1/6. Pseudo-zellweger syndrome: deficiencies in several peroxisomal oxidative activities.We describe an infant girl with a clinical, chemical, and pathologic syndrome remarkably similar to Zellweger cerebrohepatorenal syndrome but whose liver parenchymal cells contained abundant peroxisomes. Peroxisomal L-alpha hydroxy acid oxidase, catalase, and the plasmalogen synthesizing enzyme dihydroxy acetone phosphate-acyl transferase activities were normal; other peroxisomal enzymatic activities, including fatty acyl-coa oxidase and D-amino acid oxidase, were reduced by 80% to 85%. Oxidation of bile acids and pipecolic acid was also deficient. autopsy revealed the presence of neuronal heterotopia, renal cortical cysts, adrenal atrophy, and accumulation of very long chain fatty acids. The clinical and pathologic features of this case of "pseudo-zellweger syndrome" reflect a deficiency in multiple peroxisomal activities rather than a defect in peroxisomal biogenesis. The deficient enzymatic activities require flavin adenine dinucleotide, and the underlying defect may be in the utilization of this cofactor.- - - - - - - - - - ranking = 1keywords = cerebrohepatorenal (Clic here for more details about this article) |
2/6. Neonatal adrenoleukodystrophy: new cases, biochemical studies, and differentiation from Zellweger and related peroxisomal polydystrophy syndromes.Eight new cases of autopsy-confirmed or suspected neonatal adrenoleukodystrophy (NALD) are presented together with new biochemical data on very-long-chain fatty acids (VLCFA) and plasmalogens and a review of all previously published cases. The clinical, biochemical, and histopathologic abnormalities characteristic of this newly recognized form of adrenoleukodystrophy are analyzed in detail and compared to the principal characteristics of the similar disorder, the cerebrohepatorenal syndrome of Zellweger (ZS). Using strict pathologic criteria for the diagnosis of NALD, we find that, despite many clinical resemblances, NALD and the ZS are distinguishable on the basis of histology and peroxisomal biochemistry. patients with NALD demonstrate adrenal atrophy, systemic infiltration by abnormal lipid-laden macrophages, and elevations of saturated VLCFA. In contrast, patients with ZS have chondrodysplasia, glomerulocystic disease of the kidney, central nervous system dysmyelination, and elevations of unsaturated as well as saturated VLCFA, but they lack adrenal atrophy. We conclude that NALD and the ZS probably represent at least two different genetic defects.- - - - - - - - - - ranking = 1keywords = cerebrohepatorenal (Clic here for more details about this article) |
3/6. Giant cell transformation cerebrohepatorenal syndrome.An infant with cerebrohepatorenal syndrome of Zellweger had extensive hepatic giant cell transformation at 6 1/2 weeks of age. At 16 weeks the liver showed early cirrhosis and rare giant cells. Changes previously described have ranged from no abnormality in the neonate to cirrhosis at 20 weeks of age and indicate progression of liver disease in affected patients.- - - - - - - - - - ranking = 5keywords = cerebrohepatorenal (Clic here for more details about this article) |
4/6. Ultrastructure of the liver in th cerebrohepatorenal syndrome of Zellweger.Three infants with clinical and biochemical features of Zellweger's cerebrohepatorenal syndrome are presented, and the ultrastructural features of successive biopsy and autopsy liver specimens are described. No hepatocellular peroxisomes were found in these patients on routine electron microscopy or electron microscopic histochemistry. In a control group of liver biopsies from 9 patients with other pediatric liver diseases, peroxisomes were readily identifiable in each hepatocyte. Apart from the absence of peroxisomes, the hepatocytes had a remarkably "normal" aspect, even in the final stages of the disease. Mitochondrial abnormalities, which have been the subject of some controversy in this syndrome, were a highly variable and inconstant finding in our cases. We draw attention to another ultrastructural feature of the syndrome, namely the occurrence of large angulate lysosomes, containing conspicuous double lamellae, inside macrophages, which were especially abundant in later stages of the disease. These angulate lysosomes may be of additional value in the ultrastructural diagnosis of Zellweger's syndrome, especially when only poorly preserved liver tissue (e.g., paraffin-embedded or postmortem material) is available, and the absence of peroxisomes is difficult to assess. In these instances, the angulate lysosomes can still be identified with ease.- - - - - - - - - - ranking = 5keywords = cerebrohepatorenal (Clic here for more details about this article) |
5/6. Ocular histopathologic and biochemical studies of the cerebrohepatorenal syndrome (Zellweger's syndrome) and its relationship to neonatal adrenoleukodystrophy.The eyes of three infants with cerebrohepatorenal disease (Zellweger's syndrome) who died demonstrated ganglion cell loss, gliosis of the nerve fiber layer and optic nerve, optic atrophy, and changes resembling those of retinitis pigmentosa in the retina and pigment epithelium. Ultrastructural examination showed bileaflet inclusions identical to those seen in neonatal adrenoleukodystrophy in the pigment epithelium and in pigmented macrophages, but these were absent in the cornea. Biochemical analysis of tissues demonstrated an excessive amount of very-long-chain fatty acids in the ocular tissues, an abnormality also found in adrenoleukodystrophy. These histopathologic and biochemical results demonstrated that the cerebrohepatorenal syndrome and neonatal adrenoleukodystrophy are similar in regard to ocular abnormalities and the presence of saturated very-long-chain fatty acids.- - - - - - - - - - ranking = 6keywords = cerebrohepatorenal (Clic here for more details about this article) |
6/6. Hyperpipecolic acidemia. Occurrence in an infant with clinical findings of the cerebrohepatorenal (Zellweger) syndrome.An infant with clinical presentation of the cerebrohepatorenal syndrome (CHRS) of Zellweger was found to have increased plasma and urinary concentrations of pipecolic acid. When given a loading dose of DL-pipecolic acid hydrochloride, she showed a reduced clearance rate for that acid. Piperidine, delta 6-piperidine-2-carboxylic acid, and alpha-aminoadipic acid were not detected in plasma or urine. Her response to a lysine load was comparable to that of controls. These data provide further evidence of the connection between hyperpipecolic acidemia and CHRS.- - - - - - - - - - ranking = 5keywords = cerebrohepatorenal (Clic here for more details about this article) |