Journal of Inherited Metabolic Disease

, Volume 14, Issue 6, pp 853–875 | Cite as

Liver pathology and immunocytochemistry in congenital peroxisomal diseases: a review

  • F. Roels
  • M. Espeel
  • D. De Craemer


Diagnostic and pathogenetic investigations of peroxisomal disorders should include the study of the macroscopic and microscopic pathology of the liver, in addition to careful clinical observations, skeletal X-ray and brain CT scan, assays of very long-chain fatty acids and bile acid intermediates, and selected enzyme activities. This review of the literature also contains novel observations about the following syndromes: cerebro-hepato-renal (Zellweger) syndrome, X-linked and neonatal adrenoleukodystrophies (ALD, NALD), NALD-like syndromes, infantile phytanic acid storage, classical Refsum disease, rhizomelic and other forms of chondrodysplasia punctata (XD, XR, AR), hyperpipecolic acidaemia, primary hyperoxaluria I, pseudo-Zellweger and Zellweger-like syndromes, and single enzyme deficiencies. Microscopic data include catalase staining and morphometry of peroxisomes, immunolocalization ofβ-oxidation enzymes, detection of trilamellar, polarizing inclusions in PAS-positive macrophages, fibrosis and iron storage. Peroxisomal enlargement appears to be related to functional deficit inβ-oxidation disorders as well as in rhizomelic chondrodysplasia punctata. Because normal peroxisomal localization of activeβ-oxidation enzymes can accompany a C26β-oxidation deficit, other mechanisms such as impaired transport of metabolites should be investigated. ‘Ghost’-like organelles are shown in the liver of an infantile Refsum patient and in an NALD-like case; immuno-gold labelling of membrane proteins did not reveal ghosts in Zellweger livers.


Phytanic Acid Primary Hyperoxaluria Peroxisomal Disorder Acid Storage Refsum Disease 
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  1. Abe, K., Matsushima, S. and Mita, M. Estimation of the mean size of spheres from the profiles in ultrathin sections: A stereological method.J. Electron Microsc. 32 (1983) 57–60Google Scholar
  2. Balfe, A., Hoefler, G., Chen, W. W. and Watkins, P. A. Aberrant subcellular localization of peroxisomal 3-ketoacyl-CoA thiolase in the Zellweger syndrome and rhizomelic chondrodysplasia punctata.Pediatr. Res. 27 (1990) 304–310Google Scholar
  3. Beard, M. E., Sapirstein, V., Kolodny, E. H. and Holtzman, E. Peroxisomes in fibroblasts from skin of Refsum's disease patients.J. Histochem. Cytochem. 33 (1985) 480–484Google Scholar
  4. Beard, M. E., Moser, A. B., Sapirstein, V. and Holtzman, E. Peroxisomes in infantile phytanic acid storage disease: A cytochemical study of skin fibroblasts.J. Inher. Metab. Dis. 9 (1986) 321–334Google Scholar
  5. Budden, S. S., Kennaway, N. G., Buist, N. R. M., Poulos, A. and Weleber, R. G. Dysmorphic syndrome with phytanic acid oxidase deficiency, abnormal very long chain fatty acids, and pipecolic acidemia: Studies in four children.J. Pediatr. 108 (1986) 33–39Google Scholar
  6. Buechler, K. F. and Lowenstein, J. M. The involvement of carnitine intermediates in peroxisomal fatty acid oxidation: a study with 2-bromofatty acids.Arch. Biochem. Biophys. 281 (1990) 233–238Google Scholar
  7. Burton, B. K., Reed, S. P. and Remy, W. T. Hyperpipecolic acidemia: Clinical and biochemical observations in two male siblings.J. Pediatr. 99 (1981) 729–734Google Scholar
  8. Cervos-Navarro, J. Heredopathia atactica polyneuritiformis (Refsum's disease).Histol. Histopathol. 5 (1990) 439–450Google Scholar
