1/7. 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 syndrome, cerebrohepatorenal (Clic here for more details about this article) |
2/7. 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.- - - - - - - - - - ranking = 5keywords = cerebrohepatorenal syndrome, cerebrohepatorenal (Clic here for more details about this article) |
3/7. The renal lesion in syndromes of multiple congenital malformations. Cerebrohepatorenal syndrome; Jeune asphyxiating thoracic dystrophy; tuberous sclerosis; Meckel syndrome.Renal malformations in cerebrohepatorenal and the Jeune syndromes are variable, encompassing both focal cystic change and severe cystic dysplasia. Morphologic differences might reflect either genetic heterogeneity or injury to the kidney by an underlying metabolic defect at differing times in renal development. The renal lesion in the Meckel syndrome is cystic dysplasia with markedly defective nephronic differentiation. A histologically distinctive cystic tubular lesion is identified in tuberous sclerosis. These lesions must be differentiated from infantile and adult polycystic disease.- - - - - - - - - - ranking = 0.14184731425811keywords = cerebrohepatorenal (Clic here for more details about this article) |
4/7. 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 syndrome, cerebrohepatorenal (Clic here for more details about this article) |
5/7. 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 syndrome, cerebrohepatorenal (Clic here for more details about this article) |
6/7. 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 = 5.1418473142581keywords = cerebrohepatorenal syndrome, cerebrohepatorenal (Clic here for more details about this article) |
7/7. 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 = 1.5673892570325keywords = cerebrohepatorenal syndrome, cerebrohepatorenal (Clic here for more details about this article) |