MCID: ADN022
MIFTS: 37

Adenylosuccinase Deficiency

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Metabolic diseases

Aliases & Classifications for Adenylosuccinase Deficiency

MalaCards integrated aliases for Adenylosuccinase Deficiency:

Name: Adenylosuccinase Deficiency 53 49 24 55 71 13
Adenylosuccinate Lyase Deficiency 53 72 49 24 55 71 36 28 69
Adsl Deficiency 53 49 24 55 71
Adsld 53 71
Succinylpurinemic Autism 24
Adenylosuccinate Lyase 13

Characteristics:

Orphanet epidemiological data:

55
adenylosuccinate lyase deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood,Infancy,Neonatal;

OMIM:

53
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
highly variable phenotype, ranging from neonatal encephalopathy to mild mental retardation with autistic features
the lower the s-ado:saicar ratio, the more severe the phenotype


HPO:

31
adenylosuccinase deficiency:
Onset and clinical course infantile onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Adenylosuccinase Deficiency

OMIM : 53 Adenylosuccinase deficiency is an autosomal recessive inborn error of metabolism caused by an enzymatic defect in de novo purine synthesis (DNPS) pathway. ADSL deficiency leads to the accumulation of toxic intermediates, including succinyladenosine (S-Ado) and succinylaminoimidazole carboxamide riboside (SAICAr) in body fluids. There are 3 major phenotypic forms of the disorder that correlate with different values of the S-Ado and SAICAr concentration ratios (S-Ado/SAICAr) in the cerebrospinal fluid. These include the most severe fatal neonatal encephalopathy (S-Ado/SAICAr ratio less than 1); childhood form (type I) with severe psychomotor retardation (S-Ado/SAICAr ratio close to 1), and a milder form (type II) with psychomotor retardation or hypotonia (S-Ado/SAICAr ratio greater than 2) (summary by Baresova et al., 2012). (103050)

MalaCards based summary : Adenylosuccinase Deficiency, also known as adenylosuccinate lyase deficiency, is related to epilepsy and aicar transformylase/imp cyclohydrolase deficiency, and has symptoms including seizures, low-set ears and intellectual disability. An important gene associated with Adenylosuccinase Deficiency is ADSL (Adenylosuccinate Lyase), and among its related pathways/superpathways are Purine metabolism and Alanine, aspartate and glutamate metabolism. Affiliated tissues include brain, eye and skeletal muscle.

UniProtKB/Swiss-Prot : 71 Adenylosuccinase deficiency: An autosomal recessive disorder characterized by the accumulation in the body fluids of succinylaminoimidazole-carboxamide riboside (SAICA- riboside) and succinyladenosine (S-Ado). Most children display marked psychomotor delay, often accompanied by epilepsy or autistic features, or both, although some patients may be less profoundly retarded. Occasionally, growth retardation and muscular wasting are also present.

NIH Rare Diseases : 49 Adenylosuccinase deficiency is a rare, inherited metabolic condition that results from a lack of the enzyme adenylosuccinate lyase. Signs and symptoms vary greatly from person to person. In general, affected individuals may have a mix of neurological symptoms, which usually includes abnormalities with cognition and movement, autistic features, epilepsy, muscle wasting, and feeding problems. Although less common, abnormal physical features can include severe growth failure, small head, abnormally shaped head, strabismus, small nose with upturned nostrils, thin upper lip, and low set ears. Adenylosuccinase deficiency is caused by mutations in the ADSL gene and is inherited in an autosomal recessive fashion. Last updated: 9/8/2011

Genetics Home Reference : 24 Adenylosuccinate lyase deficiency is a neurological disorder that causes brain dysfunction (encephalopathy) leading to delayed development of mental and movement abilities (psychomotor delay), autistic behaviors that affect communication and social interaction, and seizures. A characteristic feature that can help with diagnosis of this condition is the presence of chemicals called succinylaminoimidazole carboxamide riboside (SAICAr) and succinyladenosine (S-Ado) in body fluids.

