Lipoprotein[a] is not present in the plasma of patients with some peroxisomal disorders.
Peroxisomal disorders arise either from defects in the biogenesis of peroxisomes 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 biosynthesis 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 (LDL) levels were found to be within the normal range, lipoprotein[a] (Lp[a]) could not be detected by enzyme-linked immunosorbent assay (ELISA) in plasma from patients with cerebro-hepato-renal (Zellweger) syndrome (ZS) and rhizomelic chondrodysplasia punctata (RCDP). Conversely, Lp[a] was clearly present in control plasma obtained from healthy newborns and from patients affected with one of two other peroxisomal disorders, X-linked adrenoleukodystrophy (X-ALD) and Refsum disease (RD) as determined by ELISA. The lack of Lp[a] in plasma of patients with ZS may result from defective secretion of apolipoprotein[a] (apo[a]) (the distinguishing protein component of Lp[a]), as apo[a] mRNA transcripts were clearly present in ZS livers as assessed by PCR, and intracellular apo[a] protein was detected in total liver homogenates from ZS patients as determined by Western blot analysis. Furthermore, LDL present in the plasma of ZS patients was able to associate with recombinant apo[a] in an in vitro Lp[a] assembly assay.
van der Hoek
Y Y
YY
Department of Biochemistry, Queen's University, Kingston, Ontario, Canada.
Wanders
R J
RJ
van den Ende
A E
AE
Kraft
H G
HG
Gabel
B R
BR
Kastelein
J J
JJ
Koschinsky
M L
ML
D000293:Adolescent; D000328:Adult; D001054:Apolipoproteins A / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D018902:Chondrodysplasia Punctata, Rhizomelic / Q000097:blood / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D007231:Infant, Newborn; D017270:Lipoprotein(a) / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018901:Peroxisomal Disorders / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015211:Zellweger Syndrome / Q000097:blood / Q000235:genetics / Q000378:metabolism
D001054:Apolipoproteins A; D017931:DNA Primers; D018076:DNA, Complementary; D017270:Lipoprotein(a); D008077:Lipoproteins, LDL; D012333:RNA, Messenger