Fabry Disease in Slovakia: How the Situation Has Changed over 20 Years of Treatment
Abstract
:1. Introduction
2. Materials and Methods
3. Results
4. Discussion
4.1. Fabry Disease in Females
4.2. Genetic Variants of Unknown Significance (GVUS)
4.3. Treatment of Fabry Disease
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Nr. | GLA Variant | Sex | Age at Diagnosis (Years) | Phenotype Previously Described | Type of Screening | Therapy | Age at Treatment (Years) | Comment |
---|---|---|---|---|---|---|---|---|
Patient with pathogenic variant | ||||||||
1 | c.128G>A (p.Gly43Asp) | M | 20 | classic | kidney | Y | 24 | son of patient nr. 2 and father of patient nr. 3 |
2 | c.128G>A (p.Gly43Asp) | F | 50 | classic | pedigree | Y | 62 | mother of patient nr. 1 |
3 | c.128G>A (p.Gly43Asp) | F | 0 | classic | pedigree | N | daughter of patient nr. 1 | |
4 | c.463G>C (p.D155H) | F | 23 | classic | pedigree | N | mother of patients nr. 5 and nr. 6, daughter of patient nr. 7 | |
5 | c.463G>C (p.D155H) | M | 4 | classic | pedigree | Y | 18 | brother of patient nr. 6 |
6 | c.463G>C (p.D155H) | M | 5 | classic | pedigree | Y | 13 | brother of patient nr. 5 |
7 | c.463G>C (p.D155H) | F | 52 | classic | pedigree | N | mother of patient nr. 4 | |
8 | NA | M | 29 | NA | NA | |||
9 | NA | M | 35 | NA | NA | Y | 35 | |
10 | c.736delA (p.Thr246HisfsTer23) | M | 25 | undescribed/classic | kidney | Y | 25 | son of patient nr. 11 and father of patient nr. 12 |
11 | c.736delA (p.Thr246HisfsTer23) | F | 59 | undescribed/classic | pedigree | N | mother of patient nr. 10 | |
12 | c.736delA (p.Thr246HisfsTer23) | F | 0 | undescribed/classic | pedigree | N | daughter of patient nr. 10 | |
13 | c.169C>T (p.Q57X) | M | 54 | classic | LVH | Y | 54 | father of patient nr. 14 |
14 | c.169C>T (p.Q57X) | F | 24 | classic | pedigree | N | daughter of patient nr. 13 | |
15 | c.98A>G (p.D33G) | M | 58 | classic | LVH | N | father of patients nr. 18 and nr. 19, grandfather of patients nr. 16 and nr. 17 | |
16 | c.98A>G (p.D33G) | M | 8 | classic | pedigree | Y | 14 | son of patient nr. 19 and brother of patient nr. 17 |
17 | c.98A>G (p.D33G) | F | 15 | classic | pedigree | N | daughter of patient nr. 19 and sister of patient nr. 16 | |
18 | c.98A>G (p.D33G) | F | 31 | classic | pedigree | N | daughter of patient nr. 15 | |
19 | c.98A>G (p.D33G) | F | 33 | classic | pedigree | N | daughter of patient nr. 15, mother of patients nr. 16 and nr. 17 | |
20 | c.334C>T (p.R112C) | M | 35 | classic | LVH | Y | 35 | father of patients nr. 21 and nr. 22 |
21 | c.334C>T (p.R112C) | F | 0 | classic | pedigree | N | daughter of patient nr. 20 | |
22 | c.334C>T (p.R112C) | F | 0 | classic | pedigree | N | daughter of patient nr. 20 | |
23 | c.334C>T (p.R112C) | M | 38 | classic | LVH | Y | 38 | |
24 | c.730G>A (p.Asp244Asn) | F | 50 | classic | LVH | Y | 51 | |
25 | c.1073A>G (p.Glu358Gly) | F | 85 | classic | LVH | N | ||
26 | c.801+1G>A, (p.L268IfsX3) | M | 55 | renal | LVH | Y | 56 | new description of phenotype—arrythmia, LVH, depression |
27 | c.758T>C (p.Ile753Thr) | M | 65 | classic | LVH | Y | 65 | brother of patients nr. 28 and nr. 29 |
