Granulocyte function in patients with L-ferritin iron-responsive element (IRE) 39C→T-positive hereditary hyperferritinaemia-cataract syndrome

• Published in: European journal of clinical investigation Vol. 34; no. 10; pp. 701 - 708
• Main Authors: Fritsche-Polanz, R., Wallner, M., Cohen, G., Eberle, C., Sunder-Plassmann, G., Födinger, M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.10.2004; Blackwell; Blackwell Publishing Ltd
• Subjects: Adolescent; Adult; Apoptosis; Biological and medical sciences; Cataract - blood; Cataract - genetics; Chemotaxis, Leukocyte; Female; Ferritins - blood; General aspects; Glucose - metabolism; granulocyte function; Granulocytes - physiology; Hereditary hyperferritinaemia cataract syndrome; Humans; Iron Metabolism Disorders - genetics; Iron Metabolism Disorders - metabolism; iron responsive element; L-ferritin; Lens diseases; Male; Medical sciences; Middle Aged; mutation analysis; Neutrophils - metabolism; Ophthalmology; Pedigree; Phagocytosis; Respiratory Burst; Syndrome; Human; Cataract; Ferritin; Granulocyte; Iron responsive element; Hereditary hyperferritinaemia cataract syndrome; Hereditary; Syndrome; Medicine; granulocyte function; Eye disease; L-ferritin; Lens disease; mutation analysis; Mutation; Anterior segment disease
• ISSN: 0014-2972; 1365-2362
• DOI: 10.1111/j.1365-2362.2004.01408.x

Background  Hereditary hyperferritinaemia–cataract syndrome (HHCS) is an autosomal dominant trait associated with mutations in the iron responsive element (IRE) of the ferritin light‐chain (L‐ferritin) gene. Patients typically show elevated serum ferritin concentrations without iron overload and a bilateral cataract. Hyperferritinaemia can be associated with granulocyte dysfunction in patients with thalassemia beta and in haemodialysis patients. The effect of increased L‐ferritin levels on granulocyte function in patients with HHCS is unknown. Material and methods  We examined glucose uptake, oxidative burst, chemotaxis, phagocytosis, apoptosis and intracellular calcium concentrations in polymorphonuclear leucocytes (PMNLs) of five affected members of a family with HHCS and in five healthy individuals matched for age and gender. Results  Mutation testing revealed a 39C→T transition in IRE in all five patients with HHCS. Serum ferritin levels of patients ranged between 907 and 2030 µg L−1, respectively. In comparison with healthy individuals, PMNLs of patients with HHCS showed a significant increase in PMA‐mediated stimulation of the oxidative burst, as well as a significantly higher stimulation of glucose uptake but no difference with respect to chemotaxis, phagocytosis, apoptosis and intracellular calcium concentrations. Conclusion  In summary, our study suggests that hyperferritinaemia in patients with IRE 39C→T‐positive HHCS is associated with activation of PMNLs but not with disturbance of fundamental PMNL function.