Table 1.
Comparison of the four cohorts.
Figure 1.
Chemical structure of Glucosylsphingosine.
This substance was only analysed by HPLC-MS/MS with high sensitivity and specificity of diagnosing GD.
Figure 2.
Analysis of Glucosylsphingosine and Internal Standard in different samples.
Measurement of Glucosylsphingosine (first peak in chromatograms (blue), second peak in chromatograms is Internal Standard (red)) in a healthy control (1.71 ng/ml) (A) and two differently affected individuals with GD (B and C). Medium level of Glucosylsphingosine is shown for the first patient (B: 17.1 ng/ml) and a high level of Glucosylsphingosine for the second (C: 319 ng/ml). Please note the changed scale in (C).
Figure 3.
Glucosylsphingosine levels in sub-cohorts.
Level of Glucosylsphingosine is illustrated in the entire cohort (A) and separated according to gender (B). Glucosylsphingosine in GD patients was compared to healthy controls, GD carriers and patients with other LSDs. The horizontal bar marks the cut-off for pathological Glucosylsphingosine values above 12 ng/ml. Notably, only GD patients feature pathological values of Glucosylsphingosine and additionally Glucosylsphingosine is not gender-dependent (B; dark green representing males and orange females).
Table 2.
Sensitivity and specificity for different biomarkers with regard to diagnosis of GD.
Figure 4.
ROC curve analysis for comparison of Glucosylsphingosine.
Glucosylsphingosine (A; red line; area under the curve (AUC) = 1.00) and Chitotriosidase (A; blue line; AUC = 0.96) as well as Glucosylsphingosine (B; red line; AUC = 1.00) and CCL18 (B; blue line; AUC = 0.86) to discriminate the accuracy of two values. Glucosylsphingosine is significantly more accurate than Chitotriosidase (A: p = 0.027, n = 228) and CCL18 (B: p<0.001, n = 207).
Table 3.
Glucosylsphingosine levels in patients carrying frequent Gaucher mutations.
Figure 5.
Monitoring of enzyme replacement therapy by Glucosylsphingosine.
Course of Glucosylsphingosine after onset of treatment, the time point zero representing the first value after onset of therapy. The course for 19 GD patients undergoing ERT is shown. In summary the following genotypes were detected: #256: N370S/N370S; #7, #8, #181, #242: N370S/L444P; #10, #113, #149, #154, #178, #184, #211 are N370S/other. Two severely affected patients, 113 and 34, had been started with ERT for 10 months (pts. 113) and 4 months (pts. 34), respectively, but stopped due to shortage of the treatment. With the beginning of the ERT Glucosylsphingosine dropped down immediately, however went back to the original level after stopping of the ERT. After a second start with ERT 19 and 20 months, respectively, after initial starting the ERT the Glucosylsphingosine concentration dropped down again.
Table 4.
Regression analysis for Glucosylsphingosine.