Table 1.
Clinical phenotype of patients with late-onset FD due to the p.F113L mutation.
| Clinical manifestations | Fabry patients (n = 203) | Fabry males (n = 79) | Fabry females (n = 124) | p |
|---|---|---|---|---|
| Age at FD diagnosis (years) (mean ± SD) | 46 ± 18 | 49 ± 15 | 44 ± 19 | 0.021 |
| α-GAL A activity (mean ± SD) | ||||
| Plasma (nmol/h/mL) | 5.1 ± 5.1 | 0.4 ± 1.4 | 8.2 ± 4.2 | <0.001 |
| Leukocytes (nmol/h/mg) | 16.6 ± 17.4 | 2.0 ± 3.6 | 26.7 ± 15.9 | <0.001 |
| Disease biomarkers (mean ± SD) | ||||
| Urinary GB3 (μg/mmol creatinine) | 91.0 ± 152.1 | 181.7 ± 208.5 | 30.2 ± 23.1 | <0.001 |
| Plasma Lyso-GB3 (ng/mL) | - | 7.7 ± 3.0 | <2a | - |
| Cardiac manifestations | ||||
| LVH (%) | 80 (40.2%) | 57 (73.1%) | 23 (19.0%) | <0.001 |
| IVS thickness (mm) (mean ± SD) | 11.6 ± 4.4 | 14.3 ± 4.0 | 9.9 ± 3.6 | <0.001 |
| PW thickness (mm) (mean ± SD) | 10.3 ± 3.5 | 12.6 ± 3.5 | 8.9 ± 2.7 | <0.001 |
| LV mass (g/m2) (mean ± SD) | 100.3 ± 49.4 | 132.5 ± 51.8 | 79.6 ± 34.7 | <0.001 |
| LV ejection fraction (%) (mean ± SD) | 66.0 ± 7.0 | 65.9 ± 7.9 | 66.0 ± 6.3 | 0.710 |
| LV diastolic dysfunction (%) | 55 (27.8%) | 35 (44.9%) | 20 (16.7%) | <0.001 |
| Abnormal relaxation pattern (%) | 32 (58.2%) | 17 (48.6%) | 15 (75.0%) | |
| Pseudonormal pattern (%) | 22 (40.0%) | 17 (48.6%) | 5 (25.0%) | 0.145 |
| Restrictive pattern (%) | 1 (1.8%) | 1 (2.9%) | 0 (0.0%) | |
| LVH on cardiac MRI (%) | 60 (36.1%) | 44 (68.8%) | 16 (15.7%) | <0.001 |
| LV mass on cardiac MRI (g/m2) | 72.2 ± 29.2 | 93.8 ± 29.8 | 58.6 ± 18.8 | <0.001 |
| Late gadolinium enhancement (%) | 36 (21.4%) | 25 (39.1%) | 11 (10.6%) | <0.001 |
| Heart failure (%) | 44 (21.9%) | 26 (32.9%) | 18 (14.8%) | 0.002 |
| NYHA Class I (%) | 34 (77.3%) | 23 (88.5%) | 11 (61.1%) | |
| NYHA Class II (%) | 9 (20.5%) | 2 (7.7%) | 7 (38.9%) | 0.034 |
| NYHA Class III (%) | 1 (2.3%) | 1 (3.8%) | 0 (0.0%) | |
| NYHA Class IV (%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | |
| Atrial fibrillation (%) | 9 (4.4%) | 6 (7.6%) | 3 (2.4%) | 0.081 |
| Atrial flutter (%) | 3 (1.5%) | 2 (2.5%) | 1 (0.8%) | 0.321 |
| Non-sustained ventricular tachycardia (%) | 18 (8.9%) | 11 (14.1%) | 7 (5.6%) | 0.040 |
| Atrioventricular block (%) | 30 (14.8%) | 16 (20.3%) | 14 (11.3%) | 0.079 |
| 1st degree (%) | 19 (10.5%) | 8 (12.3%) | 11 (9.5%) | 0.552 |
| 2nd degree (%) | 9 (4.5%) | 6 (7.6%) | 3 (2.4%) | 0.083 |
| 3rd degree (%) | 12 (5.9%) | 10 (12.7%) | 2 (1.6%) | 0.001 |
| Right bundle branch block (%) | 36 (19.6%) | 26 (38.8%) | 10 (8.5%) | <0.001 |
| Left anterior fascicular block (%) | 42 (23.0%) | 30 (45.5%) | 12 (10.3%) | <0.001 |
| Left bundle branch block (%) | 2 (1.1%) | 1 (1.6%) | 1 (0.9%) | 0.668 |
| Bifascicular block (%) | 26 (13.1%) | 19 (25.3%) | 7 (5.7%) | <0.001 |
| Pacemaker (%) | 13 (6.4%) | 10 (12.7%) | 3 (2.4%) | 0.004 |
| Implantable cardioverter-defibrillator (%) | 2 (1.0%) | 1 (1.3%) | 1 (0.8%) | 0.747 |
| Myocardial ischemic events (%) | 10 (4.9%) | 10 (12.7%) | 0 (0.0%) | <0.001 |
| Renal manifestations | ||||
| Albuminuria A2 (30-300mg/24 h) (%) | 48 (24.6%) | 28 (36.8%) | 20 (16.8%) | 0.002 |
| Albuminuria A3 (>300 mg/24 h) (%) | 18 (9.2%) | 12 (15.8%) | 6 (5.0%) | 0.011 |
