LIPOPROTEIN[A] IS NOT PRESENT IN THE PLASMA OF PATIENTS WITH SOME PEROXISOMAL DISORDERS

Peroxisomal disorders arise either from defects in the biogenesis of p eroxisomes or from the defective synthesis of one or more peroxisomal enzymes. These defects result in metabolic disturbances in peroxisomal beta-oxidation of various fatty acids and derivatives and/or in the b iosynthesis of ether lipids. In the current study, lipoprotein levels were determined in plasma samples from patients diagnosed with one of four different peroxisomal disorders. While low density lipoprotein (L DL) levels were found to be within the normal range, lipoprotein[a] (L p[a]) could not be detected by enzyme-linked immunosorbent assay (ELIS A) in plasma from patients with cerebro-hepato-renal (Zellweger) syndr ome (ZS) and rhizomelic chondrodysplasia punctata (RCDP). Conversely, Lp[a] was clearly present in control plasma obtained from healthy newb orns and from patients affected with one of two other peroxisomal diso rders, X-linked adrenoleukodystrophy (X-ALD) and Refsum disease (RD) a s determined by ELISA. The lack of Lp [a] in plasma of patients with Z S may result from defective secretion of apolipoprotein[a] (apo[a]) (t he distinguishing protein component of Lp[a]), as apo[a] mRNA transcri pts were clearly present in ZS livers as assessed by PCR, and intracel lular apo[a] protein was detected in total liver homogenates from ZS p atients as determined by Western blot analysis. Furthermore, LDL prese nt in the plasma of ZS patients was able to associate with recombinant apo[a] in an in vitro Lp[a] assembly assay.