title: Aqueous humor ferritin in hereditary hyperferritinemia cataract syndrome.
abstract: OBJECTIVE
  Hereditary hyperferritinemia cataract syndrome (HHCS) is a rare autosomal dominant hereditary disease, characterized by hyperferritinemia but with absence of body iron excess and early onset of bilateral cataracts. Although 5- to 20-fold increased serum ferritin concentrations have been reported in HHCS patients, data of ferritin levels in aqueous humor have not been obtained. We therefore aimed to investigate the ferritin levels in aqueous humor and serum and further present histological and ultrastructural data of the lens.
  
  
  METHODS
  During cataract extraction and intraocular lens implantation, aqueous humor and lens aspirate of a 37-year-old HHCS patient were obtained from both eyes. Ferritin levels in serum and aqueous humor were quantitatively analyzed via immunoassays in the HHCS patient and healthy control subjects (n = 6). Lens aspirate in HHCS was analyzed histologically and at the ultrastructural level. Further, genetic mutation screening by polymerase chain reaction and DNA sequencing in blood was performed.
  
  
  RESULTS
  Serum ferritin levels in the control group were 142.2 ± 38.7 μg/L, whereas in the HHCS patient, this parameter was excessively increased (1086 μg/L). Analysis of ferritin in aqueous humor revealed 6.4 ± 3.8 μg/L in normal control subjects and 146.3 μg/L (OD) and 160.4 μg/L (OS) in the HHCS patient. DNA analysis detected a C>A mutation on position +18, a T>G mutation on position +22, a T>C mutation on position +24, and a T>G polymorphism on position +26 in the iron-responsive element of the light-chain ferritin (L-ferritin) gene.
  
  
  CONCLUSIONS
  In the HHCS patient, a 23-fold (OD) to 25-fold (OS) increased aqueous humor ferritin level was detected. Therefore, the formation of bilateral cataract in HHCS is most likely a result of elevated aqueous humor ferritin. In addition, a novel mutation in this rare disease in the iron-responsive element of L-ferritin gene is reported.
authors.affiliation: *MD †Dr rer nat ‡PhD Department of Ophthalmology and Optometry (ML, FS, AT, AK-E, CS, MH, GG, HAR), Department of Anatomy (FS), Department of Laboratory Medicine (HW), and First Department of Internal Medicine (MS, EA), Paracelsus Medical University, Salzburg, Austria; Department of Pediatric Hematology, Oncology and Immunology, University of Heidelberg, Germany (MUM); and Molecular Medicine Partnership Unit, Heidelberg, Germany (MUM).
authors.forename: Markus
authors.initials: M
authors.lastname: Lenzhofer
authors.forename: Falk
authors.initials: F
authors.lastname: Schroedl
authors.forename: Andrea
authors.initials: A
authors.lastname: Trost
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kaser-Eichberger
authors.forename: Helmut
authors.initials: H
authors.lastname: Wiedemann
authors.forename: Clemens
authors.initials: C
authors.lastname: Strohmaier
authors.forename: Melchior
authors.initials: M
authors.lastname: Hohensinn
authors.forename: Michael
authors.initials: M
authors.lastname: Strasser
authors.forename: Martina U
authors.initials: MU
authors.lastname: Muckenthaler
authors.forename: Guenther
authors.initials: G
authors.lastname: Grabner
authors.forename: Elmar
authors.initials: E
authors.lastname: Aigner
authors.forename: Herbert A
authors.initials: HA
authors.lastname: Reitsamer
mesh_terms: D000328:Adult; D001082:Aqueous Humor / Q000378:metabolism*; D002386:Cataract / Q000151:congenital* / Q000378:metabolism; D004252:DNA Mutational Analysis; D005293:Ferritins / Q000097:blood* / Q000235:genetics; D006801:Humans; D007118:Immunoassay; D019189:Iron Metabolism Disorders / Q000151:congenital* / Q000378:metabolism; D019654:Lens Implantation, Intraocular; D007908:Lens, Crystalline / Q000473:pathology; D008297:Male; D009154:Mutation; D018918:Phacoemulsification; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide
chemical_list: D005293:Ferritins