Propionic acidemia, also known as propionic aciduria or propionyl-CoA carboxylase deficiency (PCC deficiency), is a rare autosomal recessive metabolic disorder, classified as a branched-chain organic acidemia.

The disorder presents in the early neonatal period with poor feeding, vomiting, lethargy, and lack of muscle tone. Without treatment, death can occur quickly, due to secondary hyperammonemia, infection, cardiomyopathy, or brain damage.

Propionic acidemia can vary in severity. Severe propionic acidemia lead to symptoms already seen 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.^{[citation needed]}

Long-term complications can include intellectual disability, autism, chronic kidney disease, cardiomyopathy, and prolonged QTc interval.

In healthy individuals, enzyme propionyl-CoA carboxylase converts propionyl-CoA to methylmalonyl-CoA. This is one of many steps in the process of converting certain amino acids and fats into energy. Individuals with propionic acidemia cannot perform this conversion because the enzyme propionyl-CoA carboxylase is nonfunctional. The essential amino acids valine, methionine, isoleucine, and threonine can not be converted and this leads 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 an accumulation of dangerous acids and toxins, which can cause damage to the organs.^{[citation needed]}

In many cases, propionic acidemia can damage the brain, heart, kidney, liver, cause seizures and delays to normal development such as walking or talking. The accumulation of propionic acid is known to induce differential responses in different organs. The heart and liver are specific targets of the complication. The patient may need to be hospitalized to prevent breakdown of proteins within the body. Dietary needs must be closely managed.^{[citation needed]}

Mutations in both copies of the PCCA or PCCB genes cause propionic acidemia. These genes contain instructions to form alpha- and beta-subunits of PCC, the enzyme called propionyl-CoA carboxylase.^{[citation needed]}

PCC is required for the normal breakdown of the essential amino acids valine, isoleucine, threonine, 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-CoA, propionic acid, ketones, ammonia, and other toxic compounds accumulate in the blood, causing the signs and symptoms of propionic acidemia. Hyperammonemia develops due to the inhibitory effects of propionyl-CoA on N-acetylglutamate synthase, indirectly resulting in slowing of the urea cycle.