Skip to main content
SpringerLink
Log in

Peroxisomes in infantile phytanic acid storage disease: a cytochemical study of skin fibroblasts

  • Published:
Journal of Inherited Metabolic Disease

Abstract

Cultured skin fibroblasts from six patients demonstrating clinical signs and biochemical characteristics of infantile phytanic acid storage disease (IPSD) were examined by electron microscopy, using cytochemical procedures for the demonstration of peroxisomal catalase activity. In four of the six fibroblast cell lines peroxisomes strongly reactive for catalase were present in numbers similar to those found in normal fibroblasts. Liver biopsy tissue from one of these patients showed no typical hepatic peroxisomes, but did show small, marginally reactive bodies. In two other IPSD fibroblast cell lines peroxisomes with appreciable cytochemical reactivity were rare or absent. It seems, therefore, that infantile phytanic acid storage disease is heterogeneous with respect to the presence of cytochemically recognizable peroxisomes, at least in the cases studied here. Furthermore, peroxisomes may be markedly affected in one cell type — liver — and yet not affected in another — skin fibroblasts — within a single individual.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Arias, J. A., Moser, A. B. and Goldfischer, S. L. Ultrastructural and cytochemical demonstration of peroxisomes in cultured fibroblasts from patients with peroxisomal deficiency disorders.J. Cell. Biol. 100 (1985) 1789–1792

    Google Scholar 

  • Beard, M. E., Moser, A. B., Sapirstein, V. and Holtzman, E. Is a childhood Refsum's disease a peroxisomal disorder?J. Cell. Biol. 101 (1985b) 67a

  • 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 (1985a) 480–484

    Google Scholar 

  • Bolthauser, E., Spycher, M. A., Steinman, B., Briner, J., Isler, W., Kuster, T., Poulos, A. and Pollar, A. C. Infantile phytanic acid storage disease: A variant of Refsum's disease?Eur. J. Pediatr. 139 (1982) 317

    Google Scholar 

  • Brown, F. R., McAdams, A. J., Cummins, J. W., Konkol, R., Singh, I., Moser, A. B. and Moser, H. W. Cerebro-hepato-renal (Zellweger) syndrome and neonatal adrenoleukodystrophy: Similarities in phenotype and accumulation of very long chain fatty acids.Johns Hopkins Med. J. 151 (1982) 344–361

    Google Scholar 

  • 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) 33–39

    Google Scholar 

  • Burton, B. K., Reeds, S. P. and Remy, W. T. Hyperpipecolic acidemia: Clinical and biochemical observation in two male siblings.J. Pediatr. 99 (1983) 729–734

    Google Scholar 

  • Farquhar, M. G. and Palade, G. E. Cell junctions in amphibian skin.J. Cell. Biol. 26 (1965) 263–291

    Google Scholar 

  • Goldfischer, S. Peroxisomes and human metabolic diseases: The cerebrohepatorenal syndrome, cerebrotendinosis xanthomatosis and Schilder's disease (adrenoleukodystrophy).Ann. NY Acad. Sci. 386 (1982) 526–529

    Google Scholar 

  • Goldfischer, S., Collins, J., Rappin, 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 adrenoleukodystrophies.Science 227 (1985) 67–70

    Google Scholar 

  • Goldfischer, S. L., Collins, J., Rapin, I., Neumann, P., Neglia, W., Spiro, A. J., Ishii T., Roels, F., Vamecq, J. and Van Hoff, F., Pseudo-Zellweger syndrome: Deficiencies in several peroxisomal oxidative activities.J. Pediatr. 108 (1986) 25–31

    Google Scholar 

  • Goldfischer, S., Moore, C. L., 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 cerebrohepatorenal syndrome.Science 182 (1973) 62–64

    Google Scholar 

  • Goldfischer, S. and Reddy, J. K. Peroxisomes (microbodies) in cell pathology.Int. Rev. Exp. Pathol. 26 (1984) 45–84

    Google Scholar 

  • Hagey, L. R. and Krisans, S. K.In vitro cholesterol catabolism. A new role for rat liver peroxisomes.J. Cell. Biol. 95 (1982a) 278a

  • Hagey, L. R. and Krisans, S. K. Degradation of cholesterol to propionic acid by rat liver peroxisomes.Biochem. Biophys. Res. Commun. 107 (1982b) 834–841

    Google Scholar 

  • Hajra, A. K. and Bishop, J. E. Glycerolipid biosynthesis in peroxisomes via the acyl dihydroxyacetone phosphate pathway.Ann. NY Acad. Sci. 386 (1982) 170–182

    Google Scholar 

  • Hajra, A. K., Burke, C. C. and Jones, C. L. Peroxisomal localization of acyl coenzyme A: dihydroxyacetone phosphate acyltransferase in rat liver peroxisomes.J. Biol. Chem. 254 (1979) 10896–10900

