DISTINCTION BETWEEN PEROXISOMAL BIFUNCTIONAL ENZYME AND ACYL-COA OXIDASE DEFICIENCIES

The clinical distinction between patients with a disorder of peroxisom e assembly (e.g., Zellweger syndrome) and those with a defect in a per oxisomal fatty acid beta-oxidation enzyme can be difficult. We studied 29 patients suspected of belonging to the latter group. Using complem entation analysis, 24 were found to be deficient in enoylcoenzyme A hy dratase/3-hydroxyacylcoenzyme A dehydrogenase bifunctional enzyme and 5 were deficient in acyl-CoA oxidase. Elevated plasma very long-chain fatty acids (VLCFA), impaired fibroblast VLCFA beta-oxidation, decreas ed fibroblast phytanic acid oxidation, normal plasmalogen synthesis, n ormal plasma L-pipecolic acid level, and normal subcellular catalase d istribution were characteristic findings in both disorders. The elevat ion in plasma VLCFA levels and impairment in fibroblast VLCFA beta-oxi dation were more severe in bifunctional-deficient than in oxidase-defi cient patients. The clinical course in bifunctional deficiency (profou nd hypotonia, neonatal seizures, dysmorphic features, age at death sim ilar to 9 months) was more severe than in oxidase deficiency (moderate hypotonia without dysmorphic features, development of a leukodystroph y, age at death similar to 4 yr). Based on these findings, accurate ea rly diagnosis of these deficiencies of peroxisomal beta-oxidation enzy mes is possible.