Experience of the NPC Brazil Network with a Comprehensive Program for the Screening and Diagnosis of Niemann-Pick Disease Type C
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 t...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-06-01
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| Series: | International Journal of Neonatal Screening |
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| Online Access: | https://www.mdpi.com/2409-515X/8/3/39 |
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| author | Francyne Kubaski Alberto Burlina Giulia Polo Danilo Pereira Zackary M. Herbst Camilo Silva Franciele B. Trapp Kristiane Michelin-Tirelli Franciele F. Lopes Maira G. Burin Ana Carolina Brusius-Facchin Alice B. O. Netto Larissa Faqueti Gabrielle D. Iop Edina Poletto Roberto Giugliani |
| author_facet | Francyne Kubaski Alberto Burlina Giulia Polo Danilo Pereira Zackary M. Herbst Camilo Silva Franciele B. Trapp Kristiane Michelin-Tirelli Franciele F. Lopes Maira G. Burin Ana Carolina Brusius-Facchin Alice B. O. Netto Larissa Faqueti Gabrielle D. Iop Edina Poletto Roberto Giugliani |
| author_sort | Francyne Kubaski |
| collection | DOAJ |
| 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 <i>NPC1</i> and <i>NPC2</i> 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 <i>NPC1</i> or <i>NPC2</i> 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 <i>NPC1</i> and <i>NPC2</i> 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. |
| first_indexed | 2024-03-09T23:41:16Z |
| format | Article |
| id | doaj.art-cce8ae4353fe4c76a53f67cf47819f02 |
| institution | Directory Open Access Journal |
| issn | 2409-515X |
| language | English |
| last_indexed | 2024-03-09T23:41:16Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Neonatal Screening |
| spelling | doaj.art-cce8ae4353fe4c76a53f67cf47819f022023-11-23T16:51:44ZengMDPI AGInternational Journal of Neonatal Screening2409-515X2022-06-01833910.3390/ijns8030039Experience of the NPC Brazil Network with a Comprehensive Program for the Screening and Diagnosis of Niemann-Pick Disease Type CFrancyne Kubaski0Alberto Burlina1Giulia Polo2Danilo Pereira3Zackary M. Herbst4Camilo Silva5Franciele B. Trapp6Kristiane Michelin-Tirelli7Franciele F. Lopes8Maira G. Burin9Ana Carolina Brusius-Facchin10Alice B. O. Netto11Larissa Faqueti12Gabrielle D. Iop13Edina Poletto14Roberto Giugliani15BioDiscovery Laboratory, Hospital de Clinicas de Porto Alegre, Porto Alegre 90035-903, BrazilDivision of Inherited Metabolic Diseases, Regional Center for Expanded Neonatal Screening, Department of Women and Child’s Health, University of Padova, 35129 Padova, ItalyDivision of Inherited Metabolic Diseases, Regional Center for Expanded Neonatal Screening, Department of Women and Child’s Health, University of Padova, 35129 Padova, ItalyWaters Technologies Do Brasil, São Paulo 06455-000, BrazilDepartment of Chemistry, University of Washington, Seattle, WA 98105-6250, USAWaters Technologies Do Brasil, São Paulo 06455-000, BrazilMedical Genetics Service, HCPA, Porto Alegre 90035-903, BrazilMedical Genetics Service, HCPA, Porto Alegre 90035-903, BrazilMedical Genetics Service, HCPA, Porto Alegre 90035-903, BrazilMedical Genetics Service, HCPA, Porto Alegre 90035-903, BrazilBioDiscovery Laboratory, Hospital de Clinicas de Porto Alegre, Porto Alegre 90035-903, BrazilPPGBM, UFRGS, Porto Alegre 91501-970, BrazilBioDiscovery Laboratory, Hospital de Clinicas de Porto Alegre, Porto Alegre 90035-903, BrazilBioDiscovery Laboratory, Hospital de Clinicas de Porto Alegre, Porto Alegre 90035-903, BrazilPPGBM, UFRGS, Porto Alegre 91501-970, BrazilBioDiscovery Laboratory, Hospital de Clinicas de Porto Alegre, Porto Alegre 90035-903, BrazilNiemann-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 <i>NPC1</i> and <i>NPC2</i> 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 <i>NPC1</i> or <i>NPC2</i> 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 <i>NPC1</i> and <i>NPC2</i> 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.https://www.mdpi.com/2409-515X/8/3/39Niemann-Pick disease type Clysosphingomyelin-509tandem mass spectrometrybiomarkerlysosomal storage disorderBrazil |
| spellingShingle | Francyne Kubaski Alberto Burlina Giulia Polo Danilo Pereira Zackary M. Herbst Camilo Silva Franciele B. Trapp Kristiane Michelin-Tirelli Franciele F. Lopes Maira G. Burin Ana Carolina Brusius-Facchin Alice B. O. Netto Larissa Faqueti Gabrielle D. Iop Edina Poletto Roberto Giugliani Experience of the NPC Brazil Network with a Comprehensive Program for the Screening and Diagnosis of Niemann-Pick Disease Type C International Journal of Neonatal Screening Niemann-Pick disease type C lysosphingomyelin-509 tandem mass spectrometry biomarker lysosomal storage disorder Brazil |
| title | 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_short | 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 |
| topic | Niemann-Pick disease type C lysosphingomyelin-509 tandem mass spectrometry biomarker lysosomal storage disorder Brazil |
| url | https://www.mdpi.com/2409-515X/8/3/39 |
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