title: Unexplained isolated hyperferritinemia without iron overload.
abstract: Although hyperferritinemia may be reflective of elevated total body iron stores, there are conditions in which ferritin levels are disproportionately elevated relative to iron status. Autosomal dominant forms of hyperferritinemia due to mutations in the L-ferritin IRE or in A helix of L-ferritin gene have been described, however cases of isolated hyperferritinemia still remain unsolved. We describe 12 Italian subjects with unexplained isolated hyperferritinemia (UIH). Four probands have affected siblings, but no affected parents or offspring. Sequencing analyses did not identify casual mutations in ferritin gene or IRE regions. These patients had normal levels of intracellular ferritin protein and mRNA in peripheral blood cells excluding pathological ferritin production at transcriptional and post-transcriptional level. In contrast with individuals with benign hyperferritinemia caused by mutations affecting the ferritin A helix, low rather than high glycosylation of serum ferritin was observed in our UIH subjects compared with controls. These findings suggest that subjects with UIH have a previously undescribed form of hyperferritinemia possibly attributable to increased cellular ferritin secretion and/or decreased serum ferritin clearance. The cause remains to be defined and we can only speculate the existence of mutations in gene/s not directly implicated in iron metabolism that could affect ferritin turnover including ferritin secretion.
authors.affiliation: School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.
authors.forename: Giulia
authors.identifier: http://orcid.org/0000-0003-4858-3359
authors.initials: G
authors.lastname: Ravasi
authors.affiliation: School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Pelucchi
authors.affiliation: ASST-Monza - S.Gerardo Hospital, Centre for Disorder of Iron Metabolism, Monza, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Mariani
authors.affiliation: ASST-Monza - S.Gerardo Hospital, Unit of Clinical Chemistry, Monza, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Casati
authors.affiliation: School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Greni
authors.affiliation: Consortium of Human Molecular Genetics, Monza, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Arosio
authors.affiliation: ASST-Monza - S.Gerardo Hospital, Centre for Disorder of Iron Metabolism, Monza, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Pelloni
authors.affiliation: Medical Genetics, Molecular Medicine Department, Sapienza University of Rome, San Camillo-Forlanini Hospital, Roma, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Majore
authors.affiliation: Division of Neuroscience, San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Santambrogio
authors.affiliation: Division of Neuroscience, San Raffaele Scientific Institute, Milano, Italy.|University Vita-Salute San Raffaele, Milano, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Levi
authors.affiliation: School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.|ASST-Monza - S.Gerardo Hospital, Centre for Disorder of Iron Metabolism, Monza, Italy.|Consortium of Human Molecular Genetics, Monza, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Piperno
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D005293:Ferritins / Q000097:blood*; D006031:Glycosylation; D006801:Humans; D019189:Iron Metabolism Disorders / Q000209:etiology*; D019190:Iron Overload; D007558:Italy; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D012333:RNA, Messenger / Q000097:blood; D035781:Siblings; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; D005293:Ferritins