title: New insights in the neurological phenotype of aceruloplasminemia in Caucasian patients.
abstract: The diagnosis aceruloplasminemia is usually made in patients with advanced neurological manifestations of the disease. In these patients prognosis is poor, disabilities are severe and patients often die young. The aim of our study was to facilitate recognition of aceruloplasminemia at a disease stage at which treatment can positively influence outcome. Currently, the neurological phenotype of aceruloplasminemia has been mainly described in Japanese patients. This 'classical' phenotype consists of cerebellar ataxia, hyperkinetic movement disorders and cognitive decline. In this study we describe the spectrum of neurological disease in Caucasian patients.
  
  
  
  Data on neurological presentation and follow-up were gathered from both our patients, homozygous for the G631R mutation in the CP gene, and other published Caucasian cases. Neurological features of aceruloplasminemia in Caucasian patients were compared to those summarized in Japanese patients.
  
  
  
  21 Caucasian patients, both ours and the described cases, displayed a wide range of movement disorders with predominant chorea, parkinsonism and ataxia, and also tremor and dystonia. In addition to cognitive decline, nearly half of the Caucasian patients presented with psychiatric changes, including depression, anxiety and behavioral changes. In one-third of the neurologically symptomatic Caucasian patients, cognitive- or psychiatric changes were the first neurological manifestations of aceruloplasminemia.
  
  
  
  Aceruloplasminemia in Caucasian patients can present with a wider range and a different order of neurological symptoms than previously described in Japanese patients. Psychiatric changes and parkinsonism can be added to the spectrum of neurological disease. Cognitive- or psychiatric changes may be the first neurological manifestations of aceruloplasminemia.
authors.affiliation: Department of Internal Medicine, Centre for Lysosomal and Metabolic Diseases, Erasmus MC Rotterdam, PO Box 2040, 3000 CA Rotterdam, The Netherlands. Electronic address: l.vroegindeweij@erasmusmc.nl.
authors.forename: Lena H P
authors.initials: LHP
authors.lastname: Vroegindeweij
authors.affiliation: Department of Internal Medicine, Centre for Lysosomal and Metabolic Diseases, Erasmus MC Rotterdam, PO Box 2040, 3000 CA Rotterdam, The Netherlands. Electronic address: j.g.langendonk@erasmusmc.nl.
authors.forename: Janneke G
authors.initials: JG
authors.lastname: Langendonk
authors.affiliation: Department of Internal Medicine, Centre for Lysosomal and Metabolic Diseases, Erasmus MC Rotterdam, PO Box 2040, 3000 CA Rotterdam, The Netherlands. Electronic address: m.langeveld.1@erasmusmc.nl.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Langeveld
authors.affiliation: Department of Hematology, Medical Centre Leeuwarden, PO Box 888, 8901 BR Leeuwarden, The Netherlands. Electronic address: m.hoogendoorn@znb.nl.
authors.forename: Mels
authors.initials: M
authors.lastname: Hoogendoorn
authors.affiliation: Department of Clinical Genetics, Erasmus MC Rotterdam, PO Box 2040, 3000 CA Rotterdam, The Netherlands. Electronic address: j.a.kievit@erasmusmc.nl.
authors.forename: Anneke J A
authors.initials: AJA
authors.lastname: Kievit
authors.affiliation: U.O.C. di Medicina Interna e Cardioangiologia, Dipartimento Biomedico di Medicina Interna e Specialistica, Università degli Studi di Palermo, 90127 Palermo, Italy. Electronic address: domenico.diraimondo@unipa.it.
authors.forename: Domenico
authors.initials: D
authors.lastname: Di Raimondo
authors.affiliation: Department of Internal Medicine, Centre for Lysosomal and Metabolic Diseases, Erasmus MC Rotterdam, PO Box 2040, 3000 CA Rotterdam, The Netherlands. Electronic address: j.h.p.wilson@erasmusmc.nl.
authors.forename: J H Paul
authors.initials: JHP
authors.lastname: Wilson
authors.affiliation: Department of Neurology, Erasmus MC Rotterdam, PO Box 2040, 3000 CA Rotterdam, The Netherlands. Electronic address: a.j.w.boon@erasmusmc.nl.
authors.forename: Agnita J W
authors.initials: AJW
authors.lastname: Boon
mesh_terms: D000328:Adult; D002570:Ceruloplasmin / Q000172:deficiency* / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019189:Iron Metabolism Disorders / Q000000981:diagnostic imaging* / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000000981:diagnostic imaging* / Q000453:epidemiology / Q000235:genetics*; D019636:Neurodegenerative Diseases / Q000000981:diagnostic imaging* / Q000453:epidemiology / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D044465:White People / Q000235:genetics*
chemical_list: D002570:Ceruloplasmin
keywords: Aceruloplasminemia; Neurological manifestations; Phenotypic variability; Psychiatric changes