H. Michelakakis et al., IRON OVERLOAD AND URINARY LYSOSOMAL-ENZYME LEVELS IN BETA-THALASSEMIAMAJOR, European journal of pediatrics, 156(8), 1997, pp. 602-604
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.