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Dysphagia as a risk factor for mortality in Niemann-Pick disease type C: systematic literature review and evidence from studies with miglustat

Mark Walterfang1*, Yin-Hsiu Chien2, Jackie Imrie3, Derren Rushton4, Danielle Schubiger1 and Marc C Patterson5

Author Affiliations

1 Royal Melbourne Hospital and Melbourne Neuropsychiatry Centre, Melbourne 3050, Australia

2 Departments of Paediatrics and Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan

3 University of Manchester, Manchester, UK

4 Actelion Pharmaceuticals Pty Ltd, New South Wales, Australia

5 Mayo Clinic, Rochester MN, USA

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Orphanet Journal of Rare Diseases 2012, 7:76  doi:10.1186/1750-1172-7-76

Published: 6 October 2012


Niemann-Pick disease type C (NP-C) is a rare neurovisceral disease characterised by progressive neurological deterioration and premature death, and has an estimated birth incidence of 1:120,000. Mutations in the NPC1 gene (in 95% of cases) and the NPC2 gene (in approximately 4% of cases) give rise to impaired intracellular lipid metabolism in a number of tissues, including the brain. Typical neurological manifestations include vertical supranuclear gaze palsy, saccadic eye movement abnormalities, cerebellar ataxia, dystonia, dysmetria, dysphagia and dysarthria. Oropharyngeal dysphagia can be particularly problematic as it can often lead to food or fluid aspiration and subsequent pneumonia. Epidemiological data suggest that bronchopneumonia subsequent to food or fluid aspiration is a major cause of mortality in NP-C and other neurodegenerative disorders. These findings indicate that a therapy capable of improving or stabilising swallowing function might reduce the risk of aspiration pneumonia, and could have a positive impact on patient survival. Miglustat, currently the only approved disease-specific therapy for NP-C in children and adults, has been shown to stabilise key neurological manifestations in NP-C, including dysphagia. In this article we present findings from a systematic literature review of published data on bronchopneumonia/aspiration pneumonia as a cause of death, and on the occurrence of dysphagia in NP-C and other neurodegenerative diseases. We then examine the potential links between dysphagia, aspiration, pneumonia and mortality with a view to assessing the possible effect of miglustat on patient lifespan.

Niemann-Pick disease type C; Dysphagia; Mortality; Swallowing; Pneumonia; Aspiration; Miglustat.