Phenotypic expression of swallowing function in Niemann–Pick disease type C1
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 swall...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-09-01
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| Series: | Orphanet Journal of Rare Diseases |
| Online Access: | https://doi.org/10.1186/s13023-022-02472-w |
| _version_ | 1798002986729865216 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Beth I. Solomon |
| collection | DOAJ |
| description | 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: $$\frac{7.7}{100}$$ 7.7 100 person-years and $$\frac{9.8}{100}$$ 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. |
| first_indexed | 2024-04-11T12:01:05Z |
| format | Article |
| id | doaj.art-a589af172dbf411c82f42782fcb4e9e3 |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-04-11T12:01:05Z |
| publishDate | 2022-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-a589af172dbf411c82f42782fcb4e9e32022-12-22T04:24:52ZengBMCOrphanet Journal of Rare Diseases1750-11722022-09-0117111210.1186/s13023-022-02472-wPhenotypic expression of swallowing function in Niemann–Pick disease type C1Beth I. Solomon0Andrea M. Muñoz1Ninet Sinaii2Nicole M. Farhat3Andrew C. Smith4Simona Bianconi5An Dang Do6Michael C. Backman7Leonza Machielse8Forbes D. Porter9Speech-Language Pathology Section, Mark O. Hatfield Clinical Center, National Institutes of HealthEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of HealthBiostatistics and Clinical Epidemiology Service, NIH Clinical Center, National Institutes of HealthEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of HealthEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of HealthEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of HealthEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of HealthBiostaticianEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of HealthEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of HealthAbstract 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: $$\frac{7.7}{100}$$ 7.7 100 person-years and $$\frac{9.8}{100}$$ 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.https://doi.org/10.1186/s13023-022-02472-w |
| spellingShingle | 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 Phenotypic expression of swallowing function in Niemann–Pick disease type C1 Orphanet Journal of Rare Diseases |
| title | Phenotypic expression of swallowing function in Niemann–Pick disease type C1 |
| title_full | Phenotypic expression of swallowing function in Niemann–Pick disease type C1 |
| title_fullStr | Phenotypic expression of swallowing function in Niemann–Pick disease type C1 |
| title_full_unstemmed | Phenotypic expression of swallowing function in Niemann–Pick disease type C1 |
| title_short | Phenotypic expression of swallowing function in Niemann–Pick disease type C1 |
| title_sort | phenotypic expression of swallowing function in niemann pick disease type c1 |
| url | https://doi.org/10.1186/s13023-022-02472-w |
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