J. Lipid Res.
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A more recent version of this article appeared on August 1, 2003

Papers In Press, published online ahead of print April 16, 2003
J. Lipid Res., doi:10.1194/jlr.M300121-JLR200
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Submitted on March 19, 2003
Revised on April 9, 2003
Accepted on April 15, 2003

Metabolism of phytanic acid and 3-methyl-adipic acid excretion in patients with adult Refsum's disease

Anthony S. Wierzbicki, Phillip D. Mayne, Matthew D. Lloyd, David Burston, Guam Mei, Margaret C. Sidey, Michael D. Feher, and F. Brian Gibberd

Chemical Pathology, St. Thomas' Hospital, London SE1 7EH

Corresponding Author: Anthony.Wierzbicki{at}kcl.ac.uk

Adult Refsum's disease (ARD) is associated with a biochemical defect in the metabolism of phytanic acid (PA) by alpha-oxidation. Limited metabolism of phytanic acid to 3-methyl-adipic acid (3-MAA) occurs through omega (w)-oxidation. The contribution of w-oxidation to metabolism of phytanic acid has not been systematically assessed in patients with ARD. In a 40 day study of a newly presented ARD patient, where the plasma half-life of PA was 22.4 days, w-oxidation accounted for 30% initially and later all PA excretion. A PA loading test in 2 obligate ARD heterozygotes and 4 controls showed no difference in baseline or stimulated activity. Plasma and adipose tissue PA and 3-MAA excretion were measured in a cross-sectional study of 11 patients (5 men and 6 women) with ARD. The capacity of the w-oxidation pathway was 6.9 (2.8-19.4) mg (20.4[8.3- 57.4] mmols) PA/day in ARD patients. In ARD, 3-MAA excretion correlated with plasma PA levels (r = 0.61; p=0.03) but not adipose tissue PA content. Omega-oxidation during a 56 hour fast was studied in 5 ARD patients. 3-MAA excretion increased by 208±58% in parallel with the 158 [125-603]%) rise in plasma PA. The plasma PA release curve showed a 29-hour doubling time while 3-MAA excretion followed second order kinetics with no obvious latency. Acute sequelae of ARD were noted in 3 patients (60%) after fasting. The w-oxidation pathway can metabolise all the phytanic acid ingested in patients with ARD on a low phytanic acid diet but this activity is dependent on plasma phytanic acid concentration. Omega oxidation forms a functional reserve capacity that enables patients with ARD undergoing acute stress to cope with limited increases in plasma PA levels.


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J. C. Komen, M. Duran, and R. J. A. Wanders
{omega}-Hydroxylation of phytanic acid in rat liver microsomes: implications for Refsum disease
J. Lipid Res., July 1, 2004; 45(7): 1341 - 1346.
[Abstract] [Full Text] [PDF]


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