Refsum's Disease: Defective Oxidation of Phytanic Acid in Tissue Cultures Derived from Homozygotes and Heterozygotes

Abstract

A defect in phytanic acid oxidation was demonstrated in cultured fibroblasts derived from skin biopsies of 11 patients with Refsum's disease (heredopathia atactica polyneuritiformis, or HAP). The observed rate of oxidation in cultures derived from the patients was, on the average, 3 per cent of that observed in cultures derived from control subjects. On the other hand, the HAP cultures all oxidized pristanic acid, the n-1 homologue of phytanic acid, at normal or near normal rates. These findings in 11 patients drawn from eight separate kindreds confirm earlier data obtained in three patients from two families, and strengthen the proposal that patients with HAP accumulate phytanic acid because of a block in its degradation at the initial alpha-oxidative step. Cultures derived from eight presumably heterozygous parents oxidized phytanic acid at a rate approximately half that observed in control cultures. These results provide the first evidence for the existence of a carrier state in HAP and support the assumption that the disease reflects a point mutation inherited in an autosomal recessive pattern.