Identification of a Reliable Biomarker Profile for the Diagnosis of Gaucher Disease Type 1 Patients Using a Mass Spectrometry-Based Metabolomic Approach
Abstract
:1. Introduction
2. Results and Discussion
3. Materials and Methods
3.1. Ethics Approval
3.2. Patients and Controls
Clinical Features and Biochemical Parameters
3.3. Whole Blood and Plasma Specimen Collection and Processing
3.4. Reagents
3.5. Sample Preparation
3.6. Instrumentation and Parameters
4. Conclusions
5. Study Limitations
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Appendix A
References
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Patient ID | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | 15 | 16 |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Age | 62 | 49 | 43 | 62 | 22 | 47 | 49 | 70 | 63 | 71 | 62 | 43 | 70 | 53 | 24 | 44 |
Gender | F | F | F | F | F | M | F | F | M | M | F | F | F | F | M | F |
Age at diagnosis | 28 | 40 | 36 | 16 | N/E | 12 | 40 | 42 | 19 | 21 | 3 | 36 | N/E | 44 | 13 | 27 |
Mutations | N370S N370S | N370S N370S | N370S L444P | N370S N370S | N370S W184 | N370S L444P | N370S N370S | N370S L444P | N370S R120W | N370S W378G | L444P L444P | N370S N370S | N370S L444P | N370S R496H | N370S L444P | L444P 84GG |
Treatment | No | No | No | No | No | No | No | No | No | No | No | No | No | No | No | No |
Bone disease | ||||||||||||||||
Bone pain | - | Mild | Moderate | Mild | - | Moderate | - | - | - | Mild | Moderate | Mild | Moderate | - | - | Mild |
Bone crisis | - | - | - | - | - | Moderate | - | - | Moderate | - | - | - | - | - | - | - |
Erlenmeyer flask deformity | x | - | - | - | - | - | - | - | - | x | x | - | - | x | ||
Bone marrow infiltration | x | x | x | x | - | x | - | - | - | x | - | x | x | - | x | x |
Osteopenia | - | - | - | - | - | x | - | - | x | x | x | - | x | x | - | - |
Infarction | - | - | - | - | - | x | - | - | x | - | - | - | x | - | - | x |
Avascular necrosis | - | - | - | - | - | x | - | - | - | - | - | - | - | - | - | - |
New fractures | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - |
Lytic lesions | x | - | - | - | - | - | - | - | x | - | - | - | - | - | - | - |
Decreased bone mineral density | - | - | - | - | - | x | - | - | - | x | - | - | - | x | - | - |
Bone marrow burden | DGS 5 | LL 5 S 6–7 | N/E | LL 4 S 3 | N/E | LL 4 S 3 | N/E | LL 7 S 5 | DGS 7 | N/E | N/E | LL 4 S 5–6 | DGS 7 | LL 2 S 3 | N/E | LL 7 S 7 |
Hematological and visceral manifestations | ||||||||||||||||
Anemia | - | - | x | - | - | - | - | - | x | - | x | x | - | - | - | - |
Hemoglobin (g/L) | 125 | 125 | 118 | 140 | 127 | 149 | 122 | 132 | 103 | 140 | 110 | 113 | 123 | 117 | 124 | 127 |
Thrombocytopenia and coagulopathy | - | x | x | x | - | - | x | - | x | - | - | x | x | - | x | x |
Platelet counts (/L) | 156 | 87 | 65 | 95 | 123 | 197 | 117 | 144 | 63 | 182 | 185 | 82 | 130 | 254 | 103 | 71 |
Splenomegaly | Mild | Mild | Mild | - | - | - | x | N/A | Moderate | N/A | N/A | - | N/A | - | - | N/A |
Hepatomegaly | - | Mild | Mild | Mild | - | Mild | - | Mild | Moderate | N/E | Mild | Moderate | Mild | Moderate | Severe | - |
Splenectomized | - | - | - | - | - | - | - | x | - | x | x | - | x | - | - | x |
