title: Rapid Diagnosis of 83 Patients with Niemann Pick Type C Disease and Related Cholesterol Transport Disorders by Cholestantriol Screening.
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.
authors.affiliation: Department of Pediatrics, University Hospital of Muenster, Albert-Schweitzer-Campus 1 Gebaeude A13, 48149 Muenster, Germany.
authors.forename: Janine
authors.initials: J
authors.lastname: Reunert
authors.affiliation: Center of Laboratory Medicine, University Hospital of Muenster, Albert-Schweitzer-Campus 1 Gebaeude A1, 48149 Muenster, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Fobker
authors.affiliation: Center of Laboratory Medicine, University Hospital of Muenster, Albert-Schweitzer-Campus 1 Gebaeude A1, 48149 Muenster, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Kannenberg
authors.affiliation: Department of Pediatrics, University Hospital of Muenster, Albert-Schweitzer-Campus 1 Gebaeude A13, 48149 Muenster, Germany.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Du Chesne
authors.affiliation: Department of Pediatrics, University Hospital of Muenster, Albert-Schweitzer-Campus 1 Gebaeude A13, 48149 Muenster, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Plate
authors.affiliation: Department of Pediatrics, University Hospital of Muenster, Albert-Schweitzer-Campus 1 Gebaeude A13, 48149 Muenster, Germany.
authors.forename: Judith
authors.initials: J
authors.lastname: Wellhausen
authors.affiliation: Department of Pediatrics, University Hospital of Muenster, Albert-Schweitzer-Campus 1 Gebaeude A13, 48149 Muenster, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Rust
authors.affiliation: Department of Pediatrics, University Hospital of Muenster, Albert-Schweitzer-Campus 1 Gebaeude A13, 48149 Muenster, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Marquardt
mesh_terms: D015415:Biomarkers / Q000097:blood; D002352:Carrier Proteins / Q000235:genetics; D002777:Cholestanols / Q000097:blood*; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000235:genetics; D000077296:Niemann-Pick C1 Protein; D052556:Niemann-Pick Disease, Type C / Q000097:blood* / Q000235:genetics; D013108:Sphingomyelin Phosphodiesterase / Q000235:genetics; D033921:Vesicular Transport Proteins
chemical_list: D015415:Biomarkers; D002352:Carrier Proteins; D002777:Cholestanols; D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; C106881:NPC1 protein, human; C104585:NPC2 protein, human; D000077296:Niemann-Pick C1 Protein; D033921:Vesicular Transport Proteins; C000474:cholestane-3,5,6-triol; C543066:SMPD1 protein, human; D013108:Sphingomyelin Phosphodiesterase
keywords: 7-KC, 7-ketocholesterol; CESD, cholesterol ester storage disease; Cholestantriol; Diagnostic test; EVS, exome variant server; HGMD, Human Gene Mutation Database; NPC, Niemann Pick type C; Niemann Pick type C; Oxysterols; ROC, receiver-operating-characteristic; c-triol/cholestantriol, cholestane-3β,5α,6β-triol