28 | c.758T>C (p.Ile753Thr) | F | 55 | classic | pedigree | N | sister of patient nr. 27 and nr. 29 | |
29 | c.758T>C (p.Ile753Thr) | M | 62 | classic | pedigree | N | brother of patients nr. 27 and nr. 28 | |
30 | c.157 A>C (p.Asn53His) | F | 42 | undescribed | SM | Y | 43 | arrythmia, neurological impairment |
31 | c.203T>C (p.Leu68Pro) | F | 46 | undescribed | LVH | N | hypertrophic cardiomyopathy | |
Data of 48 Slovak FD patients—part 2 | ||||||||
Patients with GVUS | ||||||||
32 | c.352C>T (p.R118C also p.Arg118Cys) | F | 75 | kidney | N | mother of patient nr.33 | ||
33 | c.352C>T (p.R118C also p.Arg118Cys) | M | 45 | pedigree | N | son of patient nr. 32 | ||
34 | c.352C>T (p.R118C also p.Arg118Cys) | M | 41 | kidney | N | |||
35 | c.427G>A(p.A143T also p.Ala143Thr) | F | 73 | kidney | N | sister of patient nr. 36 | ||
36 | c.427G>A(p.A143T also p.Ala143Thr) | M | 78 | pedigree | N | brother of patient nr. 35 | ||
37 | c.427G>A(p.A143T also p.Ala143Thr) | F | 43 | pedigree | N | daughter of patient nr. 36 | ||
38 | c.427G>A(p.A143T also p.Ala143Thr) | F | 46 | pedigree | N | daughter of patient nr. 36 | ||
39 | c.427G>A(p.A143T also p.Ala143Thr) | F | 49 | pedigree | N | daughter of patient nr. 36 | ||
40 | c.427G>A(p.A143T also p.Ala143Thr) | M | 14 | pedigree | N | son of patient nr. 37 | ||
41 | c.427G>A(p.A143T also p.Ala143Thr) | M | 62 | pedigree | N | brother of patient nr. 35 | ||
42 | c.427G>A(p.A143T also p.Ala143Thr) | M | 73 | kidney | N | father of patient nr. 43 and brother of patient nr. 44 | ||
43 | c.427G>A(p.A143T also p.Ala143Thr) | F | 43 | pedigree | N | daughter of patient nr. 42 | ||
44 | c.427G>A(p.A143T also p.Ala143Thr) | M | 69 | pedigree | N | father of patients nr.45 and nr. 46 and brother of patient nr. 42 | ||
45 | c.427G>A(p.A143T also p.Ala143Thr) | F | 45 | pedigree | N | daughter of patient nr. 44 | ||
46 | c.427G>A(p.A143T also p.Ala143Thr) | F | 46 | pedigree | N | daughter of patient nr. 44 | ||
47 | c.427G>A(p.A143T also p.Ala143Thr) | F | 82 | kidney | N | |||
48 | c.427G>A(p.A143T also p.Ala143Thr) | F | 31 | SM | N |
Nr. | Variant | Sex | Age at First Symptom (Years) | Age at Diagnosis (Years) | Phenotype Previously Described | Age at Treatment (Years) | Time from First Symptom to Diagnosis | Time from Diagnosis to Treatment | Therapy | Duration of ERT (Years) | Effect of Therapy | LysoGb3 Prior ERT | LysoGb3 after ERT (Last Value) | Age at Death (Years) and Reason |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | c.128G>A (p.Gly43Asp) | M | 14 | 20 | classic | 24 | 6 | 4 | ERT (agalsidase beta, agalsidase alfa) | 13 | stabilization of renal parameters; SWB improved | NA | NA | 37; ruptured brain aneurysm |
2 | c.128G>A (p.Gly43Asp) | F | 54 | 50 | classic | 62 | −4 | 12 | ERT (agalsidase alfa) | 7 | temporary improvement of CV parameters, improvement of physical activities | NA | 6.0 | 69; heart failure |
3 | c.463G>C (p.D155H) | M | 12 | 4 | classic | 18 | −8 | 14 | ERT (agalsidase beta) | 8 | stabilization and improvement of renal and CV parameters, SWB improved | NA | 7.9 (N 0–3.5) ng/mL | |
