The
phytanic acid found in man stems from exogenous sources, mainly as minor parts of fish and animal
fats. Free
phytol, which is easily converted to
phytanic acid in mammals, is present in
fats of vegetable origin. Healthy individuals are able to degrade the small amounts of
phytanic acid and
phytol which are ingested. Accumulation of
phytanic acid has been considered diagnostic for
Refsum's disease, and a prerequisite for this diagnosis. However, a few patients with proven
Refsum's disease have eliminated their
phytanic acid stores by dietary means. Two healthy mothers of patients with
Refsum's disease have been reported, in whom serum
phytanic acid was considerably increased. Furthermore,
phytanic acid has recently been found in patients with several socalled
peroxisomal disorders (
Zellweger's syndrome,
neonatal adrenoleukodystrophy,
infantile Refsum's disease,
hyperpipecolic acidemia,
rhizomelic chondrodysplasia punctata,
Leber disease). Skin fibroblasts both from patients with classical
Refsum's disease and from those with the
peroxisomal disorders have a defect in the alpha-oxidation of
phytanic acid, with a residual
enzyme activity less than 10% of normal. The presence of this defect in the patients with peroxisomal disease makes it tempting to suggest that alpha-oxidation of
phytanic acid normally takes place in the peroxisomes. Subcellular studies in rat liver show, however, unequivocally that the alpha-oxidation of
phytanic acid is located to the mitochondria. Thus, patients with the peroxisomal syndromes must probably have a defect also in the mitochondria, in addition to the many peroxisomal deficiencies.