Table 1.
Case | Age (yr) | Protein Change | cDNA Mutation | Mutation Category | α-Gal-A Activity (%LNL) | Plasma GL3 | GFR | UPER | RAAS Blockade | Nonrenal Fabry Features |
---|---|---|---|---|---|---|---|---|---|---|
1 | 4 | p.(Tyr216Asp) | c.646T>G | Missense | NK | NK | 92 | NK | N | NK |
2 | 5 | p.(Arg112Cys) | c.334C>T | Missense | 0% | NK | 122 | 0.460 | N | None |
3 | 7 | p.(Met267Arg) | c.800T>G | Missense | 14% | 7.5 | 106 | 0.250 | N | CO, PN, GI |
4 | 11 | p.(His302Alafs*13) | c.903_904insG | Frameshift | 0% | NK | 121 | 0.150 | N | NK |
5 | 11 | NK | NK | NK | 20% | NK | NK | 0 | N | CO, AK |
6 | 12 | NK | NK | NK | 38% | NK | NK | 0.039 | N | CO, AK |
7 | 13 | NK | NK | NK | 0% | NK | 122 | 0.169 | N | NK |
8 | 15 | NK | NK | NK | 3% | NK | 93 | 0.082 | N | NK |
9 | 15 | NK | NK | NK | 0% | NK | 103 | 0.088 | N | NK |
10 | 15 | NK | NK | NK | 3% | NK | 134 | 0.079 | N | NK |
11a | 15 | NK | NK | NK | NK | NK | NK | 0.350 | N | CO, AK, PN |
12 | 16 | p.(Arg404del) | c.1212_1214delAAG | Deletion | 49% | 13.4 | 112 | 0.090 | N | CO, AK, PN, GI |
13 | 17 | p.(Arg227Ter) | c.679C>T | Nonsense | 2% | 17.1 | 190 | 0.229 | N | CO, AK, PN |
14 | 17 | p.(Asn272Lys) | c.816C>A | Missense | 2% | NK | 107 | 0.110 | N | PN, GI |
15 | 17 | NK | NK | NK | 0% | NK | 97 | 0.082 | N | NK |
16 | 17 | NK | NK | NK | 3% | NK | 127 | 0.069 | N | NK |
17 | 18 | p.(Met267Arg) | c.800T>G | Missense | 19% | 4.8 | 96 | 0.220 | N | CO, AK, PN, GI |
18 | 18 | p.(Arg227Ter) | c.679C>T | Nonsense | 2% | 19.3 | 156 | 0.167 | N | CO, AK, PN |
19 | 20 | NK | c.802–3_802-2delCA | Intronic deletion/ splicing | 3% | NK | 153 | 0.167 | N | CO, AK |
20 | 20 | p.(Arg220Lys) | c.658C>T | Nonsense | 2% | 7.7 | 70 | 0.211 | Y | CO, AK, PN |
21 | 20 | p.(Asn272Lys) | c.816C>A | Missense | <24% | 27.3 | 131 | 0.024 | N | CO, AK, PN, GI |
22 | 21 | p.(Arg227Ter) | c.679C>T | Nonsense | 2% | 15.8 | 130 | 0.102 | N | AK, PN, GI |
23 | 21 | p.(Arg227Ter) | c.679C>T | Nonsense | NK | 2 | 289 | 0.140 | N | CO, PN, GI |
24 | 23 | p.(Asn298Lysfs*2) | c.893_894insG | Insertion | 6% | 7 | 112 | 0.102 | N | CO, AK, GI |
25 | 23 | NK | NK | NK | 5% | 8.5 | 178 | NK | N | CO, AK, LVH, PN |
26 | 23 | p.(Gly132Arg) | c.394G>A | Missense | <24% | 9.9 | 88 | NK | N | CO, AK, |
27 | 23 | p.(Arg404del) | c.1212_1214delAAG | Deletion | 14% | 8.5 | 113 | 0.240 | N | CO, PN, GI |
28 | 23 | NK | NK | NK | 6% | 10.5 | 148 | NK | N | CO, AK, PN |
29 | 24 | NK | NK | NK | 4% | 20 | 126 | 0.140 | N | CO, AK, PN |
30 | 25 | NK | NK | NK | <24% | 13.9 | 146 | 0.402 | N | CO, AK, AR, PN, GI |
31 | 25 | NK | NK | NK | 6% | NK | 110 | NA | N | CO, AK |
32 | 25 | p.([Asp55Val; Gln57Leu]) | c.(164A>T; 170A>T) | Double missense | 0% | NK | 114 | 0.018 | NK | NK |
