title: Peroxisome mosaicism in the livers of peroxisomal deficiency patients.
abstract: Peroxisomal deficiency disorders, which are genetically transmitted, are assumed to be expressed in all cells, and the use of cultured skin fibroblasts for diagnosis and research is based on this assumption. We describe three patients with clinical, biochemical, and microscopic evidence of a peroxisomal disorder. However, their liver displays mosaicism, i.e., parenchymal cells with peroxisomes are adjacent to cells without peroxisomes. Ten percent (volume), 8%, and less than 1% of the parenchyma possessed peroxisomes that can be identified in immunocytochemical tests for six matrix and membrane proteins performed by light and electron microscopy. In the bulk of the parenchyma, catalase is localized in the cytoplasm, and in such cells no peroxisomes are evident by electron microscopy and immunolabeling for the 43-kd peroxisomal membrane protein (PMP) in two patients; in the third case, peroxisomal membrane ghosts are present. Immunoblots of peroxisomal beta-oxidation enzymes show a pattern similar to that from patients with a generalized peroxisomal deficiency. In contrast to the clinical and biochemical signs of peroxisomal dysfunction and hepatic histopathology, cultured fibroblasts from two patients demonstrate normal peroxisomal functions, including very-long-chain fatty acid oxidation and plasmalogen synthesis.
authors.affiliation: Department of Human Anatomy, Embryology and Histology, University of Gent, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Espeel
authors.forename: H
authors.initials: H
authors.lastname: Mandel
authors.forename: F
authors.initials: F
authors.lastname: Poggi
authors.forename: J A
authors.initials: JA
authors.lastname: Smeitink
authors.forename: R J
authors.initials: RJ
authors.lastname: Wanders
authors.forename: I
authors.initials: I
authors.lastname: Kerckaert
authors.forename: R B
authors.initials: RB
authors.lastname: Schutgens
authors.forename: J M
authors.initials: JM
authors.lastname: Saudubray
authors.forename: B T
authors.initials: BT
authors.lastname: Poll-The
authors.forename: F
authors.initials: F
authors.lastname: Roels
mesh_terms: D001647:Bile Acids and Salts / Q000378:metabolism; D002374:Catalase / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D005227:Fatty Acids / Q000378:metabolism; D005347:Fibroblasts / Q000648:ultrastructure; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008099:Liver / Q000648:ultrastructure*; D008297:Male; D008661:Metabolism, Inborn Errors / Q000175:diagnosis / Q000473:pathology*; D008830:Microbodies / Q000201:enzymology / Q000648:ultrastructure*; D008854:Microscopy, Electron; D009030:Mosaicism; D010875:Pipecolic Acids / Q000378:metabolism
chemical_list: D001647:Bile Acids and Salts; D005227:Fatty Acids; D010875:Pipecolic Acids; D002374:Catalase; C031345:pipecolic acid