Phytanic Acid Storage Disease

  • Daniel Steinberg
  • David Hutton
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 19)


Phytanic acid storage disease (Refsum’s disease) has presumably been included in the present Symposium under the rubric “...and Allied Disorders.” In that it is an inherited lipidosis and, like so many of them, affects the nervous system, it is to that extent “allied”. However, the differences are several and important. First, phytanic acid storage disease is due to a defect in an oxidative enzyme system, not a hydrolase; second, it is a disease in which a particular fatty acid accumulates (and in essentially all lipid classes), rather than a particular subclass of lipids as in the hydrolase deficiencies; and, finally, the accumulated lipid is of exogenous rather than endogenous origin. This last difference is especially important since it affords in theory the opportunity to arrest (and possibly reverse) the storage and to determine whether that alters the progression of the disease. Methods are being actively sought to do this in the sphingolipidoses, as reported elsewhere in this Symposium, but the approaches are difficult and results remain equivocal. Thus, it may be of interest to report in some detail our encouraging experience with dietary treatment of phytanic acid storage disease. First, let us briefly review the biochemical basis of phytanate accumulation, add some recent results on the normal pathway for its oxidation and then finally summarize the clinical responses to diet observed to date.


Phytanic Acid Pellet Fraction Propionic Acidemia Acid Storage Pristanic Acid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Avigan, J. et al.: Alpha-decarboxylation, An Important Pathway for Degradation of Phytanic Acid in Animals. Biochem. Biophys. Res. Commun. 24: 838, 1966.PubMedCrossRefGoogle Scholar
  2. 2.
    Baxter, J.H.: Absorption of Chlorophyll Phytol in Normal Man and in Patients with Refsum’s Disease. J. Lipid Res. 9: 636, 1968.PubMedGoogle Scholar
  3. 3.
    Baxter, J.H. et al.: Absorption and Metabolism of Uniformly 14Clabeled Phytol and Phytanic Acid by the Intestine of Rat Studied with Thoracic Duct Cannulation. Biochim. Biophys. Acta 137: 277, 1967.PubMedCrossRefGoogle Scholar
  4. 4.
    Baxter, J.H. and Steinberg, D.: Absorption of Phytol from Dietary Chlorophyll in the Rat. J. Lipid Res. 8: 615, 1967.PubMedGoogle Scholar
  5. 5.
    Eldjarn, L. et al.: Dietary Effects on Se_rum Phytanic Acid Levels and on Clinical Manifestations in Heredopathia Atactica Polyneuritiformis. Lancet 1: 691, 1966.PubMedCrossRefGoogle Scholar
  6. 6.
    Giovanelli, J. and Stumpf, P.K.: Fat Metabolism in Higher Plants. X. Modified,Q Oxidation of Propionate by Peanut Mitochondria. J. Biol. Chem. 231: 411, 1958.PubMedGoogle Scholar
  7. 7.
    Hansen, R.P.: Occurrence of 3,7,11,15-Tetramethyl hexadecanoi c Acid in Ox Perinephric Fat. Chem. Industr. 7: 303, 1965.Google Scholar
  8. 8.
    Hansen, R.P.: 3,7,11,15-Tetramethylhexadecanoic Acid: Its Occurrence in Sheep Fat. N. Zeal. J. Sci. 8: 158, 1965.Google Scholar
  9. 9.
    Herndon, J.H., Jr., Steinberg, D., Uhlendorf, B.W. and Fales, H.M.: Refsum’s Disease: Characterization of the Enzyme Defect in Cell Culture. J. Cl in. Invest. 48: 1017, 1969.CrossRefGoogle Scholar
  10. 10.
    Herndon, J.H., Jr., Steinberg, D., Uhlendorf, B.W.: Refsum’s Disease: Defective Oxidation of Phytanic Acid in Tissue Cultures Derived from Homozygotes and Heterozygotes. New Eng. J. Med. 281: 1034, 1969.CrossRefGoogle Scholar
  11. 11.
    Hutton, D. and Stumpf, P.K.: Fat Metabolism in Higher Plants. XLII. The Pathway of Rinoleic Acid Catabolism in the Germinating Castor Bean (Rinicus communis L.) and Pea (Pisum sativum L.) Arch. Biochem. Biophys. 142: 48, 1971.CrossRefGoogle Scholar
  12. 12.
    Kahlke, W.: “Heredopathia Atactica Polyneuritiformis (Refsum’s Disease)”, in Lipids and Lipidoses. Schettler, G. (ed) New York: Springer-Verlag, pp. 352–379, 1967.CrossRefGoogle Scholar
  13. 13.
    Kark, R.A.P., Engel, W.K., Blass, J.P., Steinberg, D. and Walsh, G.O.: Heredopathia Atactica Polyneuritiformis (Refsum’s Disease): A Second Trial of Dietary Therapy in Two Patients. Nervous System. Birth Defects: Original Article Series 7: 53, 1971.Google Scholar
