Adenylosuccinate Lyase Deficiency (dADSL)

last updated: Jun 2013

Patient	Family	Gender	Country	Mutation cDNA (list)	Mutation protein (list)	Location in protein	Phenotype	SAdo (CSF) μmol/l	SAICAr (CSF) μmol/l	SAdo/ SAICAr (CSF)
6 [7]	6	F	US	c.1A>G	p.M1V	not assigned	mild	87^a,d	58^a,d	1.5^a
6 [7]	6	F	US	c.1342T>C	p.S448P	Substrate channel	mild	87^a,d	58^a,d	1.5^a
35 [7]	30	M	US	c.802G>A	p.D268N	Active site	severe
35 [7]	30	M	US	c.1400C>G	p.P467R	Central helical region	severe
60 [10]	53	F	US	c.1277G>A	p.R426H	Substrate channel	mild			2.6
60 [10]	53	F	US	c.1288G>A	p.D430N	Substrate channel	mild			2.6
67 [–]	57	F	US	c.1277G>A	p.R426H	Substrate channel	mild to severe	222		n.d.^c
67 [–]	57	F	US	c.1277G>A	p.R426H	Substrate channel	mild to severe	222		n.d.^c
68 [–]	57	F	US	n.d.^c	n.d.^c	Substrate channel	mild to severe	430		n.d.^c
75 [–]	64	M	US	1277G>A	R426H		mild
75 [–]	64	M	US	1277G>A	R426H		mild
76 [–]	64	M	US	1277G>A	R426H		mild
76 [–]	64	M	US	1277G>A	R426H		mild
56 [adsldb]	49		TR	c.1277G>A	p.R426H	Substrate channel	severe			n.d.^c
56 [adsldb]	49		TR	c.1277G>A	p.R426H	Substrate channel	severe			n.d.^c
52 [20]	46	M	PT	c.1277G>A	p.R426H	Substrate channel	severe	271	173	1.6
52 [20]	46	M	PT	c.1277G>A	p.R426H	Substrate channel	severe	271	173	1.6
53 [20]	46	M	PT	c.1277G>A	p.R426H	Substrate channel	severe	178	132	1.4
53 [20]	46	M	PT	c.1277G>A	p.R426H	Substrate channel	severe	178	132	1.4
57 [20]	50	F	PT	c.1277G>A	p.R426H	Substrate channel	severe	242	197	1.2
57 [20]	50	F	PT	c.1277G>A	p.R426H	Substrate channel	severe	242	197	1.2
10 [–]	10	F	PL	c.8C>T	p.A3V	not assigned	severe	338^a,d	323^a,d	1.0^a
10 [–]	10	F	PL	lack of mRNA	lack of mRNA	xxx	severe	338^a,d	323^a,d	1.0^a
11 [11]	11	M	PL	c.69C>G	p.S23R	Central helical region / Active site	severe	311	374	0.8
11 [11]	11	M	PL	c.1277G>A	p.R426H	Substrate channel	severe	311	374	0.8
18 [11]	17	F	PL	c.340T>C	p.Y114H	Active site	neonatal			n.d.^c
18 [11]	17	F	PL	c.725C>T	p.T242I	Active site	neonatal			n.d.^c
19 [11]	17	F	PL	c.340T>C	p.Y114H	Active site	severe	562	599	0.9
19 [11]	17	F	PL	c.725C>T	p.T242I	Active site	severe	562	599	0.9
31 [11]	27	F	PL	c.643G>C	p.D215H	Substrate channel	severe	290^a,d	215^a,d	1.3^a
31 [11]	27	F	PL	c.1052T>C	p.I351T	Central helical region / Active site	severe	290^a,d	215^a,d	1.3^a
34 [11]	29	F	PL	c.802G>C	p.D268H	Active site	mild	1816^a,d	896^a,d	2.1^a
34 [11]	29	F	PL	c.1277G>A	p.R426H	Substrate channel	mild	1816^a,d	896^a,d	2.1^a
47 [11]	41	F	PL	c.1277G>A	p.R426H	Substrate channel	moderate	198^a,d	133^a,d	1.5^a
47 [11]	41	F	PL	c.1277G>A	p.R426H	Substrate channel	moderate	198^a,d	133^a,d	1.5^a
48 [11]	42	F	PL	c.1277G>A	p.R426H	Substrate channel	moderate	210^a,d	125^a,d	1.7^a
48 [11]	42	F	PL	c.1277G>A	p.R426H	Substrate channel	moderate	210^a,d	125^a,d	1.7^a
3 [1]	3		NO	c.-49T>C	xxx	xxx	severe			n.d.^c
3 [1]	3		NO	?	p.S447P	Substrate channel	severe			n.d.^c
7 [5;8]	7	M	NL	c.5C>T	p.A2V	not assigned	neonatal	1-2^e	1-2^e	1
7 [5;8]	7	M	NL	?	p.S395R	Substrate channel	neonatal	1-2^e	1-2^e	1
36 [26]	31		NL		p.N297S		mild to severe	370	210	1.8
36 [26]	31		NL	c.907C>T	p.R303C	Active site	mild to severe	370	210	1.8
37 [26]	32		NL		p.N297S		mild	1130	390	2.1
37 [26]	32		NL	c.907C>T	p.R303C	Active site	mild	1130	390	2.1
38 [3;5;17]	33	F	NL	c.907C>T	p.R303C	Active site	mild			4
38 [3;5;17]	33	F	NL	c.907C>T	p.R303C	Active site	mild			4
49 [5;19]	43	F	NL	c.1277G>A	p.R426H	Substrate channel	severe			1
