A diagnosis of autism according to either DSM-IV or DSM-5 criteria was made for four patients with propionic acidemia resulting from biallelic variants in the PCCB gene; one additional patient with a homozygous variant in this gene presented with autistic features (Witters et al., 2016). Administration of propionic acid to rats have been shown to induce autistic-like behaviors in multiple studies (MacFabe et al., 2007; MacFabe et al., 2011; Foley et al., 2014; Foley et al., 2014; Shultz et al., 2015).
The protein encoded by this gene is a subunit of the propionyl-CoA carboxylase (PCC) enzyme, which is involved in the catabolism of propionyl-CoA. PCC is a mitochondrial enzyme that probably acts as a dodecamer of six alpha subunits and six beta subunits. This gene encodes the beta subunit of PCC. Defects in this gene are a cause of propionic acidemia type II (PA-2; OMIM 606054).