Distinction between peroxisomal bifunctional enzyme and acyl‐CoA oxidase deficiencies

The clinical distinction between patients with a disorder of peroxisome assembly (e.g., Zellweger syndrome) and those with a defect in a peroxisomal fatty acid β‐oxidation enzyme can be difficult. We studied 29 patients suspected of belonging to the latter group. Using complementation analysis, 24 were found to be deficient in enoylcoenzyme A hydratase/3‐hydroxyacylcoenzyme A dehydrogenase bifunctiona enzyme and 5 were deficient in acyl‐CoA oxidase. Elevated plasma very long‐chain fatty acids (VLCFA), impaired fibroblast VLCFA β‐oxidation, decreased fibroblast phytanic acid oxidation, normal plasmalogen synthesis, normal plasma l‐pipecolic acid level, and normal subcellular catalase distribution were characteristic findings in both disorders. The elevation in plasma VLCFA levels and impairment in fibroblast VLCFA β‐oxidation were more severe in bifunctional‐deficient than in oxidase‐deficient patients. The clinical course in bifunctional deficiency (profound hypotonia, neonatal seizures, dysmorphic features, age at death ∼9 months) was more severe than in oxidase deficiency (moderate hypotonia without dysmorphic features, development of a leukodystrophy, age at death ∼4 yr). Based on these findings, accurate early diagnosis of these deficiencies of peroxisomal β‐oxidation enzymes is possible.