ASNSD
MCID: ASP024
MIFTS: 36

Asparagine Synthetase Deficiency (ASNSD)

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

Aliases & Classifications for Asparagine Synthetase Deficiency

MalaCards integrated aliases for Asparagine Synthetase Deficiency:

Name: Asparagine Synthetase Deficiency 57 24 25 59 74 37 29 6 40 72
Asns Deficiency 57 24 25 74
Asnsd 57 25 74
Congenital Microcephaly-Severe Encephalopathy-Progressive Cerebral Atrophy Syndrome 25 59
Disorder of Asparagine Metabolism 25 59

Characteristics:

Orphanet epidemiological data:

59
congenital microcephaly-severe encephalopathy-progressive cerebral atrophy syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
progressive disorder
onset in utero or at birth
death usually in infancy


HPO:

32
asparagine synthetase deficiency:
Inheritance autosomal recessive inheritance
Onset and clinical course progressive


Classifications:



External Ids:

OMIM 57 615574
KEGG 37 H01386
MeSH 44 D000592
ICD10 via Orphanet 34 E72.8
UMLS 72 C3809971

Summaries for Asparagine Synthetase Deficiency

Genetics Home Reference : 25 Asparagine synthetase deficiency is a condition that causes neurological problems in affected individuals starting soon after birth. Most people with this condition have an unusually small head size (microcephaly) that worsens over time due to loss (atrophy) of brain tissue. They also have severe developmental delay that affects both mental and motor skills (psychomotor delay). Affected individuals cannot sit, crawl, or walk and are unable to communicate verbally or nonverbally. The few affected children who achieve developmental milestones often lose these skills over time (developmental regression). Most individuals with asparagine synthetase deficiency have exaggerated reflexes (hyperreflexia) and weak muscle tone (hypotonia). The muscle problems worsen through childhood and lead to muscle stiffness, uncontrolled movements, and ultimately, paralysis of the arms and legs (spastic quadriplegia). Many affected individuals also have recurrent seizures (epilepsy). Not all affected people experience the same type of seizure. The most common types involve a loss of consciousness, muscle rigidity, and convulsions (tonic-clonic); involuntary muscle twitches (myoclonic); or abnormal muscle contraction (tonic). People with asparagine synthetase deficiency may have an exaggerated startle reaction (hyperekplexia) to unexpected stimuli. Some affected individuals have blindness due to impairment of the area of the brain responsible for processing vision, called the occipital cortex (cortical blindness). People with asparagine synthetase deficiency typically do not survive past childhood.

MalaCards based summary : Asparagine Synthetase Deficiency, also known as asns deficiency, is related to microcephaly and cerebral atrophy, and has symptoms including seizures, feeling jittery and hyperexplexia. An important gene associated with Asparagine Synthetase Deficiency is ASNS (Asparagine Synthetase (Glutamine-Hydrolyzing)), and among its related pathways/superpathways is Alanine, aspartate and glutamate metabolism. Affiliated tissues include brain, pancreas and cortex, and related phenotypes are seizures and hyperreflexia

OMIM : 57 ASNS deficiency (ASNSD) is an autosomal recessive severe neurologic disorder characterized by microcephaly, severely delayed psychomotor development, progressive encephalopathy, cortical atrophy, and seizure or hyperekplexic activity. The disorder shows onset in utero or at birth and may result in early death (summary by Ruzzo et al., 2013). (615574)

KEGG : 37
Asparagine synthetase deficiency is an autosomal recessive disorder characterized by congenital microcephaly, intellectual disability, progressive cerebral atrophy, and intractable seizures. Recessive mutations in the ASNS gene, encoding asparagine synthetase which catalyzes the synthesis of asparagine from glutamine and aspartate, are responsible for this syndrome.

UniProtKB/Swiss-Prot : 74 Asparagine synthetase deficiency: An inborn error of asparagine biosynthesis that results in a severe neurologic disorder characterized by microcephaly, severely delayed psychomotor development, progressive encephalopathy, cortical atrophy, and seizure or hyperekplexic activity.

