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.