Ataxia associated with increased plasma concentrations of pristanic acid, phytanic acid and C-27 bile acids but normal fibroblast branched-chain fatty acid oxidation

Investigations of peroxisomal function were undertaken in an X-year-old girl who developed motor difficulties at the age of 3.5 years and went on to develop a progressive ataxia and dysarthria. There were no other neurological abnormalities and she was of normal intelligence. Analysis of plasma very long-chain fatty acids revealed a normal C-26 concentration and normal C-24/C-22 and C-26/C-22 ratios. Analysis of branched-chain fatty acids showed an elevated plasma phytanic acid concentration of 60 mu mol/L (normal < 15) and a considerably elevated pristanic acid concentration of 50 mu mol/L (normal < 2). Plasma concentrations of the C-27 bile acids 3 alpha,7 alpha-dihydroxycholestanoic acid (DHCA) and 3 alpha,7 alpha,12 alpha-trihydroxycholestanoic acid (THCA) and of the C-29-dicarboxylic acid were also increased. We postulated that these results might be due to deficiency of the peroxisomal branched-chain acyl-CoA oxidase, but when oxidation of branched-chain fatty acids was studied in cultured skin fibroblasts it was found to be normal. Alternative explanations for the accumulation of branched-chain substrates for peroxisomal beta-oxidation are discussed. Treatment with a low-phytanic acid diet arrested the progression of the ataxia and led to a slight improvement.