Wikipedia : 75 Asparagine synthetase (or aspartate-ammonia ligase) is a chiefly cytoplasmic enzyme that generates... more...

GeneReviews: NBK525916

Related Diseases for Asparagine Synthetase Deficiency

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

(show all 24)
# Related Disease Score Top Affiliating Genes
1 microcephaly 10.5
2 cerebral atrophy 10.3
3 seizure disorder 10.3
4 alacrima, achalasia, and mental retardation syndrome 10.3
5 locked-in syndrome 10.3
6 quadriplegia 10.3
7 spasticity 10.3
8 hyperekplexia 10.2
9 spastic quadriplegia 10.2
10 visual epilepsy 10.2
11 encephalopathy 10.2
12 hypotonia 10.2
13 gastroesophageal reflux 10.0
14 leukemia, acute myeloid 10.0
15 yemenite deaf-blind hypopigmentation syndrome 10.0
16 leukemia, acute lymphoblastic 10.0
17 autosomal recessive disease 10.0
18 scoliosis 10.0
19 lymphocytic leukemia 10.0
20 diaphragmatic eventration 10.0
21 cortical blindness 10.0
22 constipation 10.0
23 inherited metabolic disorder 10.0
24 myeloid leukemia 10.0

Graphical network of the top 20 diseases related to Asparagine Synthetase Deficiency:



Diseases related to Asparagine Synthetase Deficiency

Symptoms & Phenotypes for Asparagine Synthetase Deficiency

Human phenotypes related to Asparagine Synthetase Deficiency:

32 (show all 25)
# Description HPO Frequency HPO Source Accession
1 seizures 32 HP:0001250
2 hyperreflexia 32 HP:0001347
3 failure to thrive 32 HP:0001508
4 respiratory insufficiency 32 HP:0002093
5 macrotia 32 HP:0000400
6 spastic tetraplegia 32 HP:0002510
7 micrognathia 32 HP:0000347
8 feeding difficulties 32 HP:0011968
9 ventriculomegaly 32 HP:0002119
10 cerebellar hypoplasia 32 HP:0001321
11 exaggerated startle response 32 HP:0002267
12 hypsarrhythmia 32 HP:0002521
13 profound global developmental delay 32 HP:0012736
14 large hands 32 HP:0001176
15 sloping forehead 32 HP:0000340
16 encephalopathy 32 HP:0001298
17 hypoplasia of the corpus callosum 32 HP:0002079
18 cortical dysplasia 32 HP:0002539
19 delayed myelination 32 HP:0012448
20 muscular hypotonia of the trunk 32 HP:0008936
21 cerebral visual impairment 32 HP:0100704
22 hypoplasia of the pons 32 HP:0012110
23 long foot 32 HP:0001833
24 progressive microcephaly 32 HP:0000253
25 simplified gyral pattern 32 HP:0009879

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
seizures
hyperreflexia
spastic tetraplegia
cerebellar hypoplasia
hypsarrhythmia
more
Respiratory:
respiratory insufficiency

Skeletal Hands:
large hands

Head And Neck Ears:
large ears

Head And Neck Eyes:
cortical blindness

Chest Diaphragm:
diaphragmatic eventration (in one family)

Growth Other:
failure to thrive

Head And Neck Face:
micrognathia
receding forehead

Skeletal Feet:
large feet

Abdomen Gastrointestinal:
poor feeding

Head And Neck Head:
microcephaly, progressive (up to -7 sd)

Laboratory Abnormalities:
decreased asparagine levels (in some patients)

Clinical features from OMIM:

615574

UMLS symptoms related to Asparagine Synthetase Deficiency:


seizures, feeling jittery, hyperexplexia

Drugs & Therapeutics for Asparagine Synthetase Deficiency

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Study on the Mechanism of Neurodevelopment Dysplasia of Fetal Brain Caused by ASNS Gene Mutation Recruiting NCT03587155

