CYTOPLASMIC CATALASE AND GHOSTLIKE PEROXISOMES IN THE LIVER FROM A CHILD WITH ATYPICAL CHONDRODYSPLASIA PUNCTATA

In the liver biopsy from an 8.5-year-old girl with the biochemical cha racteristics of rhizomelic chondrodysplasia punctata (RCDP), but with normal limbs, normal catalase-containing peroxisomes were absent. Ligh t microscopy after diaminobenzidine staining for catalase activity (th e peroxisomal marker enzyme) and immunostaining against catalase prote in indicated a cytosolic localization of the enzyme. By electron micro scopy, rare and extremely large, irregularly shaped vesicles were foun d in the parenchymal cells. The three peroxisomal beta-oxidation enzym es (acyl-CoA oxidase, bi(tri)functional enzyme, and 3-ketoacyl-CoA thi olase) and alanine-glyoxylate aminotransferase were immunolocalized in these organelles. However, a weak to negative label was obtained afte r staining against catalase. Diaminobenzidine staining demonstrated a minimal catalase reaction product in some vesicles only. Morphometry r evealed a corrected mean d-circle of 1.44 mum and a maximum d-circle o f 2.767 mum (controls: 0.635 mum and 1.027 mum, respectively). Numeric al, volume, and surface densities were reduced to 3%, 41%, and 17% of control values, respectively. The large size, irregular shape, and rar ity of the organelles are morphologic features of peroxisomal ''ghosts .'' It seems that in this patient, apart from the known peroxisomal de fects in RCDP, catalase incorporation into the peroxisomes is impaired together with abnormal proliferation (division) of the organelles. In the cultured skin fibroblasts from the patient, however, immunoelectr on microscopy showed normal catalase-containing peroxisomes in apparen tly normal numbers.