Related Diseases for Adenylosuccinase Deficiency

Diseases related to Adenylosuccinase Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 epilepsy 10.1
2 aicar transformylase/imp cyclohydrolase deficiency 9.9
3 autism 9.9
4 microcephaly 9.9
5 encephalopathy 9.9

Graphical network of the top 20 diseases related to Adenylosuccinase Deficiency:



Diseases related to Adenylosuccinase Deficiency

Symptoms & Phenotypes for Adenylosuccinase Deficiency

Symptoms via clinical synopsis from OMIM:

53
Neurologic Central Nervous System:
myoclonus
opisthotonus
gait ataxia
spasticity
inability to walk
more
Head And Neck Eyes:
nystagmus
strabismus

Head And Neck Mouth:
wide mouth
thin upper lip

Head And Neck Nose:
anteverted nostrils
small nose

Head And Neck Face:
long smooth philtrum

Laboratory Abnormalities:
increased succinyladenosine (s-ado) in serum, urine, and csf
increased succinylaminoimidazole carboxamide ribotide (saicar)
decreased s-ado:saicar ratio
adenylosuccinase deficiency

Head And Neck Ears:
low-set ears

Head And Neck Head:
brachycephaly
microcephaly (less common)
prominent metopic suture

Neurologic Behavioral Psychiatric Manifestations:
aggressive behavior
hyperactivity
self-mutilation
autistic features
temper tantrums
more
Growth Other:
growth retardation

Muscle Soft Tissue:
muscle wasting


Clinical features from OMIM:

103050

Human phenotypes related to Adenylosuccinase Deficiency:

55 31 (show all 40)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 seizures 55 31 hallmark (90%) Very frequent (99-80%) HP:0001250
2 low-set ears 55 31 hallmark (90%) Very frequent (99-80%) HP:0000369
3 intellectual disability 55 31 hallmark (90%) Very frequent (99-80%) HP:0001249
4 abnormal facial shape 55 31 hallmark (90%) Very frequent (99-80%) HP:0001999
5 short nose 55 31 hallmark (90%) Very frequent (99-80%) HP:0003196
6 microcephaly 55 31 occasional (7.5%) Very frequent (99-80%) HP:0000252
7 smooth philtrum 55 31 hallmark (90%) Very frequent (99-80%) HP:0000319
8 anteverted nares 55 31 hallmark (90%) Very frequent (99-80%) HP:0000463
9 brachycephaly 55 31 hallmark (90%) Very frequent (99-80%) HP:0000248
10 long philtrum 55 31 hallmark (90%) Very frequent (99-80%) HP:0000343
11 severe global developmental delay 55 31 hallmark (90%) Very frequent (99-80%) HP:0011344
12 absent speech 55 31 hallmark (90%) Very frequent (99-80%) HP:0001344
13 thin upper lip vermilion 55 31 hallmark (90%) Very frequent (99-80%) HP:0000219
14 flat occiput 55 31 hallmark (90%) Very frequent (99-80%) HP:0005469
15 prominent metopic ridge 55 31 hallmark (90%) Very frequent (99-80%) HP:0005487
16 generalized hypotonia 55 31 hallmark (90%) Very frequent (99-80%) HP:0001290
17 hypointensity of cerebral white matter on mri 55 31 hallmark (90%) Very frequent (99-80%) HP:0007103
18 myoclonus 31 HP:0001336
19 opisthotonus 31 HP:0002179
20 gait ataxia 31 HP:0002066
21 nystagmus 31 HP:0000639
22 global developmental delay 31 HP:0001263
23 delayed speech and language development 31 HP:0000750
24 skeletal muscle atrophy 31 HP:0003202
25 strabismus 31 HP:0000486
26 autism 31 HP:0000717
27 growth delay 31 HP:0001510
28 inability to walk 31 HP:0002540
29 wide mouth 31 HP:0000154
30 aggressive behavior 31 HP:0000718
31 cerebellar atrophy 31 HP:0001272
32 hyperactivity 31 HP:0000752
33 cerebral atrophy 31 HP:0002059
34 cns hypomyelination 31 HP:0003429
35 brisk reflexes 31 HP:0001348
36 happy demeanor 31 occasional (7.5%) HP:0040082
37 poor eye contact 31 HP:0000817
38 self-mutilation 31 HP:0000742
39 inappropriate laughter 31 HP:0000748
40 cerebral hypomyelination 31 HP:0006808

