Phytanic Acid Storage Disease
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.
KeywordsPhytanic Acid Pellet Fraction Propionic Acidemia Acid Storage Pristanic Acid
Unable to display preview. Download preview PDF.
- 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.Hansen, R.P.: 3,7,11,15-Tetramethylhexadecanoic Acid: Its Occurrence in Sheep Fat. N. Zeal. J. Sci. 8: 158, 1965.Google Scholar
- 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.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.Klenk, E. and Kahlke, W.: Uber das Vorkommen der 220.127.116.11- 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.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
- 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
- 23.Refsum, S.: HeredopathiaAtactica Polyneuritiformis. Acta Psychiat. Scand. suppl. 38: 1, 1946.Google Scholar
- 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.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
- 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.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