  9. Challa, V. R., Geisinger, K. R. and Burton, B. B. Pathologic alterations in the brain and liver in hyperpipecolic acidemia.J. Neuropathol. Expl. Neurol. 41 (1983) 627–638Google Scholar
  10. Christiansen, E. N., Flatmark, T. and Kryvi, H. Effects of marine oil diet on peroxisomes and mitochondria of rat liver. A combined biochemical and morphometric study.Eur. J. Cell Biol. 26 (1981) 11–20Google Scholar
  11. Cooper, P. J., Danpure, C. J. and Simpson, K. J. Peroxisomal and mitochondrial proliferation and increased alanine: glyoxylate aminotransferase activity in human liver after chlorpromazine-induced cholestasis.Biochem. Soc. Trans. 17 (1989) 1071–1072Google Scholar
  12. Danks, D. M., Tippett, P., Adams, C. and Campbell, P. Cerebro-hepato-renal syndrome of Zellweger. A report of eight cases with comments upon the incidence, the liver lesion, and a fault in pipecolic acid metabolism.J. Pediatr. 86 (1975) 382–387Google Scholar
  13. De Craemer, D., Rickaert, F., Wanders, R. J. A. and Roels, F. Hepatic peroxisomes are smaller in primary hyperoxaluria type I (PH I) (cytochemistry and morphometry).Micron Microsc. Acta 20 (1989) 125–126Google Scholar
  14. De Craemer, D., Espeel, M., Langendries, M., Schutgens, R. B. H., Hashimoto, T. and Roels, F. Post-mortem visualization of peroxisomes in rat and in human liver tissue.Histochem. J. 22 (1990a) 36–44Google Scholar
  15. De Craemer, D., Kerckaert, I. and Roels, F. Alterations of hepatocellular peroxisomes in human viral hepatitis.Proc. International Symposium on Progress and Prospects in Viral Hepatitis, Bari, Italy, 1990b, Gerni Editori, San Severo, in pressGoogle Scholar
  16. De Craemer, D., Kerckaert, I. and Roels, F. Peroxisomes in alcoholic and drug-induced hepatitis: a quantitative study.Hepatology (1991a) in pressGoogle Scholar
  17. De Craemer, D., Zweens, M. G., Lyonnet, S., Poll-The, B. T., Schutgens, R. B. H., Wanders, R. J. A., Waelkens, J. J. J., Saudubray, J. M., Roels, F. Very large peroxisomes in distinct peroxisomal deficiency disorders (rhizomelic chondrodysplasia punctata and acyl-CoA oxidase deficiency): novel data.Virchows Archiv. A Pathol. Anat. (1991b) in pressGoogle Scholar
  18. Dingemans, K. P., Mooi, W. J., van den Bergh-Weerman, M. A. Angulate lysosomes.Ultrastruct. Pathol. 5 (1983) 113–122Google Scholar
  19. Draye, J. P. and Vamecq, J. The inhibition by valproic acid of the mitochondrial oxidation of monocarboxylic andω-hydroxymonocarboxylic acids: Possible implications for the metabolism of gamma-aminobutyric acid.J. Biochem. 102 (1987) 235–242Google Scholar
  20. Espeel, M., Hashimoto, T., De Craemer, D. and Roels, F. Immunocytochemical detection of peroxisomalβ-oxidation enzymes in cryostat and paraffin sections of human post mortem liver.Histochem. J. 22 (1990a) 57–62Google Scholar
  21. Espeel, M., Jauniaux, E., Hashimoto, T. and Roels, F. Immunocytochemical localization of peroxisomalβ-oxidation enzymes in human fetal liver.Prenat. Diagn. 10 (1990b) 349–357Google Scholar
  22. Espeel, M., Roels, F., De Craemer, D., Dacremont, G., Van Maldergem, L., Wanders, R. J. A. and Hashimoto, T. Peroxisomal localization of the immunoreactiveβ-oxidation enzymes in a neonate with aβ-oxidation defect. Pathological observations in liver, adrenal cortex and kidney.Virchows Archiv A Pathol. Anat. (1991) in pressGoogle Scholar
  23. Flament-Durand, J., Noel, P., Rutsaert, J., Toussaint, D., Malmendier, C. and Lyon, G. A case of Refsum's disease: clinical, pathological, ultrastructural and biochemical study.Pathol. Eur. 6 (1971) 172–191Google Scholar
