A Brazilian Rare-Disease Center’s Experience with Glucosylsphingosine (lyso-Gb1) in Patients with Gaucher Disease: Exploring a Novel Correlation with IgG Levels in Plasma and a Biomarker Measurement in CSF
Abstract
:1. Introduction
2. Results
- (A)
- Lyso-Gb1 levels in dried blood spots showed a positive correlation with the treatment status and type of Gaucher disease
- (B)
- Lyso-Gb1 levels correlated with IgG, age, and chitotriosidase in treated patients with Gaucher disease type 1
- (C)
- Lyso-Gb1 Levels in cerebrospinal fluid were higher in GD1 patients than in controls
- (D)
- Lyso-Gb1 levels followed the trend of chitotriosidase decrease after treatment in treatment-naïve patients with Gaucher disease
3. Discussion
4. Materials and Methods
4.1. Ethics
4.2. Lyso-Gb1 Quantification in Dried Blood Spots
4.3. Cerebrospinal Fluid Collection
4.4. Lyso-Gb1 Quantification in Cerebrospinal Fluid
4.5. Lysosomal Enzymes’ Activity in Cerebrospinal Fluid
4.6. Statistics
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
α-syn | α-synuclein |
α-man | α-mannosidase |
β-glu | β-glucuronidase |
β-hexo | β-hexosaminidase |
ChT | chitotriosidase |
CSF | cerebrospinal fluid |
ERT | Enzyme-replacement therapy |
GCase | β-glucocerebrosidase |
GD | Gaucher disease |
GD1 | Gaucher disease type 1 |
GD2 | Gaucher disease type 2 |
GD3 | Gaucher disease type 3 |
LSD | Lysosomal Storage Disorders |
Lyso-Gb1 | glucosylsphingosine |
MLD | Metachromatic Leukodystrophy. |
MPS | Mucopolysaccharidosis |
NMS | Non-motor symptoms |
PD | Parkinson’s disease |
SRT | Substrate-reduction therapy |
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Patient | Gaucher Type | Gender | Age (Years) | Genotype (NM_000157.3) | Treatment Duration (Years) | Current Treatment | Adherence to Treatment * | Severity Scores | Platelet (/mcL) | Hb (g/dL) | Lyso-Gb1 DBS (ng/mL) | ChT Plasma (nmol/h/mL) | IgG Plasma (mg/dL) | |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SSI | DS3 | |||||||||||||
1 | I | F | 12 | [c.(1226A>G)];[c. (721G>A)] [p.(Asn409Ser)]; [p.(Gly241Arg)] | 4 | ERT | Y | 0 | 0 | 266,000 | 13.8 | 199 | 1724 | 795 |
2 | I | M | 26 | [c.(1226A>G)];[c. (721G>A)] [p.(Asn409Ser)]; [p.(Gly241Arg)] | 18 | ERT | Y | 0 | 0.66 | 171,000 | 14.9 | 234.1 | 4951 | 1073 |
3 | I | F | 27 | [c.(1226A>G)];(RecNciI) [p. (Asn409Ser)];(RecNciI) | 19 | ERT | N | 0 | 0.16 | 239,000 | 12.5 | 76.7 | 400 | 1670 |
4 | I | F | 27 | [c.(1226A>G)];[c. (1448T>C)] [p. (Asn409Ser)];[p. (Leu483Pro)] | 6 | ERT | Y | 1 | 0 | 225,000 | 12.5 | 127 | 3095 | 1539 |
5 | I | F | 29 | [c.(1226A>G)];[c. (1448T>C)] [p. (Asn409Ser)];[p. (Leu483Pro)] | 13 | ERT | Y | 1 | 0 | 166,000 | 11.5 | 61.6 | 425 | 1018 |
6 | I | F | 29 | [c.(1226A>G)];[c.(1226A>)] [p.(Asn409Ser)];[p.(Asn409Ser)] | 20 | ERT | N | 1 | 3.75 | 154,000 | 12.2 | 793 | 17,979 | 1463 |
