Abstract
Niemann Pick type C (NP-C) is a rare neurodegenerative disorder caused by an impairment of intracellular lipid transport. Due to the heterogeneous clinical phenotype and the lack of a reliable blood test, diagnosis and therapy are often delayed for years. In the cell, accumulating cholesterol leads to increased formation of oxysterols that can be used as a powerful screening parameter for NP-C. In a large scale study, we evaluated the oxysterol cholestane-3β,5α,6β-triol (c-triol) as potential biomarker for a rapid diagnosis of NP-C. Using GC/MS, c-triol has been analyzed in 1902 plasma samples of patients with the suspicion for NP-C. Diagnosis in patients with elevated oxysterols was confirmed by genetic analysis. 71 new NP-C patients (69 NP-C1 and two NP-C2) and 12 Niemann Pick type A/B patients were identified. 24 new mutations in NPC1, one new mutation in NPC2 and three new mutations in the SMPD1 gene were found. Cholestane-3β,5α,6β-triol was elevated in Niemann Pick type C1, type C2, type A/B and in CESD disease. No other study has ever identified so many NP-C patients, proving that c-triol is a rapid and reliable biomarker to detect patients with NP-C disease and related cholesterol transport disorders. It should replace the filipin test as the first-line diagnostic assay.