Recommendations for patient screening in ultra-rare inherited metabolic diseases : What have we learned from Niemann-Pick disease type C?
(2019) In Orphanet Journal of Rare Diseases 14(1).- Abstract
Background: Rare and ultra-rare diseases (URDs) are often chronic and life-threatening conditions that have a profound impact on sufferers and their families, but many are notoriously difficult to detect. Niemann-Pick disease type C (NP-C) serves to illustrate the challenges, benefits and pitfalls associated with screening for ultra-rare inborn errors of metabolism (IEMs). A comprehensive, non-systematic review of published information from NP-C screening studies was conducted, focusing on diagnostic methods and study designs that have been employed to date. As a key part of this analysis, data from both successful studies (where cases were positively identified) and unsuccessful studies (where the chosen approach failed to identify any... (More)
Background: Rare and ultra-rare diseases (URDs) are often chronic and life-threatening conditions that have a profound impact on sufferers and their families, but many are notoriously difficult to detect. Niemann-Pick disease type C (NP-C) serves to illustrate the challenges, benefits and pitfalls associated with screening for ultra-rare inborn errors of metabolism (IEMs). A comprehensive, non-systematic review of published information from NP-C screening studies was conducted, focusing on diagnostic methods and study designs that have been employed to date. As a key part of this analysis, data from both successful studies (where cases were positively identified) and unsuccessful studies (where the chosen approach failed to identify any cases) were included alongside information from our own experiences gained from the planning and execution of screening for NP-C. On this basis, best-practice recommendations for ultra-rare IEM screening are provided. Twenty-six published screening studies were identified and categorised according to study design into four groups: 1) prospective patient cohort and family-based secondary screenings (18 studies); 2) analyses of archived 'biobank' materials (one study); 3) medical chart review and bioinformatics data mining (five studies); and 4) newborn screening (two studies). NPC1/NPC2 sequencing was the most common primary screening method (Sanger sequencing in eight studies and next-generation sequencing [gene panel or exome sequencing] in five studies), followed by biomarker analyses (usually oxysterols) and clinical surveillance. Conclusions: Historically, screening for NP-C has been based on single-patient studies, small case series, and targeted cohorts, but the emergence of new diagnostic methods over the last 5-10 years has provided opportunities to screen for NP-C on a larger scale. Combining clinical, biomarker and genetic diagnostic methods represents the most effective way to identify NP-C cases, while reducing the likelihood of misdiagnosis. Our recommendations are intended as a guide for planning screening protocols for ultra-rare IEMs in general.
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- author
- Sobrido, María Jesús ; Bauer, Peter ; De Koning, Tom LU ; Klopstock, Thomas ; Nadjar, Yann ; Patterson, Marc C. ; Synofzik, Matthis and Hendriksz, Chris J.
- publishing date
- 2019-01-21
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Diagnosis, Niemann-Pick disease, Screening, Ultra-rare disease
- in
- Orphanet Journal of Rare Diseases
- volume
- 14
- issue
- 1
- article number
- 20
- publisher
- BioMed Central (BMC)
- external identifiers
-
- scopus:85060209834
- pmid:30665446
- ISSN
- 1750-1172
- DOI
- 10.1186/s13023-018-0985-1
- language
- English
- LU publication?
- no
- id
- 0c8b3bae-a546-4d0c-a4f2-2c724fcb9993
- date added to LUP
- 2020-02-11 12:28:28
- date last changed
- 2024-02-16 10:43:06
@article{0c8b3bae-a546-4d0c-a4f2-2c724fcb9993,
abstract = {{<p>Background: Rare and ultra-rare diseases (URDs) are often chronic and life-threatening conditions that have a profound impact on sufferers and their families, but many are notoriously difficult to detect. Niemann-Pick disease type C (NP-C) serves to illustrate the challenges, benefits and pitfalls associated with screening for ultra-rare inborn errors of metabolism (IEMs). A comprehensive, non-systematic review of published information from NP-C screening studies was conducted, focusing on diagnostic methods and study designs that have been employed to date. As a key part of this analysis, data from both successful studies (where cases were positively identified) and unsuccessful studies (where the chosen approach failed to identify any cases) were included alongside information from our own experiences gained from the planning and execution of screening for NP-C. On this basis, best-practice recommendations for ultra-rare IEM screening are provided. Twenty-six published screening studies were identified and categorised according to study design into four groups: 1) prospective patient cohort and family-based secondary screenings (18 studies); 2) analyses of archived 'biobank' materials (one study); 3) medical chart review and bioinformatics data mining (five studies); and 4) newborn screening (two studies). NPC1/NPC2 sequencing was the most common primary screening method (Sanger sequencing in eight studies and next-generation sequencing [gene panel or exome sequencing] in five studies), followed by biomarker analyses (usually oxysterols) and clinical surveillance. Conclusions: Historically, screening for NP-C has been based on single-patient studies, small case series, and targeted cohorts, but the emergence of new diagnostic methods over the last 5-10 years has provided opportunities to screen for NP-C on a larger scale. Combining clinical, biomarker and genetic diagnostic methods represents the most effective way to identify NP-C cases, while reducing the likelihood of misdiagnosis. Our recommendations are intended as a guide for planning screening protocols for ultra-rare IEMs in general.</p>}},
author = {{Sobrido, María Jesús and Bauer, Peter and De Koning, Tom and Klopstock, Thomas and Nadjar, Yann and Patterson, Marc C. and Synofzik, Matthis and Hendriksz, Chris J.}},
issn = {{1750-1172}},
keywords = {{Diagnosis; Niemann-Pick disease; Screening; Ultra-rare disease}},
language = {{eng}},
month = {{01}},
number = {{1}},
publisher = {{BioMed Central (BMC)}},
series = {{Orphanet Journal of Rare Diseases}},
title = {{Recommendations for patient screening in ultra-rare inherited metabolic diseases : What have we learned from Niemann-Pick disease type C?}},
url = {{http://dx.doi.org/10.1186/s13023-018-0985-1}},
doi = {{10.1186/s13023-018-0985-1}},
volume = {{14}},
year = {{2019}},
}