UMLS symptoms related to Adenylosuccinase Deficiency:


gait ataxia, opisthotonus, myoclonus, muscle spasticity

Drugs & Therapeutics for Adenylosuccinase Deficiency

Search Clinical Trials , NIH Clinical Center for Adenylosuccinase Deficiency

Genetic Tests for Adenylosuccinase Deficiency

Genetic tests related to Adenylosuccinase Deficiency:

# Genetic test Affiliating Genes
1 Adenylosuccinate Lyase Deficiency 28 ADSL

Anatomical Context for Adenylosuccinase Deficiency

MalaCards organs/tissues related to Adenylosuccinase Deficiency:

38
Brain, Eye, Skeletal Muscle, Testes

Publications for Adenylosuccinase Deficiency

Articles related to Adenylosuccinase Deficiency:

(show top 50) (show all 69)
# Title Authors Year
1
Screening for adenylosuccinate lyase deficiency using tandem mass spectrometry analysis of succinylpurines in neonatal dried blood spots. ( 25445730 )
2015
2
Adenylosuccinate lyase deficiency. ( 25112391 )
2014
3
The need for vigilance: false-negative screening for adenylosuccinate lyase deficiency caused by deribosylation of urinary biomarkers. ( 24183879 )
2013
4
Early diagnosis of adenylosuccinate lyase deficiency using a high-throughput screening method and a trial of oral S-adenosyl-l-methionine as a treatment method. ( 23937257 )
2013
5
Attenuated Adenylosuccinate Lyase Deficiency: A Report of One Case and a Review of the Literature. ( 23504561 )
2013
6
Novel proton MR spectroscopy findings in adenylosuccinate lyase deficiency. ( 23055421 )
2013
7
Magnetic resonance imaging of the brain in adenylosuccinate lyase deficiency: a report of seven cases and a review of the literature. ( 21625931 )
2012
8
Neurologic presentation, diagnostics, and therapeutic insights in a severe case of adenylosuccinate lyase deficiency. ( 22140128 )
2012
9
Isolated neonatal seizures: adenylosuccinase deficiency is another cause! ( 22883297 )
2012
10
Novel features in the evolution of adenylosuccinate lyase deficiency. ( 21903433 )
2012
11
Molecular characterization of the AdeI mutant of Chinese hamster ovary cells: a cellular model of adenylosuccinate lyase deficiency. ( 20884265 )
2011
12
Progress Towards Simple and Direct Detection of Adenylosuccinate Lyase Deficiency in Human Urine. ( 22719107 )
2011
13
Adenylosuccinate lyase deficiency in a Malaysian patient, with novel adenylosuccinate lyase gene mutations. ( 20177786 )
2010
14
Biochemical and structural analysis of 14 mutant adsl enzyme complexes and correlation to phenotypic heterogeneity of adenylosuccinate lyase deficiency. ( 20127976 )
2010
15
Adenylosuccinate lyase deficiency in the United Kingdom pediatric population: first three cases. ( 20933180 )
2010
16
In vivo proton MR spectroscopy findings specific for adenylosuccinate lyase deficiency. ( 20175147 )
2010
17
Severe encephalopathy with brain atrophy and hypomyelination due to adenylosuccinate lyase deficiency--MRI, clinical, biochemical and neuropathological findings of Polish patients. ( 20054783 )
2009
18
Misleading behavioural phenotype with adenylosuccinate lyase deficiency. ( 18830228 )
2009
19
D-ribose therapy in four Polish patients with adenylosuccinate lyase deficiency: absence of positive effect. ( 18649008 )
2008
20
Clinical, biochemical, neuropathological and molecular findings of the first Polish case of adenylosuccinase deficiency. ( 18368630 )
2008
21
[Adenylosuccinate lyase deficiency: an unusual cause of neonatal seizure]. ( 18201882 )
2008
