Different ultrastructural patterns of early-stage Wilson’s disease

Abstract

Objective: Wilson's disease is an autosomal recessive genetic disorder of copper metabolism. Electron microscopy is a worthwhile and valuable diagnostic tool, especially in the early stages of this disease. We report two different ultrastructural patterns in patients that have similar clinical and histological features. Material and Methods: Two seven-year old female patients were admitted at the Pediatric Clinic because of abdominal pain and mild jaundice. Laboratory results showed elevated aminotransferases, low serum ceruloplasmin levels and negative serology for hepatotropic viruses. Liver biopsy was done and the biopsy specimens were fixed in glutaraldehyde and embedded in Durcupan resin. Semi-thin sections dyed with Toluidine blue and ultra-thin sections treated with uranyl acetate and lead citrate were made. Results: Light-microscopic analysis of the semi-thin sections of both cases showed early-stage cirrhosis presented by steatohepatitis and fibrosis with focal piece-meal necrosis. Electron-microscopic analysis of the ultra-thin sections in both cases showed hepatocytes` cytoplasm with a variable increase in the number of enlarged, pleomorphic mitochondria and peroxisomes, dilatation of smooth and rough endoplasmic reticulum and presence of neutral lipid vacuoles. We found two different patterns of cytoplasmic copper accumulation: electron densities with cribriform appearance and discrete, diffusely dispersed electron-dense material, especially in the perinuclear and paranuclear regions, as well as in some artificially degenerated mitochondria. Conclusions: Although these two cases have relatively similar clinical, laboratory and histological findings, they present very different and distinctive ultrastructural features, which from a diagnostic point of view can be subtle and non-specific in the early stages of this disease.