title: Iron overload and urinary lysosomal enzyme levels in beta-thalassaemia major.
abstract: The urinary levels of the lysosomal enzymes N-acetyl-beta-D-glucosaminidase (NAG) (EC 3.2.1.52) and alpha-mannosidase (EC 3.2.1.24) were evaluated in patients with beta-thalassaemia major and normal control subjects. Two groups of patients with different degrees of iron overload, as judged by their serum ferritin levels, were investigated. Renal disease was not present in any of the patients. A statistically significant 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 the control groups. No difference was observed in the urinary alpha-mannosidase 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 behaviour of the two lysosomal enzymes may reflect the intra- and inter-lysosomal heterogeneity in kidney.
  
  
  CONCLUSIONS
  Iron overload resulted in increased urinary levels of the lysosomal enzyme NAG which has been proposed as an early marker of kidney damage. Reduction of iron load, achieved 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.
authors.affiliation: Institute of Child Health, Children's Hospital, Aghia Sophia, Athens, Greece.
authors.forename: H
authors.initials: H
authors.lastname: Michelakakis
authors.forename: E
authors.initials: E
authors.lastname: Dimitriou
authors.forename: H
authors.initials: H
authors.lastname: Georgakis
authors.forename: F
authors.initials: F
authors.lastname: Karabatsos
authors.forename: C
authors.initials: C
authors.lastname: Fragodimitri
authors.forename: J
authors.initials: J
authors.lastname: Saraphidou
authors.forename: E
authors.initials: E
authors.lastname: Premetis
authors.forename: M
authors.initials: M
authors.lastname: Karagiorga-Lagana
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood / Q000652:urine; D016022:Case-Control Studies; D015913:Chelation Therapy; D002648:Child; D002675:Child, Preschool; D005260:Female; D005293:Ferritins / Q000097:blood*; D006596:Hexosaminidases / Q000652:urine*; D006801:Humans; D019190:Iron Overload; D008297:Male; D008361:Mannosidases / Q000652:urine*; D017086:beta-Thalassemia / Q000201:enzymology* / Q000628:therapy
chemical_list: D015415:Biomarkers; D005293:Ferritins; D006596:Hexosaminidases; D008361:Mannosidases