Multiple peroxisomal enzymatic deficiency disorders. A comparative biochemical and morphologic study of Zellweger cerebrohepatorenal syndrome and neonatal adrenoleukodystrophy.
Biologic, morphologic, and biochemical investigations performed in 2 patients demonstrate multiple peroxisomal deficiencies in the cerebrohepatorenal syndrome of Zellweger (CHRS) and neonatal adrenoleukodystrophy (NALD). Very long chain fatty acids, abnormal bile acids, including bile acid precursors (di- and trihydroxycoprostanoic acids), and C29-dicarboxylic acid accumulated in plasma in both patients. Generalized hyperaminoaciduria was also present. Peroxisomes could not be detected in CHRS liver and kidney; however, in the NALD patient, small and sparse cytoplasmic bodies resembling altered peroxisomes were found in hepatocytes. Hepatocellular and Kupffer cell lysosomes were engorged with ferritin and contained clefts and trilaminar structures believed to represent very long chain fatty acids. Enzymatic deficiencies reflected the peroxisomal defects. Hepatic glycolate oxidase and palmitoyl-CoA oxidase activities were deficient. No particle-bound catalase was found in cultured fibroblasts, and ether glycerolipid (plasmalogen) biosynthesis was markedly reduced. Administration of phenobarbital and clofibrate, an agent that induces peroxisomal proliferation and enzymatic activities, to the NALD patient did not bring about any changes in plasma metabolites, liver peroxisome population, or oxidizing activities.
D020642:Acatalasia; D042962:Acyl-CoA Oxidase; D000217:Acyltransferases / Q000172:deficiency; D000326:Adrenoleukodystrophy / Q000188:drug therapy / Q000201:enzymology*; D000429:Alcohol Oxidoreductases / Q000172:deficiency; D001647:Bile Acids and Salts / Q000097:blood / Q000652:urine; D001927:Brain Diseases / Q000201:enzymology*; D003605:D-Amino-Acid Oxidase / Q000172:deficiency; D002549:Diffuse Cerebral Sclerosis of Schilder / Q000201:enzymology*; D005227:Fatty Acids / Q000097:blood / Q000652:urine; D006530:Hepatorenal Syndrome / Q000188:drug therapy / Q000201:enzymology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007674:Kidney Diseases / Q000201:enzymology*; D007728:Kupffer Cells / Q000201:enzymology; D008830:Microbodies / Q000201:enzymology*; D008854:Microscopy, Electron; D010088:Oxidoreductases / Q000172:deficiency; D010743:Phospholipids / Q000378:metabolism
D001647:Bile Acids and Salts; D005227:Fatty Acids; D010743:Phospholipids; D010088:Oxidoreductases; D000429:Alcohol Oxidoreductases; C021380:L-2-hydroxyacid oxidase; D042962:Acyl-CoA Oxidase; D003605:D-Amino-Acid Oxidase; D000217:Acyltransferases; C020051:glycerone-phosphate O-acyltransferase