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Open Access 01-12-2022 | Niemann-Pick Disease | Research

Phenotypic expression of swallowing function in Niemann–Pick disease type C1

Authors: Beth I. Solomon, Andrea M. Muñoz, Ninet Sinaii, Nicole M. Farhat, Andrew C. Smith, Simona Bianconi, An Dang Do, Michael C. Backman, Leonza Machielse, Forbes D. Porter

Published in: Orphanet Journal of Rare Diseases | Issue 1/2022

Abstract

Background

Niemann–Pick disease type C1 (NPC1) is a rare autosomal recessive disease characterized by endolysosomal accumulation of unesterified cholesterol with progressive deterioration in swallowing, often leading to premature death. Although documented, the natural history of NPC1 swallowing dysfunction has yet to be delineated systematically. This manuscript aims to provide a comprehensive characterization of the phenotypic spectrum and progression of swallowing dysfunction in NPC1.

Methodology

The National Institutes of Health (NIH) NPC1 natural history study (NCT00344331) enrolled 120 patients, who underwent comprehensive interpretative swallow assessments for swallowing safety, dietary modifications, and aspiration risk. Longitudinal statistical modeling accounted for all outcomes with NPC1 disease covariates (first symptom onset, age at neurological symptom onset, seizure history, duration of neurological symptoms) as well as miglustat use (a glucosylceramide synthase inhibitor) and NIH study duration (NIHSD; the length of time an individual participated in the NIH study). Probabilities for disease progression and time to swallowing decline were conducted for the entire cohort.

Results

Time to swallowing decline with American Speech-Language-Hearing Association National Outcome Measure (ASHA-NOMS) and the NIH-adapted Penetration Aspiration Scale (NIH-PAS) were identified: \(\frac{7.7}{100}\) person-years and \(\frac{9.8}{100}\) person-years, respectively. NIHSD and seizure history consistently and significantly were associated with decline (OR_NIHSD = 1.34–2.10, 95% CI 1.04–3.4, p = 0.001–0.026; OR_Seizure = 3.26–18.22, 1.03–167.79; p = 0.001–0.046), while miglustat use revealed protection (OR_Miglustat = 0.01–0.43, 0.007–0.98; p = 0.001–0.044). The probability of decline with NPC1 neurological severity scale and annual severity increment scale were established with the aforementioned covariates, varying amongst subgroups.

Conclusion

This study represents the most extensive collection of prospective, instrumental swallowing assessments in NPC1 to date with an interpretive analysis providing an improved understanding of NPC1 disease progression with swallowing function—serving as a foundation for clinical management and future NPC1 therapeutics.

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Title: Phenotypic expression of swallowing function in Niemann–Pick disease type C1
Authors: Beth I. Solomon
Andrea M. Muñoz
Ninet Sinaii
Nicole M. Farhat
Andrew C. Smith
Simona Bianconi
An Dang Do
Michael C. Backman
Leonza Machielse
Forbes D. Porter
Publication date: 01-12-2022
Publisher: BioMed Central
Keywords: Niemann-Pick Disease
Foreign Body Aspiration
Foreign Body Aspiration
Aspiration
Niemann-Pick Disease
Published in: Orphanet Journal of Rare Diseases / Issue 1/2022
Electronic ISSN: 1750-1172
DOI: https://doi.org/10.1186/s13023-022-02472-w

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Springer Medicine

Phenotypic expression of swallowing function in Niemann–Pick disease type C1

Abstract

Background

Methodology

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methodology

Results

Conclusion

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