Propionic acidemia (PA) is an autosomal recessive inborn error in the catabolism 
of methionine, isoleucine, threonine, and valine, odd-numbered chain length 
fatty acids and cholesterol. Clinical symptoms are very heterogeneous and 
present as a severe neonatal-onset or a late-onset form. It is caused by a 
deficiency of propionyl-CoA carboxylase (PCC, EC 6.4.1.3), a biotin-dependent 
enzyme that catalyzes the carboxylation of propionyl-CoA to D-methylmalonyl-CoA. 
PCC is a heteropolymeric enzyme composed of alpha- and beta-subunits. A greater 
heterogeneity is observed in the PCCA gene, 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. We identified eight Korean patients 
with PA by organic acid analysis confirmed in five patients by the PCC enzyme 
assay in the lymphoblasts. Two neonatal-onset patients showed undetectable PCC 
activities while three cases with residual enzyme activities had relatively late 
manifestations. In the molecular analysis, we identified five novel mutations, 
Y439C, 1527del3, 1357insT, IVS12-8T-->A, and 31del10, and one known mutation, 
T428I in PCCB gene. Alleleic frequency of T428I in Korean patients with PA was 
56.3% in this study. Two neonatal-onset patients with null enzyme activities 
were homozygotes with 1527del3 and T428I, respectively. This finding implies 
that T428I and 1527del3 mutation could be responsible for their severe clinical 
courses and null enzyme activities. The mRNA of PCCB gene in T428I and 1527del3 
homozygotes were normal but in Western blot analysis, the betaPCC-subunit was 
only absent in 1527del3 homozygote patient suggesting different molecular 
pathology.