title: Aceruloplasminemia: a novel mutation in a family with marked phenotypic variability.
abstract: Hereditary aceruloplasminemia (HA) is a rare inherited disease characterized by anemia, iron overload, diabetes, and neurodegeneration. HA is caused by the homozygous mutation of the ceruloplasmin (CP) gene. We report two siblings with markedly different phenotypes carrying a novel mutation: a homozygous deletion of two nucleotides (1257-1258 TT del) causing the premature stop of the Cp protein translation (Y401X). An early diagnosis of iron overload was made in the female sibling who was subsequently treated with deferoxamine. At the age of 54, her neurologic symptoms were limited to mild akinetic signs and a history of seizures; moreover, her fasting blood glucose level never exceeded 120 mg/dL. The male sibling, who had not received any specific treatment for HA, developed severe diabetes at the age of 32 and at 48 manifested a progressively disabling neurologic disease. Possible physiopathological bases of these intrafamilial phenotypic variations are discussed.
authors.affiliation: Istituto di Neurologia, Università Cattolica del Sacro Cuore, Roma, Italy. alfonso.fasano@rm.unicatt.it
authors.forename: Alfonso
authors.initials: A
authors.lastname: Fasano
authors.forename: Cesare
authors.initials: C
authors.lastname: Colosimo
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Miyajima
authors.forename: Pietro Attilio
authors.initials: PA
authors.lastname: Tonali
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Re
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Bentivoglio
mesh_terms: D001921:Brain / Q000378:metabolism / Q000473:pathology; D002570:Ceruloplasmin / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D003676:Deferoxamine / Q000627:therapeutic use; D003920:Diabetes Mellitus / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D018450:Disease Progression; D005190:Family; D005260:Female; D020271:Heredodegenerative Disorders, Nervous System / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D007501:Iron / Q000378:metabolism; D007502:Iron Chelating Agents / Q000627:therapeutic use; D019190:Iron Overload / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology; D008279:Magnetic Resonance Imaging; D008297:Male; D008664:Metal Metabolism, Inborn Errors / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D012640:Seizures / Q000209:etiology
chemical_list: D007502:Iron Chelating Agents; D007501:Iron; D002570:Ceruloplasmin; D003676:Deferoxamine