings
Staging
Treatment Paradigm
Therapies target Pyruvate Dehydrogenase Complex stimulation and fuel provision.
Pyruvate dehydrogenase complex boosts pyruvate metabolism with thiamine, lipoic acid cofactors, and dichloroacetate for optimized activity.
Biotin supplementation may be minimally beneficial in mildly affected type C patients with partial enzyme function.
Citrate supplement decreases acidosis and fuels citric cycle.
Triheptanoin reversed hepatic failure and biochemical abnormalities in one case with acetyl-CoA source.
They enhanced pathways to reduces pyruvate and lactate levels effectively.
PCD management focuses on addressing acute metabolic crises through interventions such as central line placement, NG/G-tube placement, and dialysis in severe Type B cases to maintain proper nutrition and ventilation.
Pyruvate Carboxylase Deficiency (PC) is an autosomal recessive disorder occurs due to mutations in pyruvate carboxylase gene.
PC is an important mitochondrial enzyme using biotin to convert pyruvate to oxaloacetate for energy production pathways.
Pyruvate carboxylase converts pyruvate to oxaloacetate which is essential for Krebs cycle.
Pyruvate is converted into oxaloacetate to generate glucose. Replenishes oxaloacetate in the Krebs cycle which is essential for the proper functioning.
Lipogenesis provides oxaloacetate for the synthesis of fatty acids.
Types of Pyruvate Carboxylase Deficiency are:
Type A (Mild or North American type)
Type B (Severe or French type)
Type C (Intermittent or benign)
Citric acid cycle uses carbs for energy in gluconeogenesis to create carbs when intake is low.
Metabolic acidosis due to lactate production has nonspecific symptoms in illness. Severe pyruvate carboxylase deficiency leads to progressive neurological symptoms in infancy.
PC deficiency disrupts citrate production to impact the citric acid cycle and overall metabolism in significant ways.
Acetyl-CoA needs oxaloacetate to produce citrate and ketone bodies, while gluconeogenesis is required to prevent hypoglycemia.
Cells rely on glycolysis for energy production from glucose since citric acid cycle is inefficient. It reduced aspartic acid production increases serum ammonia levels in body.
PC creates citric acid cycle intermediates crucial for nervous system. Alpha-ketoglutarate is important for glutamate production.
PC deficiency disrupts citrate production to impact the citric acid cycle and overall metabolism in significant ways.
Acetyl-CoA needs oxaloacetate to produce citrate and ketone bodies, while gluconeogenesis is required to prevent hypoglycemia.
Cells rely on glycolysis for energy production from glucose since citric acid cycle is inefficient. It reduced aspartic acid production increases serum ammonia levels in body.
PC creates citric acid cycle intermediates crucial for nervous system. Alpha-ketoglutarate is important for glutamate production.
The causes for PCD are:
Autosomal Recessive Inheritance
PC Gene Mutations
Pyruvate Carboxylase Dysfunction
Gluconeogenesis
Fatty Acid Synthesis
Accumulation of Pyruvate
Hyperammonemia
Dietary changes and supplements can improve some biochemical issues in type B PC deficiency, but patients usually die within 6 months.
Energy deficit in CNS causes neurologic symptoms and brain malformations during neurogenesis.
Neonates may have different outcomes such as hypomyelination, cystic lesions, and grey matter degeneration due to brain abnormalities.
Patients with type A pyruvate carboxylase deficiency live into adulthood with neurologic and cognitive dysfunction.
Collect details including presenting symptoms, episodes of metabolic acidosis, medical and family history to understand clinical history of patient.
Neurological Examination
Musculoskeletal assessment
Abdominal Examination
Cardiovascular assessment
Type A symptoms are:
Failure to thrive, hypotonia, and developmental delay
Episodes of metabolic acidosis
Type B symptoms are:
Hypotonia, lethargy, seizures, episodes of vomiting, and refusal to feed,
hyperammonemia
Lactic acidosis
Leigh encephalopathy
Pyruvate dehydrogenase complex deficiency
Metabolic acidosis
Therapies target Pyruvate Dehydrogenase Complex stimulation and fuel provision.
Pyruvate dehydrogenase complex boosts pyruvate metabolism with thiamine, lipoic acid cofactors, and dichloroacetate for optimized activity.
Biotin supplementation may be minimally beneficial in mildly affected type C patients with partial enzyme function.
Citrate supplement decreases acidosis and fuels citric cycle.
Triheptanoin reversed hepatic failure and biochemical abnormalities in one case with acetyl-CoA source.
They enhanced pathways to reduces pyruvate and lactate levels effectively.
Endocrinology, Metabolism
Keep environment clean and limited exposure to potential infectious agents is essential.
Take high protein diet to maintain an anabolic state and prevent activation of gluconeogenesis.
Fasting should be avoided in this period. Dietary plan should be completed to help dietary manipulations.
Proper awareness about PCD should be provided and its related causes with management strategies.
Appointments with an endocrinologist and preventing recurrence of disorder is an ongoing life-long effort.
Endocrinology, Metabolism
Biotin:
Biotin supplementation is used to enhance residual enzyme activity and energy metabolism.
It neutralizes excess acid in the blood. It is used to correct metabolic acidosis.
Endocrinology, Metabolism
Carnitine:
It transports long-chain fatty acids into the mitochondria for energy production to reduce the accumulation of toxic fatty acid.
Endocrinology, Metabolism
Aspartic acid:
It allows the urea cycle to reduce the ammonia level.
Endocrinology, Metabolism
PCD management focuses on addressing acute metabolic crises through interventions such as central line placement, NG/G-tube placement, and dialysis in severe Type B cases to maintain proper nutrition and ventilation.
