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Recommendations for patient screening in ultra-rare inherited metabolic diseases : What have we learned from Niemann-Pick disease type C?

Sobrido, María Jesús ; Bauer, Peter ; De Koning, Tom LU ; Klopstock, Thomas ; Nadjar, Yann ; Patterson, Marc C. ; Synofzik, Matthis and Hendriksz, Chris J. (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
; ; ; ; ; ; and
publishing date
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
  • pmid:30665446
  • scopus:85060209834
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
2020-12-01 02:02:38
@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},
  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},
}