49 [5;19]	43	F	NL	c.1277G>A	p.R426H	Substrate channel	severe			1
50 [5]	44		NL	c.1277G>A	p.R426H	Substrate channel	severe			n.d.^c
50 [5]	44		NL	c.1277G>A	p.R426H	Substrate channel	severe			n.d.^c
51 [adsldb]	45		NL	c.1277G>A	p.R426H	Substrate channel	severe			n.d.^c
51 [adsldb]	45		NL	c.1277G>A	p.R426H	Substrate channel	severe			n.d.^c
54 [3]	47		NL	c.1277G>A	p.R426H	Substrate channel	severe			1.2
54 [3]	47		NL	c.1277G>A	p.R426H	Substrate channel	severe			1.2
58 [3]	51	F	NL	c.1277G>A	p.R426H	Substrate channel	severe			1.5
58 [3]	51	F	NL	c.1277G>A	p.R426H	Substrate channel	severe			1.5
61 [3]	54	F	NL	c.1277G>A	p.R426H	Substrate channel	moderate			2.5
61 [3]	54	F	NL	c.1349C>G	p.T450S	Substrate channel	moderate			2.5
62 [adsldb]	54	M	NL	c.1277G>A	p.R426H	Substrate channel	moderate			n.d.^c
62 [adsldb]	54	M	NL	c.1349C>G	p.T450S	Substrate channel	moderate			n.d.^c
27 [25]	23	M	MY	c.445C>G	p.R149G		severe	380^a,d	370^a,d	1.02^a
27 [25]	23	M	MY	c.774_778insG	p.A260GfsX24		severe	380^a,d	370^a,d	1.02^a
32 [16]	28	F	MA	c.674T>C	p.M225T	Substrate channel	severe	101^a,d	63^a,d	1.6^a
32 [16]	28	F	MA	c.674T>C	p.M225T	Substrate channel	severe	101^a,d	63^a,d	1.6^a
33 [16]	28	F	MA	c.674T>C	p.M225T	Substrate channel	severe	79^a,d	49^a,d	1.6^a
33 [16]	28	F	MA	c.674T>C	p.M225T	Substrate channel	severe	79^a,d	49^a,d	1.6^a
63 [21;23]	55	F	MA	c.1312T>C	p.S438P	Substrate channel	severe			1.5
63 [21;23]	55	F	MA	c.1312T>C	p.S438P	Substrate channel	severe			1.5
64 [21;23]	55	M	MA	c.1312T>C	p.S438P	Substrate channel	severe			1.1
64 [21;23]	55	M	MA	c.1312T>C	p.S438P	Substrate channel	severe			1.1
2 [1;2;3]	2	F	IT	c.-49T>C	xxx	xxx	severe	158	167	0.9
2 [1;2;3]	2	F	IT	c.1277G>A	p.R426H	Substrate channel	severe	158	167	0.9
15 [13]	15	F	IT	c.298C>G	p.P100A	Substrate channel	severe	75	60	1.3
15 [13]	15	F	IT	c.1264G>T	p.D422Y	Substrate channel	severe	75	60	1.3
8 [9]	8	F	GB	c.7G>C	p.A3P	not assigned	neonatal	477	921	0.5
8 [9]	8	F	GB	c.568C>T	p.R190X	xxx	neonatal	477	921	0.5
69 [27]	58	M	GB	c.-49T>C	n.d.^c		severe	362^a	401^a	1
69 [27]	58	M	GB	c.1277G>A	p.R426H		severe	362^a	401^a	1
70 [27]	59	M	GB	c.421C>T	p.R141W		severe	2030^a	1314^a	1.6
70 [27]	59	M	GB	c.1304C>T	p.P435L		severe	2030^a	1314^a	1.6
5 [6]	5	F	FR	c.1A>C	p.M1L	not assigned	severe	367	376	1
5 [6]	5	F	FR	c.1120C>T	p.R374W	Substrate channel	severe	367	376	1
40 [18]	35	F	ES	c.931C>G	p.L311V	Central helical region	severe	273	180	1.5
40 [18]	35	F	ES	c.1187G>A	p.R396H	Substrate channel	severe	273	180	1.5
41 [18]	36	F	ES	c.1090G>A	p.V364M	Substrate channel / Central helical region	severe	5^b	2.8^b	1.8^b
41 [18]	36	F	ES	c.1355G>C	p.R452P	Substrate channel	severe	5^b	2.8^b	1.8^b
42 [18]	36	F	ES	c.1090G>A	p.V364M	Substrate channel / Central helical region	severe	359	228	1.6
42 [18]	36	F	ES	c.1355G>C	p.R452P	Substrate channel	severe	359	228	1.6
43 [24]	37		ES	c.1107A>C	p.I369L	Active site / Substrate channel	severe			1.9^a
43 [24]	37		ES	c.1107A>C	p.I369L	Active site / Substrate channel	severe			1.9^a
73 [28]	62	F	ES	c.1165A>G	p.M389V		mild			3.41^a
73 [28]	62	F	ES	c.1165A>G	p.I389V		mild			3.41^a
74 [28]	63	M	ES	c.1165A>G	p.M389V		mild to severe			2.70^a
74 [28]	63	M	ES	c.1165A>G	p.I389V		mild to severe			2.70^a
72 [28]	61	M	DO	c.1107A>C	p.I369L		severe			1.88^a
72 [28]	61	M	DO	c.1107A>C	p.I369L		severe			1.88^a
4 [3;4;5]	4	M	DE	c.421C>T	p.R141W	Central helical region	neonatal	470^d	320^d	1.5