Endocrinology, Metabolism
In the initial treatment phase, evaluation of medical history and physical examination to confirm diagnosis.
Pharmacologic therapy is effective in the treatment phase as it includes use of biotin, carbonate, and aspartic acid supplementation.
In supportive care and management phase, patients should receive required attention such as lifestyle modification and intervention therapies.
The regular follow-up visits with the endocrinologist are scheduled to check the improvement of patients along with treatment response.
Pyruvate Carboxylase Deficiency (PC) is an autosomal recessive disorder occurs due to mutations in pyruvate carboxylase gene.
PC is an important mitochondrial enzyme using biotin to convert pyruvate to oxaloacetate for energy production pathways.
Pyruvate carboxylase converts pyruvate to oxaloacetate which is essential for Krebs cycle.
Pyruvate is converted into oxaloacetate to generate glucose. Replenishes oxaloacetate in the Krebs cycle which is essential for the proper functioning.
Lipogenesis provides oxaloacetate for the synthesis of fatty acids.
Types of Pyruvate Carboxylase Deficiency are:
Type A (Mild or North American type)
Type B (Severe or French type)
Type C (Intermittent or benign)
Citric acid cycle uses carbs for energy in gluconeogenesis to create carbs when intake is low.
Metabolic acidosis due to lactate production has nonspecific symptoms in illness. Severe pyruvate carboxylase deficiency leads to progressive neurological symptoms in infancy.
PC deficiency disrupts citrate production to impact the citric acid cycle and overall metabolism in significant ways.
Acetyl-CoA needs oxaloacetate to produce citrate and ketone bodies, while gluconeogenesis is required to prevent hypoglycemia.
Cells rely on glycolysis for energy production from glucose since citric acid cycle is inefficient. It reduced aspartic acid production increases serum ammonia levels in body.
PC creates citric acid cycle intermediates crucial for nervous system. Alpha-ketoglutarate is important for glutamate production.
PC deficiency disrupts citrate production to impact the citric acid cycle and overall metabolism in significant ways.
Acetyl-CoA needs oxaloacetate to produce citrate and ketone bodies, while gluconeogenesis is required to prevent hypoglycemia.
Cells rely on glycolysis for energy production from glucose since citric acid cycle is inefficient. It reduced aspartic acid production increases serum ammonia levels in body.
PC creates citric acid cycle intermediates crucial for nervous system. Alpha-ketoglutarate is important for glutamate production.
The causes for PCD are:
Autosomal Recessive Inheritance
PC Gene Mutations
Pyruvate Carboxylase Dysfunction
Gluconeogenesis
Fatty Acid Synthesis
Accumulation of Pyruvate
Hyperammonemia
Dietary changes and supplements can improve some biochemical issues in type B PC deficiency, but patients usually die within 6 months.
Energy deficit in CNS causes neurologic symptoms and brain malformations during neurogenesis.
Neonates may have different outcomes such as hypomyelination, cystic lesions, and grey matter degeneration due to brain abnormalities.
Patients with type A pyruvate carboxylase deficiency live into adulthood with neurologic and cognitive dysfunction.
Collect details including presenting symptoms, episodes of metabolic acidosis, medical and family history to understand clinical history of patient.
Neurological Examination
Musculoskeletal assessment
Abdominal Examination
Cardiovascular assessment
Type A symptoms are:
Failure to thrive, hypotonia, and developmental delay
Episodes of metabolic acidosis
Type B symptoms are:
Hypotonia, lethargy, seizures, episodes of vomiting, and refusal to feed,
hyperammonemia
Lactic acidosis
Leigh encephalopathy
Pyruvate dehydrogenase complex deficiency
Metabolic acidosis
Therapies target Pyruvate Dehydrogenase Complex stimulation and fuel provision.
Pyruvate dehydrogenase complex boosts pyruvate metabolism with thiamine, lipoic acid cofactors, and dichloroacetate for optimized activity.
Biotin supplementation may be minimally beneficial in mildly affected type C patients with partial enzyme function.
Citrate supplement decreases acidosis and fuels citric cycle.
Triheptanoin reversed hepatic failure and biochemical abnormalities in one case with acetyl-CoA source.
They enhanced pathways to reduces pyruvate and lactate levels effectively.
Endocrinology, Metabolism
Keep environment clean and limited exposure to potential infectious agents is essential.
Take high protein diet to maintain an anabolic state and prevent activation of gluconeogenesis.
Fasting should be avoided in this period. Dietary plan should be completed to help dietary manipulations.
Proper awareness about PCD should be provided and its related causes with management strategies.
Appointments with an endocrinologist and preventing recurrence of disorder is an ongoing life-long effort.
Endocrinology, Metabolism
Biotin:
Biotin supplementation is used to enhance residual enzyme activity and energy metabolism.
It neutralizes excess acid in the blood. It is used to correct metabolic acidosis.
Endocrinology, Metabolism
Carnitine:
It transports long-chain fatty acids into the mitochondria for energy production to reduce the accumulation of toxic fatty acid.
Endocrinology, Metabolism
Aspartic acid:
It allows the urea cycle to reduce the ammonia level.
Endocrinology, Metabolism
PCD management focuses on addressing acute metabolic crises through interventions such as central line placement, NG/G-tube placement, and dialysis in severe Type B cases to maintain proper nutrition and ventilation.
Endocrinology, Metabolism
In the initial treatment phase, evaluation of medical history and physical examination to confirm diagnosis.
Pharmacologic therapy is effective in the treatment phase as it includes use of biotin, carbonate, and aspartic acid supplementation.
In supportive care and management phase, patients should receive required attention such as lifestyle modification and intervention therapies.
The regular follow-up visits with the endocrinologist are scheduled to check the improvement of patients along with treatment response.
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