ATAXIA ASSOCIATED WITH INCREASED PLASMA-CONCENTRATIONS OF PRISTANIC ACID, PHYTANIC ACID AND C-27 BILE-ACIDS BUT NORMAL FIBROBLAST BRANCHED-CHAIN FATTY-ACID OXIDATION
Pt. Clayton et al., ATAXIA ASSOCIATED WITH INCREASED PLASMA-CONCENTRATIONS OF PRISTANIC ACID, PHYTANIC ACID AND C-27 BILE-ACIDS BUT NORMAL FIBROBLAST BRANCHED-CHAIN FATTY-ACID OXIDATION, Journal of inherited metabolic disease, 19(6), 1996, pp. 761-768
Investigations of peroxisomal function were undertaken in an X-year-ol
d girl who developed motor difficulties at the age of 3.5 years and we
nt on to develop a progressive ataxia and dysarthria. There were no ot
her neurological abnormalities and she was of normal intelligence. Ana
lysis of plasma very long-chain fatty acids revealed a normal C-26 con
centration and normal C-24/C-22 and C-26/C-22 ratios. Analysis of bran
ched-chain fatty acids showed an elevated plasma phytanic acid concent
ration of 60 mu mol/L (normal < 15) and a considerably elevated prista
nic acid concentration of 50 mu mol/L (normal < 2). Plasma concentrati
ons 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 branc
hed-chain acyl-CoA oxidase, but when oxidation of branched-chain fatty
acids was studied in cultured skin fibroblasts it was found to be nor
mal. Alternative explanations for the accumulation of branched-chain s
ubstrates for peroxisomal beta-oxidation are discussed. Treatment with
a low-phytanic acid diet arrested the progression of the ataxia and l
ed to a slight improvement.