1. A Novel, Highly Sensitive and Specific Biomarker for Niemann-Pick Type C1 Disease

A Novel, Highly Sensitive and Specific Biomarker for Niemann-Pick Type C1 Disease

Anne Katrin Giese, MD 1 Prof. Hermann Mascher 2 Ulrike Grittner, PhD 3 Sabrina Eichler, PhD 4 Guido Johannes Kramp, PhD 4 Jan Lukas, PhD 1 Danielle Te Vruchte 5 Nada Al Eisa, PhD 5 Mario Cortina-Borja, PhD 6 Forbes D. Porter, PhD 7 Frances M. Platt, PhD 5 Prof. Arndt Rolfs, MD 4, 1
1 University of Rostock 2 Pharm-analyt Labor GmbH 3 Charité-University, Berlin 4 CENTOGENE AG 5 University of Oxford 6 University College London 7 Eunice Kennedy Shriver National Institute of Child Health and Development, Bethesda
June 17, 2015

Giese et al. Orphanet Journal of Rare Diseases (2015) 10:78 DOI 10.1186/s13023-015-0274-1

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.