Human peroxisomal 3-oxoacyl-coenzyme A thiolase deficiency

Proc. Natl. Acad. Sci. USA Vol. 84, pp. 2494-2496, April 1987 Medical Sciences

Human peroxisomal 3-oxoacyl-coenzyme A thiolase deficiency (peroxisome/Zellweger syndrome)

ANDRE W. SCHRAM*, SIDNEY GOLDFISCHERt, CARLO W. T. VAN ROERMUNDt, ELISABETH M. BROUWER-KELDER*, JANNA COLLINSt, TAKASHI HASHIMOTO§, HUGO S. A. HEYMANSt, HENK VAN DEN BOSCH¶, RUUD B. H. SCHUTGENSt, JOSEPH M. TAGER*, AND RONALD J. A. WANDERSt *Laboratory of Biochemistry, University of Amsterdam, P.O. Box 20151, 1000 HD, The Netherlands; tDepartments of Pathology and Pediatrics and the Marion Bessin Liver Research Centre, Albert Einstein College of Medicine, Bronx, NY 10461; tDepartment of Pediatrics, University Hospital Amsterdam, 1105 AZ Amsterdam, The Netherlands; §Shinshu University School of Medicine, Asahi, Matsumoto, 390 Japan; ¶Laboratory of Biochemistry, University of Utrecht, Padualaan 8, 3584 CH Utrecht, The Netherlands

Communicated by Dominick P. Purpura, December 10, 1986 (received for review October 3, 1986)

out further studies on individual enzymes of the peroxisomal ,p-oxidation system to examine this possibility. The results described in this paper suggest that the basic defect in the patient is a deficiency ofperoxisomal 3-oxoacyl-CoA thiolase (acyl-CoA:acetyl-CoA C-acyltransferase, EC 2.3.1.16).

We investigated the peroxisomal ,8-oxidation ABSTRACT system in liver from a patient with clinical features similar to those in the cerebrohepatorenal (Zeliweger) syndrome and with elevated levels in body fluids of very-long-chain fatty acids and intermediates in the biosynthesis of bile acids. The peroxisomal fl-oxidation of fatty acids, measured as the cyanide-insensitive formation of ['4C]acetyl units from ['4C]palmitoyl-CoA, was very low in the patient (