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Infantile Refsum's disease: Biochemical findings suggesting multiple peroxisomal dysfunction

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Journal of Inherited Metabolic Disease

Abstract

Infantile Refsum's disease was diagnosed in three male patients, presenting with facial dysmorphia, retinitis pigmentosa, neurosensory hearing loss, hepatomegaly, osteopenia and delayed growth and psychomotor development.

An elevated plasma phytanic acid concentration and a deficient phytanic acid oxidase activity in fibroblasts were found with an accumulation of very long chain fatty acids in plasma and fibroblasts. There were elevated pipecolic acid levels in plasma, urine and CSF, and abnormal bile acid metabolites in plasma.

Deficient activity of acylCoA: dihydroxyacetone phosphate acyl transferase was found in thrombocytes and fibroblasts of these patients as well as an impairedde novo plasmalogen biosynthesis in fibroblasts. These biochemical abnormalities, previously described in the Zellweger syndrome, suggest multiple peroxisomal dysfunction in our patients.

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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

    Article  PubMed  CAS  Google Scholar 

  • Boltshauser, E., Spycher, M. A., Steinmann, B., Briner, J., Isler, W., Kuster, T., Poulos, A. and Pollard, 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) 344–351

    PubMed  Google Scholar 

  • 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, liver lesion and a fault in pipecolic acid metabolism.J. Pediatr. 86 (1975) 382–387

    Article  PubMed  CAS  Google Scholar 

  • Eyssen, H., Parmentier, G., Compernolle, F., Boon, J. and Eggermont, E. Trihydroxycoprostanic acid in the duodenal fluid of two children with intrahepatic bile duct anomalies.Biochim. Biophys. Acta 273 (1972) 212–221

    PubMed  CAS  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 cerebro-hepato-renal syndrome.Science 182 (1973) 62–64

    Article  PubMed  CAS  Google Scholar 

  • Hanson, R. F., Szczepanik-Van Leeuwen, P., Williams, G. C., Grabowski, G. and Sharp, H. L. Defects of bile acid synthesis in Zellweger's syndrome.Science 203 (1979) 1107–1108

    Article  PubMed  CAS  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 (1969) 1034–1038

    PubMed  CAS  Google Scholar 

  • Heymans, H. S. A., v. d. Bosch, H., Schutgens, R. B. H., Tegelaers, W. H. H., Walther, J. V., Muller-Höcker, J. and Borst, P. Deficiency of plasmalogens in the cerebro-hepatorenal (Zellweger) syndrome.Eur. J. Pediatr. 142 (1984) 10–15

    Article  PubMed  CAS  Google Scholar 

  • Kahlke, W., Goerlich, R. and Feist, D. Erhöhte phytansäurespiegel in Plasma und Leber bei einem Kleinkind mit unklarem Hirnschaden.Klin. Wochenschr. 52 (1974) 651–653

    Article  PubMed  CAS  Google Scholar 

  • Moser, H. W., Braine, H., Pyeritz, R. E., Ulman, D., Murray, C. and Asbury, A. K. Therapeutic trials of plasmapheresis in Refsum's disease and in Fabry disease.Birth Defects 16 (1980a) 91

    Google Scholar 

  • Moser, H. W., Moser, A. B., Frayer, K. K., Chen, W., Schulman, J. D., O'Neill, B. P. and Kishimoto, Y. Adrenoleukodystrophy: increased plasma content of saturated very long chain fatty acids.Neurology 31 (1981) 1241–1249

    PubMed  CAS  Google Scholar 

  • Moser, H. W., Moser, A. B., Kawamura, N., Murphy, J., Suzuki, K., Schaumburg, H. and Kishimoto, Y. Adrenoleukodystrophy: elevated C26 fatty acid in cultured skin fibroblasts.Ann. Neurol. 7 (1980b) 542–549

    Article  PubMed  CAS  Google Scholar 

  • Parmentier, G. G., Janssen, G. A., Eggermont, E. A. and Eyssen, H. J. C27 bile acids in infants with coprostanic acidemia and occurrence of a 3α,7α,12α-trihydroxy-5β-C2g dicarboxylic bile acid as a major component in their serum.Eur. J. Biochem. 102 (1979) 173–183