22
Clinical, biochemical and molecular findings in seven Polish patients with adenylosuccinate lyase deficiency. ( 18524658 )
2008
23
Adenylosuccinate lyase deficiency: the first identified polish patient. ( 17485188 )
2007
24
Lethal fetal and early neonatal presentation of adenylosuccinate lyase deficiency: observation of 6 patients in 4 families. ( 17188615 )
2007
25
Adenylosuccinate lyase deficiency. ( 16839792 )
2006
26
Preparation of 5-amino-4-imidazole-N-succinocarboxamide ribotide, 5-amino-4-imidazole-N-succinocarboxamide riboside and succinyladenosine, compounds usable in diagnosis and research of adenylosuccinate lyase deficiency. ( 15902552 )
2005
27
Adenylosuccinate lyase deficiency--first British case. ( 15571235 )
2004
28
Adenylosuccinate lyase deficiency: study of physiopathologic mechanism(s). ( 15571234 )
2004
29
Biochemical and molecular genetic correlation in adenylosuccinate lyase deficiency. ( 15571240 )
2004
30
Characterization of a mutant Bacillus subtilis adenylosuccinate lyase equivalent to a mutant enzyme found in human adenylosuccinate lyase deficiency: asparagine 276 plays an important structural role. ( 12590570 )
2003
31
Intrafamilial variability in the phenotypic expression of adenylosuccinate lyase deficiency: a report on three patients. ( 12833398 )
2003
32
The characterization of mutant Bacillus subtilis adenylosuccinate lyases corresponding to severe human adenylosuccinate lyase deficiencies. ( 12876319 )
2003
33
Screening for adenylosuccinate lyase deficiency: clinical, biochemical and molecular findings in four patients. ( 12368987 )
2002
34
Towards a suggestive facial dysmorphism in adenylosuccinate lyase deficiency? ( 12070256 )
2002
35
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. ( 12016589 )
2002
36
Neurologic aspects of adenylosuccinate lyase deficiency. ( 11392513 )
2001
37
Prenatal diagnosis in adenylosuccinate lyase deficiency. ( 10701848 )
2000
38
Clinical, biochemical and molecular genetic correlations in adenylosuccinate lyase deficiency. ( 10958654 )
2000
39
Adenylosuccinase deficiency: an unusual cause of early-onset epilepsy associated with acquired microcephaly. ( 11042421 )
2000
40
Adenylosuccinate lyase deficiency: from the clinics to molecular biology. ( 11783532 )
2000
41
Effect of uridine administration to a patient with adenylosuccinate lyase deficiency. ( 11783531 )
2000
42
Autism and adenylosuccinase deficiency. ( 10714045 )
2000
43
Effect of D-ribose on purine synthesis and neurological symptoms in a patient with adenylosuccinase deficiency. ( 9989253 )
1999
44
Adenylosuccinase deficiency: possibly underdiagnosed encephalopathy with variable clinical features. ( 10727185 )
1999
45
Mutation analysis in adenylosuccinate lyase deficiency: eight novel mutations in the re-evaluated full ADSL coding sequence. ( 10090474 )
1999
46
Genetic basis of adenylosuccinase deficiency in an Italian patient. ( 9598084 )
1998
47
Adenylosuccinase deficiency with neonatal onset severe epileptic seizures and sudden death. ( 9553952 )
1998
48
Muscle energy metabolism in human adenylosuccinase deficiency. An in vivo 31P-NMR spectroscopy study. ( 9598074 )
1998
49
[Adenylosuccinase deficiency]. ( 9590095 )
1998
50
First U.S. case of adenylosuccinate lyase deficiency with severe hypotonia. ( 9165520 )
1997

Variations for Adenylosuccinase Deficiency

UniProtKB/Swiss-Prot genetic disease variations for Adenylosuccinase Deficiency:

