Pyruvate Carboxylase Deficiency

Pyruvate carboxylase (PC) deficiency is an inherited disorder that causes build-up of lactic acid in the blood, causing damage to the nervous system. This is due to a defective enzyme called pyruvate carboxylase. There are three types of PC deficiency. Type A has moderately severe symptoms beginning in infancy that include developmental delay, intellectual disability, slow growth, fatigue, muscle weakness, and difficulty breathing. Children with type A survive into early childhood. Type B has life-threatening symptoms that begin shortly after birth, including liver disease, low blood sugar, seizures and coma. Infants with type B will also have weak muscle tone and abnormal movements. They typically survive less than three months. Type C is a mild form that has minimal symptoms with normal to mildly delayed neurological development. A carefully managed diet and certain therapies have shown to ameliorate some symptoms but none have been able to improve neurological symptoms or prolong life expectancy. Pyruvate carboxylase deficiency is caused by pathogenic variants in the PC gene.

Pyruvate carboxylase deficiency is inherited in an autosomal recessive manner. This type of inheritance requires the presence of two copies of a pathogenic variant in the gene for a person to have the genetic disease. Both parents must be carriers of a pathogenic variant in the gene in order to be at risk to have an affected child. The child must inherit a pathogenic variant from each carrier parent in order to be affected. There is a 1 in 4 chance that a baby will inherit two mutated copies of the gene and be affected when both parents are carriers.

There are generally no signs or symptoms associated with being a carrier for PC deficiency. However, the risk to have a child affected with PC deficiency is increased. Testing of reproductive partners is recommended for carriers of PC deficiency.

PC deficiency is a rare disorder found in 1 in 250,000 newborns in most populations. However, some populations have higher frequency. PC deficiency type A occurs more often in Native North American Algonquin-speaking tribes and type B occurs more often in some countries in Europe (France, Germany, and England).

Pyruvate carboxylase deficiency (http://ghr.nlm.nih.gov/)
Pyruvate carboxylase deficiency (http://www.diseaseinfosearch.org/)

OMIM [Pyruvate carboxylase deficiency: 266150] (http://www.ncbi.nlm.nih.gov/omim)
Gene Reviews: Pyruvate carboxylase deficiency (http://www.ncbi.nlm.nih.gov/books/NBK1116/)

• Full gene sequencing