A definitive diagnosis of Gaucher disease is established by:
- Glucocerebrosidase enzyme assay: demonstrating deficiency1
- GBA gene sequencing: demonstrating two pathogenic variants in trans (one from each parent). Though identification of pathogenic alleles is not required for diagnosis, it can provide secondary confirmation and important information related to phenotype
- Six pathogenic variants (N370S, R496H, V394L, 84insG, A→1G+IVS2, and L444P) account for the majority (97%) of all pathogenic alleles in patients of Ashkenazi heritage2
Gaucher disease has a wide phenotypic spectrum ranging from severe neuronopathic forms to chronic visceral forms, with a chronic neurovisceral form between these two ends of the spectrum.3,4 Gaucher disease presents with: anemia, thrombocytopenia, splenomegaly, and bone involvement due to displacement of normal marrow cells with disease-affected cells resulting in bone pain, osteopenia, and growth retardation in children.3,4
Biomarker: Glucosylsphingosine (lyso-GL-1)
Glucosylsphingosine (lyso-GL-1) is the deacylated form of glucosylceramide (GL-1). Both lyso-GL-1 and GL-1 accumulate in Gaucher disease as a direct result of acid β-glucosidase deficiency, making lyso-GL-1 a highly specific biomarker.
Pandey MK, Grabowski GA, Kohl J. Semin Immunol. 2018 June;37:30-42.
References: 1. Mistry PK, et al. Am J Hematol. 2011;86(1):110-5 2. Bronstein S, et al. Isr Med Assoc J. 2014;16:683-685 3. Baris HN, et al. Pediatr Endocrinol Rev. 2014;12:72-81. 4. McGovern MM, et al. Orphanet J Rare Dis. 2017;12(1):41