J. tnher. Metab. Dis. 19 (1996) 761-768 © SSIEMand Kluwer AcademicPublishers.Printed in the Netherlands Ataxia associated with increased plasma concentrations of pristanic acid, phytanic and Cz7 bile acids but normal fibroblast branched-chain fatty acid oxidation P. T. CLAYTON 1., A. W. JOHNSON 1, K. A. MILLS, G. W. LYNES1, J. WILSON 1, M. CASTEELS 2 and G. MANNAERTS 2 ~Biochemistry Unit, Institute of Child Health and Great Ormond Street Hospital for Children, London WC1N 1EI-I, UK; 2Katholieke Universiteit Leuven, Afdeling Farmacologie, Leuven, Belgium *Correspondence: Division of Biochemistry and Genetics, Institute of Child Health, 30 GuilJbrct Street, London WCIN 1EH, UK MS received 5.3.96 Accepted 9.4.96 acid Summary: Investigations of peroxisomal function were undertaken in an 8-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 C26 concentration and normal C24/C22 and C26/C22ratios. Analysis of branched-chain fatty acids showed an elevated plasma phytanic acid concentration of 60/tmol/L (normal < 15) and a considerably elevated pristanic acid concentration of 50pmol/L (normal <2). Plasma concentrations of the C27 bile acids 3a,7a- dihydroxycholestanoic acid (DHCA) and 3a,7a,12a-trihydroxycholestanoic acid (THCA) and of the Czg-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 t-oxidation are discussed. Treatment with a low-phytanic acid diet arrested the progression of the ataxia and led to a slight improvement. In 1990, Christensen and colleagues described a 5-year-old girl with ataxia, dysarthria, sensorineural deafness, mental retardation and dry skin associated with increased plasma concentrations of phytanic acid, pristanic acid and the C27 bile acids 3a,7a-dihydroxy- cholestanoic acid (DHCA) and 3a,7a,12a-trihydroxychotestanoic acid (THCA) (Christensen et al 1990; Vanhove et al 1991; ten Brink et at 1994). Plasma very long-chain fatty acids (VLCFA) were normal. These results could most easily be explained by a deficiency of the peroxisomal branched-chain acyl-CoA oxidase which catalyses the first 761