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Article Dans Une Revue Orphanet Journal of Rare Diseases Année : 2018

Adult Niemann-Pick disease type C in France: clinical phenotypes and long-term miglustat treatment effect

1 CHU Pitié-Salpêtrière [AP-HP]
2 Department of Pediatrics, Helios Clinic Sangerhausen, Sangerhausen
3 Neurologic/Cardiologic Diseases Unit, Lyon East Biochemistry/Molecular Biology Department, CBPE,Hospices Civils de Lyon, Lyon
4 Department of Neurology, Montpellier CHU, Gui De Chauliac Hospital, Montpellier
5 Clinical Neurosciences, Timone CHU, Marseille Hospital, Marseille
6 IGBMC - Institut de génétique et biologie moléculaire et cellulaire
7 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire
8 Strasbourg Federation of Translational Medicine (FMTS), Strasbourg University, Strasbourg
9 Service Médecine physique et de réadaptation [CHU Toulouse]
10 Department of Neurology and Movement Disorders, Roger Salengro Hospital, Lille
11 Centre de Référence Neurogénétique, Service de Génétique, Hôpital Pellegrin, University Hospital of Bordeaux
12 Laboratoire MRGM, INSERM U1211, University of Bordeaux, Bordeaux
13 Department of Neurology, Pierre-Wertheimer Hospital, Civilian Hospices of Lyon, Lyon
14 Department of Internal Medicine, Hôpital Emile Muller, Mulhouse and South Alsace Regional Hospital Group, Mulhouse
15 Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL]
16 IMPACT - Integrative Multisensory Perception, Action and Cognition
17 Department of Neurology, Hautepierre Hospital, Strasbourg
18 TIMONE - Hôpital de la Timone [CHU - APHM]
19 CRMBM - Centre de résonance magnétique biologique et médicale
20 CEMEREM - Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - APHM]
21 LilNCog - Lille Neurosciences & Cognition - U 1172
22 St André Clinic, Reims
23 ICM - Institut du Cerveau = Paris Brain Institute
24 GRC Neurométabolisme
25 INSERM U820, Lyon
26 Laboratoire Gillet-Mérieux, CBPE, Hospices Civils de Lyon, Lyon
27 Reference Centre for Lysosomal Diseases (CRML), Department of Pediatric Neurology, Paris
28 CHU Trousseau [APHP]
Yann Nadjar
Foudil Lamari

Résumé

Background Niemann-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. Methods Observational 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. Results In 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 disability at the start of miglustat treatment (p = 0.02). Conclusion The proportion of adolescent/adult-onset NP-C cases diagnosed in France increased 2.5-fold since 2009 compared with the 2000–2008 period due to improved awareness. Adolescent/adult-onset NP-C frequently presented initially with a non-specific isolated neuro-psychiatric manifestation (motor, cognitive or psychotic). Patients with less severe neurological disability responded better to miglustat therapy.
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hal-03541909 , version 1 (24-10-2023)

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Paternité

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Yann Nadjar, Ana Lucia Hütter-Moncada, Philippe Latour, Xavier Ayrignac, Elsa Kaphan, et al.. Adult Niemann-Pick disease type C in France: clinical phenotypes and long-term miglustat treatment effect. Orphanet Journal of Rare Diseases, 2018, 13 (1), pp.175. ⟨10.1186/s13023-018-0913-4⟩. ⟨hal-03541909⟩
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