  24. Fringes, B. and Reith, A. R. Time course of peroxisome biogenesis during adaptation to mild hyperthyroidism in rat liver.Lab. Invest. 47 (1982) 19–26Google Scholar
  25. Gatfield, P. D., Taller, E., Hinton, G. G., Wallace, A. C., Abdelnour, G. M. and Haust, M. D. Hyperpipecolatemia: A new metabolic disorder associated with neuropathy and hepatomegaly: A case study.Can. Med. Assoc. J. 99 (1968) 1215–1233Google Scholar
  26. Ghatak, N. R., Nochlin, D., Peris, M. and Myer, E. C. Morphology and distribution of cytoplasmic inclusions in adrenoleukodystrophy.J. Neurol. Sci. 50 (1981) 391–398Google Scholar
  27. Gilchrist, K. W., Gilbert, E. F., Goldfarb, S., Goll, U., Spranger, J. W. and Opitz, M. Studies on malformation syndromes of man. XIB: the cerebro-hepato-renal syndrome of Zellweger: Comparative pathology.Eur. J. Pediatr. 121 (1976) 99–118Google Scholar
  28. Goldfischer, S., Moore, C. J., Johnson, A. B., Spiro, A. J., Valsamis, M. P., Wisniewski, H. K., Ritch, R. H., Norton, W. T., Rapin, I. and Gartner, L. M. Peroxisomal and mitochondrial defects in the cerebro-hepato-renal syndrome.Science 182 (1973) 62–64Google Scholar
  29. Goldfischer, S., Collins, J., Rapin, I., Coltoff-Schiller, B., Chang, C. H., Nigro, M., Black, V. H., Javitt, N. B., Moser, H. W. and Lazarow, P. B. Peroxisomal defects in neonatal-onset and X-linked adrenoleukodystrophy.Science 227 (1985) 67–70Google Scholar
  30. Goldfischer, S., Collins, J., Rapin, I., Neumann, P., Neglia, W., Spiro, A. J., Ishii, T., Roels, F., Vamecq, J. and Van Hoof, F. Pseudo-Zellweger syndrome: Deficiencies in several peroxisomal oxidative activities.J. Pediatr. 108 (1986) 25–32Google Scholar
  31. Haas, J. E., Johnson, E. S. and Farrell, D. L. Neonatal-onset adrenoleukodystrophy in a girl.Ann. Neurol. 12 (1982) 449–457Google Scholar
  32. Hartl, F. U. and Just, W. W. Integral membrane polypeptides of rat liver peroxisomes: Topology and response to different metabolic states.Arch. Biochem. Biophys. 255 (1987) 109–119Google Scholar
  33. Heymans, H. S. A. Cerebro-hepato-renal (Zellweger) syndrome. Clinical and biochemical consequences of peroxisomal dysfunction. Doctoral Thesis, Amsterdam, 1984Google Scholar
  34. Heymans, H. S. A., Oorthuys, J. W. E., Nelck, G., Wanders, R. J. A., Dingemans, K. P. and Schutgens, R. B. H. Peroxisomal abnormalities in rhizomelic chondrodysplasia punctata.J. Inher. Metab. Dis. 9 (Suppl. 2) (1986) 329–331Google Scholar
  35. Hughes, J. L., Poulos, A., Robertson, E., Chow, C. W., Sheffield, L. J., Christodoulou, J. and Carter, R. F. Pathology of hepatic peroxisomes and mitochondria in patients with peroxisomal disorders.Virchows Archiv A Pathol. Anat. 416 (1990) 255–264Google Scholar
  36. Iancu, T. C. and Danpure, C. J. Primary hyperoxaluria type I: Ultrastructural observations in liver biopsies.J. Inher. Metab. Dis. 10 (1987) 330–338Google Scholar
  37. Jaffe, R., Crumrine, P., Hashida, Y. and Moser, W. Neonatal adrenoleukodystrophy. Clinical, pathologic and biochemical delineation of a syndrome affecting both males and females.Am. J. Pathol. 108 (1982) 100–111Google Scholar
  38. Johnson, A. B., Schaumburg, H. H. and Powers, J. M. Histochemical characteristics of the striated inclusions of adrenoleukodystrophy.J. Histochem. Cytochem. 24 (1976) 725–730Google Scholar
  39. Kelley, R. I. and Corkey, B. E. Increased sensitivity of cerebrohepatorenal syndrome fibroblasts to antimycin A.J. Inher. Metab. Dis. 6 (1983) 158–162Google Scholar