| Albuminuria A2 or A3 (≥30 mg/24 h) (%) | 66 (33.7%) | 40 (52.6%) | 26 (21.7%) | <0.001 |
| Chronic kidney disease stages | ||||
| G1 (eGFR ≥90 mL/min/1.73m2) (%) | 139 (70.6%) | 45 (60.0%) | 94 (77.0%) | 0.011 |
| G2 (eGFR 60-89 mL/min/1.73m2) (%) | 45 (22.8%) | 23 (30.7%) | 22 (18.0%) | 0.040 |
| G3a (eGFR 45-59 mL/min/1.73m2) (%) | 10 (5.1%) | 6 (8.0%) | 4 (3.3%) | 0.143 |
| G3b (eGFR 30-44 mL/min/1.73m2) (%) | 1 (0.5%) | 0 (0.0%) | 1 (0.8%) | 0.432 |
| G4 (eGFR 15-29 mL/min/1.73m2) (%) | 1 (0.5%) | 1 (1.3%) | 0 (0.0%) | 0.201 |
| G5 (eGFR <15 mL/min/1.73m2) (%) | 1 (0.5%) | 0 (0.0%) | 1 (0.8%) | 0.432 |
| Chronic kidney disease stage ≥ G3 (%) | 13 (6.6%) | 7 (9.3%) | 6 (4.9%) | 0.225 |
| Neurological and neuropsychiatric manifestations | ||||
| Stroke (%) | 6 (3.0%) | 3 (3.8%) | 3 (2.4%) | 0.572 |
| Transient ischemic attack (%) | 1 (0.5%) | 0 (0.0%) | 1 (0.8%) | 0.424 |
| Brain white matter lesions (%) | 83 (50.3%) | 35 (53.8%) | 48 (48.0%) | 0.463 |
| Brain haemorrhage (%) | 2 (1.0%) | 2 (2.6%) | (0.0%) | 0.073 |
| Carpal tunnel syndrome (%) | 36 (19.7%) | 17 (23.9%) | 19 (17.0%) | 0.247 |
| Acroparesthesias (%) | 62 (30.7%) | 14 (17.9%) | 48 (38.7%) | 0.002 |
| Hypohidrosis (%) | 3 (1.5%) | 0 (0.0%) | 3 (2.4%) | 0.166 |
| Cold, heat or exercise intolerance (%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | - |
| Depression (%) | 41 (20.8%) | 12 (15.8%) | 29 (24.0%) | 0.169 |
| Anxiety (%) | 58 (29.3%) | 22 (28.9%) | 36 (29.5%) | 0.933 |
| Eye manifestations | ||||
| Cornea verticillata (%) | 19 (10.3%) | 11 (15.5%) | 8 (7.1%) | 0.068 |
| Cataracts (%) | 25 (13.5%) | 10 (14.3%) | 15 (13.0%) | 0.811 |
| Retinal vessel tortuosity (%) | 6 (3.3%) | 2 (2.9%) | 4 (3.5%) | 0.814 |
| Ear manifestations | ||||
| Sensorineural deafness (%) | 80 (44.7%) | 46 (62.2%) | 34 (32.4%) | <0.001 |
| Tinnitus (%) | 30 (16.3%) | 17 (23.0%) | 13 (11.8%) | 0.045 |
| Dermatological manifestations | ||||
| Angiokeratomas (%) | 4 (2.1%) | 0 (0.0%) | 4 (3.5%) | 0.106 |
| Pulmonary manifestations | ||||
| Lung obstructive disease (%) | 29 (17.5%) | 15 (22.7%) | 14 (14.0%) | 0.147 |
| Gastrointestinal manifestations (%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | – |
| Comorbidities | ||||
| Hypertension (%) | 66 (32.7%) | 30 (38.0%) | 36 (29.3%) | 0.198 |
| Diabetes mellitus (%) | 23 (11.4%) | 13 (16.5%) | 10 (8.1%) | 0.069 |
| Dyslipidemia (%) | 85 (42.1%) | 46 (58.2%) | 39 (31.7%) | <0.001 |
| Smoking (%) | 21 (10.4%) | 18 (22.8%) | 3 (2.4%) | <0.001 |
| Concomitant medications | ||||
| ACEI/ARB (%) | 79 (38.9%) | 41 (51.9%) | 38 (30.6%) | 0.002 |
p: Males vs. Females.
p < .05 are marked in bold.
Valid percentages are shown.
ACEI, angiotensin-converting-enzyme inhibitors; α-GAL A, α- galactosidase A; ARB, angiotensin II receptor blocker; e-GFR, estimated glomerular filtration rate; FD, Fabry disease; IVS, interventricular septum; LV, left ventricular; LVH, left ventricular hypertrophy; NYHA, New York Heart Association; PW, posterior wall.
Reference values: Enzymatic activity of α-galactosidase A on plasma 6–19 nmol/h/mL, and on leukocytes 36–80 nmol/h/mg; urinary GB3 0.87–13 μg/mmol creatinine; plasma Lyso-GB3 0–1.9 ng/mL
a
Below lower level of quantitation of plasma lyso-GB3 (2 ng/mL).