Experience of the NPC Brazil network with a comprehensive program for the screening and diagnosis of Niemann-Pick disease type C
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRGS |
Texto Completo: | http://hdl.handle.net/10183/245584 |
Resumo: | Niemann-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. |
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Kubaski, FrancyneBurlina, AlbertoPolo, GiuliaPereira, DaniloHerbst, Zackary M.Silva, CamiloTrapp, Franciele BarbosaTirelli, Kristiane MichelinLopes, Franciele FátimaBurin, Maira GraeffFacchin, Ana Carolina BrusiusNetto, Alice Brinckmann OliveiraFaqueti, Larissa GabrielaIop, Gabrielle DineckPoletto, ÉdinaGiugliani, Roberto2022-07-28T04:44:51Z20222409-515Xhttp://hdl.handle.net/10183/245584001145353Niemann-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.application/pdfengInternational journal of neonatal screening. Basel. Vol. 8, no. 3 (2022), 39, 10 p.Doença de Niemann-Pick tipo CBiomarcadoresDoenças por armazenamento dos lisossomosEspectrometria de massas em TandemNiemann-Pick disease type CLysosphingomyelin-509Tandem mass spectrometryBiomarkerLysosomal storage disorderBrazilExperience of the NPC Brazil network with a comprehensive program for the screening and diagnosis of Niemann-Pick disease type CEstrangeiroinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSTEXT001145353.pdf.txt001145353.pdf.txtExtracted Texttext/plain40715http://www.lume.ufrgs.br/bitstream/10183/245584/2/001145353.pdf.txtf21f521803444731f375c0ad6e258488MD52ORIGINAL001145353.pdfTexto completo (inglês)application/pdf1103820http://www.lume.ufrgs.br/bitstream/10183/245584/1/001145353.pdf70b3616058e7767ede060f8aff17399eMD5110183/2455842022-09-21 04:54:05.237953oai:www.lume.ufrgs.br:10183/245584Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2022-09-21T07:54:05Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false |
dc.title.pt_BR.fl_str_mv |
Experience of the NPC Brazil network with a comprehensive program for the screening and diagnosis of Niemann-Pick disease type C |
title |
Experience of the NPC Brazil network with a comprehensive program for the screening and diagnosis of Niemann-Pick disease type C |
spellingShingle |
Experience of the NPC Brazil network with a comprehensive program for the screening and diagnosis of Niemann-Pick disease type C Kubaski, Francyne Doença de Niemann-Pick tipo C Biomarcadores Doenças por armazenamento dos lisossomos Espectrometria de massas em Tandem Niemann-Pick disease type C Lysosphingomyelin-509 Tandem mass spectrometry Biomarker Lysosomal storage disorder Brazil |
title_short |
Experience of the NPC Brazil network with a comprehensive program for the screening and diagnosis of Niemann-Pick disease type C |
title_full |
Experience of the NPC Brazil network with a comprehensive program for the screening and diagnosis of Niemann-Pick disease type C |
title_fullStr |
Experience of the NPC Brazil network with a comprehensive program for the screening and diagnosis of Niemann-Pick disease type C |
title_full_unstemmed |
Experience of the NPC Brazil network with a comprehensive program for the screening and diagnosis of Niemann-Pick disease type C |
title_sort |
Experience of the NPC Brazil network with a comprehensive program for the screening and diagnosis of Niemann-Pick disease type C |
author |
Kubaski, Francyne |
author_facet |
Kubaski, Francyne Burlina, Alberto Polo, Giulia Pereira, Danilo Herbst, Zackary M. Silva, Camilo Trapp, Franciele Barbosa Tirelli, Kristiane Michelin Lopes, Franciele Fátima Burin, Maira Graeff Facchin, Ana Carolina Brusius Netto, Alice Brinckmann Oliveira Faqueti, Larissa Gabriela Iop, Gabrielle Dineck Poletto, Édina Giugliani, Roberto |
author_role |
author |
author2 |
Burlina, Alberto Polo, Giulia Pereira, Danilo Herbst, Zackary M. Silva, Camilo Trapp, Franciele Barbosa Tirelli, Kristiane Michelin Lopes, Franciele Fátima Burin, Maira Graeff Facchin, Ana Carolina Brusius Netto, Alice Brinckmann Oliveira Faqueti, Larissa Gabriela Iop, Gabrielle Dineck Poletto, Édina Giugliani, Roberto |
author2_role |
author author author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Kubaski, Francyne Burlina, Alberto Polo, Giulia Pereira, Danilo Herbst, Zackary M. Silva, Camilo Trapp, Franciele Barbosa Tirelli, Kristiane Michelin Lopes, Franciele Fátima Burin, Maira Graeff Facchin, Ana Carolina Brusius Netto, Alice Brinckmann Oliveira Faqueti, Larissa Gabriela Iop, Gabrielle Dineck Poletto, Édina Giugliani, Roberto |
dc.subject.por.fl_str_mv |
Doença de Niemann-Pick tipo C Biomarcadores Doenças por armazenamento dos lisossomos Espectrometria de massas em Tandem |
topic |
Doença de Niemann-Pick tipo C Biomarcadores Doenças por armazenamento dos lisossomos Espectrometria de massas em Tandem Niemann-Pick disease type C Lysosphingomyelin-509 Tandem mass spectrometry Biomarker Lysosomal storage disorder Brazil |
dc.subject.eng.fl_str_mv |
Niemann-Pick disease type C Lysosphingomyelin-509 Tandem mass spectrometry Biomarker Lysosomal storage disorder Brazil |
description |
Niemann-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. |
publishDate |
2022 |
dc.date.accessioned.fl_str_mv |
2022-07-28T04:44:51Z |
dc.date.issued.fl_str_mv |
2022 |
dc.type.driver.fl_str_mv |
Estrangeiro info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
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publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10183/245584 |
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2409-515X |
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001145353 |
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http://hdl.handle.net/10183/245584 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.pt_BR.fl_str_mv |
International journal of neonatal screening. Basel. Vol. 8, no. 3 (2022), 39, 10 p. |
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info:eu-repo/semantics/openAccess |
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openAccess |
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