  14. 14.
    Kesner, L. and Muntwyler, E.M.: “Separation of Citric Acid Cycle and Related Compounds by Partition Column Chromatography”, in Methods in Enzymology. Colowick, S.P. and Kaplan, N.O. (eds) New York: Academic Press, Vol. XII, p. 415.Google Scholar
  15. 15.
    Klenk, E. and Kahlke, W.: Uber das Vorkommen der Tetramethyl hexadecansaure (Phytansaure) in den Cholesterenistern und anderen Lipoidfraktionen der Organe bei einem Krankheitsfall unbekannter Genese (Verdacht auf Heredopathi a atactica polyneurififormisRefsum’s Syndrome). Hoppe Seyler Z Physiol. Chem. 333: 133, 1963.Google Scholar
  16. 16.
    Klenk, E. and Kremer, G.J.: Untersuchungen zum Stoffwechsel des Phytols, Dihydrophytols und der Phytansaure. Hoppe Seyler Z Physiol. Chem. 343: 39, 1965.Google Scholar
  17. 17.
    Kolodny, E.H., Hass, W.K., Lane, B. and Drucker, W.D.: Refsum’s Syndrome: Report of a Case Including Electron Microscopic Studies of the Liver. Arch. Neurol. 12: 583, 1965.PubMedCrossRefGoogle Scholar
  18. 18.
    Mize, C.E. et al.: A pathway for Oxidative Degradation of Phytanic Acid in Mammals. Biochem. Biophys. Res. Commun. 25: 359, 1966.PubMedCrossRefGoogle Scholar
  19. 19.
    Mize, C.E. et al.: Effects of Dietary Phytol and Phytanic Acid in Animals. J. Lipid Res. 7: 684, 1966.PubMedGoogle Scholar
  20. 20.
    Mize, C.E. et al.: Phytanic Acid Storage in Refsum’s Disease Due to Defective Alpha-Hydroxylation. Clin. Res. 16:346, 1968 (Abs).Google Scholar
  21. 21.
    Mize, E.C. et al.: A Major Pathway for the Oxidative Degradation of Phytanic Acid. Biochim. Biophys. Acta 176: 720, 1969.PubMedCrossRefGoogle Scholar
  22. 22.
    Overath, P., Raufuss, E.M., Stoffel, W. and Ecker, W.: The Induction of Enzymes of Fatty Acid Degradation in E. Col i. Biochem. Biophys. Res. Commun. 29: 28, 1967.CrossRefGoogle Scholar
  23. 23.
    Refsum, S.: HeredopathiaAtactica Polyneuritiformis. Acta Psychiat. Scand. suppl. 38: 1, 1946.Google Scholar
  24. 24.
    Rosenberg, L., Hsia, Y.E. and Scully, K.J.: Defective Propionate Carboxylation in Ketotic Hyperglycinaemia. Lancet 1: 757, 1969.PubMedGoogle Scholar
  25. 25.
    Sonnevald, W., Begeman, P.H., van Beers, G.J., Kenning, R. and Schogt, J.0.M.: 3,7,11,15-Tetramethylhexadecanoi c Acid, A Constituent of Butterfat. J. Lipid Res. 3: 351, 1962.Google Scholar
  26. 26.
    Steinberg, D.: Phytanic Acid Storage Disease, in Metabolic Basis of Inherited Diseases. Stanbury, J.B., Wyngaarden, J.B. andFred-rickson, D.S. (eds) 3rd Edition. New York: McGraw-Hill Book Co., (in press).Google Scholar
  27. 27.
    Steinberg, D., Avigan, J., Mize, C.E., Baxter, J.H., Cammermeyer, J., Fales, H.M. and Highet, P.F.: Effects of Dietary Phytol and Phytanic Acid in Animals. J. Lipid Res. 7: 684, 1966.PubMedGoogle Scholar
  28. 28.
    Steinberg, D. and Herndon, J.H., Jr.: Refsum’s Disease, in The Cellular and Molecular Basis of Neurologic Disease. Shy, G.M., Goldensohn, E.S. and Appel, S.H. (eds). Philadelphia: Lea and Febiger, 1971 (in press).Google Scholar
  29. 29.
    Steinberg, D., Mize, C.E., Avigan, J. Fates, H.M., Eldjarn, L., Try, K. Stokke, O. and Refsum, S.: On the Metabolic Error in Refsum’s Disease. J. Cl in. Invest. 45:1076, 1966 (Abs) .Google Scholar
  30. 30.
    Steinberg, D. Mize, C.E., Avigan, J., Fales, H.M., Eldjarn, L., Try, K., Stokke, O. and Refsum, S.: Studies on the Metabolic Error in Refsum’s Disease. J. Invest. 46: 313, 1967.CrossRefGoogle Scholar
  31. 31.
    Steinberg, D., Mize, C.E., Herndon, J.H., Jr., Fales, H.M., Engel, W.K. and Vroom, F,Q.: Phytanic Acid in Patients with Refsum’s Syndrome and Response to Dietary Treatment. Arch. Int. Med. 125: 75, 1970.CrossRefGoogle Scholar
  32. 32.
    Steinberg, D. et al.: Refsum’s Disease - A Recently Characterized Lipidosis Involving the Nervous System. Ann. Int. Med. 66: 365, 1967.PubMedGoogle Scholar
  33. 33.
    Tsai, S.C. et al.: The Formation of Alpha-hydroxy Phytanic Acid from Phytanic Acid in Mammalian Tissues. Biochem. Biophys. Res. Commun. 28: 571, 1967.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1972

Authors and Affiliations

  • Daniel Steinberg
    • 1
  • David Hutton
    • 1
  1. 1.Department of Medicine, School of MedicineUniversity of California, San DiegoLa JollaUSA

Personalised recommendations