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Journal of Lipid Research, Vol. 44, 1481-1488, August 2003
Copyright © 2003 by American Society for Biochemistry and Molecular Biology

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

Anthony S. Wierzbicki^1,*,, Phillip D. Mayne^*, Matthew D. Lloyd, David Burston^*, Guam Mei^*, Margaret C. Sidey, Michael D. Feher and F. Brian Gibberd

^* Department of Chemical Pathology, Chelsea & Westminster Hospital, 369 Fulham Road, London, United Kingdom
Refsum Disease Clinic, Chelsea & Westminster Hospital, 369 Fulham Road, London, United Kingdom
Department of Pharmacy & Pharmacology, University of Bath, Claverton Down, Bath, United Kingdom

¹ To whom correspondence should be addressed. e-mail: anthony.wierzbicki{at}kcl.ac.uk

Adult Refsum disease (ARD) is associated with defective -oxidation of phytanic acid (PA). -Oxidation of PA to 3-methyl-adipic acid (3-MAA) occurs although its clinical significance is unclear. In a 40 day study of a new ARD patient, where the plasma half-life of PA was 22.4 days, -oxidation accounted for 30% initially and later all PA excretion. Plasma and adipose tissue PA and 3-MAA excretion were measured in a cross-sectional study of 11 patients. The capacity of the -oxidation pathway was 6.9 (2.8–19.4) mg [20.4 (8.3–57.4) µmol] PA/day. 3-MAA excretion correlated with plasma PA levels (r = 0.61; P = 0.03) but not adipose tissue PA content. -Oxidation during a 56 h fast was studied in five patients. 3-MAA excretion increased by 208 ± 58% in parallel with the 158 (125–603)% rise in plasma PA. Plasma PA doubled every 29 h, while 3-MAA excretion followed second-order kinetics. Acute sequelae of ARD were noted in three patients (60%) after fasting. The -oxidation pathway can metabolise PA ingested by patients with ARD, but this activity is dependent on plasma PA concentration.

-Oxidation forms a functional reserve capacity that enables patients with ARD undergoing acute stress to cope with limited increases in plasma PA levels.

Abbreviations: 2,6-DMOA, 2,6-dimethyloctanedioic acid; 3-MAA, 3-methyl-adipic acid

Supplementary key words organic acid • -oxidation • -oxidation

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