Pyruvate carboxylase deficiency

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Reviewed August 2006

What is pyruvate carboxylase deficiency?

Pyruvate carboxylase deficiency is an inherited disorder that causes lactic acid and other potentially toxic compounds to accumulate in the blood. High levels of these substances can damage the body's organs and tissues, particularly in the nervous system.

Researchers have identified at least three types of pyruvate carboxylase deficiency, which are distinguished by the severity of their signs and symptoms. Type A, which has been identified mostly in people from North America, has moderately severe symptoms that begin in infancy. Characteristic features include developmental delay and a buildup of lactic acid in the blood (lactic acidosis). Increased acidity in the blood can lead to vomiting, abdominal pain, extreme tiredness (fatigue), muscle weakness, and difficulty breathing. In some cases, episodes of lactic acidosis are triggered by an illness or periods without food (fasting). Children with pyruvate carboxylase deficiency type A typically survive only into early childhood.

Pyruvate carboxylase deficiency type B has life-threatening signs and symptoms that become apparent shortly after birth. This form of the condition has been reported mostly in Europe, particularly France. Affected infants have severe lactic acidosis, a buildup of ammonia in the blood (hyperammonemia), and liver failure. They experience neurological problems including weak muscle tone (hypotonia), abnormal movements, seizures, and coma. Infants with this form of the condition usually survive for less than 3 months after birth.

A milder form of pyruvate carboxylase deficiency, sometimes called type C, has also been described. This type is characterized by slightly increased levels of lactic acid in the blood and minimal signs and symptoms affecting the nervous system.

How common is pyruvate carboxylase deficiency?

Pyruvate carboxylase deficiency is a rare condition, with an estimated incidence of 1 in 250,000 births worldwide. This disorder appears to be much more common in some Algonkian Indian tribes in eastern Canada.

What genes are related to pyruvate carboxylase deficiency?

Mutations in the PC gene cause pyruvate carboxylase deficiency.

The PC gene provides instructions for making an enzyme called pyruvate carboxylase. This enzyme is active in mitochondria, which are the energy-producing centers within cells. It is involved in several important cellular functions including the generation of glucose, a simple sugar that is the body's main energy source. Pyruvate carboxylase also plays a role in the formation of the protective sheath that surrounds certain nerve cells (myelin) and the production of brain chemicals called neurotransmitters.

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. Researchers suggest that the loss of pyruvate carboxylase function in the nervous system, particularly the role of the enzyme in myelin formation and neurotransmitter production, also contributes to the neurologic features of pyruvate carboxylase deficiency.

How do people inherit pyruvate carboxylase deficiency?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of pyruvate carboxylase deficiency?

These resources address the diagnosis or management of pyruvate carboxylase deficiency and may include treatment providers.

You might also find information on the diagnosis or management of pyruvate carboxylase deficiency inEducational resources and Patient support.

General information about the diagnosis and management of genetic conditions is available in the Handbook. Read more about genetic testing, particularly the difference between clinical tests and research tests.

To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.

Where can I find additional information about pyruvate carboxylase deficiency?

You may find the following resources about pyruvate carboxylase deficiency helpful. These materials are written for the general public.

MedlinePlus - Health information (3 links)
Genetic and Rare Diseases Information Center - Information about genetic conditions and rare diseases
Educational resources - Information pages (3 links)
Patient support - For patients and families (4 links)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

Gene Reviews - Clinical summary
Genetic Testing Registry - Repository of genetic test information (1 link)
ACT Sheets - Newborn screening follow up (1 link)
ClinicalTrials.gov - Linking patients to medical research
PubMed - Recent literature
OMIM - Genetic disorder catalog

What other names do people use for pyruvate carboxylase deficiency?

Ataxia with Lactic Acidosis, Type II
PC deficiency
Pyruvate Carboxylase Deficiency Disease

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines and How are genetic conditions and genes named? in the Handbook.

What if I still have specific questions about pyruvate carboxylase deficiency?

Ask the Genetic and Rare Diseases Information Center

Where can I find general information about genetic conditions?

The Handbook provides basic information about genetics in clear language.

These links provide additional genetics resources that may be useful.

What glossary definitions help with understanding pyruvate carboxylase deficiency?

acidity ; acidosis ; ammonia ; ataxia ; autosomal ; autosomal recessive ; carboxylase ; cell ; coma ;deficiency ; developmental delay ; enzyme ; fasting ; gene ; glucose ; hyperammonemia ; hypotonia ;incidence ; lactic acid ; lactic acidosis ; liver failure ; mitochondria ; muscle tone ; nervous system ;neurologic ; neurological ; neurotransmitters ; newborn screening ; recessive ; screening ; simple sugar ;toxic

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.

References (6 links)

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook.