A NEW-TYPE OF PEROXISOMAL DISORDER WITH VARIABLE EXPRESSION IN LIVER AND FIBROBLASTS

We describe two siblings, presently 5 and 9 years of age, who had neur odegenerative symptoms after the first year of life. Although they lac ked clinical characteristics of a peroxisomal disorder, they had eleva ted levels of plasma very long chain fatty acids, pipecolic and phytan ic acids, and abnormal bile acid intermediates, which suggested a gene ralized peroxisome deficiency disorder. Immunocytochemical study and e lectron microscopy of the liver disclosed absence of peroxisomes in ap proximately 90% of hepatocytes. However, the remaining 10% of the hepa tocytes had numerous normal-looking peroxisomes containing catalase ac tivity and catalase antigen. Alanine glyoxylate aminotransferase and t he peroxisomal beta-oxidation enzymes acyl-coenzyme A oxidase and 3-ke toacyl coenzyme A thiolase were also present in the organelles. Both c ell types were grouped in clusters. In contrast to most of the liver c ells, fibroblasts cultured from skin biopsy specimens had normal perox isomal functions. Thus this defect in peroxisome biogenesis is charact erized by variable expression in different tissues (liver vs fibroblas ts), as well as within individual cells in the same tissue (liver mosa icism). Awareness of the heterogeneity in tissue expression of peroxis omal disorders could be of critical importance in prenatal diagnosis.