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

Anne Katrin Giese, MD Prof. Hermann Mascher Ulrike Grittner, PhD Sabrina Eichler, PhD Guido Johannes Kramp, PhD Jan Lukas, PhD Danielle Te Vruchte Nada Al Eisa, PhD Mario Cortina-Borja, PhD Forbes D. Porter, PhD Frances M. Platt, PhD Prof. Arndt Rolfs, MD
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.