TY - JOUR
T1 - Dysphagia as a risk factor for mortality in Niemann-Pick disease type C
T2 - Systematic literature review and evidence from studies with miglustat
AU - Walterfang, Mark
AU - Chien, Yin Hsiu
AU - Imrie, Jackie
AU - Rushton, Derren
AU - Schubiger, Danielle
AU - Patterson, Marc C.
N1 - Funding Information:
None of the authors received honoraria for their roles in the production of this article. MW has received travel expenses, research grant funds and consulting honoraria from Actelion Pharmaceuticals Ltd. Y-HC has received consultancy honoraria from Actelion Pharmaceuticals Ltd. JI has received travel expenses and consultancy honoraria from Actelion Pharmaceuticals Ltd. DR is an employee of Actelion Pharmaceuticals pty Ltd, Australia. DS has received an educational grant from Actelion Pharmaceuticals pty Ltd. MCP has received a research grant, travel expenses, and consulting honoraria (directed to Mayo Clinic) from Actelion Pharmaceuticals Ltd; travel expenses and consulting honoraria (directed to the Mayo Clinic) from Shire Human Genetic Therapies, an honorarium for acting as the Chair of a Data Monitoring Committee from Stem Cells Inc., and royalties as an editor of Up-To-Date. He receives research funding from the National Institutes of Health, and has received travel expenses from the Institute of Medicine for service on the Committee to Review Adverse Effects of Vaccines.
PY - 2012
Y1 - 2012
N2 - Abstract. 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.
AB - Abstract. 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.
KW - Aspiration
KW - Dysphagia
KW - Miglustat.
KW - Mortality
KW - Niemann-Pick disease type C
KW - Pneumonia
KW - Swallowing
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U2 - 10.1186/1750-1172-7-76
DO - 10.1186/1750-1172-7-76
M3 - Article
C2 - 23039766
AN - SCOPUS:84867030083
SN - 1750-1172
VL - 7
JO - Orphanet Journal of Rare Diseases
JF - Orphanet Journal of Rare Diseases
IS - 1
M1 - 76
ER -