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

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

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.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers / blood*
  • Child
  • Female
  • Humans
  • Male
  • Middle Aged
  • Niemann-Pick Disease, Type C / blood*
  • Niemann-Pick Disease, Type C / diagnosis*
  • Sphingosine / analogs & derivatives*
  • Sphingosine / blood*
  • Young Adult

Substances

  • Biomarkers
  • Sphingosine