title: Ataxia associated with increased plasma concentrations of pristanic acid, phytanic acid and C27 bile acids but normal fibroblast branched-chain fatty acid oxidation.
abstract: 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/C22 ratios. Analysis of branched-chain fatty acids showed an elevated plasma phytanic acid concentration of 60 mumol/L (normal < 15) and a considerably elevated pristanic acid concentration of 50 mumol/L (normal < 2). Plasma concentrations of the C27 bile acids 3 alpha, 7 alpha-dihydroxycholestanoic acid (DHCA) and 3 alpha, 7 alpha, 12 alpha-trihydroxycholestanoic acid (THCA) and of the C29-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.
authors.affiliation: Biochemistry Unit, Institute of Child Health, London, UK.
authors.forename: P T
authors.initials: PT
authors.lastname: Clayton
authors.forename: A W
authors.initials: AW
authors.lastname: Johnson
authors.forename: K A
authors.initials: KA
authors.lastname: Mills
authors.forename: G W
authors.initials: GW
authors.lastname: Lynes
authors.forename: J
authors.initials: J
authors.lastname: Wilson
authors.forename: M
authors.initials: M
authors.lastname: Casteels
authors.forename: G
authors.initials: G
authors.lastname: Mannaerts
mesh_terms: D001259:Ataxia / Q000378:metabolism* / Q000628:therapy; D001647:Bile Acids and Salts / Q000097:blood*; D002648:Child; D005227:Fatty Acids / Q000097:blood* / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D010084:Oxidation-Reduction; D010831:Phytanic Acid / Q000097:blood*
chemical_list: D001647:Bile Acids and Salts; D005227:Fatty Acids; D010831:Phytanic Acid; C002844:pristanic acid