  40. Kerckaert, I., Dingemans, K. P., Heymans, H. S. A., Vamecq, J. and Roels, F. Polarizing inclusions in some organs of children with congenital peroxisomal diseases (Zellweger's Refsum's, Chondrodysplasia punctata (rhizomelic form), X-linked adrenoleukodystrophy).J. Inher. Metab. Dis. 11 (1988) 372–386Google Scholar
  41. Kerckaert, I., Claeys, A., Just, W., Cornelis, A. and Roels, F. Automated image analysis of rat liver peroxisomes after treatment with thyroid hormones: changes in number, size and catalase reaction.Micron Microsc. Acta 20 (1989) 59–62Google Scholar
  42. Kyllerman, M., Blomstrand, S., Mansson, J. E., Conradi, N. G., Hindmarsh, T. Central nervous system malformations and white matter changes in pseudo-neonatal adrenoleukodystrophy.Neuropediatrics 21 (1990) 199–201Google Scholar
  43. Lake, B. D., Clayton, P. T., Leonard, J. V., Bhuiyan, A. K. M. J., Bartlett, K. and Green, A. A. Ultrastructure of liver in inherited disorders of fat oxidation.Lancet 1 (1987) 382–383Google Scholar
  44. Litwin, J., Völkl, A., Müller-Höcker, J., Hashimoto, T. and Fahimi, H. D. Immunocytochemical localization of peroxisomal enzymes in human liver biopsies.Am. J. Pathol. 128 (1987) 141–150Google Scholar
  45. MacCollin, M., De Vivo, D. C., Moser, A. B. and Beard, M. Ataxia and peripheral neuropathy: a benign variant of peroxisome dysgenesis.Ann. Neurol. 28 (1990) 833–836Google Scholar
  46. Manz, H. J., Schuelein, M., McCullough, D. C., Kishimoto, Y. and Eiben, R. M. New phenotypic variant of adrenoleukodystrophy. Pathologic, ultrastructural and biochemical study in two brothers.J. Neurol. Sci. 45 (1980) 245–260Google Scholar
  47. Mathis, R. K., Watkins, J. B., Szczepanik-Van Leeuwen, P. and Lot, I. T. Liver in the cerebro-hepato-renal syndrome: Defective bile acid synthesis and abnormal mitochondria.Gastroenterology 79 (1980) 1311–1317Google Scholar
  48. Mooi, W. J., Dingemans, K. P., Heymans, H. S. A., van den Bergh-Weerman, M. A., Jöbsis, A. C. and Barth, P. G. Ultrastructure of the liver in the cerebro-hepato-renal syndrome of Zellweger.Ultrastruct. Pathol. 5 (1983) 135–144Google Scholar
  49. Naidu, S., Hoefler, G., Watkins, P. A., Chen, W. W., Moser, A. B., Hoefler, S., Rance, N. E., Powers, J. M., Beard, M., Green, W. R., Hashimoto, T. and Moser, H. W. Neonatal seizures and retardation in a girl with biochemical features of X-linked adrenoleukodystrophy.Neurology 38 (1988) 1100–1107Google Scholar
  50. Partin, J. C., Schubert, W. K. and Partin, J. S. Mitochondrial ultrastructure in Reye's syndrome (Encephalopathy and fatty degeneration of the viscera).N. Engl. J. Med. 285 (1971) 1339–1343Google Scholar
  51. Pfeifer, U. and Sandhage, K. Licht- und elektronenmikroskopische Leberbefunde beim cerebrohepato-renalen Syndrom nach Zellweger (Peroxisomen-Defizienz).Virchows Archiv A Pathol. Anat. 384 (1979) 269–284Google Scholar
  52. Poll-The, B. T., Saudubray, J. M., Ogier, H. A. M., Odièvre, M., Scotto, J. M., Monnens, L., Govaerts, L. C. P., Roels, F., Cornelis, A., Schutgens, R. B. H., Wanders, R. J. A., Schram, A. W. and Tager, J. M. Infantile Refsum disease: an inherited peroxisomal disorder. Comparison with Zellweger syndrome and adrenoleukodystrophy.Eur. J. Pediatr. 146 (1987a) 477–483Google Scholar
  53. Poll-The, B. T., Saudubray, J. M., Rocchioccioli, F., Scotto, J., Roels, F., Boue, J., Ogier, H., Dumez, Y., Wanders, R. J. A., Schutgens, R. B. H., Schram, A. W. and Tager, J. M. Prenatal diagnosis and confirmation of infantile Refsum's disease.J. Inher. Metab. Dis. 10 (Suppl. 2) (1987b) 229–232Google Scholar
  54. Poll-The, B. T., Lombes, A., Lenoir, G., Parvy, P., Scotto, J. M., Vamecq, J., Roels, F. and Saudubray, J. M. Joubert's syndrome associated with hyperpipecolatemia. Three siblings. Doctoral Thesis, Amsterdam (1988a) 201–219Google Scholar
