Peroxisomal function was evaluated in a male infant with clinical features of
neonatal adrenoleukodystrophy. Very long chain
fatty acid levels were elevated in both plasma and fibroblasts, and beta-oxidation of very long chain
fatty acids in cultured fibroblasts was significantly impaired. Although the level of the
bile acid intermediate trihydroxycoprostanoic
acid was slightly elevated in plasma,
phytanic acid and
L-pipecolic acid levels were normal, as was
plasmalogen synthesis in cultured fibroblasts. The latter three parameters distinguish this case from classical
neonatal adrenoleukodystrophy. In addition, electron microscopy and
catalase subcellular distribution studies revealed that, in contrast to
neonatal adrenoleukodystrophy, peroxisomes were present in the patient's tissues. Immunoblot studies of peroxisomal beta-oxidation
enzymes revealed that the bifunctional
enzyme (
enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase) was deficient in postmortem liver samples, whereas
acyl-CoA oxidase and the mature form of
beta-ketothiolase were present. Density gradient centrifugation of fibroblast homogenates confirmed that intact peroxisomes were present. Immunoblots of fibroblasts peroxisomal fractions showed that they contained
acyl-CoA oxidase and
beta-ketothiolase, but bifunctional
enzyme was not detected. Northern analysis, however, revealed that
mRNA coding for the bifunctional
enzyme was present in the patient's fibroblasts. These results indicate that the primary biochemical defect in this patient is a deficiency of
peroxisomal bifunctional enzyme. It is of interest that the phenotype of this patient resembled
neonatal adrenoleukodystrophy and would not have been distinguished from this disorder by clinical study alone.