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

Yann Nadjar, Ana Lucia Hütter-Moncada, Philippe Latour, Xavier Ayrignac, Elsa Kaphan, Christine Tranchant, Pascal Cintas, Adrian Degardin, Cyril Goizet, Chloe Laurencin, Lionel Martzolff, Caroline Tilikete, Mathieu Anheim, Bertrand Audoin, Vincent Deramecourt, Thierry Dubard De Gaillarbois, Emmanuel Roze, Foudil Lamari, Marie T. Vanier, Bénédicte Héron
Orphanet J Rare Dis. 2018-10-01; 13(1):
DOI: 10.1186/s13023-018-0913-4

PubMed
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1. Orphanet J Rare Dis. 2018 Oct 1;13(1):175. doi: 10.1186/s13023-018-0913-4.

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

Nadjar Y(1), Hütter-Moncada AL(2), Latour P(3), Ayrignac X(4), Kaphan E(5),
Tranchant C(6)(7)(8), Cintas P(9), Degardin A(10), Goizet C(11), Laurencin C(12),
Martzolff L(13), Tilikete C(14), Anheim M(6)(7)(8), Audoin B(15)(16), Deramecourt
V(17), De Gaillarbois TD(18), Roze E(19)(20), Lamari F(21), Vanier MT(22)(23),
Héron B(24).

Author information:
(1)Department of Neurology, Reference Center for Lysosomal Diseases (CRLM), UF
Neuro-Genetics and Metabolism, Hôpital Pitié-Salpêtrière, 47-87, Boulevard de
l’Hôpital, 75013, Paris, France. .
(2)Department of Pediatrics, Helios Clinic Sangerhausen, Sangerhausen, Germany.
(3)Neurologic/Cardiologic Diseases Unit, Lyon East Biochemistry/Molecular Biology
Department, CBPE,Hospices Civils de Lyon, Lyon, France.
(4)Department of Neurology, Montpellier CHU, Gui De Chauliac Hospital,
Montpellier, France.
(5)Clinical Neurosciences, Timone CHU, Marseille Hospital, Marseille, France.
(6)Department of Neurology, Hautepierre Hospital, Strasbourg, France.
(7)Institute of Genetics and Molecular and Cellular Biology (IGBMC), INSERM-U964,
Strasbourg University, Illkirch, France.
(8)Strasbourg Federation of Translational Medicine (FMTS), Strasbourg University,
Strasbourg, France.
(9)Reference Centre for Neuromuscular Pathologies, Toulouse CHU, Pierre Paul
Riquet Hospital, Toulouse, France.
(10)Department of Neurology and Movement Disorders, Roger Salengro Hospital,
Lille, France.
(11)Centre de Référence Neurogénétique, Service de Génétique, Hôpital Pellegrin,
University Hospital of Bordeaux and Laboratoire MRGM, INSERM U1211, University of
Bordeaux, Bordeaux, France.
(12)Department of Neurology, Pierre Wertheimer Neurology Hospital, Lyon, France.
(13)Department of Internal Medicine, Hôpital Emile Muller, Mulhouse and South
Alsace Regional Hospital Group, Mulhouse, France.
(14)Hospices Civils de Lyon, Neuro-Ophthalmology and Neurocognition, Hôpital
Neurologique Pierre Wertheimer, Lyon I University, and CRNL INSERM U1028 CNRS
UMR5292, ImpAct Team, F-69676, Bron, France.
(15)CRMBM UMR 7339, CNRS, Aix-Marseille Université, Marseille, France.
(16)APHM, Hôpital de la Timone, Clinical Neurosciences, Department of Neurology,
Marseille, France.
(17)University of Lille, INSERM, CHU Lille, Degenerative & Vascular Cognitive
Disorders, Lille, France.
(18)St André Clinic, Reims, France.
(19)Department of Neurology, Reference Center for Lysosomal Diseases (CRLM), UF
Neuro-Genetics and Metabolism, Hôpital Pitié-Salpêtrière, 47-87, Boulevard de
l’Hôpital, 75013, Paris, France.
(20)Sorbonne UPMC University, INSERM U 1127, and the Institute for the Brain and
Spinal Cord, Paris, France.
(21)Department Metabolic Biochemistry and GRC 13-Neurometabolism-UPMC, Hôpital
Pitié-Salpêtrière, Paris, France.
(22)INSERM U820, Lyon, France.
(23)Laboratoire Gillet-Mérieux, CBPE, Hospices Civils de Lyon, Lyon, France.
(24)Reference Centre for Lysosomal Diseases (CRML), Department of Pediatric
Neurology, and Sorbonne Université, GRC n°19, Pathologies Congénitales du
Cervelet-LeucoDystrophies, AP-HP, Hôpital Armand Trousseau, F-75012, Paris,
France.

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 

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