    Article  PubMed  CAS  Google Scholar 

  • Poulos, A. Diagnosis of Refsum's disease using (1-14C)phytanic acid as substrate.Clin. Genet. 20 (1981) 247–253

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  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

    Article  PubMed  CAS  Google Scholar 

  • Poulos, A. and Whiting, M. J. Identification of 3α,7α,12α-trihydroxy-5β-cholestan-26-oic acid, an intermediate in cholic acid synthesis, in the plasma of patients with Refsum's disease.J. Inher. Metab. Dis. 8 (1985) 13–17

    Article  PubMed  CAS  Google Scholar 

  • Schrakamp, G., Schutgens, R. B. H., Wanders, R. J. A., Heymans, H. S. A., Tager, J. M. and v. d. Bosch, H. The cerebro-hepato-renal (Zellweger) syndrome. Impairedde novo biosynthesis of plasmalogens in cultured skin fibroblasts.Biochim. Biophys. Acta 833 (1985) 170–174

    PubMed  CAS  Google Scholar 

  • Schutgens, R. B. H., Romeyn, G. F., Wanders, R. J. A., v. d. Bosch, H., Schrakamp, G. and Heymans, H. S. A. Deficiency of acyl-CoA:dihydroxyacetone phosphate acyl transferase in patients with Zellweger (cerebro-hepato-renal) syndrome.Biochem. Biophys. Res. Commun. 120 (1984) 179–184

    Article  PubMed  CAS  Google Scholar 

  • Scotto, J. M., Hadchouel, M., Odiévre, M., Laudat, M.-H., Saudubray, J.-M., Dulac, C., 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) 83–90

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Trijbels, J. M. F., Monnens, L. A. H., Bakkeren, J. A. J. M., Van-Raay-Selten, A. H. J. and Corstiaensen, J. M. B. Biochemical studies in the cerebro-hepato-renal syndrome of Zellweger: a disturbance in the metabolism of pipecolic acid.J. Inher. Metab. Dis. 2 (1979) 39–42

    Article  CAS  Google Scholar 

  • Wanders, R. J. A., Schutgens, R. B. H., Schrakamp, G., v. d. Bosch, H., Tager, J. M., Schram, A. W., Poll-The, B. T. and Saudubray, J. M. Infantile Refsum's disease: absence of catalase containing particles (peroxisomes), alkyldihydroxy acetone phosphate synthase and two β-oxidation enzyme proteins.Eur. J. Pediatr. 1986 in press.

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Authors and Affiliations

  1. Clinique de Génétique et INSERM U12, Hôpital des Enfants Malades, 75015, Paris, France

    B. T. Poll-The, J. M. Saudubray & H. Ogier

  2. Department of Pediatrics, University Hospital, Amsterdam, The Netherlands

    R. B. H. Schutgens & R. J. A. Wanders

  3. Laboratory of Biochemistry, State University of Utrecht, The Netherlands

    G. Schrakamp & H. van den Bosch

  4. Department of Pediatrics, University of Nijmegen, The Netherlands

    J. M. F. Trijbels

  5. Department of Chemical Pathology, Adelaide Children's Hospital, 5042, Adelaide, South Australia

    A. Poulos

  6. The John F. Kennedy Institute, Baltimore, Maryland, USA

    H. W. Moser

  7. Rega Institute, Katholieke Universiteit Leuven, B-3000, Leuven, Belgium

    J. van Eldere & H. J. Eyssen

Authors
  1. B. T. Poll-The
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  2. J. M. Saudubray
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  3. H. Ogier
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  4. R. B. H. Schutgens
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  5. R. J. A. Wanders
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  6. G. Schrakamp
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  7. H. van den Bosch
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  8. J. M. F. Trijbels
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  9. A. Poulos
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  10. H. W. Moser
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  11. J. van Eldere
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  12. H. J. Eyssen
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Poll-The, B.T., Saudubray, J.M., Ogier, H. et al. Infantile Refsum's disease: Biochemical findings suggesting multiple peroxisomal dysfunction. J Inherit Metab Dis 9, 169–174 (1986). https://doi.org/10.1007/BF01799455

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  • DOI: https://doi.org/10.1007/BF01799455

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