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Orphanet J Rare Dis. 2015 Jun 17;10:78. doi: 10.1186/s13023-015-0274-1.

A novel, highly sensitive and specific biomarker for Niemann-Pick type C1 disease.

Author information

1
Albrecht-Kossel-Institute for Neuroregeneration, Medical University of Rostock, Gehlsheimer Str. 20, 18147, Rostock, Germany. anne-katrin.giese@med.uni-rostock.de.
2
PharmAnalyt Labor GmbH, Ferdinand-Pichler Gasse 2, 2500, Baden, Austria. hermann.mascher@pharm-analyt.at.
3
Department for Biostatistics and Clinical Epidemiology, Charité-University Medical Centre, Berlin, Germany. ulrike.grittner@charite.de.
4
Centogene AG, Schillingallee 68, 18055, Rostock, Germany. sabrina.eichler@centogene.de.
5
Centogene AG, Schillingallee 68, 18055, Rostock, Germany. Guido.Kramp@centogene.com.
6
Albrecht-Kossel-Institute for Neuroregeneration, Medical University of Rostock, Gehlsheimer Str. 20, 18147, Rostock, Germany. jan.lukas@med.uni-rostock.de.
7
Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, UK. danielle.tevruchte@pharm.ox.ac.uk.
8
Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, UK. nada.aleisa@wolfson.ox.ac.uk.
9
Population, Policy and Practice Programme, Institute of Child Health, University College London, 30 Guilford Street, London, WC1N 1EH, UK. m.cortina@ucl.ac.uk.
10
Eunice Kennedy Shriver National Institute of Child Health and Development, National Institutes of Health, 10 Center Drive, Bethesda, MD, 20892, USA. fdporter@mail.nih.gov.
11
Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, UK. frances.platt@pharm.ox.ac.uk.
12
Albrecht-Kossel-Institute for Neuroregeneration, Medical University of Rostock, Gehlsheimer Str. 20, 18147, Rostock, Germany. arndt.rolfs@med.uni-rostock.de.
13
Centogene AG, Schillingallee 68, 18055, Rostock, Germany. arndt.rolfs@med.uni-rostock.de.

Abstract

BACKGROUND:

Lysosomal storage disorders (LSDs), are a heterogeneous group of rare disorders caused by defects in genes encoding for proteins involved in the lysosomal degradation of macromolecules. They occur at a frequency of about 1 in 5,000 live births, though recent neonatal screening suggests a higher incidence. New treatment options for LSDs demand a rapid, early diagnosis of LSDs if maximal clinical benefit is to be achieved.

METHODS:

Here, we describe a novel, highly specific and sensitive biomarker for Niemann-Pick Type C disease type 1 (NPC1), lyso-sphingomyelin-509. We cross-validate this biomarker with cholestane-3β,5α,6β-triol and relative lysosomal volume. The primary cohort for establishment of the biomarker contained 135 NPC1 patients, 66 NPC1 carriers, 241 patients with other LSDs and 46 healthy controls.

RESULTS:

With a sensitivity of 100.0% and specificity of 91.0% a cut-off of 1.4 ng/ml was established. Comparison with cholestane-3β,5α,6β-triol and relative acidic compartment volume measurements were carried out with a subset of 125 subjects. Both cholestane-3β,5α,6β-triol and lyso-Sphingomyelin-509 were sufficient in establishing the diagnosis of NPC1 and correlated with disease severity.

CONCLUSION:

In summary, we have established a new biomarker for the diagnosis of NPC1, and further studies will be conducted to assess correlation to disease progress and monitoring treatment.

PMID:
26082315
PMCID:
PMC4479076
DOI:
10.1186/s13023-015-0274-1
[Indexed for MEDLINE]
Free PMC Article

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