Gaucher disease (GD) is a lysosomal storage disorder caused by mutations in the glucocerebrosidase gene (GBA1), leading to acid β-glucosidase deficiency and the accumulation of glucosylceramide-derived glycosphingolipids. Its three phenotypes (non-neuronopathic, acute neuronopathic, and chronic neuronopathic) have variable clinical presentations including hepatosplenomegaly, cytopenia, bone disease, and neurological involvement. Early diagnosis and treatment are critical for improving outcomes, but GD is under-recognized due to non-specific symptoms and limited access to appropriate diagnostic testing. Glucosylsphingosine (lyso-Gb1), a deacylated metabolite of glucosylceramide, has been identified as a candidate biomarker for diagnosis and monitoring. This narrative review examines the role of biomarkers in GD, focusing on lyso-Gb1 as a potential diagnostic and prognostic biomarker. Lyso-Gb1 is markedly elevated in GD patients and correlates with disease burden, severity, and response to therapy. It is detectable in plasma and dried blood spots, making it suitable for newborn screening, diagnosis, and monitoring. Lyso-Gb1 is a sensitive and specific biomarker for GD, facilitating early detection, guiding treatment decisions, and enabling personalized disease management. Lyso-Gb1 levels reflect substrate accumulation and therapeutic response more reliably than other biomarkers such as chitotriosidase or CCL18. Ongoing research aims to refine diagnostic thresholds and integrate lyso-Gb1 monitoring into routine clinical practice for optimal patient outcomes.
Carubbi et al. (2026) studied this question.