NOVEL SUBTYPE OF PEROXISOMAL ACYL-COA OXIDASE DEFICIENCY AND BIFUNCTIONAL ENZYME DEFICIENCY WITH DETECTABLE ENZYME PROTEIN - IDENTIFICATIONBY MEANS OF COMPLEMENTATION ANALYSIS

We describe four infants with a novel subtype of an isolated deficienc y of one of the peroxisomal beta-oxidation enzymes with detectable enz yme protein. The patients showed characteristic clinical and biochemic al abnormalities, including hypotonia, psychomotor retardation, hepato megaly, typical facial appearance, accumulation of very-long-chain fat ty acids, and decreased lignoceric acid oxidation. However, beta-oxida tion enzyme proteins were detected by immunoblot analyses, and large p eroxisomes were identified by immunofluorescence staining. In order to identify the underlying defect in these patients, complementation ana lysis was introduced using fibroblasts from these patients and patient s with an established deficiency of either acyl-CoA oxidase or bifunct ional enzyme, as identified by immunoblotting. In the complementing co mbinations, fused cells showed increased lignoceric acid oxidation, re sistance against 1-pyrene dodecanoic acid/UV selection, and normalizat ion of the size and the distribution of peroxisomes. The results indic ate that two patients with a more severe clinical course were sufferin g from bifunctional enzyme deficiency and that the other two infants, who were siblings and had a less severe clinical presentation, were th e first patients with acyl-CoA oxidase deficiency with detectable enzy me protein.