  55. Poll-The, B. T., Roels, F., Ogier, H., Scotto, J., Vamecq, J., Schutgens, R. B. H., Wanders, R. J., Van Roermund, C. W. T., Van Wyland, M. J. A., Schram, A. W., Tager, J. M. and Saudubray, J. M. A new peroxisomal disorder with enlarged peroxisomes and a specific deficiency of acyl-CoA oxidase (Pseudo-neonatal adrenoleukodystrophy).Am. J. Hum. Genet. 42 (1988b) 422–434Google Scholar
  56. Poll-The, B. T., Skjeldal, O. H., Stokke, O., Poulos, A., Demaugre, F. and Saudubray, J. M. Phytanic acid alpha-oxidation and complementation analysis of classical Refsum and peroxisomal disorders.Hum. Genet. 81 (1989) 175–181Google Scholar
  57. Poole, B., Higashi, T. and de Duve, C. The synthesis and turnover of rat liver peroxisomes: III. The size distribution of peroxisomes and the incorporation of new catalase.J. Cell Biol. 45 (1970) 408–415Google Scholar
  58. Poulos, A., Sheffield, L., Sharp, P., Sherwood, G., Johnson, D., Beckman, K., Fellenberg, A. J., Wraith, J. E., Chow, C. W., Usher, S. and Singh, H. Rhizomelic chondrodysplasia punctata: Clinical, pathologic, and biochemical findings in two patients.J. Pediatr. 113 (1988) 685–690Google Scholar
  59. Powers, J. M. Adreno-leukodystrophy (Adreno-testiculo-leukomyelo-neuropathic-complex).Clin. Neuropathol. 4 (1985) 181–199Google Scholar
  60. Prendiville, J. S., Zaparackas, Z. G. and Esterly, N. B. Normal peroxisomal function and absent skeletal manifestations in Conradi-Hünermann syndrome.Arch. Dermatol. 127 (1991) 539–542Google Scholar
  61. Riede, U. N., Riede, P. R., Horn, N., Batthiany, R., Kiefer, G. and Sandritter, W. Mechanisms of adaptation of hepatocytes to a chronical hypothyroidism (A cytophotometrical and morphometrical study).Pathol. Res. Pract. 162 (1978) 398–419Google Scholar
  62. Robertson, E. F., Poulos, A., Sharp, P., Manson, J., Wise, G., Jaunzems, A. and Carter, R. Treatment of infantile phytanic acid storage disease: clinical, biochemical and ultrastructural findings in two children treated for 2 years.Eur. J. Pediatr. 147 (1988) 133–142Google Scholar
  63. Roels, F.Peroxisomes, a Personal Account. V.U.B. University Press, Brussels, 1991, pp. 1–140Google Scholar
  64. Roels, F. and Cornelis, A. Heterogeneity of catalase staining in human hepatocellular peroxisomes.J. Histochem. Cytochem. 37 (1989) 331–337Google Scholar
  65. Roels, F. and Goldfischer, S. Cytochemistry of human catalase: the demonstration of hepatic and renal peroxisomes by a high temperature procedure.J. Histochem. Cytochem. 27 (1979) 1471–1477Google Scholar
  66. Roels, F., Pauwels, M., Cornelis, A., Kerckaert, I., Van der Spek, P., Goovaerts, G., Versieck, J. and Goldfischer, S. Peroxisomes (microbodies) in human liver: cytochemical and quantitative studies of 85 biopsies.J. Histochem. Cytochem. 31 (1983) 235–237Google Scholar
  67. Roels, F., Cornelis, A., Poll-The, B. T., Aubourg, P., Ogier, H., Scotto, J. M. and Saudubray, J. M. Hepatic peroxisomes are deficient in infantile Refsum disease. A cytochemical study of 4 cases.Am. J. Med. Genet. 25 (1986) 257–271Google Scholar
  68. Roels, F., Verdonck, V., Pauwels, M., De Catte, L., Lissens, V., Liebaers, I. and Elleder, M. Light microscopic visualization of peroxisomes and plasmalogens in first trimester chorionic villi.Prenat. Diagn. 7 (1987) 525–530Google Scholar
  69. Roels, F., Pauwels, M., Poll-The, B. T., Scotto, J., Ogier, H., Aubourg, P. and Saudubray, J. M. Hepatic peroxisomes in adrenoleukodystrophy and related syndromes: cytochemical and morphometric data.Virchows Archiv A Pathol. Anat. 413 (1988) 275–285Google Scholar
