Case Report
Volume: 2 | Issue: 2 | Published: Nov 25, 2019 | Pages: 147 - 150 | DOI: 10.24911/JBCGenetics/183-1562077620
Metabolic biomarker testing facilitates genetic diagnosis of Niemann-Pick disease by enabling classification of novel SMPD1 variants
Authors:
Vindhya Lakmali Miyanawala
, Christian Beetz
, Samantha Waidyanatha
, Sabine Schroder
, Vasiliki Karageorgou
, Claudia Cozma
, Eresha Jasinge
, Arndt Rolfs
Article Info
Authors
Vindhya Lakmali Miyanawala
Department of Chemical Pathology, Lady Ridgeway Hospital for Children, Colombo, Sri Lanka
Samantha Waidyanatha
Department of Chemical Pathology, Lady Ridgeway Hospital for Children, Colombo, Sri Lanka
Sabine Schroder
CENTOGENE AG, Rostock, Germany
Vasiliki Karageorgou
CENTOGENE AG, Rostock, Germany
Claudia Cozma
CENTOGENE AG, Rostock, Germany
Eresha Jasinge
CENTOGENE AG, Rostock, Germany, Rostock Medical University, Rostock, Germany
Arndt Rolfs
CENTOGENE AG, Rostock, Germany
Publication History
Received: July 02, 2019
Revised: October 07, 2019
Accepted: October 17, 2019
Published: November 25, 2019
Abstract
Background: Niemann–Pick (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.
Keywords: Biomarker, enzymatic testing, Niemann–Pick disease, SMPD1, variant classification
Pubmed Style
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. JBC Genetics. 2019; 25 (November 2019): 147-150. doi:10.24911/JBCGenetics/183-1562077620
Web Style
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. https://www.jbcgenetics.com/articles/2186 [Access: April 27, 2025]. doi:10.24911/JBCGenetics/183-1562077620
AMA (American Medical Association) Style
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. JBC Genetics. 2019; 25 (November 2019): 147-150. doi:10.24911/JBCGenetics/183-1562077620
Vancouver/ICMJE Style
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. JBC Genetics. (2019), [cited April 27, 2025]; 25 (November 2019): 147-150. doi:10.24911/JBCGenetics/183-1562077620
Harvard Style
Vindhya Lakmali Miyanawala, Christian Beetz, Samantha Waidyanatha, Sabine Schroder, Vasiliki Karageorgou, Claudia Cozma, Eresha Jasinge, Arndt Rolfs (2019) Metabolic biomarker testing facilitates genetic diagnosis of Niemann-Pick disease by enabling classification of novel SMPD1 variants. JBC Genetics, 25 (November 2019): 147-150. doi:10.24911/JBCGenetics/183-1562077620
Chicago Style
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." 25 (2019), 147-150. doi:10.24911/JBCGenetics/183-1562077620
MLA (The Modern Language Association) Style
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." 25.November 2019 (2019), 147-150. Print. doi:10.24911/JBCGenetics/183-1562077620
APA (American Psychological Association) Style
Vindhya Lakmali Miyanawala, Christian Beetz, Samantha Waidyanatha, Sabine Schroder, Vasiliki Karageorgou, Claudia Cozma, Eresha Jasinge, Arndt Rolfs (2019) Metabolic biomarker testing facilitates genetic diagnosis of Niemann-Pick disease by enabling classification of novel SMPD1 variants. , 25 (November 2019), 147-150. doi:10.24911/JBCGenetics/183-1562077620