Heterogeneity in di/Trihydroxycholestanoic Acidaemia

Abstract

Peroxisomes play an important role in the degradation of, among others, very long chain fatty acids (VLCFA), phytanic and pristanic acids, and pipecolic acid, and in the formation of primary bile acids, cholic acid and chenodeoxycholic acid, by {j-oxidation of diand trihydroxycholestanoic acids (DHCA and THCA). Recently, two cases have been described of di/trihydroxycholestanoic acidaemia due to a presumed THCA-CoA oxidase deficiency.L? In the first patient! next to accumulation of DHCA and THCA in plasma, an elevated plasma phytanic acid level was observed as the only additional biochemical abnormality. Since phytanic acid a-oxidation, measured in cultured fibroblasts as the production of 14COZ from [1_l4C] phytanic acid, was normal, accumulation of phytanic acid was explained by an inhibitory effect of the accumulating bile acid intermediates on phytanic acid a-oxidation. In the second patientaccumulation of DHCA and THCA in plasma was associated with undetectable THCACoA oxidase activity in post mortem liver, although the significance of this finding may be questioned since activities of palmitoyl-CoA oxidase and catalase were also found to be decreased, probably due to the long delay between the moment of death and the time of tissue sampling. Although both patients were assumed to suffer from a common enzyme defect, their clinical presentation was different. Since accumulation of phytanic acid (which was observed only in patient 1) may not only result from a primary defect in phytanic acid a-oxidation, but may also be secondary to a defective pristanic acid {j-oxidation,3