33 | 26 | p.(Trp204Ter) | c.612G>A | Nonsense | 6% | 9.9 | 96 | NK | N | CO, AK, PN, GI |
34 | 30 | p.(Arg404del) | c.1212_1214delAAG | Deletion | 28% | 10.2 | 86 | 0.220 | N | CO, AK, PN, GI |
35 | 31 | NK | c.639+4A>T | Splicing | 3% | 5.3 | 167 | 1.150 | N | CO |
36 | 33 | p.(Asp244Asn) | c.730G>A | Missense | NK | NK | 115 | 0.023 | NK | NK |
37 | 33 | p.(Val339Alafs*32) | c.1016_1026delTGTGGGAACGA | Deletion | 0% | 7.7 | 103 | 0.383 | N | CO, AK, PN |
38 | 34 | p.(Tyr216Cys) | c.647A>G | Missense | 0% | NK | 119 | 0.029 | NK | NK |
39 | 34 | NK | c.639+4A>T | Splicing | 3% | 29.5 | 137 | 0.297 | N | CO, AK, LVH, AR, MI, PN |
40 | 35 | p.(Ser102Glnfs*19) | c.304delC | Deletion | 3% | 16.9 | 102 | NK | Y | CO, AK, PN |
41 | 35 | p.(Gly144Val) | c.431G>T | Missense | 0% | NK | 105 | 0.009 | NK | NK |
42 | 36 | p.(Val281_Thr282delinsAla) | c.842_844delTAA | Deletion | <24% | 10.8 | 102 | 1.267 | N | CO, AK, PN |
43 | 37 | p.(Ser148Arg) | c.444T>G | Missense | 6% | 13.7 | 101 | 0.359 | N | CO, AK, PN |
44 | 38 | NK | NK | NK | <24% | 35.5 | 135 | 1.615 | N | CO, AK, PN |
45 | 38 | p.(Ser148Arg) | c.444T>G | Missense | 6% | 12 | 101 | NA | N | CO, AK, MI |
46 | 40 | p.(Asp153del) | c.457_459delGAC | Deletion | 0% | NK | 76 | 3.380 | Y | LVH |
47 | 40 | p.(Arg112Cys) | c.334C>T | Missense | NK | 4.8 | 79 | 0.230 | N | CO, AK, LVH |
48 | 40 | p.(Arg301Ter) | c.901C>T | Nonsense | 0% | 19.2 | 133 | 0.462 | N | CO, AK, GI |
49 | 45 | p.(Pro259Arg) | c.776C>G | Missense | 3% | NK | 104 | 0.027 | NK | NK |
50 | 45 | p.(Ala156Thr) | c.466G>A | Missense | NK | NK | 74 | 0.016 | NK | NK |
51 | 45 | p.(Leu243Phe) | c.729G>C | Missense | 0% | NK | 104 | 0.008 | NK | NK |
52 | 46 | NK | NK | NK | <24% | 25.3 | 154 | 0.209 | N | CO, AK, LVH, PN, GI |
53 | 52 | p.(Asp33Gly) | c.98A>G | Missense | 0% | NK | 83 | 0.016 | NK | NK |
54 | 53 | p.(Trp44Cys) | c.132G>T | Missense | NK | NK | 75 | 0.090 | Y | CO, AK, LVH, GI |
55 | 60 | p.(Asp322Glu) | c.966C>G | Missense | 1% | NK | NK | NK | NK | NK |
Plasma GL3 measred in μg/mL; GFR measured in ml/min per 1.73 m2; UPER, measured in mg/g if urine protein-creatinine ratio or g/d if 24 h collection. LNL, lower normal limit; RAAS, renin-angiotensin aldosterone system; NK, not known; N, no; CO, corneal opacity; PN, peripheral neuropathy; GI, gastrointestinal; AK, angiokeratoma; Y, yes; AR, arrhythmia; LVH, left ventricular hypertrophy; MI, myocardial infarction.
Fabry disease diagnosis confirmed by clinical history of periodic lower-extremity pain crises with and without fevers, angiokeratomas, cornea verticillata, mild proteinuria at age 14 yr, kidney biopsy findings consistent with Fabry nephropathy in the absence of lysosomotrophic medications, and a maternal uncle with acroparesthesias and cardiac disease who died prematurely at age 40 yr.