4 [3;4;5]	4	M	DE	c.618C>A	p.206-218del	xxx	neonatal	470^d	320^d	1.5
12 [3;4;5]	12	M	DE	?	p.M26L	Central helical region / Active site	severe	370^a,d	400^a,d	0.9^a
12 [3;4;5]	12	M	DE	c.1277G>A	p.R426H	Substrate channel	severe	370^a,d	400^a,d	0.9^a
22 [14]	20	M	DE	c.340T>C	p.Y114H	Active site	neonatal			1.1^a
22 [14]	20	M	DE	c.1277G>A	p.R426H	Substrate channel	neonatal			1.1^a
23 [14]	20	M	DE	c.340T>C	p.Y114H	Active site	neonatal			n.d.^c
23 [14]	20	M	DE	c.1277G>A	p.R426H	Substrate channel	neonatal			n.d.^c
24 [14]	20	M	DE	c.340T>C	p.Y114H	Active site	neonatal			n.d.^c
24 [14]	20	M	DE	c.1277G>A	p.R426H	Substrate channel	neonatal			n.d.^c
30 [14]	26		DE	c.580C>T	p.R194C	Subunit interface	neonatal
30 [14]	26		DE	c.1186C>T	p.R396C	Substrate channel	neonatal
45 [7]	39	M	DE	c.1277G>A	p.R426H	Substrate channel	severe			n.d.^c
45 [7]	39	M	DE	c.1277G>A	p.R426H	Substrate channel	severe			n.d.^c
59 [26]	52		DE	c.1277G>A	p.R426H	Substrate channel	severe	292	207	1.4
59 [26]	52		DE	c.1277G>A	p.R426H	Substrate channel	severe	292	207	1.4
71 [–]	60	M	DE	c.731C>T	p.T244I		moderate	440^a,d		n.d.^c
71 [–]	60	M	DE	1191+5G>C	splice		moderate	440^a,d		n.d.^c
9 [10]	9	F	CZ	c.8C>T	p.A3V	not assigned	severe	126	147	0.9
9 [10]	9	F	CZ	c.1009C>T	p.R337X	xxx	severe	126	147	0.9
16 [10]	16	M	CZ	c.340T>C	p.Y114H	Active site	mild	283	127	2.2
16 [10]	16	M	CZ	c.569G>A	p.R190Q	Central helical region	mild	283	127	2.2
17 [10]	16	F	CZ	c.340T>C	p.Y114H	Active site	mild	260	125	2.1
17 [10]	16	F	CZ	c.569G>A	p.R190Q	Central helical region	mild	260	125	2.1
20 [14]	18	M	CZ	c.340T>C	p.Y114H	Active site	neonatal	684	1100	0.6
20 [14]	18	M	CZ	c.1128G>C	p.E376D	Active site / Subunit interface	neonatal	684	1100	0.6
21 [7]	19	M	CZ	c.340T>C	p.Y114H	Active site	severe	649	953	0.7
21 [7]	19	M	CZ	c.1187G>A	p.R396H	Substrate channel	severe	649	953	0.7
25 [14]	21	F	CZ	c.340T>C	p.Y114H	Active site	neonatal	169	330	0.5
25 [14]	21	F	CZ	c.1277G>A	p.R426H	Substrate channel	neonatal	169	330	0.5
26 [–]	22	M	CZ	c.340T>C	p.Y114H	Active site	neonatal			1.1^a
26 [–]	22	M	CZ	c.1277G>A	p.R426H	Substrate channel	neonatal			1.1^a
29 [10]	25	F	CZ	c.580C>T	p.R194C	Subunit interface	severe	269	281	1
29 [10]	25	F	CZ	c.802G>A	p.D268N	Active site	severe	269	281	1
55 [10]	48	M	CZ	c.1277G>A	p.R426H	Substrate channel	severe			1.2
55 [10]	48	M	CZ	c.1277G>A	p.R426H	Substrate channel	severe			1.2
65 [18]	56	M	CO	n.d.^c	n.d.^c		neonatal	160	164	1
66 [18]	56	M	CO	n.d.^c	n.d.^c		neonatal
13 [5]	13		BE	c.214A>G	p.I72V	Substrate channel	severe			n.d.^c
13 [5]	13		BE	c.736A>G	p.K246E	Subunit interface	severe			n.d.^c
28 [5;15]	24	F	BE	c.569G>A	p.R190Q	Central helical region	moderate	379	214	1.8
28 [5;15]	24	F	BE	c.736A>G	p.K246E	Subunit interface	moderate	379	214	1.8
46 [3;17]	40		BE	c.1277G>A	p.R426H	Substrate channel	severe			1.3
46 [3;17]	40		BE	c.1277G>A	p.R426H	Substrate channel	severe			1.3
1 [1;12]	1	F	AU	c.-49T>C	xxx	xxx	severe	4.9^a,f	6.9^a,f	0.7^a
1 [1;12]	1	F	AU	c.953C>T	p.P318L	Central helical region	severe	4.9^a,f	6.9^a,f	0.7^a
14 [12;22]	14	M	AU	c.240A>C	p.E80D	Active site	mild	1.89^a,f	0.87^a,f	2.4^a
14 [12;22]	14	M	AU	c.261T>G	p.D87E	Active site	mild	1.89^a,f	0.87^a,f	2.4^a
39 [3;7]	34		?	c.907C>T	p.R303C	Active site	mild			3
39 [3;7]	34		?	c.907C>T	p.R303C	Active site	mild			3
44 [adsldb]	38		?	c.1267C>G	p.L423V	Substrate channel	moderate			n.d.^c
44 [adsldb]	38		?	c.1277G>A	p.R426H	Substrate channel	moderate			n.d.^c

