Rapid Diagnosis of 83 Patients with Niemann Pick Type C Disease and Related Cholesterol Transport Disorders by Cholestantriol Screening
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...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2016-02-01
|
| Series: | EBioMedicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396415302462 |
| _version_ | 1818544546622996480 |
|---|---|
| author | Janine Reunert Manfred Fobker Frank Kannenberg Ingrid Du Chesne Maria Plate Judith Wellhausen Stephan Rust Thorsten Marquardt |
| author_facet | Janine Reunert Manfred Fobker Frank Kannenberg Ingrid Du Chesne Maria Plate Judith Wellhausen Stephan Rust Thorsten Marquardt |
| author_sort | Janine Reunert |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T22:49:55Z |
| format | Article |
| id | doaj.art-51d7b9d47036446b8f31492c21889196 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-11T22:49:55Z |
| publishDate | 2016-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-51d7b9d47036446b8f31492c218891962022-12-22T00:47:29ZengElsevierEBioMedicine2352-39642016-02-014C17017510.1016/j.ebiom.2015.12.018Rapid Diagnosis of 83 Patients with Niemann Pick Type C Disease and Related Cholesterol Transport Disorders by Cholestantriol ScreeningJanine Reunert0Manfred Fobker1Frank Kannenberg2Ingrid Du Chesne3Maria Plate4Judith Wellhausen5Stephan Rust6Thorsten Marquardt7Department of Pediatrics, University Hospital of Muenster, Albert-Schweitzer-Campus 1 Gebaeude A13, 48149 Muenster, GermanyCenter of Laboratory Medicine, University Hospital of Muenster, Albert-Schweitzer-Campus 1 Gebaeude A1, 48149 Muenster, GermanyCenter of Laboratory Medicine, University Hospital of Muenster, Albert-Schweitzer-Campus 1 Gebaeude A1, 48149 Muenster, GermanyDepartment of Pediatrics, University Hospital of Muenster, Albert-Schweitzer-Campus 1 Gebaeude A13, 48149 Muenster, GermanyDepartment of Pediatrics, University Hospital of Muenster, Albert-Schweitzer-Campus 1 Gebaeude A13, 48149 Muenster, GermanyDepartment of Pediatrics, University Hospital of Muenster, Albert-Schweitzer-Campus 1 Gebaeude A13, 48149 Muenster, GermanyDepartment of Pediatrics, University Hospital of Muenster, Albert-Schweitzer-Campus 1 Gebaeude A13, 48149 Muenster, GermanyDepartment of Pediatrics, University Hospital of Muenster, Albert-Schweitzer-Campus 1 Gebaeude A13, 48149 Muenster, GermanyNiemann 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.http://www.sciencedirect.com/science/article/pii/S2352396415302462Niemann Pick type COxysterolsCholestantriolDiagnostic test |
| spellingShingle | Janine Reunert Manfred Fobker Frank Kannenberg Ingrid Du Chesne Maria Plate Judith Wellhausen Stephan Rust Thorsten Marquardt Rapid Diagnosis of 83 Patients with Niemann Pick Type C Disease and Related Cholesterol Transport Disorders by Cholestantriol Screening EBioMedicine Niemann Pick type C Oxysterols Cholestantriol Diagnostic test |
| title | Rapid Diagnosis of 83 Patients with Niemann Pick Type C Disease and Related Cholesterol Transport Disorders by Cholestantriol Screening |
| title_full | Rapid Diagnosis of 83 Patients with Niemann Pick Type C Disease and Related Cholesterol Transport Disorders by Cholestantriol Screening |
| title_fullStr | Rapid Diagnosis of 83 Patients with Niemann Pick Type C Disease and Related Cholesterol Transport Disorders by Cholestantriol Screening |
| title_full_unstemmed | Rapid Diagnosis of 83 Patients with Niemann Pick Type C Disease and Related Cholesterol Transport Disorders by Cholestantriol Screening |
| title_short | Rapid Diagnosis of 83 Patients with Niemann Pick Type C Disease and Related Cholesterol Transport Disorders by Cholestantriol Screening |
| title_sort | rapid diagnosis of 83 patients with niemann pick type c disease and related cholesterol transport disorders by cholestantriol screening |
| topic | Niemann Pick type C Oxysterols Cholestantriol Diagnostic test |
| url | http://www.sciencedirect.com/science/article/pii/S2352396415302462 |
| work_keys_str_mv | AT janinereunert rapiddiagnosisof83patientswithniemannpicktypecdiseaseandrelatedcholesteroltransportdisordersbycholestantriolscreening AT manfredfobker rapiddiagnosisof83patientswithniemannpicktypecdiseaseandrelatedcholesteroltransportdisordersbycholestantriolscreening AT frankkannenberg rapiddiagnosisof83patientswithniemannpicktypecdiseaseandrelatedcholesteroltransportdisordersbycholestantriolscreening AT ingridduchesne rapiddiagnosisof83patientswithniemannpicktypecdiseaseandrelatedcholesteroltransportdisordersbycholestantriolscreening AT mariaplate rapiddiagnosisof83patientswithniemannpicktypecdiseaseandrelatedcholesteroltransportdisordersbycholestantriolscreening AT judithwellhausen rapiddiagnosisof83patientswithniemannpicktypecdiseaseandrelatedcholesteroltransportdisordersbycholestantriolscreening AT stephanrust rapiddiagnosisof83patientswithniemannpicktypecdiseaseandrelatedcholesteroltransportdisordersbycholestantriolscreening AT thorstenmarquardt rapiddiagnosisof83patientswithniemannpicktypecdiseaseandrelatedcholesteroltransportdisordersbycholestantriolscreening |