Refsum disease, peroxisomes and phytanic acid oxidation: A review

Refsum disease was first recognized as a distinct disease entity by Sigvald Refsum in the 1940s. The discovery of markedly elevated levels of the bran ched-chain fatty, acid phytanic acid in certain patients marked Refsum dise ase as a disorder of lipid metabolism. Although it was immediately recogniz ed that the accumulation of phytanic acid is due to its deficient breakdown in Refsum disease patients, the true enzymatic defect remained mysterious until recently. A major breakthrough in this respect was the resolution of the mechanism of phytanic acid a-oxidation in humans. Ill this review we de scribe the many aspects of Refsum disease from the clinical signs and sympt oms to the enzyme and molecular defect plus the recent identification of ge netic heterogeneity in Refsum disease.