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

Publication History

Article published online:
25 September 2024

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