Diagnostic tests for Niemann-Pick disease type C (NP-C): A critical review.
Molecular Genetics and Metabolism. 2016-08-01; 118(4): 244-254
DOI: 10.1016/j.ymgme.2016.06.004
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1. Mol Genet Metab. 2016 Aug;118(4):244-54. doi: 10.1016/j.ymgme.2016.06.004. Epub
2016 Jun 7.
Diagnostic tests for Niemann-Pick disease type C (NP-C): A critical review.
Vanier MT(1), Gissen P(2), Bauer P(3), Coll MJ(4), Burlina A(5), Hendriksz CJ(6),
Latour P(7), Goizet C(8), Welford RW(9), Marquardt T(10), Kolb SA(11).
Author information:
(1)INSERM Unit 820, 7 Rue Guillaume Paradin, 69008 Lyon, France; Laboratoire
Gillet-Mérieux, Centre de Biologie et Pathologie Est, Hospices Civils de Lyon,
69500 Bron, France. Electronic address: .
(2)UCL Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK; Great
Ormond Street Hospital, London WC1N 3JH, UK. Electronic address:
.
(3)Institute of Medical Genetics and Applied Genomics, University Hospital of
Tübingen, 72076 Tübingen, Germany. Electronic address:
.
(4)Inborn Errors of Metabolism Section, Biochemistry and Molecular Genetics
Service, Hospital Clínic of Barcelona, 08036 Barcelona, Spain; CIBERER, Spain.
Electronic address: .
(5)Division of Inherited Metabolic Diseases, Department of Pediatrics, University
Hospital, 35129 Padova, Italy. Electronic address: .
(6)The Mark Holland Metabolic Unit, Salford Royal Foundation NHS Trust, Salford,
Manchester M68HD, UK; University of Pretoria, Steve Biko Academic Hospital,
Department of Paediatrics and Child Health, Pretoria 0001, South Africa.
Electronic address: .
(7)UF de Neurogénétique Moléculaire, Centre de Biologie et Pathologie Est,
Hospices Civils de Lyon, 69500 Bron, France. Electronic address:
.
(8)CHU Bordeaux, Department of Medical Genetics, 33076 Bordeaux, France; INSERM
Unit 1211, University of Bordeaux, 33076 Bordeaux, France. Electronic address:
.
(9)Actelion Pharmaceuticals Ltd., Gewerbestrasse 16, 4123 Allschwil, Switzerland.
Electronic address: .
(10)Unit for Inborn Errors of Metabolism, University Hospital Münster, 48149
Münster, Germany. Electronic address: .
(11)Actelion Pharmaceuticals Ltd., Gewerbestrasse 16, 4123 Allschwil,
Switzerland. Electronic address: .
Niemann-Pick disease type C (NP-C) is a neurovisceral lysosomal cholesterol
trafficking and lipid storage disorder caused by mutations in one of the two
genes, NPC1 or NPC2. Diagnosis has often been a difficult task, due to the wide
range in age of onset of NP-C and clinical presentation of the disease, combined
with the complexity of the cell biology (filipin) laboratory testing, even in
combination with genetic testing. This has led to substantial delays in
diagnosis, largely depending on the access to specialist centres and the level of
knowledge about NP-C of the physician in the area. In recent years, advances in
mass spectrometry has allowed identification of several sensitive plasma
biomarkers elevated in NP-C (e.g. cholestane-3β,5α,6β-triol, lysosphingomyelin
isoforms and bile acid metabolites), which, together with the concomitant
progress in molecular genetic technology, have greatly impacted the strategy of
laboratory testing. Specificity of the biomarkers is currently under
investigation and other pathologies are being found to also result in elevations.
Molecular genetic testing also has its limitations, notably with unidentified
mutations and the classification of new variants. This review is intended to
increase awareness on the currently available approaches to laboratory diagnosis
of NP-C, to provide an up to date, comprehensive and critical evaluation of the
various techniques (cell biology, biochemical biomarkers and molecular genetics),
and to briefly discuss ongoing/future developments. The use of current tests in
proper combination enables a rapid and correct diagnosis in a large majority of
cases. However, even with recent progress, definitive diagnosis remains
challenging in some patients, for whom combined genetic/biochemical/cytochemical
markers do not provide a clear answer. Expertise and reference laboratories thus
remain essential, and further work is still required to fulfill unmet needs.
Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
DOI: 10.1016/j.ymgme.2016.06.004
PMID: 27339554 [Indexed for MEDLINE]