  70. Roels, F., Espeel, M., Van Maldergem, L., Dacremont, G., Wanders, R. J. A., Schutgens, R. B. H., Evrard, J., Van Hoof, F., Wiemer, E. and Hashimoto, T. Accumulation of very long chain fatty acids (VLCFA's) in a newborn with trilamellar inclusions in the liver but normal localization of peroxisomalβ-oxidation enzyme proteins. 22nd Conference of the ‘Mitteleuropäische Stoffwechselgruppe’ (MILUPA), 1989, p. 6Google Scholar
  71. Roels, F., Espeel, M., Rehder, H., Van Maldergem, L., Litwin, J., Yokota, S., Tager, J. and Hashimoto, T. Liver pathology and immunocytochemistry in congenital peroxisomal disorders. 28th Annual Symposium SSIEM, Birmingham, UK, 1990Google Scholar
  72. Roels, F., Espeel, M., Pauwels, M., De Craemer, D., Egberts, H. J. A. and Van der Spek, P. Different types of peroxisomes in human duodenal epithelium.Gut 32 (1991) 858–865Google Scholar
  73. Santos, M. J., Imanaka, T., Shio, H. and Lazarow, P. B. Peroxisomal integral membrane proteins in control and Zellweger fibroblasts.J. Biol. Chem. 263 (1988) 10502–10509Google Scholar
  74. Sarnat, H. B., Machim, G., Darwish, H. Z. and Rubin, S. Z. Mitochondrial myopathy of cerebro-hepato-renal (Zellweger) syndrome.Can. J. Neurol. Sci. 10 (1983) 170–177Google Scholar
  75. Schaumburg, H. H., Powers, J. M., Suzuki, K. and Raine, C. S. Adrenoleukodystrophy (Sex-linked Schilder disease). Ultrastructural demonstration of specific cytoplasmic inclusions in the central nervous system.Arch. Neurol. 31 (1974) 210–213Google Scholar
  76. Schaumburg, H. H., Powers, J. M., Raine, C. S., Suzuki, K. and Richardson Jr, E. P. Adrenoleukodystrophy. A clinical and pathological study of 17 cases.Arch. Neurol. 32 (1975) 577–591Google Scholar
  77. Schram, A. W., Strijland, A., Hashimoto, T., Wanders, R. J. A., Schutgens, R. B. H., van den Bosch, H. and Tager, J. M. Biosynthesis and maturation of peroxisomalβ-oxidation enzymes in fibroblasts in relation to the Zellweger syndrome and infantile Refsum disease.Proc. Natl Acad. Sci. USA 83 (1986) 6156–6158Google Scholar
  78. Schutgens, R. B. H., Heymans, H. S. A., Wanders, R. J. A., Oorthuys, J. W. E., Tager, J. M., Schrakamp, G., van den Bosch, H. and Beemer, F. A. Multiple peroxisomal enzyme deficiencies in Rhizomelic Chondrodysplasia punctata. Comparison with Zellweger syndrome, Conradi-Hünermann syndrome and the X-linked dominant type of chondrodysplasia punctata. In Goldberg, D. M., Moss, D. W., Schmidt, E. and Schmidt, F. W. (eds.)Enzymes — Tools and Targets, Advances in Clinical Enzymology, 6, S. Karger, Basel, 1988, pp. 57–65Google Scholar
  79. Scotto, J. M., Hadchouel, M., Odièvre, M., Laudat, M. M., Saudubray, J. M., Dulac, O., Beucler, I. and Beaune, P. Infantile phytanic acid storage disease, a possible variant of Refsum's disease: three cases including ultrastructural studies of the liver.J. Inher. Metab. Dis. 5 (1982) 83–90Google Scholar
  80. Sherratt, H. S. A., Bartlett, K., Bone, A. J., Koundakjian, P. P., Turnbull, D. M., Osmundsen, H. and Van Hoof, F. Hepatic peroxisomal proliferation caused by ethyl 2(5(4-chlorophenyl)pentyl)oxiran-2-carboxylate (CPOC): A hypoglycemic inhibitor of mitochondrial fatty acid oxidation.Ann. NY Acad. Sci. 386 (1982) 446–448Google Scholar
  81. Simpson, R. H. W., Rodda, J. and Reinecke, C. J. Adrenoleukodystrophy in a mother and son.J. Neurol. Neurosurg. Psychiatry 50 (1987) 1165–1172Google Scholar
  82. Singh, I., Lazo, O., Contreras, M., Stanley, W., Hashimoto, T. Rhizomelic chondrodysplasia punctata: biochemical studies of peroxisomes isolated from cultured skin fibroblasts.Arch. Biochem. Biophys. 286 (1991) 277–283Google Scholar