Search NIH Clinical Center for Asparagine Synthetase Deficiency

Genetic Tests for Asparagine Synthetase Deficiency

Genetic tests related to Asparagine Synthetase Deficiency:

# Genetic test Affiliating Genes
1 Asparagine Synthetase Deficiency 29 ASNS

Anatomical Context for Asparagine Synthetase Deficiency

MalaCards organs/tissues related to Asparagine Synthetase Deficiency:

41
Brain, Pancreas, Cortex, Fetal Brain, Pons

Publications for Asparagine Synthetase Deficiency

Articles related to Asparagine Synthetase Deficiency:

(show all 20)
# Title Authors PMID Year
1
Asparagine Synthetase deficiency-report of a novel mutation and review of literature. 38 4 8 71
28776279 2017
2
Diaphragmatic Eventration in Sisters with Asparagine Synthetase Deficiency: A Novel Homozygous ASNS Mutation and Expanded Phenotype. 38 4 8 71
27469131 2017
3
Deficiency of asparagine synthetase causes congenital microcephaly and a progressive form of encephalopathy. 4 8 71
24139043 2013
4
Clinical whole exome sequencing from dried blood spot identifies novel genetic defect underlying asparagine synthetase deficiency. 38 8 71
29375865 2018
5
Asparagine Synthetase Deficiency 38 71
30234940 2018
6
Characterization of a novel variant in siblings with Asparagine Synthetase Deficiency. 38 4
29279279 2018
7
The first report of Japanese patients with asparagine synthetase deficiency. 38 4
27743885 2017
8
Hyperekplexia, microcephaly and simplified gyral pattern caused by novel ASNS mutations, case report. 38 4
27422383 2016
9
Worsening of Seizures After Asparagine Supplementation in a Child with Asparagine Synthetase Deficiency. 38 4
27268761 2016
10
Asparagine Synthetase Deficiency causes reduced proliferation of cells under conditions of limited asparagine. 38 4
26318253 2015
11
Asparagine synthetase deficiency detected by whole exome sequencing causes congenital microcephaly, epileptic encephalopathy and psychomotor delay. 38 4
25227173 2015
12
Asparagine Synthetase Deficiency: New Inborn Errors of Metabolism. 38 4
25663424 2015
13
Epileptic Phenotype of Two Siblings with Asparagine Synthesis Deficiency Mimics Neonatal Pyridoxine-Dependent Epilepsy. 4
27522229 2016
14
Molecular cloning of a gene that is necessary for G1 progression in mammalian cells. 4
3470743 1987
15
Cyst-Peritoneal Shunt for the Treatment of a Progressive Intracerebral Cyst Associated with ASNS Mutation: Case Report and Literature Review. 38
30844524 2019
16
Clinical outcomes of two patients with a novel pathogenic variant in ASNS: response to asparagine supplementation and review of the literature. 38
31123592 2019
17
Report of four novel variants in ASNS causing asparagine synthetase deficiency and review of literature. 38
29405484 2018
18
Erratum to: Asparagine synthetase deficiency-report of a novel mutation and review of literature. 38
28875262 2017
19
Asparagine synthetase: Function, structure, and role in disease. 38
29084849 2017
20
Antenatal manifestations of inborn errors of metabolism: autopsy findings suggestive of a metabolic disorder. 38
27106218 2016

Variations for Asparagine Synthetase Deficiency

ClinVar genetic disease variations for Asparagine Synthetase Deficiency:

