Vanier, MT;
Gissen, P;
Bauer, P;
Coll, MJ;
Burlina, A;
Hendriksz, CJ;
Latour, P;
... Kolb, SA; + view all
(2016)
Diagnostic tests for Niemann-Pick disease type C (NP-C): A critical review.
Molecular Genetics and Metabolism
, 118
(4)
pp. 244-254.
10.1016/j.ymgme.2016.06.004.
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Abstract
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.
| Type: | Article |
|---|---|
| Title: | Diagnostic tests for Niemann-Pick disease type C (NP-C): A critical review |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.ymgme.2016.06.004 |
| Publisher version: | http://dx.doi.org/10.1016/j.ymgme.2016.06.004 |
| Language: | English |
| Additional information: | © 2016 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Endocrinology & Metabolism, Genetics & Heredity, Medicine, Research & Experimental, Research & Experimental Medicine, Niemann-Pick Disease Type C, Filipin, Oxysterol, Lysosphingomyelin, Npc1 Gene, Npc2 Gene, Intracellular Cholesterol Trafficking, Drug-Induced Phospholipidosis, Low-Density-Lipoprotein, Chitotriosidase Enzyme-Activity, Sphingolipid-Storage Diseases, Dried Blood Spots, Nogo-B Receptor, Lysosomal Cholesterol, Rapid Diagnosis, Liquid-Chromatography |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1520251 |
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