EXCESS ZINC ASSOCIATED WITH SEVERE PROGRESSIVE CHOLESTASIS IN CREE AND OJIBWAY-CREE CHILDREN

Background High hepatic copper concentrations have been reported in se veral liver disorders. We report six Native Canadian children with sev ere chronic cholestatic liver disease, who had excess hepatic copper a nd zinc. Methods The children, aged 22 months to 8 years, dame from no rthern Ontario, Canada. All were referred for possible liver transplan tation because of end-stage liver disease. We examined explanted liver samples (or liver biopsy material in one case) by scanning transmissi on electronmicroscopic (STEM) X-ray elemental microanalysis and atomic absorption spectrophotometry. Samples from four controls (two with no liver pathology, one with biliary atresia, and one with Wilson's dise ase) were also analysed by atomic absorption spectrophotometry. Findin gs The explanted livers showed similar distinctive signs of advanced b iliary cirrhosis, and on electronmicroscopy there were dense deposits in enlarged lyosomes and in cytoplasm. Hepatic copper concentrations w ere many times higher in the five patients with measurements (47.6-56. 9 mu g/g dry weight) than in two samples of normal control liver tissu e (2.3 and 2.9 mu g/g). Similarly, hepatic zinc concentrations were ma ny times higher in the patients than in controls (104-128 vs 1.9-3.2 m u g/g dry weight). Interpretation The excess copper may be due to chro nic cholestasis but the excess zinc is unexplained. Since three of the patients are related (shared grandparents), a genetic disorder of met al metabolism is possible, but we cannot exclude environmental factors .