A new type of peroxisomal disorder with variable expression in liver and fibroblasts

• Published in: The Journal of pediatrics Vol. 125; no. 4; pp. 549 - 555
• Main Authors: Mandel, Hanna, Espeel, Marck, Roels, Frank, Sofer, Neomi, Luder, Anthony, Iancu, Theodore C., Aizin, Anna, Berant, Moshe, Wanders, Ronald J.A., Schutgens, Ruud B.H.
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01-10-1994; Elsevier; Mosby-Year Book, Inc
• Subjects: Biological and medical sciences; Child; Child, Preschool; Errors of metabolism; Fatty Acids - metabolism; Fibroblasts - metabolism; Fibroblasts - ultrastructure; Humans; Lipids (lysosomal enzyme disorders, storage diseases); Liver - metabolism; Liver - pathology; Liver - ultrastructure; Male; Medical sciences; Metabolic diseases; Metabolism, Inborn Errors - metabolism; Metabolism, Inborn Errors - pathology; Microbodies - metabolism; Microbodies - pathology; Microbodies - physiology; Microscopy, Electron; Psychomotor Performance; DHAPAT; EM; CoA; VLCFA; Human; Immunohistochemistry; Nervous system diseases; Family study; Liver; Clinical form; Metabolic diseases; Sibling; Enzymopathy; Fatty acids; Genetic disease; Pathology; Symptomatology; Peroxisomal disorders; Degenerative disease; Child; Lipoidosis
• ISSN: 0022-3476; 1097-6833
• DOI: 10.1016/S0022-3476(94)70006-0

We describe two siblings, presently 5 and 9 years of age, who had neurodegenerative symptoms after the first year of life. Although they lacked clinical characteristics of a peroxisomal disorder, they had elevated levels of plasma very long chain fatty acids, pipecolic and phytanic acids, and abnormal bile acid intermediates, which suggested a generalized peroxisome deficiency disorder. Immunocytochemical study and electron microscopy of the liver disclosed absence of peroxisomes in approximately 90% of hepatocytes. However, the remaining 10% of the hepatocytes had numerous normal-looking peroxisomes containing catalase activity and catalase antigen. Alanine glyoxylate aminotransferase and the peroxisomal β-oxidation enzymes acyl-coenzyme A oxidase and 3-ketoacyl coenzyme A thiolase were also present in the organelles. Both cell types were grouped in clusters. In contrast to most of the liver cells, fibroblasts cultured from skin biopsy specimens had normal peroxisomal functions. Thus this defect in peroxisome biogenesis is characterized by variable expression in different tissues (liver vs fibroblasts), as well as within individual cells in the same tissue (liver mosaicism). Awareness of the heterogeneity in tissue expression of peroxisomal disorders could be of critical importance in prenatal diagnosis. (J P
EDIATR 1994;125:549-55)