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 54 50 24 25 56 71 13
Adenylosuccinate Lyase Deficiency 72 50 25 56 71 29 69
Adsl Deficiency 50 25 56 71
Succinylpurinemic Autism 25
Adenylosuccinate Lyase 13
Adsld 71

Characteristics:

Orphanet epidemiological data:

56
adenylosuccinate lyase deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood,Infancy,Neonatal;

OMIM:

54
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:

32
adenylosuccinase deficiency:
Onset and clinical course infantile onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Adenylosuccinase Deficiency

OMIM : 54
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 microcephaly, and has symptoms including absent speech, seizures and microcephaly. An important gene associated with Adenylosuccinase Deficiency is ADSL (Adenylosuccinate Lyase). Affiliated tissues include brain, skeletal muscle and eye.

NIH Rare Diseases : 50 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

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.

Genetics Home Reference : 25 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.

Wikipedia : 72 Adenylosuccinate lyase deficiency, also called adenylosuccinase deficiency, is a rare autosomal... more...

Related Diseases for Adenylosuccinase Deficiency

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

id Related Disease Score Top Affiliating Genes
1 epilepsy 10.0
2 microcephaly 9.8
3 encephalopathy 9.8

Symptoms & Phenotypes for Adenylosuccinase Deficiency

Symptoms via clinical synopsis from OMIM:

54

Neurologic- Central Nervous System:
hypotonia
mental retardation
myoclonus
hypomyelination
spasticity
more
Head And Neck- Eyes:
nystagmus
strabismus

Growth- Other:
growth retardation

Neurologic- Behavioral Psychiatric Manifestations:
hyperactivity
aggressive behavior
self-mutilation
autistic features
stereotypic movements
more
Muscle Soft Tissue:
muscle wasting

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- Nose:
anteverted nostrils
small nose

Head And Neck- Mouth:
wide mouth
thin upper lip

Head And Neck- Ears:
low-set ears

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

Head And Neck- Face:
long smooth philtrum


Clinical features from OMIM:

103050

Human phenotypes related to Adenylosuccinase Deficiency:

56 32 (show all 41)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 absent speech 56 32 hallmark (90%) Very frequent (99-80%) HP:0001344
2 seizures 56 32 hallmark (90%) Very frequent (99-80%) HP:0001250
3 microcephaly 56 32 occasional (7.5%) Very frequent (99-80%) HP:0000252
4 low-set ears 56 32 hallmark (90%) Very frequent (99-80%) HP:0000369
5 short nose 56 32 hallmark (90%) Very frequent (99-80%) HP:0003196
6 anteverted nares 56 32 hallmark (90%) Very frequent (99-80%) HP:0000463
7 intellectual disability 56 32 hallmark (90%) Very frequent (99-80%) HP:0001249
8 long philtrum 56 32 hallmark (90%) Very frequent (99-80%) HP:0000343
9 brachycephaly 56 32 hallmark (90%) Very frequent (99-80%) HP:0000248
10 generalized hypotonia 56 32 hallmark (90%) Very frequent (99-80%) HP:0001290
11 smooth philtrum 56 32 hallmark (90%) Very frequent (99-80%) HP:0000319
12 flat occiput 56 32 hallmark (90%) Very frequent (99-80%) HP:0005469
13 thin upper lip vermilion 56 32 hallmark (90%) Very frequent (99-80%) HP:0000219
14 prominent metopic ridge 56 32 hallmark (90%) Very frequent (99-80%) HP:0005487
15 abnormal facial shape 56 32 hallmark (90%) Very frequent (99-80%) HP:0001999
16 severe global developmental delay 56 32 hallmark (90%) Very frequent (99-80%) HP:0011344
17 hypointensity of cerebral white matter on mri 56 32 hallmark (90%) Very frequent (99-80%) HP:0007103
18 nystagmus 32 HP:0000639
19 myoclonus 32 HP:0001336
20 strabismus 32 HP:0000486
21 wide mouth 32 HP:0000154
22 cerebral atrophy 32 HP:0002059
23 poor eye contact 32 HP:0000817
24 global developmental delay 32 HP:0001263
25 hyperactivity 32 HP:0000752
26 autism 32 HP:0000717
27 aggressive behavior 32 HP:0000718
28 self-mutilation 32 HP:0000742
29 gait ataxia 32 HP:0002066
30 cerebellar atrophy 32 HP:0001272
31 inability to walk 32 HP:0002540
32 happy demeanor 32 occasional (7.5%) HP:0040082
33 muscular hypotonia 32 HP:0001252
34 opisthotonus 32 HP:0002179
35 brisk reflexes 32 HP:0001348
36 delayed speech and language development 32 HP:0000750
37 growth delay 32 HP:0001510
38 inappropriate laughter 32 HP:0000748
39 skeletal muscle atrophy 32 HP:0003202
40 cns hypomyelination 32 HP:0003429
41 cerebral hypomyelination 32 HP:0006808

