title: Aceruloplasminaemia: a family with a novel mutation and long-term therapy with deferasirox.
abstract: Ceruloplasmin is a member of the multicopper oxidase family that plays a major role in the transport of iron in the body. Aceruloplasminaemia (ACP) is a rare disease and is clinically identified by iron overload in liver, pancreas, brain, and other organs, and by microcytic anaemia. So far, the iron chelator deferasirox was given for therapy only up to 6 months due to side effects. Here, we describe a novel mutation leading to ACP and report for the first time a long-term therapy, that is, 2 years with deferasirox. ACP was diagnosed in 3 siblings using clinical and biochemical characteristics, HFE and ceruloplasmin mutational analysis, liver biopsy, brain-, liver-, and heart-MRI. For iron depletion, a starting dose of deferasirox 7.5 mg/kg/day was increased to 15 mg/kg/day and maintained at 4-7.5 mg/kg/day with a patient follow-up for 2 years. A novel homozygous mutation of the ceruloplasmin gene on chromosome 3 (3q23-q25, exon 12, G708S) was found. Iron was selectively and successfully removed by long-term therapy with deferasirox, as confirmed by follow-up liver biopsies, normalisation of serum ferritin concentrations, and improved glucose metabolism. Unexpectedly, iron depletion ameliorated anaemia. Low-dose deferasirox is an effective and safe long-term treatment option for patients with ACP.
authors.affiliation: Department of Internal Medicine II, Gastroenterology, Hepatology, Endocrinology, Metabolic Disorders, Oncology, Klinikum Chemnitz gGmbH, 09116 Chemnitz, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Lindner
authors.affiliation: Molecular and Translational Medicine, Department of Internal Medicine I, Johannes Gutenberg-University of Mainz Medical School, 55131 Mainz, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Schuppan
authors.affiliation: MVZ Labor PD Dr. Volkmann und Kollegen, 76133 Karlsruhe, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Schleithoff
authors.affiliation: Center of Histopathology, 09117 Chemnitz, Germany.
authors.forename: J-O
authors.initials: JO
authors.lastname: Habeck
authors.affiliation: Institute of Diagnostic Radiology, Klinikum Chemnitz gGmbH, 09116 Chemnitz, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Grodde
authors.affiliation: Institute of Diagnostic and Interventional Radiology and Neuroradiology Klinikum Chemnitz gGmbH, 09113 Chemnitz, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Kirchhof
authors.affiliation: Department of Internal Medicine II, Gastroenterology, Hepatology, Endocrinology, Metabolic Disorders, Oncology, Klinikum Chemnitz gGmbH, 09116 Chemnitz, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Stoelzel
mesh_terms: D000328:Adult; D001565:Benzoates / Q000627:therapeutic use*; D001786:Blood Glucose / Q000032:analysis; D002570:Ceruloplasmin / Q000032:analysis / Q000172:deficiency* / Q000235:genetics; D002614:Chelating Agents / Q000627:therapeutic use*; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D000077588:Deferasirox; D005260:Female; D005858:Germany; D006801:Humans; D007501:Iron / Q000032:analysis; D019189:Iron Metabolism Disorders / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008099:Liver / Q000737:chemistry / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D001565:Benzoates; D001786:Blood Glucose; D002614:Chelating Agents; D014230:Triazoles; D007501:Iron; D002570:Ceruloplasmin; D000077588:Deferasirox