A new peroxisomal disease with impaired phytanic and pipecolic acid oxidation.

Phytanic acid (PA) accumulates in patients with adult Refsum disease (ARD) and with peroxisomal disorders. In three related patients with ARD, PA levels were moderately increased in plasma, whereas phytanic oxidation was severely deficient in the fibroblasts. Two of these patients had a significant increase of pipecolic acid in plasma, a finding not reported in ARD, and a fourth related patient, a brother, died at age 17 from a progressive neurologic disorder with unusual clinical and neuropathologic (a spongy degeneration of the white matter) abnormalities for ARD. The first step of L-pipecolic acid degradation occurs in peroxisome. In these patients, the accumulation of PA could have resulted from an impaired capacity to degrade pristanic acid rather than PA. The activity of pristanic oxidase, measured in fibroblasts, was normal, as were two other peroxisomal enzymes, lignoceric acid oxidase and dihydroxyacetone phosphate transferase. Since both mitochondria and peroxisomes are involved in PA alpha-oxidation, we propose that these four related patients presented various phenotypical variants of a novel peroxisomal disease with impairment of PA and pipecolic acid oxidation.