PA (Propionic Acidemia)

Propionic acidemia, also known as propionic aciduriapropionyl-CoA carboxylase deficiency and ketotic glycinemia,[1] is an autosomal recessive[2] metabolic disorder, classified as a branched-chain organic acidemia.[3]

The disorder presents in the early neonatal period with progressive encephalopathy. Death can occur quickly, due to secondary hyperammonemia, infection, cardiomyopathy, or basal ganglial stroke.[4]

Propionic Acidemia is a rare disorder that is inherited from both parents. Being autosomal recessive, neither parent shows symptoms, but both carry a defective gene responsible for this disease. It takes two faulty genes to cause PA, so there is a 1 in 4 chance for these parents to have a child with PA.

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[edit]Pathophysiology

Methylmalonic acidemia is caused by a defect in the vitamin B12-dependent enzyme methylmalonyl CoA mutase.

In healthy individuals, the enzyme propionyl CoA carboxylase converts propionyl CoA to methylmalonyl CoA. This is one step in the process of converting certain amino acids and fats into sugar for energy. Individuals with PA cannot perform this conversion because the enzyme propionyl CoA carboxylase is nonfunctional. The essential amino acids isoleucine, valine, threonine, and methionine and odd-chain fatty acids are simply converted to propionyl CoA, before the process stops, leading to a buildup of propionyl CoA. Instead of being converted to methylmalonyl CoA, propionyl CoA is then converted into propionic acid, which builds up in the bloodstream. This in turn causes a build-up of dangerous acids and toxins, which can cause damage to the organs.

In many cases, PA can damage the brain, heart, and liver, cause seizures, and delays to normal development like walking and talking. During times of illness the affected person may need to be hospitalized to prevent breakdown of proteins within the body. Each meal presents a challenge to those with PA. If not constantly monitored, the effects would be devastating. Dietary needs must be closely managed by a metabolic geneticist or metabolic dietician.

Mutations in both copies of the PCCA or PCCB genes cause propionic acidemia.[5] These genes are responsible for the formation of the enzyme propionyl-CoA carboxylase (EC 6.4.1.3), referred to as PCC.

PCC is required for the normal breakdown of the essential amino acids valineisoleucinethreonine, and methionine, as well as certain odd-chained fatty-acids. Mutations in the PCCA or PCCB genes disrupt the function of the enzyme, preventing these acids from being metabolized. As a result, propionyl-CoApropionic acidketones and other toxic compounds accumulate in the blood, causing the signs and symptoms of propionic acidemia.

[edit]Symptoms

Propionic acidemia is characterized almost immediately in newborns. Symptoms include poor feeding, vomitingdehydration,acidosis, low muscle tone (hypotonia), seizures, and lethargy. The effects of propionic acidemia quickly become life-threatening.

[edit]Genetic prevalence

Propionic acidemia has an autosomal recessive pattern of inheritance.

Propionic acidemia is inherited in an autosomal recessive pattern and is found in about 1 in 35,000[5] live births in the United States. The condition appears to be more common in Saudi Arabia,[6] with a frequency of about 1 in 3,000.[5] The condition also appears to be common in Amish and Mennonite populations.[7]

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