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Oxysterol/chitotriosidase based selective screening for Niemann-Pick type C in infantile cholestasis syndrome patientsстатья
- Авторы: Degtyareva Anna V., Proshlyakova Tatiana Y., Gautier Marina S., Degtyarev Dmitry N., Kamenets Elena A., Baydakova Galina V., Rebrikov Denis V., Zakharova Ekaterina Y.
- Журнал: BMC Medical Genetics
- Том: 20
- Номер: 1
- Год издания: 2019
- Издательство: BioMed Central
- Местоположение издательства: London
- DOI: 10.1186/s12881-019-0857-0
- Аннотация: 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 NGSsequenced. 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.
- Добавил в систему: Ребриков Денис Владимирович