7 | I | M | 30 | [c.(1226A>G)];[c c.1388+1G>A)] [p.(Asn409Ser)];[p. ?] | 19 | ERT | Y | 3 | 1.2 | 149,000 | 15.4 | 453 | 1988 | 1018 |
8 | I | M | 32 | [c.(1226A>G)];[c.(1448T>G)] [p.(Asn409Ser)];[p.(Leu483Arg)] | 27 | ERT | NA | 1 | 2.5 | 157,000 | 13.3 | 263.4 | 15,917 | 1463 |
9 | I | F | 32 | [c.(1226A>G)];(RecNciI) [p. (Asn409Ser)];(RecNciI) | 22 | SRT | Y | 0 | 2.5 | 146,000 | 11.6 | 371 | 3699 | 1098 |
10 | I | M | 35 | [c.(1226A>G)];(RecNciI) [p. (Asn409Ser)];(RecNciI) | 21 | ERT | Y | 3 | 1 | 212,000 | 16.1 | 77 | 1243 | NA |
11 | I | F | 37 | [c.(1226A>G)];[c. (1448T>C)] [p. (Asn409Ser)];[p. (Leu483Pro)] | 19 | ERT | Y | 0 | 0 | 182,000 | 13.3 | 192.7 | 2306 | NA |
12 | I | F | 40 | [c.(1226A>G)];(RecNciI) [p. (Asn409Ser)];(RecNciI) | 27 | ERT | N | NA | NA | 141,000 | NA | 1057.7 | 8657 | 1255 |
13 | I | F | 41 | [c.(1226A>G)];[c. (1448T>C)] [p. (Asn409Ser)];[p. (Leu483Pro)] | 13 | ERT | N | 9 | 2.9 | 148,000 | 10.7 | 71.6 | 7464 | 1923 |
14 | I | M | 42 | [c.(1226A>G)];[c. (1448T>C)] [p. (Asn409Ser)];[p. (Leu483Pro)] | 11 | ERT | Y | 0 | 0 | 142,000 | 14.4 | 112 | 1194 | 2020 |
15 | I | F | 43 | [c.(1226A>G)];(RecNciI) [p. (Asn409Ser)];(RecNciI) | 7 | ERT | Y | 2 | 1 | 221,000 | 13 | 589 | 736 | 954 |
16 | I | F | 44 | [c.(1226A>G)];[c. (1448T>C)] [p. (Asn409Ser)];[p. (Leu483Pro)] | 14 | ERT | Y | 1 | 0.7 | 171,000 | 15 | 122 | 3022 | 1078 |
17 | I | F | 48 | [c.(1226A>G)];[c.(1226A>G)] [p.(Asn409Ser)];[p.(Asn409Ser)] | 1 | ERT | NA | NA | NA | NA | NA | 246 | NA | NA |
18 | I | M | 49 | [c.(1226A>G)];[c. (1448T>C)] [p. (Asn409Ser)];[p. (Leu483Pro)] | 10 | ERT | Y | 5 | 0.4 | 199,000 | 14.4 | 15 | 116 | NA |
19 | I | F | 53 | [c.(1162G>A)];[c.(1214G>A)] [p.(Glu388Lys)];[p.(Ser405Asn)] | 10 | ERT | Y | 3 | 1.8 | 285,000 | 14.7 | 23.57 | 643 | 885 |
20 | I | F | 55 | [c.(1226A>G)];(RecNciI) [p. (Asn409Ser)];(RecNciI) | 20 | ERT | Y | 5.7 | 13 | 405,000 | 14.7 | 113 | 1216 | 1700 |
21 | I | F | 56 | [c.(1162G>A)];[c.(1214G>A)] [p.(Glu388Lys)];[p.(Ser405Asn)] | 8 | ERT | Y | 4 | 0.4 | 248,000 | 13,4 | 98 | 492 | 1202 |
22 | I | M | 57 | [c.(1226A>G)];(RecNciI)] [p. (Asn409Ser)];(RecNciI)] | 11 | ERT | Y | 2 | 0.5 | 141,000 | 14.9 | 183.5 | 965 | NA |
23 | I | M | 61 | [c.(1226A>G)];(RecNciI)] [p. (Asn409Ser)];(RecNciI)] | 10 | ERT | Y | 3 | 0 | 160,000 | 16.1 | 64.56 | 1170 | 1209 |
24 | I | F | 66 | [c.(1226A>G)];(RecNciI)] [p. (Asn409Ser)];(RecNciI)] | 24 | ERT | Y | 23 ¥ | 1 | 127,000 | 12.8 | 76 | 1741 | 783 |
25 | I | F | 67 | [c.(1226A>G)];(RecNciI)] [p. (Asn409Ser)];(RecNciI)] | 10 | ERT | Y | 4 | 4.5 | 143,000 | 14.8 | 52 | 146 | 876 |
26 | I | M | 67 | [c.(1226A>G)];(RecNciI)] [p. (Asn409Ser)];(RecNciI)] | 14 | ERT | Y | 8 | 2.1 | 213,000 | 14.5 | 71.58 | 401 | 1816 |
