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.