UMLS symptoms related to Adenylosuccinase Deficiency:


muscle spasticity, myoclonus, opisthotonus, gait ataxia

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:

id Genetic test Affiliating Genes
1 Adenylosuccinate Lyase Deficiency 29
2 Adenylosuccinase Deficiency 24 ADSL

Anatomical Context for Adenylosuccinase Deficiency

MalaCards organs/tissues related to Adenylosuccinase Deficiency:

39
Brain, Skeletal Muscle, Eye, Testes

Publications for Adenylosuccinase Deficiency

Articles related to Adenylosuccinase Deficiency:

(show all 23)
id Title Authors Year
1
Isolated neonatal seizures: adenylosuccinase deficiency is another cause! ( 22883297 )
2012
2
Clinical, biochemical, neuropathological and molecular findings of the first Polish case of adenylosuccinase deficiency. ( 18368630 )
2008
3
Adenylosuccinase deficiency: an unusual cause of early-onset epilepsy associated with acquired microcephaly. ( 11042421 )
2000
4
Autism and adenylosuccinase deficiency. ( 10714045 )
2000
5
Adenylosuccinase deficiency: possibly underdiagnosed encephalopathy with variable clinical features. ( 10727185 )
1999
6
Effect of D-ribose on purine synthesis and neurological symptoms in a patient with adenylosuccinase deficiency. ( 9989253 )
1999
7
Muscle energy metabolism in human adenylosuccinase deficiency. An in vivo 31P-NMR spectroscopy study. ( 9598074 )
1998
8
[Adenylosuccinase deficiency]. ( 9590095 )
1998
9
Adenylosuccinase deficiency with neonatal onset severe epileptic seizures and sudden death. ( 9553952 )
1998
10
Genetic basis of adenylosuccinase deficiency in an Italian patient. ( 9598084 )
1998
11
Inborn errors of the purine nucleotide cycle: adenylosuccinase deficiency. ( 9211192 )
1997
12
Adenylosuccinase deficiency: clinical and biochemical findings in 5 Czech patients. ( 9266351 )
1997
13
Adenylosuccinase deficiency presenting with epilepsy in early infancy. ( 9266401 )
1997
14
Adenylosuccinase deficiency: a patient with impaired erythrocyte activity and anomalous response to intravenous fructose. ( 8598641 )
1995
15
Residual adenylosuccinase activities in fibroblasts of adenylosuccinase-deficient children: parallel deficiency with adenylosuccinate and succinyl-AICAR in profoundly retarded patients and non-parallel deficiency in a mildly retarded girl. ( 8412002 )
1993
16
Functional studies in fibroblasts of adenylosuccinase-deficient children. ( 8412003 )
1993
17
Adenylosuccinase deficiency: a newly recognized variant. ( 1405483 )
1992
18
Adenylosuccinase activity and succinylpurine production in fibroblasts of adenylosuccinase-deficient children. ( 1781383 )
1991
19
Urine test for adenylosuccinase deficiency in autistic children. ( 2563072 )
1989
20
Adenylosuccinase deficiency: an inborn error of purine nucleotide synthesis. ( 3234432 )
1988
21
Detection of inherited adenylosuccinase deficiency by two dimensional thin layer chromatography of urinary imidazoles. ( 3728154 )
1986
22
Adenylosuccinase deficiency. ( 3014834 )
1986
23
Diagnosis of inherited adenylosuccinase deficiency by thin-layer chromatography of urinary imidazoles and by automated cation exchange column chromatography of purines. ( 3719985 )
1986

Variations for Adenylosuccinase Deficiency

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

71 (show all 27)
id 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
id 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 rs119450944 GRCh37 Chromosome 22, 40756440: 40756440
6 ADSL ADSL, -49T-C 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

GO Terms for Adenylosuccinase Deficiency

Sources for Adenylosuccinase Deficiency

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