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