Increased Lyso-Gb1 Levels in an Obese Splenectomized Gaucher Disease Type 1 Patient Treated with Eliglustat: Unacknowledged Poor Compliance or Underlying Factors

first_pagesettingsOrder Article Reprints Open AccessCase Report Increased Lyso-Gb1 Levels in an Obese Splenectomized Gaucher Disease Type 1 Patient Treated with Eliglustat: Unacknowledged Poor Compliance or Underlying Factors by Evelina Maines 1,Roberto Franceschi 1ORCID,Giacomo Luppi 2,Giacomo Marchi 3ORCID,Giovanni Piccoli 4,Nicola Vitturi 5ORCID,Massimo Soffiati 1,Annalisa Campomori 6 andSilvana Anna Maria Urru 6,*ORCID 1 Division of Pediatrics, S. Chiara General Hospital, APSS Trento, 38122 Trento, Italy 2 Division of Radiology, S. Chiara General Hospital, APSS Trento, 38122 Trento, Italy 3 Department of Medicine, University of Verona, 37129 Verona, Italy 4 CIBIO, Department of Cellular, Computational and Integrative Biology, University of Trento, 37129 Trento, Italy 5 Division of Metabolic Diseases, Department of Medicine, Padova University Hospital, 35128 Padova, Italy 6 Hospital Pharmacy Unit, S. Chiara General Hospital, APSS Trento, 38122 Trento, Italy * Author to whom correspondence should be addressed. Metabolites 2025, 15(7), 427; https://doi.org/10.3390/metabo15070427 Submission received: 22 May 2025 / Revised: 12 June 2025 / Accepted: 19 June 2025 / Published: 23 June 2025 (This article belongs to the Special Issue The Multifaceted Roles of Biomarkers in Metabolic Disorders: From Diagnosis and Monitoring to Prediction, Management, and Treatment) Downloadkeyboard_arrow_down Browse Figures Review Reports Versions Notes Abstract Eliglustat (Cerdelga®) is a potent and specific inhibitor of the enzyme glucosylceramide synthase and serves as a substrate reduction therapy for adult patients with Gaucher disease type 1 (GD1). It prevents the accumulation of several lipids, including glucosylsphingosine (also known as Lyso-Gb1). In addition to its role in diagnostics, Lyso-Gb1 has been proven to be a reliable biomarker for assessing disease severity and monitoring treatment efficacy. We present the case of an obese, splenectomized GD1 patient on long-term enzyme replacement therapy (ERT) who reported worsening fatigue and showed a progressive increase in Lyso-Gb1 levels after switching treatment from ERT to eliglustat. We provide a discussion of the potential clinical factors contributing to this outcome. As seen with ERT, Lyso-Gb1 levels during eliglustat treatment appear to respond earlier than other biochemical and clinical parameters. An increase in Lyso-Gb1 may signal early compromised clinical efficacy of the treatment. Data on biochemical and clinical outcomes in splenectomized or obese patients treated with eliglustat are limited, and the role of specific genotypes requires further clarification. The variability in responses to eliglustat highlights the complexity of GD and underscores the need for personalized approaches to treatment and monitoring.