title: Heterogeneity and frequency of movement disorders in juvenile and adult-onset Niemann-Pick C disease.
abstract: Niemann-Pick type C disease (NPC) is a recessive neurolipidosis. We report five adolescent and adult NPC cases to underscore the frequency and heterogeneity of movement disorders in NPC. Clinical, morphologic, biochemical and genetic study was performed in the five patients. Disease onset was between 8 and 50 years. Movement disorders were present in all cases, were heterogeneous and often combined [cerebellar ataxia (5/5), myoclonus (3/5), dystonia (2/5), chorea (1/5) and tremor (1/5)] and were the first sign in 4/5. Two patients were reported to have no vertical supranuclear gaze palsy (VSGP) at the first examination. Two patients experienced acute neuropsychiatric signs leading to death in one case due to myoclonic storm. Filipin staining was always positive. Two NPC1 mutations were identified in three patients, only one in two siblings. NPC should be considered in case of unexplained movement disorders, even when VSGP or cataplexy are not reported. Filipin staining remains a strong support for the diagnosis. Treatment with miglustat should be considered which is currently the only approved disease-specific treatment of NPC in children and adults.
authors.affiliation: Service de Neurologie, CHU de Strasbourg-Hôpital de Hautepierre, 1, Avenue Molière, 67098, Strasbourg, France, mathieu.anheim@chru-strasbourg.fr.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Anheim
authors.forename: Ouhaïd
authors.initials: O
authors.lastname: Lagha-Boukbiza
authors.forename: Marie-Céline
authors.initials: MC
authors.lastname: Fleury-Lesaunier
authors.forename: Maria-Paola
authors.initials: MP
authors.lastname: Valenti-Hirsch
authors.forename: Edouard
authors.initials: E
authors.lastname: Hirsch
authors.forename: Hélène
authors.initials: H
authors.lastname: Gervais-Bernard
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Broussolle
authors.forename: Stéphane
authors.initials: S
authors.lastname: Thobois
authors.forename: Marie T
authors.initials: MT
authors.lastname: Vanier
authors.forename: Philippe
authors.initials: P
authors.lastname: Latour
authors.forename: Christine
authors.initials: C
authors.lastname: Tranchant
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D058256:Brain Waves / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004569:Electroencephalography; D005260:Female; D005372:Filipin; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D009069:Movement Disorders / Q000209:etiology* / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D000077296:Niemann-Pick C1 Protein; D052556:Niemann-Pick Disease, Type C / Q000150:complications* / Q000235:genetics; D055815:Young Adult
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; C106881:NPC1 protein, human; D000077296:Niemann-Pick C1 Protein; D005372:Filipin