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

Orphanet Journal of Rare Diseases

Arndt Rolfs⁶  Frances M Platt³  Forbes D Porter⁴  Mario Cortina-Borja¹  Nada Al Eisa³  Danielle te Vruchte³  Jan Lukas⁷  Guido Kramp⁶  Sabrina Eichler⁶  Ulrike Grittner²  Hermann Mascher⁵  Anne-Katrin Giese⁷ 

[1] Population, Policy and Practice Programme, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK;Department for Biostatistics and Clinical Epidemiology, Charité-University Medical Centre, Berlin, Germany;Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK;Eunice Kennedy Shriver National Institute of Child Health and Development, National Institutes of Health, 10 Center Drive, Bethesda 20892, MD, USA;PharmAnalyt Labor GmbH, Ferdinand-Pichler Gasse 2, Baden, 2500, Austria;Centogene AG, Schillingallee 68, Rostock, 18055, Germany;Albrecht-Kossel-Institute for Neuroregeneration, Medical University of Rostock, Gehlsheimer Str. 20, Rostock, 18147, Germany

关键词: HPLC-MS/MS;    Biomarker;    NPC1;    Niemann-Pick type C1 disease;   

Others  :  1219121
DOI  :  10.1186/s13023-015-0274-1

 received in 2015-01-09, accepted in 2015-04-24,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Giese et al.

【 图 表 】

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