27 | I | M | 68 | [c.(1226A>G)];[c.(1226A>G)] [p.(Asn409Ser)];[p.(Asn409Ser)] | 12 | ERT | Y | 0 | 0.5 | 160,000 | 14.2 | 85.86 | 1529 | 1573 |
28 | I | F | 71 | [c.(1226A>G)];[c.(1448T>G)] [p.(Asn409Ser)];[p.(Leu483Arg)] | 11 | ERT | Y | 10 | 4.5 | 309,000 | 13.9 | 120.57 | 257 | 1116 |
29 | III | M | 25 | [c. (1448T>C)]; [c. (1448T>C)] [p. (Leu483Pro)];[ p. (Leu483Pro)] | 23 | ERT | Y | 20 ¥ | 0 | 184,000 | 15.7 | 837 | 4365 | 1561 |
30 | III | M | 30 | [c. (1448T>C)]; [c. (1448T>C)] [p. (Leu483Pro)];[ p. (Leu483Pro)] | 16 | ERT | Y | NA | 19.5 | 586,000 | 12.5 | 802 | 11,801 | NA |
31 | III | F | 33 | [c. (1448T>C)]; [c. (1448T>C)] [p. (Leu483Pro)];[ p. (Leu483Pro)] | 18 | ERT | Y | 25 ¥ | 0.6 | 401,000 | 12.4 | 689 | 12,560 | 1458 |
Patient | Lyso-Gb1 (pmol/L) | Cht (nmol/h/mL) | β-hexo A (nmol/h/mL) | β-hexo B (nmol/h/mL) | Total β-hexo (nmol/h/mL) | % β-hexo A | β-glu (nmol/h/mL) | α-man (nmol/h/mL) | NMD (n) |
---|---|---|---|---|---|---|---|---|---|
7 | 109.04 | 102 | 104 | 3 | 107 | 97 | 3.3 | 2.2 | 2 |
10 | 83.49 | 97 | 81 | 107 | 188 | 43 | 5.5 | 0.8 | 1 |
13 | 57.13 | 19 | 105 | 15 | 120 | 88 | 7 | 0.9 | 2 |
16 | 154.87 | 81 | 190 | 59 | 249 | 76 | 8.5 | 4.7 | 0 |
19 | 66.43 | 17 | 36 | 28 | 65 | 56 | 5 | 0.25 | 3 |
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Vernet Machado Bressan Wilke, M.; Iop, G.D.; Faqueti, L.; Lemos da Silva, L.A.; Kubaski, F.; Poswar, F.O.; Michelin-Tirelli, K.; Randon, D.; Borelli, W.V.; Giugliani, R.; et al. A Brazilian Rare-Disease Center’s Experience with Glucosylsphingosine (lyso-Gb1) in Patients with Gaucher Disease: Exploring a Novel Correlation with IgG Levels in Plasma and a Biomarker Measurement in CSF. Int. J. Mol. Sci. 2024, 25, 2870. https://doi.org/10.3390/ijms25052870
Vernet Machado Bressan Wilke M, Iop GD, Faqueti L, Lemos da Silva LA, Kubaski F, Poswar FO, Michelin-Tirelli K, Randon D, Borelli WV, Giugliani R, et al. A Brazilian Rare-Disease Center’s Experience with Glucosylsphingosine (lyso-Gb1) in Patients with Gaucher Disease: Exploring a Novel Correlation with IgG Levels in Plasma and a Biomarker Measurement in CSF. International Journal of Molecular Sciences. 2024; 25(5):2870. https://doi.org/10.3390/ijms25052870
Chicago/Turabian StyleVernet Machado Bressan Wilke, Matheus, Gabrielle Dineck Iop, Larissa Faqueti, Layzon Antonio Lemos da Silva, Francyne Kubaski, Fabiano O. Poswar, Kristiane Michelin-Tirelli, Dévora Randon, Wyllians Vendramini Borelli, Roberto Giugliani, and et al. 2024. "A Brazilian Rare-Disease Center’s Experience with Glucosylsphingosine (lyso-Gb1) in Patients with Gaucher Disease: Exploring a Novel Correlation with IgG Levels in Plasma and a Biomarker Measurement in CSF" International Journal of Molecular Sciences 25, no. 5: 2870. https://doi.org/10.3390/ijms25052870