Evaluation of Lysosphingolipid Analysis for the Diagnosis of Lysosomal Storage Disease

Abstract

Lysosomal storage disorders (LSD) are a group of inherited inborn metabolism errors that are characterized by a deficiency in the lysosomal enzyme. In patients with suspected lipid storage disorders, confirmation of the diagnosis relies predominantly on the measurement of specific enzymatic activities and molecular genetic studies. New approaches to the measurement of lysosphingolipids have been developed that may serve as a rapid first-tier screening tests for the evaluation of lysosomal storage disorders. The present study evaluates the results of lysosphingolipid screening tests in patients with suspected lysosomal storage diseases. Lysosphingolipid elevation was detected in five patients examined with suspected lysosomal storage disease, and a definitive diagnosis was reached based on genetic analysis. Our data support recent evidence of the primary role of LysoSLs in the diagnosis of sphingolipidosis, and suggest that these biomarkers may be used for diagnosis and treatment monitoring in the future.

Zusammenfassung

Lysosomale Speicherstörungen (LSD) sind eine Gruppe erblicher angeborener Stoffwechselstörungen, die durch einen Mangel des lysosomalen Enzyms gekennzeichnet sind. Bei Patienten mit Verdacht auf Lipidspeicherstörungen stützt sich die Diagnosesicherung überwiegend auf die Messung spezifischer enzymatischer Aktivitäten und molekulargenetische Untersuchungen. Es wurden neue Ansätze zur Messung von Lysosphingolipiden entwickelt, die als schnelle Screening-Tests der ersten Stufe zur Beurteilung lysosomaler Speicherstörungen dienen können. Die vorliegende Studie wertet die Ergebnisse von Lysosphingolipid-Screeningtests bei Patienten mit Verdacht auf lysosomale Speicherkrankheiten aus. Bei fünf untersuchten Patienten mit Verdacht auf eine lysosomale Speicherkrankheit wurde ein Anstieg des Lysosphingolipids festgestellt, und auf der Grundlage einer genetischen Analyse konnte eine endgültige Diagnose gestellt werden. Unsere Daten stützen aktuelle Hinweise auf die primäre Rolle von LysoSLs bei der Diagnose von Sphingolipidose und legen nahe, dass diese Biomarker in Zukunft für die Diagnose und Behandlungsüberwachung verwendet werden könnten.

Keywords

lysosomal storage diseases - biomarkers - lysosphingolipid analyses - Inborn errors of metabolism

Schlüsselwörter

lysosomale Speicherkrankheiten - Biomarker - Lysosphingolipid-Analysen - Angeborene Stoffwechselstörungen

Publikationsverlauf

Artikel online veröffentlicht:
25. September 2024

• References

• 1 Schulze H, Sandhoff K. Sphingolipids and lysosomal pathologies. Biochim Biophys Acta 2014; 1841: 799-810
• 2 Platt FM. Sphingolipid lysosomal storage disorders. Nature 2014; 510: 68-75 24899306
• 3 Öktem RM, Biberoğlu G. Tanıda yenilikler: Biyobelirteçler ve tarama testleri. Tümer L, editör. Lizozomal Hastalıkların Tanı ve Tedavisinde Yenilikler. 1. Baskı. Ankara: Türkiye Klinikleri; 2021. p.8-15. [Innovations in diagnosis: Biomarkers and screening tests. Tumer L, editor. Innovations in Diagnosis and Treatment of Lysosomal Diseases. 1^st Edition. Ankara: Turkey Clinics. 2021: 8-15
• 4 Ferraz MJ, Kallemeijn WW, Mirzaian M. et al. Gaucher disease and Fabry disease: New markers and insights in pathophysiology for two distinct glycosphingolipidoses. Biochim Biophys Acta 2014; 1841: 811-825
• 5 Aerts JM, Groener JE, Kuiper S. et al. Elevated globotriaosylsphingosine is a hallmark of Fabry disease. Proc Natl Acad Sci USA 2008; 105: 2812-2817
• 6 Charrow KPAH, Kolodny J, Mistry EH. et al. The Gaucher registry: demographics and disease characteristics of 1698 patientswith Gaucher disease. Arch Intern Med 2000; 160: 2835-2843
• 7 Dekker N, van Dussen L, Hollak CE. et al. Elevated plasma glucosylsphingosine in Gaucher disease: relation to phenotype, storage cell markers, and therapeutic response. Blood 2011; 118: e118-e127
• 8 Chuang WL, Pacheco J, Zhang XK. et al. Determination of psychosine concentration in dried blood spots from newborns that were identified via newborn screening to be at risk for Krabbe disease. Clin Chim Acta 2013; 419: 73-76
• 9 Chuang WL, Pacheco J, Cooper S. et al. Lyso-sphingomyelin is elevated in dried blood spots of Niemann-Pick B patients. Mol Genet Metab 2014; 111: 209-211
• 10 Giese AK, Mascher H, Grittner U. et al. A novel, highly sensitive and specific biomarker for Niemann-Pick type C1 disease. Orphanet J Rare Dis. 2015; 10: 78 PMID: 26082315 PMC4479076
• 11 Voorink-Moret M, Goorden SMI, van Kuilenburg ABP. et al. Rapid screening for lipid storage disorders using biochemical markers. Expert center data and review of the literature. Mol Genet Metab 2018; 123: 76-84
• 12 Polo G, Burlina AP, Kolamunnage TB. et al. Diagnosis of sphingolipidoses: a new simultaneous measurement of lysosphingolipids by LC-MS/MS. Clin Chem Lab Med 2017; 55: 403-414
• 13 Kasapkara ÇS, Ceylan AC, Yılmaz D. et al. CLN3-Associated NCL Case with a Preliminary Diagnosis of Niemann Pick Type C. Mol Syndromol. 2023; 14: 30-34 Epub 2022 Jun 21 PMID: 36777709 PMC9911989
• 14 Tang C, Jia X, Tang F. et al. Detection of glucosylsphingosine in dried blood spots for diagnosis of Gaucher disease by LC-MS/MS. Clin Biochem 2021; 87: 79-84
• 15 Simonetta I, Tuttolomondo A, Daidone M. et al. Biomarkers in Anderson-Fabry Disease. Int J Mol Sci. 2020; 21: 8080 PMID: 33138098 PMC7662984
• 16 Maruyama H, Miyata K, Mikame M. et al. Effectiveness of plasma lysoGb3 as a biomarker for selecting high-risk patients with Fabry disease from multispecialty clinics for genetic analysis. Genet Med 2019; 21: 44-52
• 17 Jiang X, Ory DS. Advancing Diagnosis and Treatment of Niemann-Pick C disease through Biomarker Discovery. Explor Neuroprotective Ther. 2021; 1: 146-158 PMID: 35356760 PMC8963791
• 18 Deodato F, Boenzi S, Taurisano R. et al. The impact of biomarkers analysis in the diagnosis of Niemann-Pick C disease and acid sphingomyelinase deficiency. Clin Chim Acta 2018; 486: 387-394
• 19 Hochstein JN, Schulz A, Nickel M. et al. Natural history of MRI brain volumes in patients with neuronal ceroid lipofuscinosis 3: a sensitive imaging biomarker. Neuroradiology 2022; 64: 2059-2067
• 20 Cotman SL. Lefrancois SCLN3, at the crossroads of endocytic trafficking. Neurosci Lett 2021; 762: 136117