The branched-chain
fatty acid phytanic acid is a constituent of the diet, present in diary products, meat and fish. Degradation of this
fatty acid in the human body is preceded by activation to
phytanoyl-CoA and starts with one cycle of alpha-oxidation. Intermediates in this pathway are 2-hydroxy-phytanoyl-CoA and
pristanal; the product is
pristanic acid. After activation,
pristanic acid is degraded by peroxisomal beta-oxidation. Several disorders have been described in which
phytanic acid accumulates, in some cases in combination with
pristanic acid. In classical
Refsum disease, the
enzyme that converts
phytanoyl-CoA into 2-hydroxyphytanoyl-CoA--phytanoyl-CoA
hydroxylase--is deficient, resulting in highly elevated levels of
phytanic acid in blood and tissues. Also in
rhizomelic chondrodysplasia punctata,
phytanic acid accumulates, owing to a deficiency in the peroxisomal import of
proteins with a peroxisomal targeting sequence type 2. In patients affected with generalized
peroxisomal disorders, degradation of both
phytanic acid and
pristanic acid is impaired owing to absence of functional peroxisomes. In bifunctional
protein deficiency, the disturbed oxidation of
pristanic acid results in elevated levels of this
fatty acid and a secondary elevation of
phytanic acid. In addition, several variant
peroxisomal disorders with unknown aetiology have been described in which
phytanic acid and/or
pristanic acid accumulate. This review describes the discovery of
phytanic acid and
pristanic acid and the initial attempts to elucidate the origins and fates of these
fatty acids. The current knowledge on the alpha-oxidation and beta-oxidation of these branched-chain
fatty acids is summarized. The disorders in which
phytanic acid and/or
pristanic acid accumulate are described and some remarks are made on the pathogenic mechanisms of elevated levels of
phytanic acid and
pristanic acid.