title: [Hereditary hyperferritinemia cataract syndrome--the first family in Germany].
abstract: We report on a 23-year-old woman who presented with elevated serum ferritin values at our department. She had undergone cataract surgery at the age of 14 and her family pedigree showed hereditary autosomal-dominant cataract. The combination of isolated hyperferritinemia with autosomal-dominant hereditary cataract led to the diagnosis of the hereditary hyperferritinemia cataract syndrome (HHCS) which we now describe in a German family for the first time. HHCS was confirmed by detection of a causal mutation at position 32 within the iron responsive element (IRE) of L-ferritin leading to a guanine to adenine exchange and the pathognomonic star-shaped cataract. This mutation interrupts the post-transcriptional control of L-ferritin. It prevents binding of the iron regulatory protein 1 (IRP1) to the 5alpha untranslated region of L-ferritin resulting in uncontrolled L-ferritin synthesis and high serum ferritin levels independent of the body iron stores. Premature cataract is eventually caused by deposition of L-ferritin crystals in the lens of the eye. Our family shows the typical autosomal-dominant inheritance of HHCS over four generations affecting a total of 17 family members. The causal mutation, star-shaped cataract and typical laboratory configuration were confirmed in five patients. Thus, in gastroenterological practice, HHCS should be added as a differential diagnosis of hyperferritinemia in Germany. Importantly, patients with HHCS can be spared from invasive diagnostics such as liver biopsy.
authors.affiliation: Alkoholforschungszentrum Universität Heidelberg und Medizinische Klinik, KH Salem, Heidelberg, Germany. gunda.millonig@uni-heidelberg.de
authors.forename: G
authors.initials: G
authors.lastname: Millonig
authors.forename: M P
authors.initials: MP
authors.lastname: Holzer
authors.forename: G
authors.initials: G
authors.lastname: Tolle
authors.forename: G U
authors.initials: GU
authors.lastname: Auffarth
authors.forename: M U
authors.initials: MU
authors.lastname: Muckenthaler
authors.forename: H K
authors.initials: HK
authors.lastname: Seitz
authors.forename: S
authors.initials: S
authors.lastname: Mueller
mesh_terms: D000328:Adult; D001052:Apoferritins / Q000235:genetics*; D002386:Cataract / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D019189:Iron Metabolism Disorders / Q000175:diagnosis* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D013577:Syndrome
chemical_list: D001052:Apoferritins