6 (show all 18)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 ASNS NM_183356.3(ASNS): c.601del (p.Met201fs) deletion Pathogenic rs1481539409 7:97488597-97488597 7:97859285-97859285
2 ASNS NM_183356.3(ASNS): c.1084T> G (p.Phe362Val) single nucleotide variant Pathogenic rs398122973 7:97484718-97484718 7:97855406-97855406
3 ASNS NM_183356.3(ASNS): c.478del (p.Glu160fs) deletion Pathogenic rs797045307 7:97493580-97493580 7:97864268-97864268
4 ASNS NM_183356.3(ASNS): c.413A> T (p.Asp138Val) single nucleotide variant Pathogenic rs797045306 7:97493645-97493645 7:97864333-97864333
5 ASNS NM_183356.3(ASNS): c.569T> G (p.Leu190Ter) single nucleotide variant Pathogenic 7:97488629-97488629 7:97859317-97859317
6 ASNS NM_183356.3(ASNS): c.1019G> A (p.Arg340His) single nucleotide variant Pathogenic 7:97486013-97486013 7:97856701-97856701
7 ASNS NM_183356.3(ASNS): c.1097G> A (p.Gly366Glu) single nucleotide variant Pathogenic 7:97484705-97484705 7:97855393-97855393
8 ASNS NM_183356.3(ASNS): c.1138G> T (p.Ala380Ser) single nucleotide variant Pathogenic 7:97483992-97483992 7:97854680-97854680
9 ASNS NM_183356.3(ASNS): c.202C> A (p.Pro68Thr) single nucleotide variant Likely pathogenic rs1554350554 7:97498267-97498267 7:97868955-97868955
10 ASNS NM_183356.3(ASNS): c.1165G> C (p.Glu389Gln) single nucleotide variant Likely pathogenic rs948326794 7:97483965-97483965 7:97854653-97854653
11 ASNS NM_183356.3(ASNS): c.1648C> T (p.Arg550Cys) single nucleotide variant Likely pathogenic rs398122974 7:97481609-97481609 7:97852297-97852297
12 ASNS NM_183356.3(ASNS): c.17C> A (p.Ala6Glu) single nucleotide variant Likely pathogenic rs398122975 7:97498452-97498452 7:97869140-97869140
13 ASNS NM_183356.3(ASNS): c.728T> C (p.Val243Ala) single nucleotide variant Likely pathogenic rs148111963 7:97488213-97488213 7:97858901-97858901
14 ASNS NM_183356.3(ASNS): c.1030+1G> A single nucleotide variant Likely pathogenic rs780288372 7:97486001-97486001 7:97856689-97856689
15 ASNS NM_183356.3(ASNS): c.146G> A (p.Arg49Gln) single nucleotide variant Conflicting interpretations of pathogenicity rs769236847 7:97498323-97498323 7:97869011-97869011
16 ASNS ; CZ1P-ASNS NM_183356.3(ASNS): c.1465G> A (p.Val489Ile) single nucleotide variant Uncertain significance rs772079299 7:97482383-97482383 7:97853071-97853071
17 ASNS NM_183356.3(ASNS): c.29G> A (p.Ser10Asn) single nucleotide variant Uncertain significance 7:97498440-97498440 7:97869128-97869128
18 ASNS NM_183356.3(ASNS): c.203C> T (p.Pro68Leu) single nucleotide variant Uncertain significance 7:97498266-97498266 7:97868954-97868954

UniProtKB/Swiss-Prot genetic disease variations for Asparagine Synthetase Deficiency:

74
# Symbol AA change Variation ID SNP ID
1 ASNS p.Ala6Glu VAR_070896 rs398122975
2 ASNS p.Phe362Val VAR_070897 rs398122973
3 ASNS p.Arg550Cys VAR_070898 rs398122974

Expression for Asparagine Synthetase Deficiency

Search GEO for disease gene expression data for Asparagine Synthetase Deficiency.

Pathways for Asparagine Synthetase Deficiency

Pathways related to Asparagine Synthetase Deficiency according to KEGG:

37
# Name Kegg Source Accession
1 Alanine, aspartate and glutamate metabolism hsa00250

GO Terms for Asparagine Synthetase Deficiency

Sources for Asparagine Synthetase Deficiency

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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