^a … in urine ^b … in plasma ^c … not determined ^d … mmol/mol creat. ^e … mmol/l ^f … μmol/mg creat.

CSF … cerebrospinal fluid

[1] Marie S, Race V, Nassogne MC, Vincent MF, Van den Berghe G. 2002. Mutation of a nuclear respiratory factor 2 binding site in the 5 untranslated region of the ADSL gene in three patients with adenylosuccinate lyase deficiency. Am J Hum Genet 71(1):14-21. [abstract]

[2] Nassogne M, Henrot B, Aubert G, Bonnier C, Marie S, Saint-Martin C, Van den Berghe G, Sebire G, Vincent M. 2000. Adenylosuccinase deficiency: an unusual cause of early-onset epilepsy associated with acquired microcephaly. Brain Dev 22(6):383-6.[abstract]

[3] Race V, Marie S, Vincent MF, Van Den Berghe G. 2000. Clinical, biochemical and molecular genetic correlations in adenylosuccinate lyase deficiency. Hum Mol Genet 9(14):2159-65. [abstract]

[4] Kohler M, Assmann B, Brautigam C, Storm W, Marie S, Vincent MF, Van den Berghe G, Simmonds HA, Hoffmann GF. 1999. Adenylosuccinase deficiency: possibly underdiagnosed encephalopathy with variable clinical features. Eur J Paediatr Neurol 3(1):3-6. [abstract]

[5] Marie S, Cuppens H, Heuterspreute M, Jaspers M, Tola EZ, Gu XX, Legius E, Vincent MF, Jaeken J, Cassiman JJ and others. 1999. Mutation analysis in adenylosuccinate lyase deficiency: eight novel mutations in the re-evaluated full ADSL coding sequence. Hum Mutat 13(3):197-202. [abstract]

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[18] Castro M, Perez-Cerda C, Merinero B, Garcia MJ, Bernar J, Gil Nagel A, Torres J, Bermudez M, Garavito P, Marie S and others. 2002. Screening for adenylosuccinate lyase deficiency: clinical, biochemical and molecular findings in four patients. Neuropediatrics 33(4):186-9. [abstract]

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