Table 3.
Clinical presentation of females with and without ERT with ERT indications with nonsense and missense mutations
| Females with ERT | Females without ERT | |||
|---|---|---|---|---|
| Clinical presentation, laboratory parameters and medication | Mmissense mutations (n = 65) | Nonsense mutations (n = 59) | Missense mutations (n = 51) | Nonsense mutations (n = 25) |
| Age [y] | 53 ± 14 | 53 ± 15 | 45 ± 15 | 40 ± 13 |
| ERT duration [months] | 57 ± 47 | 81 ± 46** | - | - |
| α-galactosidase A activity below reference [n] | 24 (60.0) | 18 (51.4) | 11 (39.3) | 13 (76.5)* |
| Lyso-Gb3 value [ng/ml] | 6.3 ± 4.1 | 8.6 ± 8.0 | 6.9 ± 6.0 | 9.9 ± 5.0 |
| Lyso-Gb3 value above reference [n] | 30 (88.2) | 40 (100.0)* | 26 (70.3) | 17 (94.4) |
| Angiokeratoma [n] | 25 (39.7) | 34 (60.7)* | 10 (20.4) | 10 (41.7) |
| Edema [n] | 10 (15.4) | 18 (30.5) | 0 (0.0) | 1 (4.2) |
| Gastrointestinal pain [n] | 22 (33.9) | 10 (17.5) | 19 (40.4) | 7 (29.2) |
| Hypohidrosis [n] | 22 (34.4) | 27 (47.4) | 15 (29.4) | 7 (29.7) |
| Cornea verticillata [n] | 37 (63.8) | 39 (67.2) | 16 (50.0) | 13 (65.0) |
| Tinnitus [n] | 23 (35.9) | 19 (32.2) | 9 (18.8) | 4 (16.7) |
| Hypacusis [n] | 19 (24.6) | 11 (19.0) | 4 (8.3) | 3 (13.0) |
| FD-related pain [n] | 41 (63.1) | 41 (69.5) | 21 (41.2) | 16 (66.7)* |
| Fatigue [n] | 32 (50.8) | 30 (51.7) | 11 (21.6) | 4 (16.7) |
| Ever TIA [n] | 4 (6.4) | 9 (15.8) | 2 (4.1) | 2 (8.3) |
| Ever stroke [n] | 11 (19.0) | 10 (19.6) | 3 (5.9) | 0 (0.0) |
| SFN [n] | 10 (29.4) | 12 (29.3) | 3 (7.9) | 6 (27.3) |
| Disease severity score | ||||
| MSSI score | 21.8 ± 12.0 | 19.6 ± 9.4 | 7.5 ± 5.3 | 6.9 ± 5.1 |
| Cardiac measures | ||||
| Septal diameter [mm] | 11.8 ± 2.7 | 12.8 ± 4.4 | 9.6 ± 2.2 | 9.6 ± 1.7 |
| LVH [n] | 33 (55.0) | 31 (56.4) | 10 (20.0) | 4 (16.7) |
| Posterior wall diameter [mm] | 11.2 ± 2.8 | 11.5 ± 3.4 | 9.5 ± 1.9 | 9.1 ± 1.7 |
| RWT [cm] | 0.52 ± 0.14 | 0.54 ± 0.21 | 0.42 ± 0.10 | 0.39 ± 0.07 |
| Pacemaker [n] | 10 (15.4) | 8 (13.6) | 0 (0.0) | 0 (0.0) |
| Myocardial infarction [n] | 3 (5.7) | 4 (8.3) | 0 (0.0) | 0 (0.0) |
| Renal measures | ||||
| Albumin/creatinine-ratio [mg/gCreatinine] | 66 [0–1148] | 39 [0–4773] | 37 [0–734] | 36 [6–535] |
| Albuminuria [n] | 34 (64.2) | 26 (59.1) | 19 (55.9) | 11 (64.7) |
| Creatinine [mg/dl] | 1.07 ± 1.24 | 0.89 ± 0.34 | 0.76 ± 0.16 | 0.74 ± 0.12 |
| eGFRcreat [ml/min/1.73 m2]a | 81.3 ± 25.4 | 81.0 ± 25.3 | 96.7 ± 19.8 | 101.0 ± 18.4 |
| Manifestations in different organs justifying ERT (per patient) [n] | 2 [1–5] | 3 [1–4] | 1 [1–3] | 1 [1–3] |
Nonsense mutations include single nucleotide exchanges, resulting in a stop codon (termination), deletion or insertions of nucleotides resulting in a frame shift or large deletions within the protein, or splice site mutations, resulting in altered splice products of mRNA. Categorical data are presented as n and are % of total in parenthesis. Otherwise data are presented as mean ± SD or median [range]. eGFR estimated glomerular filtration rate (aexcluding patients with dialysis and/or kidney transplant), LVH Left ventricular hypertrophy, MSSI Mainz Severity Score Index, SFN small fiber neuropathy, RWT relative wall thickness, TIA transitory ischemic attack. eGFRcreat is calculated via the CKD-EPI formula according to Levey et al. 2009. missense vs. nonsense mutations: * p < 0.05, ** p < 0.01