BIOCHEMICAL FEATURES OF A PATIENT WITH ZELLWEGER-LIKE-SYNDROME WITH NORMAL PTS-1 AND PTS-2 PEROXISOMAL PROTEIN IMPORT SYSTEMS - A NEW PEROXISOMAL DISEASE

The peroxisomal disorders represent a group of inherited metabolic dis orders that derive from defects of peroxisomal biogenesis and/or from dysfunction of single or multiple peroxisomal enzymes. We described ea rlier an 8 1/2-year-old with a history of progressive developmental de lay, micronodular cirrhosis, and elevated very long chain fatty acids in plasma and skin fibroblasts. These findings were felt to be compati ble with both neonatal adrenoleukodystrophy (nALD) and Zellweger syndr ome (ZS). This patient is now 21 years old and his clinical course, in consistent with either nALD or ZS, led us to examine his peroxisomal s tatus in light of a possible new peroxisomal disease. The normal level s of bile acid precursors found in this patient suggest that peroxisom al beta-oxidation is functional. The activities of dihydroxyacetone ph osphate acyltransferase and oxidation of lignoceric acid and phytanic acid were 14, 17, and 15% of the control, respectively. This partial a ctivity for oxidation and the normal levels of bile acid precursors su ggests that this patient has peroxisomes containing beta-oxidation enz ymes. Western blot analysis of subcellular organelles showed that beta -oxidation enzyme proteins are present at normal levels in catalase-ne gative peroxisomes of density equivalent to normal peroxisomes. The pr esence of acyl-CoA oxidase and 3-ketoacyl-CoA thiolase in catalase-neg ative peroxisomes suggests that both peroxisomal targeting signal-1 (P TS-1)- and peroxisomal targeting signal-2 (PTS-S)-mediated protein tra nsport processes into peroxisomes are normal in this patient. These fi ndings of catalase-negative peroxisomes of normal density and normal P TS-1 and PTS-2 import machinery with partial peroxisomal functions cle arly demonstrate that this patient differs from those with known disor ders of peroxisomal biogenesis. (C) 1997 Academic Press.