title: Pseudo infantile Refsum's disease: catalase-deficient peroxisomal particles with partial deficiency of plasmalogen synthesis and oxidation of fatty acids.
abstract: Zellweger syndrome, neonatal adrenoleukodystrophy, and infantile Refsum's disease are genetic disorders characterized by the virtual absence of catalase-positive peroxisomes and a general impairment of peroxisomal functions. Recent studies in these three disorders have provided morphologic evidence of peroxisomal "ghosts" of density 1.10 g/cm3 that contain membrane proteins but lack a majority of the matrix enzyme activities. We report here the biochemical studies in a female infant with clinical features of infantile Refsum's disease whose liver and fibroblasts contained cytosolic catalase but no catalase-positive peroxisomes. Oxidation of phytanic and pipecolic acids was severely impaired, whereas oxidation of very-long-chain fatty acids and dihydroxyacetone phosphate acyltransferase activity were only partially decreased. Immunoblot analysis showed that the three peroxisomal beta-oxidation enzymes (acyl-CoA oxidase, enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase, and 3-ketoacyl-CoA thiolase) were detectable in liver tissues. The 3-ketoacyl-CoA thiolase was of the mature form (41 kD), in contrast with other peroxisomal disorders with multiple enzyme deficiencies. The majority of these peroxisomal enzyme activities were associated with two subcellular membrane vesicle fractions lacking catalase: one had the density of normal peroxisomes (1.17 g/cm3), the other, yet undescribed, a lower density (1.137 g/cm3). This suggests that peroxisomes (density = 1.17 g/cm3) and structures with lower density (density = 1.137 g/cm3) found in this patient's cultured skin fibroblasts, although lacking catalase, contained functional peroxisomal enzymes. This distinguishes this disorder from other disorders of peroxisome biogenesis.
authors.affiliation: INSERM U342, Hôpital Saint Vincent de Paul, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Aubourg
authors.forename: K
authors.initials: K
authors.lastname: Kremser
authors.forename: M O
authors.initials: MO
authors.lastname: Roland
authors.forename: F
authors.initials: F
authors.lastname: Rocchiccioli
authors.forename: I
authors.initials: I
authors.lastname: Singh
mesh_terms: D020642:Acatalasia; D000595:Amino Acid Sequence; D002478:Cells, Cultured; D003937:Diagnosis, Differential; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000201:enzymology / Q000648:ultrastructure; D015417:Hereditary Sensory and Motor Neuropathy / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007231:Infant, Newborn; D007425:Intracellular Membranes / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008830:Microbodies / Q000201:enzymology* / Q000473:pathology; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D010831:Phytanic Acid / Q000097:blood; D010955:Plasmalogens / Q000096:biosynthesis*; D012035:Refsum Disease / Q000175:diagnosis*; D015211:Zellweger Syndrome / Q000175:diagnosis
chemical_list: D005227:Fatty Acids; D010955:Plasmalogens; D010831:Phytanic Acid