IRON OVERLOAD AND URINARY LYSOSOMAL-ENZYME LEVELS IN BETA-THALASSEMIAMAJOR

The urinary levels of the lysosomal enzymes N-acetyl-beta-D-glucosamin idase (NAG) (EC 3.2.1.52) and alpha-mannosidase (EC 3.2.1.24) were eva luated in patients with beta-thalassaemia major and normal control sub jects. Two groups of patients with different degrees of iron overload, as judged by their serum ferritin levels, were investigated. Renal di sease was not present in any of the patients. A statistically signific ant increase in the levels of NAG was observed in the high ferritin (> 3,000 mg/dl) group compared to the low ferritin (< 3,000 mg/dl) and t he control groups. No difference was observed in the urinary alpha-man nosidase levels between the groups examined. The finding of increased NAG levels in the patients with the increased iron load suggests that kidney lysosomes are a target of iron toxicity. The different behaviou r of the two lysosomal enzymes may reflect the intra- and inter-lysoso mal heterogeneity in kidney. Conclusion Iron overload resulted in incr eased urinary levels of the lysosomal enzyme NAG, which has been propo sed as an early marker of kidney damage. Reduction of iron load, achie ved by regular desferrioxamine infusion, resulted in normalisation of the urinary enzyme levels. Thus kidney lysosomes appear to be a target and possibly a mediator of iron toxicity in this tissue.