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Open Access 01-12-2019 | Niemann-Pick Disease | Research article

Oxysterol/chitotriosidase based selective screening for Niemann-Pick type C in infantile cholestasis syndrome patients

Authors: Anna V. Degtyareva, Tatiana Y. Proshlyakova, Marina S. Gautier, Dmitry N. Degtyarev, Elena A. Kamenets, Galina V. Baydakova, Denis V. Rebrikov, Ekaterina Y. Zakharova

Published in: BMC Medical Genetics | Issue 1/2019

Abstract

Background

Niemann-Pick disease type C (NP-C) is an inherited neurodegenerative disease (1 per 100 000 newborns) caused by NPC proteins impairment that leads to unesterified cholesterol accumulation in late endosomal/lysosomal compartments. To date the NP-C diagnostics is usually based on cholesterol detection in fibroblasts using an invasive and time-consuming Filipin staining and we need more arguments to widely introduce oxysterols as a biomarkers in NP-C.

Methods

Insofar as NP-C represents about 8% of all infant cholestases, in this prospective observational study we tried to re-assess the specificity plasma oxysterol and chitotriosidase as a biochemical screening markers of NP-C in children with cholestasis syndrome of unknown origin. For 108 patients (aged from 2 weeks to 7 years) the levels of cholestane-3β,5α,6β-triol (C-triol) and chitotriosidase (ChT) were measured. For patients with elevated C-triol and/or ChT the NPC1 and NPC2 genes were Sanger-sequenced and 47 additional genes (from the custom liver damage panel) were NGS-sequenced.

Results

Increased C-triol level (> 50 ng/ml) was detected in 4 (of 108) infants with cholestasis syndrome of unknown origin, with following molecular genetic NP-C diagnosis for one patient. Plasma cholesterol significantly correlates with C-triol (p < 0.05). NGS of high C-triol infants identified three patients with mutations in JAG1 (Alagille syndrome) and ABCB11 (Byler disease) genes. Increased ChT activity was detected in 8 (of 108) patients with various aetiologies, including NP-C, Byler disease and biliary atresia.

Conclusion

Combined analysis of ChT activity and C-triol levels is an effective method for identifying NP-C.

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Title: Oxysterol/chitotriosidase based selective screening for Niemann-Pick type C in infantile cholestasis syndrome patients
Authors: Anna V. Degtyareva
Tatiana Y. Proshlyakova
Marina S. Gautier
Dmitry N. Degtyarev
Elena A. Kamenets
Galina V. Baydakova
Denis V. Rebrikov
Ekaterina Y. Zakharova
Publication date: 01-12-2019
Publisher: BioMed Central
Keywords: Niemann-Pick Disease
Niemann-Pick Disease
Biomarkers
Published in: BMC Medical Genetics / Issue 1/2019
Electronic ISSN: 1471-2350
DOI: https://doi.org/10.1186/s12881-019-0857-0

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Oxysterol/chitotriosidase based selective screening for Niemann-Pick type C in infantile cholestasis syndrome patients

Abstract

Background

Methods

Results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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