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

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.