Gammopathies and malignancy | - | - | - | - | - | - | - | - | - | x | - | - | - | - | - | - |
Pulmonary disease | - | - | ||||||||||||||
Elevated arterial pressure | - | - | - | - | - | - | - | - | - | x | x | - | - | - | - | - |
Severe pulmonary hypertension | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - |
Hepatopulmonary syndrome | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - |
Respiratory failure | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - |
Other | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - |
Parameters | Description |
---|---|
Column | Halo HILIC 2.7 |
ID x Length | 4.6 × 150 mm |
Particle size | 2.7 μm |
Column temperature | 30 °C |
Weak Wash solvent | 94.5:2.5:2.5:0.5 ACN:MeOH:H2O:FA + 5 mM Amm. Form. |
Strong Wash solvent | ACN |
Injection volume | 10 μL |
Injection mode | Partial Loop |
Autosampler temperature | 10 °C |
Mobile phase A | 94.5:2.5:2.5:0.5 ACN:MeOH:H2O:FA + 5 mM Amm. Form. |
Mobile phase B | 10:89.5:0.5 ACN:H2O:FA + 5 mM Amm. Form. |
Flow rate | 0.5 mL/min |
Gradient (% mobile phase B) | 0 to 5min: 0% |
5.0 to 20.0 min: 0–10% (Linear gradient) | |
20.0 to 25.0 min: 10% | |
25.0 to 35.0 min: 10–60% (Linear gradient) | |
35.0 to 40.0 min: 60 | |
40.0 to 45.0 min: 0% |
Parameters | Description |
---|---|
Scan Mode | MS-TOF |
Ionization Mode | Electrospray Ionization |
Polarity | Positive |
Analyzer Mode | V |
Dynamic Range | Extended |
Capillary Voltage | 1.4 kV |
Sampling Cone Voltage | 10 V |
Extraction Cone Voltage | 5.0 V |
Source Temperature | 150 °C |
Desolvation Temperature | 450 °C |
Cone Gas Flow | 30 L/h |
Desolvation Gas Flow | 700 L/h |
Trap Collision Energy | 4.0 V |
Transfer Collision Energy | 2.0 V |
Data Format | Centroid |
Mass Range | 50–1000 Da |
Scan Time | 0.1 s |
Lock mass | |
Compound | Terfenadine (500 nM) |
Exact Mass | 472.3215 Da |
Solvent | 94.5:5:0.5 H2O:ACN:FA |
Scan Time | 0.5 s |
Interval | 5.0 s |
Sampling Cone Voltage | 5 V |
Trap Collision Energy | 10 |
Mass Window | ±0.2 Da |
Scan Average | 3 |
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Menkovic, I.; Boutin, M.; Alayoubi, A.; Mercier, F.E.; Rivard, G.-É.; Auray-Blais, C. Identification of a Reliable Biomarker Profile for the Diagnosis of Gaucher Disease Type 1 Patients Using a Mass Spectrometry-Based Metabolomic Approach. Int. J. Mol. Sci. 2020, 21, 7869. https://doi.org/10.3390/ijms21217869
Menkovic I, Boutin M, Alayoubi A, Mercier FE, Rivard G-É, Auray-Blais C. Identification of a Reliable Biomarker Profile for the Diagnosis of Gaucher Disease Type 1 Patients Using a Mass Spectrometry-Based Metabolomic Approach. International Journal of Molecular Sciences. 2020; 21(21):7869. https://doi.org/10.3390/ijms21217869
Chicago/Turabian StyleMenkovic, Iskren, Michel Boutin, Abdulfatah Alayoubi, François E. Mercier, Georges-Étienne Rivard, and Christiane Auray-Blais. 2020. "Identification of a Reliable Biomarker Profile for the Diagnosis of Gaucher Disease Type 1 Patients Using a Mass Spectrometry-Based Metabolomic Approach" International Journal of Molecular Sciences 21, no. 21: 7869. https://doi.org/10.3390/ijms21217869