4 | c.463G>C (p.D155H) | M | 13 | 5 | classic | 13 | −7 | 8 | ERT (agalsidase beta) | 4 | renal and CV parameters in reference level; normal psychomotor development | 142.9 (N 0–3.5) ng/ml | 11.1 (N 0–3.5) ng/mL | |
5 | NA | M | 15 | 35 | NA | 35 | 20 | 0 | ERT (agalsidase beta) | NA | NA | NA | NA | |
6 | c.736delA (p.Thr246HisfsTer23) | M | 14 | 25 | undescribed/classic | 25 | 11 | 0 | ERT (agalsidase beta) | 16 | stabilization and improvement of renal parameters; pain relief; SWB improved | NA | 25.1 (N 0–3.5) ng/mL | |
7 | c.169C>T (p.Q57X) | M | 35 | 54 | classic | 54 | 19 | 0 | ERT (agalsidase alfa) | 8 | temporary improvement of CV parameters, stabilization of renal parameters, SWB improved | NA | 40 (N 0–1.8) ng/mL | 62; multiorgan failure after repeated stroke |
8 | c.98A>G (p.D33G) | M | 14 | 8 | classic | 14 | −6 | 6 | ERT (agalsidase alfa) | 2 | stabilization of renal parameters; normal psychomotor development | 38 (N 0–1.8) ng/ml | 11.7 (N 0–1.8) ng/mL | |
9 | c.334C>T (p.R112C) | M | 14 | 35 | classic | 35 | 21 | 0 | ERT (agalsidase alfa) | 9 | stabilization and improvement of renal and CV parameters; SWB improved | NA | 14.7 (N 0–3.5) ng/mL | |
10 | c.334C>T (p.R112C) | M | 10 | 38 | classic | 38 | 28 | 0 | ERT (agalsidase beta) | 3 | stabilization of renal and CV parameters, improvement of physical activities | 89.5 (N 0–3.5) ng/ml | 16.0 (N 0–3.5) ng/mL | |
11 | c.730G>A (p.Asp244Asn) | F | 16 | 50 | classic | 51 | 34 | 1 | ERT (agalsidase alfa) | 1 | stabilization and improvement of renal and CV parameters; SWB improved | 5.7 (N 0–1.8) ng/mL | 4.2 (N 0–1.8) ng/mL | |
12 | c.801+1G>A, (p.L268IfsX3) | M | 10 | 55 | renal | 56 | 45 | 1 | ERT (agalsidase alfa) | 3.5 | stabilization of renal parameters; end of ERT after 3.5 years, due to deterioration of cardiological findings | 95.8 (N 0–1.8) ng/mL | 48.1 (N 0–1.8) ng/mL | |
13 | c.758T>C (p.Ile753Thr) | M | 64 | 65 | classic | 65 | 1 | 0 | ERT (agalsidase beta) | 3 | stabilization of renal and improvement of CV parameters, improvement of physical activities | 18.1 (N 0–3.5) ng/mL | 8.6 (N 0–3.5) ng/mL | |
14 | c.157 A>C p.(Asn53His) | F | 16 | 42 | undescribed | 43 | 26 | 1 | ERT (agalsidase alfa) | 1 | stabilization of renal and CV parameters; improvement in gross motor function and self-activity | 1.3 (N 0–1.8) ng/mL | 1.0 (N 0–1.8) ng/mL |
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Jurickova, K.; Jungova, P.; Petrovic, R.; Mattosova, S.; Hlavata, T.; Kostalova, L.; Hlavata, A. Fabry Disease in Slovakia: How the Situation Has Changed over 20 Years of Treatment. J. Pers. Med. 2022, 12, 922. https://doi.org/10.3390/jpm12060922
Jurickova K, Jungova P, Petrovic R, Mattosova S, Hlavata T, Kostalova L, Hlavata A. Fabry Disease in Slovakia: How the Situation Has Changed over 20 Years of Treatment. Journal of Personalized Medicine. 2022; 12(6):922. https://doi.org/10.3390/jpm12060922
Chicago/Turabian StyleJurickova, Katarina, Petra Jungova, Robert Petrovic, Slavomira Mattosova, Tereza Hlavata, Ludmila Kostalova, and Anna Hlavata. 2022. "Fabry Disease in Slovakia: How the Situation Has Changed over 20 Years of Treatment" Journal of Personalized Medicine 12, no. 6: 922. https://doi.org/10.3390/jpm12060922