Propionyl-CoA carboxylase deficiency
Propionic acidemia, also known as propionic aciduria, propionyl-CoA carboxylase deficiency and ketotic glycinemia, is an autosomal recessive metabolic disorder, classified as a branched-chain organic acidemia.
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.
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.
Propionic acidemia is characterized almost immediately in newborns. Symptoms include poor feeding, vomiting, dehydration, acidosis, low muscle tone (hypotonia), seizures, and lethargy. The effects of propionic acidemia quickly become life-threatening.
Individuals with PA can not break down parts of protein and some types of fat due to a non-functioning enzyme called PCC. Without the enzyme propionyl CoA carboxylase, four essential amino acids in protein (isoleucine, valine, threonine, and methionine) are only partially processed. Too much protein causes propionic acid to build-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.
Patients with propionic acidemia should be started as early as possible on a low protein diet. In addition to a protein mixture that is devoid of methionine, threonine, valine, and isoleucine, the patient should also receive L-carnitine treatment and should be given antibiotics 10 days per month in order to remove the intestinal propiogenic flora. The patient should have diet protocols prepared for him with a "well day diet" with low protein content, a "half emergency diet" containing half of the protein requirements, and an "emergency diet" with no protein content. These patients are under the risk of severe hyperammonemia during infections that can lead to comatose states.
Liver transplant is gaining a role in the management of these patients, with small series showing improved quality of life.