1st Faculty of Medicine Charles University 1st Faculty of Medicine Charles University ADENYLOSUCCINATE LYASE DEFICIENCY
02.09.2021

Database of patients

Patient Family Country Mutations in cDNA Mutations in protein Phenotype SAdo [umol/l] in CSF *** SAICAr [umol/l]in CSF SAdo/ SAICAr in CSF Ref.
1 1 Australia -49T>C
severe 4.9# 6.9# 0.7# [21]
953C>T P318L
2 2 Italy -49T>C severe 158 167 0.9 [26]

1277G>A R426H
3 3 Norway -49T>C severe [21]

1339T>C S447P
4 4 Germany 421C>T R141W neonatal 470## 320## 1.5## [16]

618C>A
206-218del 

5 5 France 1A>C M1L severe 367 376 1.0 [8]

1120C>T R374W
6 6 United States 1A>G M1V mild 87* 58* 1.5* [31]

1342T>C S448P
7 7 Netherlands 5C>T A2V neonatal 1-2## 1-2## 1.0## [34]

S395R
8 8 United Kingdom 7G>C A3P neonatal 477 921 0.5 [22]

578C>T R190X
9 9 Czech Republic 8C>T A3V severe 126 147 0.9 [15]

1009C>T R337X
10 10 Poland 8C>T A3V severe 338* 323* 1.0* [33]


lack of mRNA
11 11 Poland 69C>G S23R severe 311 374 0.8 [14]

1277G>A R426H
12 12 Germany 76A>T M26L severe 370* 400* 0.9* [16]

1277G>A R426H
13 13 Belgium 214A>G I72V severe n.d. n.d. [20]

736A>G K246E
14 14 Australia 240A>C E80D mild 1.89# 0.87# 2.4# [30]


261T>G D87E
15 15 Italy 298C>G P100A severe 75* 60* 1.3* [36]


1264G>T D422Y
16 16 Czech Republic 340T>C Y114H mild 283 127 2.2 [15]


569G>A R190Q
17 16 Czech Republic 340T>C Y114H mild 260 125 2.1 [15]


569G>A R190Q
18 17 Poland 340T>C Y114H neonatal n.d. n.d. [14]


725C>T T242I
19 17 Poland 340T>C Y114H severe 562 599 0.9 [14]


725C>T T242I
20 18 Czech Republic 340T>C Y114H neonatal 684 1100 0.6 [25]


1128G>C E376D
21 19 Czech Republic 340T>C Y114H severe 649 953 0.7 [31]


1187G>A R396H
22 20 Germany 340T>C Y114H neonatal 1.1* [25]


1277G>A R426H
23 20 Germany 340T>C Y114H neonatal n.d. n.d. [25]


1277G>A R426H
24 20 Germany 340T>C Y114H neonatal n.d. n.d. [25]


1277G>A R426H
25 21 Czech Republic 340T>C Y114H neonatal 169 330 0.5 [25]


1277G>A R426H
26 22 Czech Republic 340T>C Y114H neonatal 1.1* [33]

1277G>A R426H
27 23 Malaysia 445C>G R194G severe 380* 370* 1.0* [10]

774_778insG A260GfsX24
28 24 Belgium 569G>A R190Q moderate 379 214 1.8 [11]

736A>G K246E
29 25 Czech Republic 580C>T R194C severe 269 281 1.0 [15]

802G>A
D268N
30 26 Germany 580C>T R194C neonatal n.d. n.d. [25]

1186C>T
R396C
31 27 Poland 643G>C D215H severe 290* 215* 1.3* [14]

1052T>C
I351T
32 28 Morocco 674T>C M225T severe 101* 63* 1.6* [6]

674T>C
M225T
33 28 Morocco 674T>C M225T severe 79* 49* 1.6* [6]

674T>C
M225T
34 29 Poland 802G>C D268H mild 1816* 896* 2.0* [14]

1277G>A
R426H
35 30 United States 802G>A D268N severe n.d. n.d. [31]

1400C>G
P467R
36 31 Netherlands N297S mild to severe 370 210 1.8 [7]

907C>T
R303C
37 32 Netherlands N297S mild 1130 390 2.9 [7]

907C>T
R303C
38 33 Netherlands 907C>T R303C mild 4.0 [12]

907C>T
R303C
39 34 ? 907C>T R303C mild 3.0 [28]

907C>T R303C
40 35 Spain 931C>G L311V severe 273 180 1.5 [2]

1187G>A R396H
41 36 Spain 1090G>A V364M severe 5.0** 2.8** 1.8** [2]

1355G>C R452P
42 36 Spain 1090G>A V364M severe 359 228 1.6 [2]

1355G>C R452P
43 37 Spain 1107A>C I369L severe 1.9* [29]

1107A>C I369L
44 38 ? 1267C>G L423V moderate n.d. n.d. [9]

1277G>A R426H
45 39 Germany 1277G>A R426H severe n.d. n.d. [31]

1277G>A R426H
46 40 Belgium 1277G>A R426H severe 1.3 [12]

1277G>A R426H
47 41 Poland 1277G>A R426H moderate 198* 133* 1.5* [14]

1277G>A R426H
48 42 Poland 1277G>A R426H moderate 210* 125* 1.7* [14]

1277G>A R426H
49 43 Netherlands 1277G>A R426H severe 218 213 1.0 [9]

1277G>A R426H
50 44 Netherlands 1277G>A R426H severe [9]

1277G>A R426H
51 45 Netherlands 1277G>A R426H severe [9]

