Propionyl-CoA carboxylase deficiency

Barry Wolf MD PhD (Dr. Wolf of Lurie Children's Hospital of Chicago has no relevant financial relationships to disclose.)
Originally released February 7, 1994; last updated January 12, 2020; expires January 12, 2023

This article includes discussion of propionyl-CoA carboxylase deficiency, propionic acidemia, propionicacidemia, and ketotic hyperglycinemia. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.


The author explains that individuals with propionic acidemia are surviving into adolescence and adulthood; therefore, we are beginning to see additional complications of the disorder, such as psychiatric problems, optic neuropathy, and chronic renal failure in some of them.

Key points


• Propionyl-CoA carboxylase deficiency or propionic acidemia, an inherited metabolic disorder, is due to deficient propionyl-CoA carboxylase activity and usually presents during infancy and early childhood with neurologic symptoms, metabolic acidosis, hyperammonemia, and organic aciduria.


• Although propionyl-CoA carboxylase is a biotin-dependent enzyme, individuals with the disorder do not usually respond to biotin therapy.


• Individuals with propionic acidemia are usually treated with a protein-restricted, high-carbohydrate diet and carnitine supplementation.


• Children with propionic acidemia can be identified by mass spectroscopy on newborn screening, but they are also identified by the characteristic organic aciduria during infancy or childhood when they are symptomatic.

Historical note and terminology

In 1961, a patient was described with ketosis and increased plasma glycine concentrations and was designated as having idiopathic hyperglycinemia (Childs et al 1961; Nyhan et al 1961). The name of the disorder was subsequently changed to "ketotic hyperglycinemia" to distinguish it from disorders with hyperglycinemia without ketosis. Some patients excreted high concentrations of methylmalonic acid and were considered to have methylmalonic acidemia, whereas others excreted high concentrations of propionate derivatives in their urine and were considered to have propionic acidemia (Rosenberg et al 1968; Ando et al 1971). In 1968, a patient with propionic acidemia was found to have increased excretion of hydroxypropionate and odd-numbered carbon-chain fatty acids (Hommes et al 1968). These findings suggested that propionic acidemia was due to a defect in the conversion of propionyl-CoA to methylmalonyl-CoA. In 1969, the absence of propionate oxidation was demonstrated in the peripheral blood leukocytes of the sibling of the first patient described with ketotic hyperglycinemia (Hsia et al 1969). The next year, deficient propionyl-CoA carboxylase activity was shown in the fibroblasts of an affected patient (Hsia et al 1971). Propionyl-CoA carboxylase deficiency was shown in the liver extracts of another patient (Gompertz et al 1970). Subsequently, more than 100 children with propionic acidemia have been reported. The human enzyme has been purified to homogeneity, the cDNA encoding for both of its 2 subunits have been sequenced, and various molecular mutations have been identified.

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