Pyruvate carboxylase deficiency

Pyruvate carboxylase deficiency
Oxaloacetate is the product of pyruvate carboxylase
ICD-10	E74.4
OMIM	266150
DiseasesDB	7378
eMedicine	med/1979  ped/1967
MeSH	D015324

WikiDoc Resources for Pyruvate carboxylase deficiency
Articles
Most recent articles on Pyruvate carboxylase deficiency Most cited articles on Pyruvate carboxylase deficiency Review articles on Pyruvate carboxylase deficiency Articles on Pyruvate carboxylase deficiency in N Eng J Med, Lancet, BMJ
Media
Powerpoint slides on Pyruvate carboxylase deficiency Images of Pyruvate carboxylase deficiency Photos of Pyruvate carboxylase deficiency Podcasts & MP3s on Pyruvate carboxylase deficiency Videos on Pyruvate carboxylase deficiency
Evidence Based Medicine
Cochrane Collaboration on Pyruvate carboxylase deficiency Bandolier on Pyruvate carboxylase deficiency TRIP on Pyruvate carboxylase deficiency
Clinical Trials
Ongoing Trials on Pyruvate carboxylase deficiency at Clinical Trials.gov Trial results on Pyruvate carboxylase deficiency Clinical Trials on Pyruvate carboxylase deficiency at Google
Guidelines / Policies / Govt
US National Guidelines Clearinghouse on Pyruvate carboxylase deficiency NICE Guidance on Pyruvate carboxylase deficiency NHS PRODIGY Guidance FDA on Pyruvate carboxylase deficiency CDC on Pyruvate carboxylase deficiency
Books
Books on Pyruvate carboxylase deficiency
News
Pyruvate carboxylase deficiency in the news Be alerted to news on Pyruvate carboxylase deficiency News trends on Pyruvate carboxylase deficiency
Commentary
Blogs on Pyruvate carboxylase deficiency
Definitions
Definitions of Pyruvate carboxylase deficiency
Patient Resources / Community
Patient resources on Pyruvate carboxylase deficiency Discussion groups on Pyruvate carboxylase deficiency Patient Handouts on Pyruvate carboxylase deficiency Directions to Hospitals Treating Pyruvate carboxylase deficiency Risk calculators and risk factors for Pyruvate carboxylase deficiency
Healthcare Provider Resources
Symptoms of Pyruvate carboxylase deficiency Causes & Risk Factors for Pyruvate carboxylase deficiency Diagnostic studies for Pyruvate carboxylase deficiency Treatment of Pyruvate carboxylase deficiency
Continuing Medical Education (CME)
CME Programs on Pyruvate carboxylase deficiency
International
Pyruvate carboxylase deficiency en Espanol Pyruvate carboxylase deficiency en Francais
Business
Pyruvate carboxylase deficiency in the Marketplace Patents on Pyruvate carboxylase deficiency
Experimental / Informatics
List of terms related to Pyruvate carboxylase deficiency

Please Take Over This Page and Apply to be Editor-In-Chief for this topic: There can be one or more than one Editor-In-Chief. You may also apply to be an Associate Editor-In-Chief of one of the subtopics below. Please mail us [1] to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch.

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. 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.

Classification

Researchers have identified at least three types of pyruvate carboxylase deficiency, which are distinguished by the severity of their signs and symptoms.

Type A

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. Children with pyruvate carboxylase deficiency type A typically survive only into early childhood.

Type B

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.

Type C

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.

Genetics

Pyruvate carboxylase deficiency is inherited in an autosomal recessive pattern.

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.

This condition is inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder are carriers of one copy of the altered gene but do not show signs and symptoms of the disorder.

Reference

• Pyruvate carboxylase deficiency at NLM Genetics Home Reference