Ultrastructure of the Liver in Th Cerebrohepatorenal Syndrome of Zellweger

Three infants with clinical and biochemical features of Zellweger's cerebrohepatorenal syndrome are presented, and the ultrastructural features of successive biopsy and autopsy liver specimens are described. No hepatocellular peroxisomes were found in these patients on routine electron microscopy or electron microscopic histochemistry. In a control group of liver biopsies from 9 patients with other pediatric liver diseases, peroxisomes were readily identifiable in each hepatocyte. Apart from the absence of peroxisomes, the hepatocytes had a remarkably "normal" aspect, even in the final stages of the disease. Mitochondrial abnormalities, which have been the subject of some controversy in this syndrome, were a highly variable and inconstant finding in our cases. We draw attention to another ultrastructural feature of the syndrome, namely the occurrence of large angulate lysosomes, containing conspicuous double lamellae, inside macrophages, which were especially abundant in later stages of the disease. These angulate lysosomes may be of additional value in the ultrastructural diagnosis of Zellweger's syndrome, especially when only poorly preserved liver tissue (e.g., paraffin-embedded or postmortem material) is available, and the absence of peroxisomes is difficult to assess. In these instances, the angulate lysosomes can still be identified with ease.