    Google Scholar 

  • Herndon, J. H. D., Steinberg, D. and Uhlendorf, B. W. Refsum's disease: defective oxidation of phytanic acid in tissue cultures derived from homozygotes and heterozygotes.N. Engl. J. Med. 281 (1969a) 1034–1038

    Google Scholar 

  • Herndon, J. H. D., Steinberg, D., Uhlendorf, B. W. and Fales, H. M. Refsum's disease: Characterization of the enzyme defect in cell culture.J. Clin. Invest. 48 (1969b) 1017–1022

    Google Scholar 

  • Heymans, H. S. A., Oorthuys, J. W. E., Nelck, G., Wanders, R. J. A. and Schutgens, R. B. H. Rhizomelic chondrodysplasia punctata: Another peroxisomal disorder.N. Engl. J. Med. 313 (1985) 187–188

    Google Scholar 

  • Heymans, H. S. A., Schutgens, R. B. H., Tan, R., van den Bosch, H. and Borst, P. Severe plasmalogen deficiency in tissues of infants without peroxisomes (Zellweger syndrome).Nature 306 (1983) 69–70

    Google Scholar 

  • Kase, F., Bjorkhem, I. and Pedersen, J. I. Formation of cholic acid from 3α, 7α, 12α-trihydroxy-5β-cholestanoic acid by rat liver peroxisomes.J. Lipid Res. 24 (1983) 1560–1567

    Google Scholar 

  • Kindl, H. and Lazarow, P. B. (eds.) Peroxisomes and glyoxysomes.Ann. NY Acad. Sci. vol. 386 (1982).

  • Krisans, S. K., Thompson, S. L., Pena, L. A. and Kok, E. Bile acid synthesis by rat liver peroxisomes.J. Cell. Biol. 99 (1984) 360a

    Google Scholar 

  • Lazarow, P. B., Black, V., Shio, H., Fujiki, Y., Hajra, A. K., Datta, N. S., Bangaru, B. S. and Dancis, J. Zellweger syndrome: Biochemical and morphological studies on two patients treated with clofibrate.Pediatr. Res. 19 (1985) 1356–1363

    Google Scholar 

  • Lazarow, P. B. and deDuve, C. A fatty acyl-CoA oxidizing system in rat liver peroxisomes: Enhancement by clofibrate, a hypolipidemic drug.Proc. Natl. Acad. Sci., 73 (1976) 2043–2046

    Google Scholar 

  • Masters, C. and Crane, D. C. The role of peroxisomes in lipid metabolism.Trends Biochem. Sci. 9 (1984) 314–317

    Google Scholar 

  • Monnens, L., Bakkeren, J. and Parmentier, G. Disturbances of bile acid metabolism of infants with Zellweger (cerebrohepatorenal) syndrome.Eur. J. Pediatr. 133 (1980) 31–35

    Google Scholar 

  • Moser, H. W. and Goldfischer, S. The peroxisomal disorders.Hospital Practice (Sept) (1985) 61–70

  • Novikoff, A. B. and Goldfischer, S. Visualization of peroxisomes (microbodies) and mitochondria with diaminobenzidine.J. Histochem. Cytochem. 17 (1973) 675–680

    Google Scholar 

  • Ogier, H., Roels, F., Cornelius, A., Poll-The, B.T., Scotto, J. M., Odievre, M. and Saudubray, J. M. Absence of hepatic peroxisomes in a case of infantile Refsum's disease.Scand. J. Clin. Lab. Invest. 45 (1985) 767–768

    Google Scholar 

  • Partin, J. S. and McAdams, A. J. Absence of hepatic peroxisomes in neonatal adrenoleukodystrophy.Pediatr. Res. 17 (1983) 294a.

    Google Scholar 

  • Poll-The, B.T., Ogier, H., Saudubray, J. M., Schutgens, R. B. H., Wanders, R. J. A., van den Bosch H. and Schrakamp, G. Impaired plasmalogen metabolism in infantile Refsum's disease.Eur. J. Pediatr. 144 (1985) 514–515

    Google Scholar 

  • Poll-The, B.T., Saudubray, J. M., Ogier, H., Schutgens, R. B. H., Wanders, R. J. A., Schrakamp, G., van den Bosch, H., Trijbels, J. M. F., Poulos, A., Moser, H. W., van Elder, J. and Eyssen, H. J. Infantile Refsum's disease: biochemical findings suggesting a generalized dysfunction of peroxisomes.J. Inher. Metab. Dis. 9 (1986) 169–174

    Google Scholar 

  • Poll-The, B.T., Schutgens, R. B. H., Wanders, R. J. A., Roels, F., Poulos, A., Ogier, H. and Saudubray, J. M. Infantile Refsum's disease: Generalized peroxisomal dysfunctions in three revised patients. Joint Unesco-IUB Workshop,Peroxisomes and Their Metabolites in Cellular Functions, Zeist, Holland, 1985b

