Propionic acidemia is an autosomal recessive
metabolic disease resulting from a deficiency of
propionyl CoA carboxylase (PCC) activity. We have analyzed the molecular heterogeneity of Japanese
propionic acidemia patients using anti-human PCC antiserum and
cDNA clones coding for the two
protein subunits (alpha and beta) of the
enzyme. The steady state levels of both alpha and beta subunits of PCC from 15 Japanese patients were determined by Western blot. Three patients had neither alpha nor beta subunits, and the amounts of both alpha and beta subunits were low in 3 other patients. According to our previous data, we classified these 6 patients as having alpha subunit deficiency. In the remaining 8 patients, alpha subunits were normal, but the beta subunits were aberrant. Two patients had low levels of normal-sized beta subunits and 6 had beta subunits smaller than normal in size and greatly reduced in quantity. These 8 patients were assigned to the beta subunit deficiency category. One patient had apparently normal alpha and beta subunits. We could not determine this patient's primary defect. These data reveal the genetic heterogeneity of molecular defects causing
propionic acidemia in the Japanese. Southern blot analysis did not reveal any gross alteration in gene structure when
DNA was digested with HindIII, EcoRI and TaqI. However,
DNA from 3 beta-subunit-deficient patients, when digested with MspI and probed with beta PCC
cDNA, revealed a unique 2.7-kb band not observed in blots of
DNA from any other patient or 15 normal controls. We conclude that this altered MspI restriction map is the result of a mutation in the beta subunit gene of these patients.