1277G>A R426H
52 46 Portugal 1277G>A R426H severe 271 173 1.6 [4]

1277G>A R426H
53 46 Portugal 1277G>A R426H severe 178 132 1.4 [4]
1277G>A R426H
54 47 Netherlands 1277G>A R426H severe 1.2 [28]

1277G>A R426H
55 48 Czech Republic 1277G>A R426H severe 1.2* [15]

1277G>A R426H
56 49 Turkey 1277G>A R426H severe [9]

1277G>A R426H
57 50 Portugal 1277G>A R426H severe 242 197 1.2 [4]

1277G>A R426H
58 51 Netherlands 1277G>A R426H severe 1.5 [28]

1277G>A R426H
59 52 Germany 1277G>A R426H severe 292 207 1.4 [7]

1277G>A R426H
60 53 United States 1277G>A R426H mild 2.6* [15]

1288G>A D430N
61 54 Netherlands 1277G>A R426H moderate 2.5 [28]

1349C>G T450S
62 54 Netherlands 1277G>A R426H moderate [9]

1349C>G T450S
63 55 Morocco 1312T>C S438P severe 162 111 1.5 [32]

1312T>C S438P
64 55 Morocco 1312T>C S438P severe 166 154 1.1 [32]

1312T>C S438P
65 56 Colombia nd nd neonatal 160 164 1.0 [2]

nd nd
66 56 Colombia nd nd neonatal n.d. n.d. [2]

nd nd
67 57 United States 1277G>A R426H mild to severe 222 n.d. [33]

1277G>A R426H
68 57 United States nd nd mild to severe 430 n.d. [33]

nd nd
69 58 United Kingdom -49T>C severe 0.4## 0.4## 1.0## [17]
1277G>A R426H
70 59 United Kingdom 421C>T R141W severe 2.0## 1.3## 1.6## [17]

1304C>T P435L
71 60 Germany 731C>T T244I moderate 440* n.d.* [33]

1191+5G>C splice
72 61 Dominican Republic 1107A>C I369L severe 1.9* [27]

1107A>C I369L
73 62 Spain 1165A>G M389V mild 3.4* [27]

1165A>G M389V
74 63 Spain 1165A>G M389V mild to severe 2.7* [27]

1165A>G M389V
75 64 Ireland 340T>C Y114H severe 0.3## 0.2## 1.7##

no RNA prob.splice
76 65 France 340T>C Y114H mild [23]

1253G>C G418A
77 65 France 340T>C Y114H mild 322* 241* 1.3* [23]

1253G>C G418A
78 65 France 340T>C Y114H severe [23]

1253G>C G418A
79 66 Australia -49T>C severe 421* 324* 1.3* [35]

889_891
dupAAT
80 67 Poland 1277G>A R426H mild 332* 161* [13]

802G>C D268H
81 68 ? 736 A>G K246E severe 120 117 1.0 [37]

nd nd
82 69 ? IVS12+1/G>C splice site exon 12 severe 305 436 0.7 [37]

802G>A D268N
83 70 ? 736A>G K246Q severe 282* [3]

947T>C M316Y
84 71 ? 1277G>A R426H severe [3]

1277G>A R426H
85 72 ? 1277G>A R426H severe 124* [3]

1277G>A R426H
86 72 ? 1277G>A R426H severe 97* [3]

1277G>A R426H
87 73 China 71C>T P24L severe [19]

1387-1389delGAG E463-
88 73 China 71C>T P24L severe [19]

1387-1389delGAG E463-
89 74 China 71C>T P24L severe [19]

134G>A W45*
90 74 China 71C>T P24L severe [19]

134G>A W45*
91 75 ? 926G>A R309H mild 116* 58* 2.0* [18]

1191+5G>C splice site
92 76 Italy 340T>C Y114H severe 236* 38* 6.2* [23]

65C>T A22V
93 77 Germany 76A>T M26L mild 22* 6* 3.6* [18]

1187G>A R396H
94 77 Germany 76A>T M26L mild 20* 5* 3.7* [18]

1187G>A R396H
95 78 Israel (Arab) 1027G>A Q343K moderate 122## [24]

1027G>A Q343K
96 79 Turkey 1277G>A R426H moderate [5]

910T>G C304G
97 80 Qatar 1343_1345
delCTT
S448del neonatal 208* 223* 0.9* [23]

502G>A V168I
98 81 ? 1277G>A R426H severe 457 [23]

1277G>A R426H
99 82 ? 1277G>A R426H severe 856 [23]

1277G>A R426H
100 83 ? 1277G>A R426H severe 674 [23]

1277G>A R426H
101 84 ? R149G severe positive [23]

W175C
102 85 ? 421C>T R141W severe 1.4* [23]

P318L
103 86 ? 1277G>A R426H severe 311 374 0.8 [23]

S23R
104 87 ? 1277G>A R426H moderate [23]

1277G>A R426H
105 87 ? 1277G>A R426H ? [23]

1277G>A R426H
106 88 ? E343K mild 123* [23]

E343K
107 89 ? 1277G>A R426H mild 469* [23]

D430D
108 90 ? T450S mild 176* 73* 2.4* [23]

D332H
109 91 ? 701+1G>G/A intron 6 severe positive MR spect positive MR spect [1]
926G>G/A intron 9


# umol/mg of creatinine (in urine)## mmol/l (in urine) * mmol/mol of creatinine (in urine)** umol/l (in plasma)*** CSF = cerebrospinal fluid

References:
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[33] unpublished
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