  • Poulos, A. and Sharp, P. Plasma and skin fibroblasts. C26 fatty acids in infantile Refsum's disease.Neurology 34 (1984) 1606–1609

    Google Scholar 

  • Poulos, A., Sharp, P., Fellenberg, A. J. and Danks, D. M. Cerebro-hepatorenal (Zellweger) syndrome, adrenoleukodystrophy and Refsum's. Plasma changes and skin fibroblast phytanate oxidase.Hum. Genet. 70 (1985) 172–177

    Google Scholar 

  • Poulos, A., Sharp, P. and Whiting, M. Infantile Refsum's disease (phytanic acid storage disease): A variant of Zellweger's syndrome?Clin. Genet. 26 (1984) 579–586

    Google Scholar 

  • Refsum, S., Heredopathic atactica polyneuritiformis. A familial syndrome not hitherto described.Acta Psychiatr. Neurol. Suppl. 38 (1946) 1

    Google Scholar 

  • Refsum, S., Heredopathic atactica polyneuritiformis. Phytanic acid storage disease (Refsum's disease) In:Handbook of Clinical Neurology 21 (1975) 181–182

    Google Scholar 

  • Reynolds, S. The use of lead citrate at high pH as an electron opaque stain for electron microscopy.J. Cell. Biol. 17 (1963) 208–212

    Google Scholar 

  • Schutgens, R. B. H., Heymans, H. S. A., Wanders, R. J. A., van den Bosch, H. and Trager, J. M. Peroxisomal disorders. A newly recognized group of genetic diseases.Eur. J. Pediatr. 612 (1986) 1–11

    Google Scholar 

  • Schutgens, R. B. H., Romeyn, G. J., Wanders, R. J. A., van den Bosch, H., Schrakamp, G. and Heymans, H. S. A. Deficiency of acyl-CoA dihydroxyacetone phosphate acyltransferase in patients with Zellweger (cerebrohepatorenal) syndrome.Biochem. Biophys. Res. Commun. 120 (1984) 179–184

    Google Scholar 

  • Scotto, J. M., Hadchouel, M., Odievre, M., Laudat, M-H, Saudubray, J. M., Dulac, C., Beucler, I. and Beaune, P. Infantile phytanic acid storage disease, three cases, including ultrastructural studies of the liver.J. Inher. Metab. Dis. 5 (1982) 83–90

    Google Scholar 

  • Singh, I., Moser, A. B., Moser, H. W. and Kishimoto, Y. Adrenoleukodystrophy: Impaired oxidation of very long-chain fatty acids in white blood cells, cultured skin fibroblasts and amniocytes.Pediatr. Res. 18 (1984) 286–290

    Google Scholar 

  • Singh, I., Moser, H. W., Moser, A. B. and Kishimoto, Y. Adrenoleukodystrophy: Impaired oxidation of long-chain fatty acids in cultured skin fibroblasts and adrenal cortex.Biochem. Biophys. Res. Commun. 102 (1981) 1223–1229

    Google Scholar 

  • Steinberg, D. Phytanic acid storage disease (Refsum's disease). In Stanbury, J. B., Wyngaarden, J. B. and Fredrickson, D. S. (eds.),The Metabolic Basis of Inherited Disease, McGraw-Hill, New York, 1983, pp. 731–747

    Google Scholar 

  • Steinberg, D., Herndon, J. H. D., Uhlendorf, B. W., Mize, C. E., Avigan, J. and Milne, G. W. A. Refsum's disease: Nature of the enzyme defect.Science 156 (1967) 1740–1742

    Google Scholar 

  • Stokke, O., Skrede, S., Ek, J. and Bjorkhem, I. Refsum's disease, adrenoleukodystrophy and the Zellweger syndrome.Scand. J. Clin. Lab. Invest. 44 (1984) 463–464

    Google Scholar 

  • Tsai, S-C., Avigan, J. and Steinberg, D. Studies on the α-oxidation of phytanic acid by rat liver mitochondria.J. Biol. Chem. 144 (1965) 2682–2692

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biological Sciences, Columbia University, 10027, New York, NY, USA

    M. E. Beard & E. Holtzman

  2. John F. Kennedy Center for Handicapped Children and Department of Neurology, Johns Hopkins University, 21205, Baltimore, MD, USA

    A. B. Moser

  3. Eunice K. Shriver Center for Mental Retardation and Department of Biological Chemistry, Harvard Medical School, 02254, Waltham, MA, USA

    V. Sapirstein

Authors
  1. M. E. Beard
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. B. Moser
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. V. Sapirstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E. Holtzman
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Beard, M.E., Moser, A.B., Sapirstein, V. et al. Peroxisomes in infantile phytanic acid storage disease: a cytochemical study of skin fibroblasts. J Inherit Metab Dis 9, 321–334 (1986). https://doi.org/10.1007/BF01800481

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01800481

Keywords

Search

Navigation