Mutations in the PC gene reduce the amount of pyruvate carboxylase in cells or disrupt the enzymes activity. The missing or altered enzyme cannot carry out its essential role in generating glucose, which impairs the bodys 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. Loss of pyruvate carboxylase function in the nervous system, particularly the role of the enzyme in myelin formation and neurotransmitter production, may contribute to the neurological features of pyruvate carboxylase deficiency. Diagnosis
Classification
There are 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 build-up 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
This type is characterised by its late onset and is associated with isolated mild intellectual delay. Treatment
Pyruvate carboxylase deficiency treatment typically consists of providing the body with alternate sources of energy (anaplerotic therapy). This may include a diet rich in proteins and carbohydrates but not lipids. Acutely, triheptanoin may be administered as a source of acetyl-CoA. Epidemiology
Pyruvate carboxylase deficiency is very rare, and is estimated to affect around 1 in 250,000 people. References
External links

GeneReview/NCBI/NIH/UW entry on Pyruvate Carboxylase Deficiency
Pyruvate carboxylase deficiency at NLM Genetics Home Reference  This article incorporates text from this source, which is in the public domain.