Pyruvate carboxylase deficiency
Pyruvate carboxylase deficiency | |
---|---|
Other names | Leigh necrotizing encephalopathy due to pyruvate carboxylase deficiency, congenital |
Types | A, B, C |
Causes | mutation to gene for pyruvate carboxylase |
Treatment | anaplerotic therapy, low-fat diet |
Pyruvate carboxylase deficiency is an inherited disorder that causes lactic acid to accumulate in the blood.[2] 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. Type A of the disease appears to be much more common in some Algonkian Indian tribes in eastern Canada, while the type B disease is more present in European populations.[3]
Signs and symptoms
Pyruvate carboxylase deficiency causes
Genetics
Pyruvate carboxylase deficiency is caused by mutations in the PC gene. The PC gene provides instructions for making an enzyme called pyruvate carboxylase.
This condition is inherited in an
Mechanism
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. 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
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
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.[4]
Epidemiology
Pyruvate carboxylase deficiency is very rare, and is estimated to affect around 1 in 250,000 people.
References
- ^ "Pyruvate carboxylase deficiency | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 11 April 2019.
- ^ "Pyruvate carboxylase deficiency". MedlinePlus. NIH - U.S. National Library of Medicine. Retrieved 29 November 2020.
- ^ "Pyruvate Carboxylase Deficiency". NORD (National Organization for Rare Disorders). Retrieved 2021-05-26.
- ^ PMID 15781190 – via ScienceDirect.
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.