Contributors: CHU Pitié-Salpêtrière AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU); Department of Pediatrics, Helios Clinic Sangerhausen, Sangerhausen; Neurologic/Cardiologic Diseases Unit, Lyon East Biochemistry/Molecular Biology Department, CBPE,Hospices Civils de Lyon, Lyon; Department of Neurology, Montpellier CHU, Gui De Chauliac Hospital, Montpellier; Clinical Neurosciences, Timone CHU, Marseille Hospital, Marseille; Institut de génétique et biologie moléculaire et cellulaire (IGBMC); Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC); Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Strasbourg Federation of Translational Medicine (FMTS), Strasbourg University, Strasbourg; Service Médecine physique et de réadaptation CHU Toulouse; Pôle Neurosciences CHU Toulouse; Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Santé publique et médecine publique CHU Toulouse; Centre Hospitalier Universitaire de Toulouse (CHU Toulouse); Department of Neurology and Movement Disorders, Roger Salengro Hospital, Lille; Centre de Référence Neurogénétique, Service de Génétique, Hôpital Pellegrin, University Hospital of Bordeaux; Laboratoire MRGM, INSERM U1211, University of Bordeaux, Bordeaux; Department of Neurology, Pierre-Wertheimer Hospital, Civilian Hospices of Lyon, Lyon; Department of Internal Medicine, Hôpital Emile Muller, Mulhouse and South Alsace Regional Hospital Group, Mulhouse; Hôpital neurologique et neurochirurgical Pierre Wertheimer CHU - HCL; Hospices Civils de Lyon (HCL); Integrative Multisensory Perception, Action and Cognition (IMPACT); Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL); Université Claude Bernard Lyon 1 (UCBL); Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL); Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Department of Neurology, Hautepierre Hospital, Strasbourg; Hôpital de la Timone CHU - APHM (TIMONE); Centre de résonance magnétique biologique et médicale (CRMBM); Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS); Centre d'Exploration Métabolique par Résonance Magnétique Hôpital de la Timone - APHM (CEMEREM); Hôpital de la Timone CHU - APHM (TIMONE)-Centre de résonance magnétique biologique et médicale (CRMBM); Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS); Lille Neurosciences & Cognition - U 1172 (LilNCog); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille); St André Clinic, Reims; Institut du Cerveau = Paris Brain Institute (ICM); Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS); GRC Neurométabolisme; Sorbonne Université (SU); INSERM U820, Lyon; Laboratoire Gillet-Mérieux, CBPE, Hospices Civils de Lyon, Lyon; Reference Centre for Lysosomal Diseases (CRML), Department of Pediatric Neurology, Paris; CHU Trousseau APHP
نبذة مختصرة : International audience ; BackgroundNiemann-Pick disease type C (NP-C) is a neurodegenerative lysosomal lipid storage disease caused by autosomal recessive mutations in the NPC1 or NPC2 genes. The clinical presentation and evolution of NP-C and the effect of miglustat treatment are described in the largest cohort of patients with adolescent/adult-onset NP-C studied to date.MethodsObservational study based on clinical chart data from adult patients with NP-C (> 18 year old) diagnosed in France between 1990 and 2015. Retrospective data from patients at diagnosis, onset of miglustat therapy (if applicable), and last follow up were analysed.ResultsIn France, patients with an adolescent-adult neurological form constituted approximately 25% of all NP-C cases diagnosed during the study period. Forty-seven patients (46 with NP-C1 and one with NP-C2; 53% female) were included. Mean ± SD (range) ages at neurological onset and diagnosis were 23.9 ± 12.5 (8–56) years and 34 ± 13.5 (15–65) years, respectively. At presentation, patients mainly had 1) impaired gait due to cerebellar ataxia and/or dystonia, 2) and/or cognitive/behavioural manifestations, 3) and/or psychotic signs. Initially, almost half of patients had only one of the above three neuro-psychiatric manifestations. Vertical supranuclear gaze palsy, usually occurring without patient complaint, was only detected on careful clinical examination and was recorded in most patients (93%) at the time of diagnosis, several years after neurological onset. Thirty-seven patients (79%) received miglustat, among whom seventeen (46%) continued beyond 2 years (at last follow up) to a maximum of 9.8 years. Eight patients (22%) discontinued treatment early due to side effects (n = 3) or perceived lack of efficacy (n = 5).Miglustat treatment duration correlated significantly with reduced neurological worsening (p < 0.001). Treatment for≥2 years was associated with improved patient survival (p = 0.029). Good responses to miglustat were associated with less severe neurological ...
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