Disease and patient characteristics in NP-C patients: findings from an international disease registry.

Marc Patterson (1) , Eugen Mengel (2) , Frits Wijburg (3) , Audrey Muller (4) , Barbara Schwierin (4) , Harir Drevon (5) , Marie Vanier (6) , Mercé Pineda (7)

1 Department of Neurology
2 Villa Metabolica
3 AMC - Academic Medical Center - Academisch Medisch Centrum [Amsterdam]
4 Actelion Pharmaceuticals Ltd
5 Numerus Ltd
6 Métabolomique et maladies métaboliques
7 Department of Child Neurology

ABSTRACT: BACKGROUND: Niemann-Pick disease type C (NP-C) is a rare neurovisceral disease characterized by progressive neurodegeneration and premature death. We report data recorded at enrolment in an ongoing international NP-C registry initiated in September 2009 to describe disease natural history, clinical course and treatment experience of NP-C patients in clinical practice settings. METHODS: The NPC Registry is a prospective observational cohort study. Participating sites are encouraged to evaluate all consecutive patients with a confirmed diagnosis of NP-C, regardless of their treatment status. All patients undergo clinical assessments and medical care as determined by their physicians. Data are collected through a secure internet-based data collection system. RESULTS: As of 19th March, 2012, 163 patients have been enrolled in centres across 14 European countries, Australia, Brazil and Canada. The mean (SD) age at enrolment was 19.6 (13.0) years. In general there was a long lag time between the mean (SD) age at neurological onset (10.9 (9.8) years) and age at diagnosis (15.0 (12.2) years). Among all enrolled patients, 107 were diagnosed based on combined genetic testing and filipin staining. Sixteen (11%) out of 145 patients with available age-at-neurological-onset data had early-infantile neurological onset, 45 (31%) had late-infantile onset; 45 (31%) had juvenile onset and 39 (27%) had adolescent/adult onset. The frequencies of neonatal jaundice, hepatomegaly and/or splenomegaly during infancy were greatest among early-infantile patients, and decreased with increasing age at neurological onset. The most frequent neurological manifestations were: ataxia (70%), vertical supranuclear gaze palsy (VSGP; 70%), dysarthria (66%), cognitive impairment (62%), dysphagia (52%). There were no notable differences in composite NP-C disability scores between age-at-neurological-onset groups. Miglustat therapy at enrolment was recorded in 117/163 (72%) patients. CONCLUSIONS: Approximately two-thirds of this NP-C cohort had infantile or juvenile onset of neurological manifestations, while the remaining third presented in adolescence or adulthood. While systemic symptoms were most common among patients with early-childhood onset disease, they were also common among patients with adolescent/adult onset. The profiles of neurological manifestations in this Registry were in line with previous publications.

Mots clés: Niemann-Pick disease type C; Diagnosis; Symptoms; Neurological; Hepatomegaly; Splenomegaly; Cholestasis; Vertical supranuclear palsy

Domaines: Génétique

Marc Patterson, Eugen Mengel, Frits Wijburg, Audrey Muller, Barbara Schwierin, et al.. Disease and patient characteristics in NP-C patients: findings from an international disease registry.. Orphanet Journal of Rare Diseases, 2013, 8 (1), pp.12. ⟨10.1186/1750-1172-8-12⟩. ⟨inserm-00782437⟩