Show simple item record

dc.contributor.authorKubaski, Francynept_BR
dc.contributor.authorBurlina, Albertopt_BR
dc.contributor.authorPolo, Giuliapt_BR
dc.contributor.authorPereira, Danilopt_BR
dc.contributor.authorHerbst, Zackary M.pt_BR
dc.contributor.authorSilva, Camilopt_BR
dc.contributor.authorTrapp, Franciele Barbosapt_BR
dc.contributor.authorTirelli, Kristiane Michelinpt_BR
dc.contributor.authorLopes, Franciele Fátimapt_BR
dc.contributor.authorBurin, Maira Graeffpt_BR
dc.contributor.authorFacchin, Ana Carolina Brusiuspt_BR
dc.contributor.authorNetto, Alice Brinckmann Oliveirapt_BR
dc.contributor.authorFaqueti, Larissa Gabrielapt_BR
dc.contributor.authorIop, Gabrielle Dineckpt_BR
dc.contributor.authorPoletto, Édinapt_BR
dc.contributor.authorGiugliani, Robertopt_BR
dc.date.accessioned2022-07-28T04:44:51Zpt_BR
dc.date.issued2022pt_BR
dc.identifier.issn2409-515Xpt_BR
dc.identifier.urihttp://hdl.handle.net/10183/245584pt_BR
dc.description.abstractNiemann-Pick disease type C (NPC) is a lysosomal disorder caused by impaired cholesterol metabolism. Levels of lysosphingomyelin 509 (LysoSM509) have been shown elevated in dried blood spots (DBS) of NPC and acid sphingomyelinase deficiency patients. In this study, we report our experience using a two-tier approach (1st tier is the quantification of lysoSM509 by ultra-performance liquid chromatography tandem mass spectrometry followed by the 2nd tier with next-generation sequencing of the NPC1 and NPC2 genes). DBS samples from 450 suspected patients were received by the NPC Brazil network. Of these, 33 samples had elevated levels of lysoSM509, and in 25 of them, variants classified as pathogenic, likely pathogenic, or of unknown significance were identified in the NPC1 or NPC2 genes by next-generation sequencing. The quantification of lysoSM509 in DBS as a first-tier test for the diagnosis of NPC followed by molecular analysis of the NPC1 and NPC2 genes almost doubled the detection rate when compared to the performance of chitotriosidase activity as a first-tier biomarker, and it could likely be increased with the addition of a third tier with MLPA of the two genes involved. This strategy seems suitable for the neonatal screening (NBS) of NPC if this disease is eventually adopted by NBS programs.en
dc.format.mimetypeapplication/pdfpt_BR
dc.language.isoengpt_BR
dc.relation.ispartofInternational journal of neonatal screening. Basel. Vol. 8, no. 3 (2022), 39, 10 p.pt_BR
dc.rightsOpen Accessen
dc.subjectDoença de Niemann-Pick tipo Cpt_BR
dc.subjectNiemann-Pick disease type Cen
dc.subjectLysosphingomyelin-509en
dc.subjectBiomarcadorespt_BR
dc.subjectTandem mass spectrometryen
dc.subjectDoenças por armazenamento dos lisossomospt_BR
dc.subjectBiomarkeren
dc.subjectEspectrometria de massas em Tandempt_BR
dc.subjectLysosomal storage disorderen
dc.subjectBrazilen
dc.titleExperience of the NPC Brazil network with a comprehensive program for the screening and diagnosis of Niemann-Pick disease type Cpt_BR
dc.typeArtigo de periódicopt_BR
dc.identifier.nrb001145353pt_BR
dc.type.originEstrangeiropt_BR


Files in this item

Thumbnail
   

This item is licensed under a Creative Commons License

Show simple item record