  83. Sternlieb, I. and Quintana, N. The peroxisomes of human hepatocytes.Lab. Invest. 36 (1977) 140–149Google Scholar
  84. Suzuki, Y., Orii, T. and Hashimoto, T. Biosynthesis of peroxisomalβ-oxidation enzymes in infants with Zellweger syndrome.J. Inher. Metab. Dis. 9 (1986) 292–296Google Scholar
  85. Suzuki, Y., Shimazowa, N., Orii, T., Igarashi, N., Kono, N., Matsui, A., Inoue, Y., Yokota, S. and Hashimoto, T. Molecular analysis of peroxisomalβ-oxidation enzymes in infants with Zellweger syndrome and Zellweger-like syndrome: further heterogeneity of the peroxisomal disorder.Clin. Chim. Acta 172 (1988a) 65–76Google Scholar
  86. Suzuki, Y., Shimazowa, N., Orii, T., Igarashi, N., Kono, N., Matsui, A., Inoue, Y., Yokota, S. and Hashimoto, T. Zellweger-like syndrome with detectable hepatic peroxisomes: A variant form of peroxisomal disorder.J. Pediatr. 113 (1988b) 841–845Google Scholar
  87. Suzuki, Y., Yamaguchi, S., Orii, T., Tsuneoka, M. and Tashiro, Y. Nonspecific lipid transfer protein (Sterol Carrier Protein-2) defective in patients with deficient peroxisomes.Cell Struct. Funct. 15 (1990) 301–308Google Scholar
  88. Svoboda, D. J. and Reddy, J. K. Pathology of the liver in Reye's syndrome.Lab. Invest. 32 (1975) 571–579Google Scholar
  89. Tager, J. M., Brul, S., Wiemer, E. A. C., Strijland, A., Van Driel, R., Schutgens, R. B. H., van den Bosch, H., Wanders, R. J. A. and Westerveld, A. Genetic relationship between the Zellweger syndrome and other peroxisomal disorders characterized by an impairment in the assembly of peroxisomes. In Tanaka, K. and Coates, P. M. (eds.)Fatty Acid Oxidation: Clinical, Biochemical and Molecular Aspects, Alan R. Liss, New York, 1990, pp. 546–558Google Scholar
  90. Trijbels, J. M. F., Berden, J. A., Monnens, L. A. H., Willems, J. L., Janssen, A. J. M., Schutgens, R. B. H. and van de Broek-van Essen, M. Biochemical studies in the liver and muscle of patients with Zellweger syndrome.Pediatr. Res. 17 (1983) 514–517Google Scholar
  91. Ulrich, J., Herschkowitz, N., Heitz, Ph., Sigrist, Th. and Baerlocher, P. Adrenoleukodystrophy. Preliminary report of a connatal case. Light-and electron-microscopical, immunohistochemical and biochemical findings.Acta Neuropathol. 43 (1978) 77–83Google Scholar
  92. Vamecq, J., Draye, J. P., Van Hoof, F., Misson, J. P., Evrard, P., Verellen, G., Eyssen, H. J., Van Eldere, J., Schutgens, R. B. H., Wanders, R. J. A., Roels, F. and Goldfischer, S. Multiple peroxisomal enzymatic deficiency disorders. A comparative biochemical and morphologic study of Zellweger cerebrohepatorenal syndrome and neonatal adrenoleukodystrophy.Am. J. Pathol. 125 (1986) 524–535Google Scholar
  93. Vamecq, J., Roels, F., Van den Branden, C. and Draye, J. P. Peroxisomal proliferation in heart and liver of mice receiving chlorpromazine, ethyl 2(5(4-chlorophenyl)pentyl)oxiran-2-carboxylic acid or high fat diet: A biochemical and morphometrical comparative study.Pediatr. Res. 22 (1987) 748–754Google Scholar
  94. Van den Branden, C., Vamecq, J., Wybo, I. and Roels, F. Phytol and peroxisome proliferation in mice.Pediatr. Res. 20 (1986) 411–415Google Scholar
  95. Van Hoof, F. and Roels, F. Liver ultrastructure and diagnosis of inborn metabolic disorders.Micron Microsc. Acta 20 (1989) 59–62Google Scholar
