Localization of the oxidative defect in phytanic acid degradation in patients with refsum's disease

The rate of oxidation of phytanic acid-U-¹⁴C to ¹⁴CO₂ in three patients with Refsum's disease was less than 5% of that found in normal volunteers. In contrast, the rate of oxidation of α-hydroxyphytanic acid-U-¹⁴C and of pristanic acid-U-¹⁴C to ¹⁴CO₂, studied in two patients, while somewhat less than that in normal controls, was not grossly impaired. These studies support the conclusion that the defect in phytanic acid oxidation in Refsum's disease is located in the first step of phytanic acid degradation, that is, in the alpha oxidation step leading to formation of α-hydroxyphytanic acid.

The initial rate of disappearance of plasma free fatty acid radioactivity after intravenous injection of phytanic acid-U-¹⁴C (t½ = 5.9 min) was slower than that seen with pristanic acid-U-¹⁴C (t½ = 2.7 min) or palmitic acid-1-¹⁴C (t½ = 2.5 min). There were no differences between patients and normal controls in these initial rates of free fatty acid disappearance for any of the three substrates tested.

There was no detectable lipid radioactivity found in the plasma 7 days after the injection of palmitic acid-1-¹⁴C or pristanic acid-U-¹⁴C in either patients or controls. After injection of phytanic acid-U-¹⁴C, however, the two patients showed only a very slow decline in plasma lipid radioactivity (estimated t½ = 35 days), in contrast to the normals who had no detectable radioactivity after 2 days. Incorporation of radioactivity from phytanic acid-U-¹⁴C into the major lipid ester classes of plasma was studied in one of the patients; triglycerides accounted for by far the largest fraction of the total present between 1 and 4 hr.

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