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

Abstract

Adult Refsum disease (ARD) is associated with defective α-oxidation of phytanic acid (PA). ω-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, ω-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 ω-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. ω-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 ω-oxidation pathway can metabolise PA ingested by patients with ARD, but this activity is dependent on plasma PA concentration.ω-Oxidation forms a functional reserve capacity that enables patients with ARD undergoing acute stress to cope with limited increases in plasma PA levels.

Keywords

• organic acid
• α-oxidation
• ω-oxidation