Dysphagia as a risk factor for mortality in Niemann-Pick disease type C

Systematic literature review and evidence from studies with miglustat

Mark Walterfang, Yin Hsiu Chien, Jackie Imrie, Derren Rushton, Danielle Schubiger, Marc C. Patterson

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number76
JournalOrphanet Journal of Rare Diseases
Volume7
Issue number1
DOIs
StatePublished - 2012

Fingerprint

Type C Niemann-Pick Disease
Deglutition Disorders
Aspiration Pneumonia
Mortality
Bronchopneumonia
Cerebellar Ataxia
Neurologic Manifestations
Neurodegenerative Diseases
Eye Abnormalities
Food
Dysarthria
Premature Mortality
Dystonia
Saccades
Deglutition
Rare Diseases
Lipid Metabolism
Paralysis
Genes
Cause of Death

Keywords

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

ASJC Scopus subject areas

  • Medicine(all)
  • Genetics(clinical)
  • Pharmacology (medical)

Cite this

Dysphagia as a risk factor for mortality in Niemann-Pick disease type C : Systematic literature review and evidence from studies with miglustat. / Walterfang, Mark; Chien, Yin Hsiu; Imrie, Jackie; Rushton, Derren; Schubiger, Danielle; Patterson, Marc C.

In: Orphanet Journal of Rare Diseases, Vol. 7, No. 1, 76, 2012.

Research output: Contribution to journalArticle

Walterfang, Mark ; Chien, Yin Hsiu ; Imrie, Jackie ; Rushton, Derren ; Schubiger, Danielle ; Patterson, Marc C. / Dysphagia as a risk factor for mortality in Niemann-Pick disease type C : Systematic literature review and evidence from studies with miglustat. In: Orphanet Journal of Rare Diseases. 2012 ; Vol. 7, No. 1.
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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.

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