71 (show all 27)
# Symbol AA change Variation ID SNP ID
1 ADSL p.Ser438Pro VAR_000680 rs119450940
2 ADSL p.Ile72Val VAR_007972
3 ADSL p.Arg141Trp VAR_007973 rs756210458
4 ADSL p.Arg190Gln VAR_007974 rs28941471
5 ADSL p.Lys246Glu VAR_007975 rs119450944
6 ADSL p.Arg303Cys VAR_007976 rs373458753
7 ADSL p.Ser395Arg VAR_007977
8 ADSL p.Arg426His VAR_007978 rs119450941
9 ADSL p.Ala2Val VAR_016930 rs143083947
10 ADSL p.Met26Leu VAR_016931
11 ADSL p.Thr450Ser VAR_016932 rs372895468
12 ADSL p.Ala3Val VAR_017078
13 ADSL p.Pro100Ala VAR_017079 rs119450942
14 ADSL p.Tyr114His VAR_017080 rs374259530
15 ADSL p.Arg194Cys VAR_017081
16 ADSL p.Asp268Asn VAR_017082 rs746501563
17 ADSL p.Leu311Val VAR_017083
18 ADSL p.Pro318Leu VAR_017084 rs202064195
19 ADSL p.Val364Met VAR_017085 rs370851726
20 ADSL p.Arg374Trp VAR_017086 rs376533026
21 ADSL p.Arg396Cys VAR_017087 rs755492501
22 ADSL p.Arg396His VAR_017088 rs763542069
23 ADSL p.Asp422Tyr VAR_017089 rs119450943
24 ADSL p.Leu423Val VAR_017090
25 ADSL p.Asp430Asn VAR_017091 rs554254383
26 ADSL p.Ser447Pro VAR_017092 rs777821034
27 ADSL p.Arg452Pro VAR_017093

ClinVar genetic disease variations for Adenylosuccinase Deficiency:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 ADSL NM_000026.3(ADSL): c.1312T> C (p.Ser438Pro) single nucleotide variant Pathogenic rs119450940 GRCh37 Chromosome 22, 40761004: 40761004
2 ADSL NM_000026.3(ADSL): c.1277G> A (p.Arg426His) single nucleotide variant Pathogenic rs119450941 GRCh37 Chromosome 22, 40760969: 40760969
3 ADSL NM_000026.3(ADSL): c.298C> G (p.Pro100Ala) single nucleotide variant Pathogenic rs119450942 GRCh37 Chromosome 22, 40745980: 40745980
4 ADSL NM_000026.3(ADSL): c.569G> A (p.Arg190Gln) single nucleotide variant Pathogenic rs28941471 GRCh37 Chromosome 22, 40754954: 40754954
5 ADSL NM_000026.3(ADSL): c.736A> G (p.Lys246Glu) single nucleotide variant Pathogenic/Likely pathogenic rs119450944 GRCh37 Chromosome 22, 40756440: 40756440
6 ADSL ADSL, -49T-C, PROMOTER single nucleotide variant Pathogenic
7 ADSL NM_000026.3(ADSL): c.674T> C (p.Met225Thr) single nucleotide variant Pathogenic rs119450945 GRCh37 Chromosome 22, 40755283: 40755283
8 ADSL NM_000026.3(ADSL): c.340T> C (p.Tyr114His) single nucleotide variant Pathogenic rs374259530 GRCh37 Chromosome 22, 40746022: 40746022
9 ADSL NM_000026.3(ADSL): c.907C> T (p.Arg303Cys) single nucleotide variant Pathogenic rs373458753 GRCh37 Chromosome 22, 40757536: 40757536

Expression for Adenylosuccinase Deficiency

Search GEO for disease gene expression data for Adenylosuccinase Deficiency.

Pathways for Adenylosuccinase Deficiency

Pathways related to Adenylosuccinase Deficiency according to KEGG:

36
# Name Kegg Source Accession
1 Purine metabolism hsa00230
2 Alanine, aspartate and glutamate metabolism hsa00250

GO Terms for Adenylosuccinase Deficiency

Sources for Adenylosuccinase Deficiency

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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