How is NPC diagnosed?
Diagnosis of Niemann-Pick type C disease begins with a thorough physical exam, which can show an early warning sign such as an enlarged liver or spleen. Your doctor will also take a detailed medical history and discuss symptoms and family health history. Niemann-Pick type C disease is rare, and its symptoms can be confused with other diseases.
If an individual has a high clinical suspicion of NP-C, diagnosis of NP-C involves a combination of biomarkers and genetic testing*.
1. Biomarkers profiling
Plasma oxysterols (oxidised cholesterol products): cholestane-3β,5α,6β-triol (C-triol) and 7-ketocholesterol (7-KC)
Plasma lysosphingomyelin (Lyso-SM-509) and lysosphingomyelin (Lyso-SM)
Bile acids: 3β,5α,6β-trihydroxy-cholanoyl-glycine
The biomarkers alone do not provide a definitive diagnosis of NP-C, as they may not allow differentiation between NP-C and related diseases such as NP-A and NP-B.
2. Genetic testing
Definitive diagnosis of NP-C by identifying mutations in NPC1 and NPC2 genes
3. Filipin staining test
A traditional first-line test for NP-C diagnosis by taking a skin biopsy to assess if there is an abnormal buildup of cholesterol and other fats in the cells.
This is now an optional diagnostic test for NP-C. It is useful for assessing the level of disease-causing NPC1 or NPC2 function.
*Patterson, M. C., P. Clayton, P. Gissen, M. Anheim, P. Bauer, O. Bonnot, A. Dardis, C. Dionisi-Vici, H. H. Klunemann, P. Latour, C. M. Lourenco, D. S. Ory, A. Parker, M. Pocovi, M. Strupp, M. T. Vanier, M. Walterfang and T. Marquardt (2017). "Recommendations for the detection and diagnosis of Niemann-Pick disease type C: An update." Neurol Clin Pract 7(6): 499-511[YHH1].