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Pyruvate Carboxylase Deficiency

Last updated Jan. 9, 2019

Approved by: Krish Tangella MD, MBA, FCAP

Pyruvate Carboxylase Deficiency is an inherited and rare metabolic disorder characterized by the accumulation of excess lactic acid and other toxic compounds in blood, which affects the functioning of body organs and tissues, leading to damage of the nervous system.

What are the other Names for this Condition? (Also known as/Synonyms)

  • Anaplerosis
  • PC Deficiency
  • Type II Ataxia with Lactic Acidosis

What is Pyruvate Carboxylase Deficiency? (Definition/Background Information)

  • Pyruvate Carboxylase Deficiency is an inherited and rare metabolic disorder characterized by the accumulation of excess lactic acid and other toxic compounds in blood, which affects the functioning of body organs and tissues, leading to damage of the nervous system
  • Pyruvate carboxylase (PC) is an important enzyme that plays an important role in energy production by converting pyruvate to oxaloacetate, which is an important substance in gluconeogenesis (a process by which new glucose is synthesized in the body)
  • Deficiency of this important enzyme causes the body to produce less energy, resulting in developmental delays, failure to thrive, and recurrent seizures
  • The condition is managed through medications, supplementations, and symptomatic treatment. However, the prognosis remains guarded

There are many forms of Pyruvate Carboxylase Deficiency. The 3 common forms of PC Deficiency include:

  • Infantile form or Type A: It begins in infancy and children with this form of the disorder usually live up to adulthood
  • Neonatal form or Type B: It is the most severe form, which begins at birth; children usually die within the first few months of life
  • Benign form or Type C: It is a mild form of PC Deficiency with normal life expectancy

Who gets Pyruvate Carboxylase Deficiency? (Age and Sex Distribution)

  • Pyruvate Carboxylase Deficiency is an inherited disorder that is present at the time of birth
  • The onset of symptoms depends on the severity of the condition. With most severe forms of PC Deficiency, the symptoms may be present during early infancy or in the prenatal period itself
  • There is no gender predilection; both male and female babies are affected

What are the Risk Factors for Pyruvate Carboxylase Deficiency? (Predisposing Factors)

The risk factors that increase the incidence of Pyruvate Carboxylase Deficiency are:

  • Genetic factors: PC Deficiency is an inherited condition that is transmitted from parents to their children
  • Race: The Algonquian Indian tribes in Eastern Canada are most commonly affected by this deficiency disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Pyruvate Carboxylase Deficiency? (Etiology)

  • Pyruvate carboxylase (PC) is an enzyme which plays a significant role in the process of converting pyruvate to oxaloacetate. Oxaloacetate is an important organic chemical which is required for gluconeogenesis (synthesis of new glucose in the body) and for the removal of ammonia from the body
  • Pyruvate Carboxylase Deficiency is an inherited condition transmitted in an autosomal recessive manner. It is caused by a mutation in the pyruvate carboxylase (PC) gene

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children, born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Pyruvate Carboxylase Deficiency?

The signs and symptoms manifested by Pyruvate Carboxylase Deficiency differ as per the severity of the disorder. The signs and symptoms may include:

  • Developmental delays and mental retardation
  • Poor feeding, loss of appetite
  • Lethargy and fatigue
  • Seizures, neonatal fits
  • Abdominal pain and vomiting
  • Breathing difficulties
  • Psychomotor retardation: Mental or emotional depression which causes a slowing down of one’s physical movement
  • Hypoglycemia: A medical condition in which the blood sugar is very low
  • Microcephaly (small head)
  • Poor vision, abnormal eye movements (failure of both the eyes to turn together in the same direction)
  • Ataxia (improper co-ordination of muscle movements), muscle weakness, spasticity (muscular stiffness and rigidity)
  • Cheyne-Stokes respiration - an abnormal breathing pattern

How is Pyruvate Carboxylase Deficiency Diagnosed?

The physician may undertake a complete evaluation of the medical history and a thorough physical exam towards the diagnosis of Pyruvate Carboxylase Deficiency disorder. The tests that may be performed to diagnose the disorder include:

  • Random blood glucose level
  • Blood ammonia level
  • Blood sodium level
  • Serum lactate level
  • Serum pyruvate level
  • Serum alanine level
  • Serum lysine level
  • Serum proline level
  • Genetic studies
  • MRI scan of the brain

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Pyruvate Carboxylase Deficiency?

The complications associated with Pyruvate Carboxylase Deficiency include:

  • Liver failure
  • Hypotonia (decreased muscle tone)
  • Ataxia (poorly-coordinated muscle movements)
  • Tremors
  • Quadriplegia (paralysis of both arms and legs)
  • Blindness
  • Respiratory failure
  • Coma and death

How is Pyruvate Carboxylase Deficiency Treated?

The aim of treatment in Pyruvate Carboxylase Deficiency is to provide an alternate source of energy. The treatment of this disorder may include:

  • Anaplerotic therapy: It is based on the fact that the energy deficit found in these deficiencies can be rectified by providing alternative substrates
  • Administering thiamine, lipoic acid, and dichloroacetate as supplements will improve the pyruvate metabolism and reduce pyruvate and lactate levels
  • Administering biotin can help increase the enzyme activity
  • Citrate supplementation reduces acidosis
  • Supplementing with aspartic acid helps in reducing the ammonia level
  • Administering nocturnal gastric drip feeding of uncooked cornstarch has been found to be beneficial
  • Triheptanoin helps in reducing hepatic failure and biochemical abnormalities
  • Orthotropic liver transplantation may also be considered as an option

How can Pyruvate Carboxylase Deficiency be Prevented?

  • Currently, there are no specific methods or guidelines to prevent Pyruvate Carboxylase Deficiency, since it is a genetic condition
  • Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
  • If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
  • Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

What is the Prognosis of Pyruvate Carboxylase Deficiency? (Outcomes/Resolutions)

  • The prognosis of Pyruvate Carboxylase Deficiency is poor. Most of the affected children die within the first 6 months of life
  • Children, who survive for a longer period, have to cope with severe mental and physical disabilities
  • Infants suffering from milder (benign) forms of the deficiency disorder experience mild disability with normal life expectancy

Additional and Relevant Useful Information for Pyruvate Carboxylase Deficiency:

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Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: July 30, 2015
Last updated: Jan. 9, 2019