LIGHT AND ELECTRON-MICROSCOPIC LIVER CHANGES IN THE CEREBRO-HEPATO-RENAL SYNDROME OF ZELLWEGER (PEROXISOME DEFICIENCY)

For histologic differential diagnosis of fibrotic and cirrhotic liver changes in early infancy Zellweger's cerebro-hepato-renal syndrome has to be considered. A case is reported where a female newborn failed to thrive and developed severe muscular hypotonia, defective intelligence, and seizures. At an age of 12 months an open biopsy was taken from the enlarged liver. Biochemical tests for disorders of carbohydrate metabolism were negative. The light microscopic examination showed severe fibrosis, lobular disarray, and single cell necroses. Neither siderin nor bile pigment could be detected. There were no changes of the small bile ducts and no signs of inflammation - the child died at 18 months. A postmortem needle biopsy of the liver showed the advanced stage of micronodular cirrhosis. The electron microscopic examination of the first biopsy revealed hypertrophy of smooth endoplasmic reticulum, probably induced by anticonvulsive drugs. The mitochondria showed an increase in the density of their matrix and in the number of sometimes tubular cristae. In accordance with reports in literature, no regular peroxisomes (microbodies) could be found in the hepatocytes. Only a very few profiles with an average diameter of 0.16 μm looked like rather small peroxisomes. The cytoplasmic volume fraction of those organelles, however, amounted to 3×10-5 which is only 1/500 of the normal value in human hepatocytes. Although the significance of the absence of peroxisomes is not yet definitively proved, the term 'Peroxisome Deficiency' is proposed as a name which probably is more closely related to the pathogenetic mechanism than the hitherto usual designation cerebro-hepato-renal syndrome. © 1979 Springer-Verlag.