Work

Correlation of Plasma Lyso-GL1 Levels with Clinical Phenotype and Treatment Decisions in Patients with Gaucher Disease

Year: 2025

Type: article

Abstract: In Gaucher disease (GD), clinical management is complicated by heterogeneity and the lack of standardized guidelines for treatment initiation. As patients are being identified pre-symptomatically or as mildly affected through carrier and newborn screening programs, timing of treatment is an increasingly important issue. This study evaluated the utility of plasma lyso-GL1 as an objective biomarker to inform treatment decisions. Retrospective data were analyzed from 240 GD patients with lyso-GL1 levels measured primarily at a single laboratory between June 2018 and September 2023. The study population included both adult ( n = 194, 80.8 %) and pediatric ( n = 46, 19.2 %) patients predominantly diagnosed with type 1 GD ( n = 234, 97.5 %) and self-identified as Jewish (82.1 %). Among 25 patients who initiated GD-specific treatment during the study period with available pre-treatment lyso-GL1 data, the median age at treatment initiation was 33 years. In this group, the median baseline lyso-GL1 was 91.6 ng/mL, which declined to 19.5 ng/mL following treatment with a median follow-up of 2.9 years. In contrast, untreated patients had a median baseline lyso-GL1 of 14.2 ng/mL, which increased to 17.0 ng/mL over a similar follow-up period. Logistic regression and receiver operating characteristic analysis identified a lyso-GL1 threshold of 78.9 ng/mL that effectively discriminated treatment status in GD1 patients, with an area under the curve of 0.865, sensitivity of 73 %, and specificity of 96 %. The predictive performance of this identified threshold was comparable to that reported in a previous study, underscoring the reproducibility and potential utility of lyso-GL1 as a reliable and objective biomarker to guide treatment initiation in Gaucher disease. • GD-specific biomarkers like lyso-GL1 may be helpful in treatment decisions. • Clinical phenotype and treatment were correlated with lyso-GL1 in a large GD cohort. • Lyso-GL1 levels varied by GBA genotype and correlated with chitotriosidase activity. • Higher lyso-GL1 values predicted the need for treatment. • This study supports the clinical utility of lyso-GL1 in guiding treatment in GD.

Source: Molecular Genetics and Metabolism

DOI: 10.1016/j.ymgme.2025.109286