title: Novel hyperkinetic dystonia-like manifestation and neurological disease course of Swedish Gaucher patients.
abstract: Neuronopathic Gaucher disease type 3 (GD3) is frequent in northern Sweden, whereas GD1 is found throughout the country. In a nation-wide study, we examined neurological manifestations and clinical course in 12 patients with GD3 and 13 patients with GD1.
  
  
  
  The patients were evaluated by standardized neurological assessments. Every sixth month, the GD3 patients were rated with the modified Severity Scoring Tool. At baseline and at the 3years follow-up, patients underwent University of Pennsylvania Smell Identification Test, Montreal Cognitive Assessment and Hospital Anxiety and Depression Scale. When clinical signs were present, additional examinations were undertaken.
  
  
  
  Marked clinical heterogeneity was evident in both GD3 and GD1 groups. Several GD3 patients had a hitherto unreported rapid and repetitive dystonia-like hyperkinetic movement disorder. Most patients with GD3 have abnormalities of horizontal gaze, ataxia and focal epilepsy, some also had cognitive impairment, anxiety and hyposmia. Six GD3 patients, all homoallelic for L444P GBA1 mutations, have lived beyond 40years of age; and none has developed Parkinsonism. Two of the GD1 patients suffer from Parkinsonism; mild to complete hyposmia was present in six GD3 and five GD1 patients. Neither the group of GD3 nor GD1 patients had detectable progression of their neurological manifestations.
  
  
  
  These middle-aged and older Swedish GD3 or GD1 patients are clinically stable over time. However, we have identified unusual clinical features, discordant phenotypes and a hyperkinetic dystonia-like movement disorder which appears unique to this Swedish disease variant and expands the phenotype for GD.
authors: Hematology Center Karolinska and Department of Medicine at Huddinge, Karolinska Institutet, Karolinska University Hospital Huddinge, M54, Stockholm, Sweden. Electronic address: maciej.machaczka@ki.se.
authors: Maciej
authors: M
authors: Machaczka
authors: Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, SE-171 76 Stockholm, Sweden.
authors: Martin
authors: M
authors: Paucar
authors: Department of Medicine, Sunderby Regional Hospital of Norrbotten County, Luleå, Sweden.
authors: Cecilia Kämpe
authors: CK
authors: Björkvall
authors: School of Medicine, University of Adelaide, Adelaide, Australia.
authors: Nicholas J C
authors: NJC
authors: Smith
authors: Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
authors: Timothy M
authors: TM
authors: Cox
authors: Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
authors: Lars
authors: L
authors: Forsgren
authors: Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, SE-171 76 Stockholm, Sweden. Electronic address: per.svenningsson@ki.se.
authors: Per
authors: P
authors: Svenningsson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001007:Anxiety / Q000150:complications / Q000453:epidemiology; D060825:Cognitive Dysfunction / Q000150:complications / Q000453:epidemiology; D003863:Depression / Q000150:complications / Q000453:epidemiology; D018450:Disease Progression; D004421:Dystonia / Q000150:complications* / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D005776:Gaucher Disease / Q000150:complications* / Q000453:epidemiology; D006801:Humans; D006948:Hyperkinesis / Q000150:complications* / Q000453:epidemiology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D013548:Sweden / Q000453:epidemiology; D055815:Young Adult
keywords: Dystonia; GBA1; Gaucher disease; Glucocerebrosidase; Parkinson's disease