D-3-HYDROXYACYL-COA DEHYDRATASE D-3-HYDROXYACYL-COA DEHYDROGENASE BIFUNCTIONAL PROTEIN-DEFICIENCY - A NEWLY IDENTIFIED PEROXISOMAL DISORDER

Peroxisomal beta-oxidation proceeds from enoyl-CoA through D-3-hydroxy acyl-CoA to 3-ketoacyl-CoA by the D-3-hydroxyacyl-CoA dehydratase/D-3- hydroxy-acyl-CoA dehydrogenase bifunctional protein (D-bifunctional pr otein), and the oxidation of bile-acid precursors also has been sugges ted as being catalyzed by the D-bifunctional protein. Because of the i mportant roles of this protein, we reinvestigated two Japanese patient s previously diagnosed as having enoyl-CoA hydratase/L-3-hydroxyacyl-C oA dehydrogenase bifunctional protein (L-bifunctional protein) deficie ncy, in complementation studies. We found that both the protein and th e enzyme activity of the D-bifunctional protein were hardly detectable in these patients but that the active L-bifunctional protein was pres ent. The mRNA level in patient 1 was very low and, for patient 2, mRNA was of a smaller size. Sequencing analysis of the cDNA revealed a 52- bp deletion in patient 1 and a 237-bp deletion in patient 2. This seem s to be the first report of D-bifunctional protein deficiency. Patient s previously diagnosed as cases of L-bifunctional protein deficiency p robably should be reexamined for a possible D-bifunctional protein def iciency.