Following clinical and differential diagnosis, the laboratory test confirms the diagnosis of NP-C:
1. Filipin test
Fibroblasts cultured from skin biopsy are used to conduct the filipin staining unesterified cholesterol demonstrating impaired intracellular trafficking. The test remains the key diagnostic test for NP-C, proving positive results in 80-85%. However, inconclusive test results of ‘variant’ staining pattern increases with age.
The cholesterol esterification test is no longer recommended.
2. Genetic test
To assure the diagnoses of NP-C, DNA sequencing should ideally be performed in parallel with filipin staining examination, where possible.
In addition, gene testing should be undertaken in all newly diagnosed patients to:
Inconclusive findings from DNA sequencing as well as filipin staining do not discount a possible diagnosis of NP-C. Patients with clinical manifestations strongly suggestive of NP-C should undergo further analyses.
3. Other tests
Light microscopy: Foamy cells in bone marrow aspirates (maybe minimal in early disease stage)
Electron microscopy: Polymorpheous cytoplasmic bodies in skin, rectal neurons or liver.
Pending further data on the utility of plasma oxysterol profiling, these potential new biomarkers may form useful ancilliary test to aid diagnosis in difficult cases with unclear biochemical phenotypes and NP-C gene mutations.