Quantitation of a Urinary Profile of Biomarkers in Gaucher Disease Type 1 Patients Using Tandem Mass Spectrometry

Gaucher disease is a rare inherited disorder caused by a deficiency of the lysosomal acid beta-glucocerebrosidase enzyme. Metabolomic studies by our group targeted several new potential urinary biomarkers. Apart from lyso-Gbi, these studies highlighted lyso-Gbi analogs -28, -26, -12 (A/B), +2, +14, +16 (A/B), +30, and +32 Da, and polycyclic lyso-Gbi analogs 362,366,390, and 394 Da. The main objective of the current study was to develop and validate a robust UPLC-MS/MS method to study the urine distribution of these biomarkers in patients. Method: Urine samples were purified using solid-phase extraction. A 12 min UPLC-MS/MS method was developed. Results: Validation assays revealed high precision and accuracy for creatinine and lyso-Gbi. Most lyso-Gbi analogs had good recovery rates and high intra- and interday precision assays. Biomarker-estimated LOD and LOQ levels ranged from 56-109 pM to 186-354 pM, respectively. Comparison between GD patients and healthy controls showed significant differences in most biomarker levels. Typically, treated GD patients presented lower biomarker levels compared to untreated patients. Conclusions: These data suggest that the metabolites investigated might be interesting GD biomarkers. More studies with a larger cohort of patients will be needed to better understand the clinical significance of these GD biomarkers.