  96. Van Maldergem, L., Espeel, M., Roels, F., Draye, J. P., Van Hoof, F., Dacremont, G., Wanders, R. J. A., Schutgens, R. B. H., Gérard, P., Hashimoto, T., Gillerot, Y. and Koulischer, L. Pseudo-neonatal adrenoleukodystrophy (pseudo-NALD) in a newborn male with immunoreactive but defective acyl-CoA oxidase. 27th Annual Symposium of the Society for the Study of Inborn Errors of Metabolism, Munchen, 1989Google Scholar
  97. Van Maldergem, L., Espeel, M., Roels, F., Petit, C., Wanders, R. J. A., Verloes, A. and Gillerot, Y. X-linked recessive chondrodysplasia punctata with XY translocation in a stillborn fetus.Hum. Genet. (1991a) in pressGoogle Scholar
  98. Van Maldergem, L., Espeel, M., Wanders, R. J. A., Roels, F., Gérard, P., Scalais, E., Mannaerts, G. P., Casteels, M. and Gillerot, Y. Neonatal seizures and hypotonia with elevation of very long chain fatty acids, normal bile acids, normal fatty acyl-CoA oxidase and intraperoxisomal localization of the threeβ-oxidation enzymes: A novel peroxisomal disease?Neurology (1991b) submittedGoogle Scholar
  99. Veitch, K., Draye, J. P., Vamecq, J., Causey, A. G., Bartlett, K., Sherratt, H. S. A. and Van Hoof, F. Altered acyl-CoA metabolism in riboflavin deficiency.Biochem. Biophys. Acta 1006 (1989) 335–343Google Scholar
  100. Wanders, R. J. A., Heymans, H. S. A., Schutgens, R. B. H., Barth, P. G., van den Bosch, H. and Tager, J. M. Peroxisomal disorders in neurology.J. Neurol. Sci. 88 (1988a) 1–39Google Scholar
  101. Wanders, R. J. A., Heymans, H. S. A., Schutgens, R. B. H., Poll-Thé, B. T., Saudubray, J. M., Tager, J. M., Schrakamp, G. and van den Bosch, H. Peroxisomal functions in classical Refsum's disease: comparison with the infantile form of Refsum's disease.J. Neurol. Sci. 84 (1988b) 147–155Google Scholar
  102. Wanders, R. J. A., van Roermund, C. W. T., van Wijland, M. J. A., Schutgens, R. B. H., van den Bosch, H. and Thomas, G. H. Peroxisomes and peroxisomal functions in hyperpipecolic acidemia.J. Inher. Metab. Dis. 11 (1988c) (Suppl. 2), 161–166Google Scholar
  103. Watkins, P. A., Chen, W. W., Harris, C. J., Hoefler, G., Hoefler, S., Blake Jr., D. C., Balfe, A., Kelley, R. I., Moser, A. B., Beard, M. E. and Moser, H. W. Peroxisomal bifunctional enzyme deficiency.J. Clin. Invest. 83 (1989) 771–777Google Scholar
  104. Watkins, P. A., Mihalik, S. J. and Skjeldal, O. H. Mitochondrial oxidation of phytanic acid in human and monkey liver. Implication that Refsum's disease is not a peroxisomal disorder.Biochem. Biophys. Res. Commun. 167 (1990) 580–586Google Scholar
  105. Weibel, E. R.Stereological methods, Vol. 1. Practical Methods for Biological Morphometry. Academic Press, London, 1979Google Scholar
  106. Wiemer, E. A. C., Brul, S., Just, W. W., Van Driel, R., Brouwer-Kelder, E., Van Den Berg, M., Weijers, P. J., Schutgens, R. B. H., van den Bosch, H., Schram, A., Wanders, R. J. A. and Tager, J. M. Presence of peroxisomal membrane proteins in liver and fibroblasts from patients with the Zellweger syndrome and related disorders: evidence for the existence of peroxisomal ghosts.Eur. J. Cell Biol. 50 (1989) 407–414Google Scholar
  107. Wiemer, E. A. C., Out, M., Schelen, A., Wanders, R. J. A., Schutgens, R. B. H., van den Bosch, H. and Tager, J. M. Phenotypic heterogeneity in cultured skin fibroblasts from patients with disorders of peroxisome biogenesis belonging to the same complementation group. PhD Thesis, Amsterdam, 1991Google Scholar

Copyright information

© SSIEM and Kluwer Academic Publishers 1991

Authors and Affiliations

  • F. Roels
    • 1
  • M. Espeel
    • 1
  • D. De Craemer
    • 1
  1. 1.Human Anatomy and Embryology, Faculty of Medicine and PharmacyVrije Unversiteit BrusselBrusselsBelgium

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