The
peroxisomal disorders represent a group of inherited metabolic disorders that derive from defects of peroxisomal biogenesis and/or from dysfunction of single or multiple peroxisomal
enzymes. We described earlier an 8 1/2 year-old with a history of progressive developmental delay, micronodular
cirrhosis, and elevated very long chain
fatty acids in plasma and skin fibroblasts. These findings were felt to be compatible with both
neonatal adrenoleukodystrophy (nALD) and
Zellweger syndrome (ZS). This patient is now 21 years old and his
clinical course, inconsistent with either nALD or ZS, led us to examine his peroxisomal status in light of a possible new peroxisomal disease. The normal levels of
bile acid precursors found in this patient suggest that peroxisomal beta-oxidation is functional. The activities of
dihydroxyacetone phosphate acyltransferase and oxidation of
lignoceric acid and
phytanic acid were 14, 17, and 15% of the control, respectively. This partial activity for oxidation and the normal levels of
bile acid precursors suggests that this patient has peroxisomes containing beta-oxidation
enzymes. Western blot analysis of subcellular organelles showed that beta-oxidation
enzyme proteins are present at normal levels in
catalase-negative peroxisomes of density equivalent to normal peroxisomes. The presence of
acyl-CoA oxidase and 3-ketoacyl-CoA thiolase in
catalase-negative peroxisomes suggests that both peroxisomal targeting signal-1 (PTS-1), and peroxisomal targeting signal-2 (PTS-2)-mediated protein transport processes into peroxisomes are normal in this patient. These findings of
catalase-negative peroxisomes of normal density and normal PTS-1 and PTS-2 import machinery with partial peroxisomal functions clearly demonstrate that this patient differs from those with known disorders of peroxisomal biogenesis.