Adult Refsum disease is an inherited disorder in which
phytanic acid accumulates in tissues and serum. Two hypotheses have been proposed to explain the pathogenesis of this condition. The molecular distortion hypothesis suggests that
phytanic acid may alter membrane composition and structure, thereby affecting membrane function(s). The anti-metabolite hypothesis suggests that an accumulation of
phytanic acid in membranes may interfere with
vitamin E function. These two hypotheses were investigated by studying the effects of modulating
phytanic acid and
alpha-tocopherol concentrations on the
fatty acid composition and certain physical parameters of cultured
retinal cells. Results showed that (a) the
phospholipid fraction of
retinal cells readily incorporated
phytanic acid, (b) the incorporation of
phytanic acid increased membrane fluidity, (c) there was no competition for uptake between
phytanic acid and
alpha-tocopherol, and (d) the incorporation of
phytanic acid did not increase the susceptibility of membranes to lipid peroxidation in vitro. These results obtained with cultured
retinal cells suggest that the molecular distortion hypothesis, but not the anti-metabolite hypothesis, could explain the pathogenesis of
adult Refsum disease. In vitro tissue culture models can, however, only approximate to the much more complex situation that occurs in vivo.