Maciej Machaczka1, Martin Paucar2, Cecilia Kämpe Björkvall3, Nicholas J C Smith4, Timothy M Cox5, Lars Forsgren6, Per Svenningsson7. 1. Hematology Center Karolinska and Department of Medicine at Huddinge, Karolinska Institutet, Karolinska University Hospital Huddinge, M54, Stockholm, Sweden. Electronic address: maciej.machaczka@ki.se. 2. Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, SE-171 76 Stockholm, Sweden. 3. Department of Medicine, Sunderby Regional Hospital of Norrbotten County, Luleå, Sweden. 4. School of Medicine, University of Adelaide, Adelaide, Australia. 5. Department of Medicine, University of Cambridge, Cambridge, United Kingdom. 6. Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden. 7. Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, SE-171 76 Stockholm, Sweden. Electronic address: per.svenningsson@ki.se.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: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. METHODS: The patients were evaluated by standardized neurological assessments. Every sixth month, the GD3patients 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. RESULTS: Marked clinical heterogeneity was evident in both GD3 and GD1 groups. Several GD3patients 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 GD3patients, all homoallelic for L444PGBA1 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. CONCLUSIONS: 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: Ellen Hertz; Måns Thörnqvist; Björn Holmberg; Maciej Machaczka; Ellen Sidransky; Per Svenningsson Journal: Mov Disord Clin Pract Date: 2019-03-07
Authors: Josefine Blume; Stanislav Beniaminov; Cecilia Kämpe Björkvall; Maciej Machaczka; Per Svenningsson Journal: Front Neurol Date: 2017-06-22 Impact factor: 4.003