Metabolic biomarker testing facilitates genetic diagnosis of Niemann-Pick disease by enabling classification of novel SMPD1 variants
Background: NiemannPick (NP) disease is a genetically heterogeneous metabolic disorder caused by bi-allelic variants in NPC1, NPC2, or SMPD1, with initial symptoms and age at onset varying widely. The interpretation of variants in NP disease genes is challenging when these alterations have never bee...
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| Format: | Article |
| Language: | English |
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Discover STM Publishing Ltd
2019-12-01
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| Series: | Journal of Biochemical and Clinical Genetics |
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| Online Access: | http://www.ejmanager.com/fulltextpdf.php?mno=55059 |
| _version_ | 1797816640348356608 |
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| author | Vindhya Lakmali Miyanawala Christian Beetz Samantha Waidyanatha Sabine Schroder Vasiliki Karageorgou Claudia Cozma Eresha Jasinge Arndt Rolfs |
| author_facet | Vindhya Lakmali Miyanawala Christian Beetz Samantha Waidyanatha Sabine Schroder Vasiliki Karageorgou Claudia Cozma Eresha Jasinge Arndt Rolfs |
| author_sort | Vindhya Lakmali Miyanawala |
| collection | DOAJ |
| description | Background: NiemannPick (NP) disease is a genetically heterogeneous metabolic disorder caused by bi-allelic variants in NPC1, NPC2, or SMPD1, with initial symptoms and age at onset varying widely. The interpretation of variants in NP disease genes is challenging when these alterations have never been observed before, and when parental samples are not available. Case Presentation: We clinically, genetically, and biochemically characterized an infant with a complex presentation and a negative family history. Clinical and paraclinical observations were consistent with NP disease. Genetic screening identified two previously unreported SMPD1 missense variants, which were initially classified as variants of unknown significance. Based on strongly increased plasma levels of lysosphingomyelin-509, both variants could be re-classified as likely pathogenic, thus establishing a diagnosis of NP disease type A/B. Conclusion: A combination of genetics with biochemical approaches facilitates conclusive diagnosis of metabolic disorders including NP disease. Blood-based biomarkers are particularly promising in this respect. [JBCGenetics 2019; 2(2.000): 147-150] |
| first_indexed | 2024-03-13T08:40:41Z |
| format | Article |
| id | doaj.art-0a1891e43d3a4922948ccf6bf049d5ef |
| institution | Directory Open Access Journal |
| issn | 1658-807X |
| language | English |
| last_indexed | 2024-03-13T08:40:41Z |
| publishDate | 2019-12-01 |
| publisher | Discover STM Publishing Ltd |
| record_format | Article |
| series | Journal of Biochemical and Clinical Genetics |
| spelling | doaj.art-0a1891e43d3a4922948ccf6bf049d5ef2023-05-30T11:45:05ZengDiscover STM Publishing LtdJournal of Biochemical and Clinical Genetics1658-807X2019-12-012214715010.24911/JBCGenetics/183-156207762055059Metabolic biomarker testing facilitates genetic diagnosis of Niemann-Pick disease by enabling classification of novel SMPD1 variantsVindhya Lakmali Miyanawala0Christian Beetz1Samantha Waidyanatha2Sabine Schroder3Vasiliki Karageorgou4Claudia Cozma5Eresha Jasinge6Arndt RolfsDepartment of Chemical Pathology, Lady Ridgeway Hospital for Children, Colombo, Sri Lanka CENTOGENE AG, Rostock, Germany Department of Chemical Pathology, Lady Ridgeway Hospital for Children, Colombo, Sri Lanka CENTOGENE AG, Rostock, Germany CENTOGENE AG, Rostock, Germany CENTOGENE AG, Rostock, Germany CENTOGENE AG, Rostock, Germany, Rostock Medical University, Rostock, GermanyBackground: NiemannPick (NP) disease is a genetically heterogeneous metabolic disorder caused by bi-allelic variants in NPC1, NPC2, or SMPD1, with initial symptoms and age at onset varying widely. The interpretation of variants in NP disease genes is challenging when these alterations have never been observed before, and when parental samples are not available. Case Presentation: We clinically, genetically, and biochemically characterized an infant with a complex presentation and a negative family history. Clinical and paraclinical observations were consistent with NP disease. Genetic screening identified two previously unreported SMPD1 missense variants, which were initially classified as variants of unknown significance. Based on strongly increased plasma levels of lysosphingomyelin-509, both variants could be re-classified as likely pathogenic, thus establishing a diagnosis of NP disease type A/B. Conclusion: A combination of genetics with biochemical approaches facilitates conclusive diagnosis of metabolic disorders including NP disease. Blood-based biomarkers are particularly promising in this respect. [JBCGenetics 2019; 2(2.000): 147-150]http://www.ejmanager.com/fulltextpdf.php?mno=55059biomarkerenzymatic testingniemannpick diseasesmpd1variant classification |
| spellingShingle | Vindhya Lakmali Miyanawala Christian Beetz Samantha Waidyanatha Sabine Schroder Vasiliki Karageorgou Claudia Cozma Eresha Jasinge Arndt Rolfs Metabolic biomarker testing facilitates genetic diagnosis of Niemann-Pick disease by enabling classification of novel SMPD1 variants Journal of Biochemical and Clinical Genetics biomarker enzymatic testing niemannpick disease smpd1 variant classification |
| title | Metabolic biomarker testing facilitates genetic diagnosis of Niemann-Pick disease by enabling classification of novel SMPD1 variants |
| title_full | Metabolic biomarker testing facilitates genetic diagnosis of Niemann-Pick disease by enabling classification of novel SMPD1 variants |
| title_fullStr | Metabolic biomarker testing facilitates genetic diagnosis of Niemann-Pick disease by enabling classification of novel SMPD1 variants |
| title_full_unstemmed | Metabolic biomarker testing facilitates genetic diagnosis of Niemann-Pick disease by enabling classification of novel SMPD1 variants |
| title_short | Metabolic biomarker testing facilitates genetic diagnosis of Niemann-Pick disease by enabling classification of novel SMPD1 variants |
| title_sort | metabolic biomarker testing facilitates genetic diagnosis of niemann pick disease by enabling classification of novel smpd1 variants |
| topic | biomarker enzymatic testing niemannpick disease smpd1 variant classification |
| url | http://www.ejmanager.com/fulltextpdf.php?mno=55059 |
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