Propionic acidemia is an inborn error of metabolism caused by a deficiency of 
propionyl-CoA carboxylase, a heteropolymeric mitochondrial enzyme involved in 
the catabolism of branched chain amino acids, odd-numbered chain length fatty 
acids, cholesterol, and other metabolites. The enzyme is composed of alpha and 
beta subunits which are encoded by the PCCA and PCCB genes, respectively. 
Mutations in both genes can cause propionic acidemia. The identification of the 
responsible gene, previous to mutation analysis, can be performed by 
complementation assay or, in some instances, can be deduced from peculiarities 
relevant to either gene, including obtaining normal enzyme activity in the 
parents of many patients with PCCB mutations, observing combined absence of 
alpha and beta subunits by Western blot of many PCCA patients, as well as 
conventional mRNA-minus result of Northern blots for either gene or beta subunit 
deficiency in PCCB patients. Mutations in both the PCCA and PCCB genes have been 
identified by sequencing either RT-PCR products or amplified exonic fragments, 
the latter specifically for the PCCB gene for which the genomic structure is 
available. To date, 24 mutations in the PCCA gene and 29 in the PCCB gene have 
been reported, most of them single base substitutions causing amino acid 
replacements and a variety of splicing defects. A greater heterogeneity is 
observed in the PCCA gene-no mutation is predominant in the populations 
studied-while for the PCCB gene, a limited number of mutations is responsible 
for the majority of the alleles characterized in both Caucasian and Oriental 
populations. These two populations show a different spectrum of mutations, only 
sharing some involving CpG dinucleotides, probably as recurrent mutational 
events. Future analysis of the mutations identified, of their functional effect 
and their clinical relevance, will reveal potential genotype-phenotype 
correlations for this clinically heterogeneous disorder.