ASNSD
MCID: ASP024
MIFTS: 37

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 25 43 58 72 36 29 6 39 70
Asns Deficiency 57 25 43 72
Asnsd 57 43 72
Congenital Microcephaly-Severe Encephalopathy-Progressive Cerebral Atrophy Syndrome 43 58
Disorder of Asparagine Metabolism 43 58

Characteristics:

Orphanet epidemiological data:

58
congenital microcephaly-severe encephalopathy-progressive cerebral atrophy syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive

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


HPO:

31
asparagine synthetase deficiency:
Inheritance autosomal recessive inheritance
Onset and clinical course progressive


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


Summaries for Asparagine Synthetase Deficiency

MedlinePlus Genetics : 43 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. The drug Asparagine has been mentioned in the context of this disorder. Affiliated tissues include cortex, pancreas and brain, and related phenotypes are hyperreflexia and failure to thrive

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 may show onset in utero or at birth and may result in early death (summary by Ruzzo et al., 2013); it may also present with early normal development followed by infantile-onset seizures and neurodevelopmental delays (Sacharow et al., 2018). (615574) (Updated 05-Apr-2021)

KEGG : 36 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 : 72 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 : 73 Asparagine synthetase (or aspartate-ammonia ligase) is a chiefly cytoplasmic enzyme that generates... more...

GeneReviews: NBK525916

Related Diseases for Asparagine Synthetase Deficiency

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:

31 (show all 26)
# Description HPO Frequency HPO Source Accession
1 hyperreflexia 31 HP:0001347
2 failure to thrive 31 HP:0001508
3 respiratory insufficiency 31 HP:0002093
4 macrotia 31 HP:0000400
5 spastic tetraplegia 31 HP:0002510
6 micrognathia 31 HP:0000347
7 ventriculomegaly 31 HP:0002119
8 profound global developmental delay 31 HP:0012736
9 cerebellar hypoplasia 31 HP:0001321
10 large hands 31 HP:0001176
11 sloping forehead 31 HP:0000340
12 hypoplasia of the corpus callosum 31 HP:0002079
13 encephalopathy 31 HP:0001298
14 feeding difficulties 31 HP:0011968
15 muscular hypotonia of the trunk 31 HP:0008936
16 cerebral visual impairment 31 HP:0100704
17 hypoplasia of the pons 31 HP:0012110
18 hypsarrhythmia 31 HP:0002521
19 long foot 31 HP:0001833
20 cortical dysplasia 31 HP:0002539
21 delayed myelination 31 HP:0012448
22 exaggerated startle response 31 HP:0002267
23 progressive microcephaly 31 HP:0000253
24 simplified gyral pattern 31 HP:0009879
25 diaphragmatic eventration 31 HP:0009110
26 seizure 31 HP:0001250

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
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 (Updated 05-Apr-2021)

UMLS symptoms related to Asparagine Synthetase Deficiency:


seizures; feeling jittery; hyperexplexia

Drugs & Therapeutics for Asparagine Synthetase Deficiency

Drugs for Asparagine Synthetase Deficiency (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Asparagine Approved, Investigational, Nutraceutical 70-47-3 6267

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 Unknown status 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:

40
Cortex, Pancreas, Brain, Fetal Brain, Pons

Publications for Asparagine Synthetase Deficiency

Articles related to Asparagine Synthetase Deficiency:

(show all 29)
# Title Authors PMID Year
1
Characterization of a novel variant in siblings with Asparagine Synthetase Deficiency. 6 25 57 61
29279279 2018
2
Asparagine Synthetase deficiency-report of a novel mutation and review of literature. 6 57 25 61
28776279 2017
3
Diaphragmatic Eventration in Sisters with Asparagine Synthetase Deficiency: A Novel Homozygous ASNS Mutation and Expanded Phenotype. 57 25 6 61
27469131 2017
4
Deficiency of asparagine synthetase causes congenital microcephaly and a progressive form of encephalopathy. 25 57 6
24139043 2013
5
Clinical whole exome sequencing from dried blood spot identifies novel genetic defect underlying asparagine synthetase deficiency. 6 57 61
29375865 2018
6
Epileptic Phenotype of Two Siblings with Asparagine Synthesis Deficiency Mimics Neonatal Pyridoxine-Dependent Epilepsy. 25 6
27522229 2016
7
Report of four novel variants in ASNS causing asparagine synthetase deficiency and review of literature. 61 6
29405484 2018
8
The first report of Japanese patients with asparagine synthetase deficiency. 61 25
27743885 2017
9
Hyperekplexia, microcephaly and simplified gyral pattern caused by novel ASNS mutations, case report. 25 61
27422383 2016
10
Worsening of Seizures After Asparagine Supplementation in a Child with Asparagine Synthetase Deficiency. 25 61
27268761 2016
11
Asparagine Synthetase Deficiency causes reduced proliferation of cells under conditions of limited asparagine. 25 61
26318253 2015
12
Asparagine synthetase deficiency detected by whole exome sequencing causes congenital microcephaly, epileptic encephalopathy and psychomotor delay. 61 25
25227173 2015
13
Prevalence of inherited neurotransmitter disorders in patients with movement disorders and epilepsy: a retrospective cohort study. 6
25758715 2015
14
Asparagine Synthetase Deficiency: New Inborn Errors of Metabolism. 25 61
25663424 2015
15
Molecular cloning of a gene that is necessary for G1 progression in mammalian cells. 25
3470743 1987
16
Asparagine Synthetase Deficiency with Intracranial Hemorrhage Can Mimic Molybdenum Cofactor Deficiency. 61
33271615 2020
17
Clinical, molecular, and biochemical delineation of asparagine synthetase deficiency in Saudi cohort. 61
32741967 2020
18
Fetal MRI and ultrasound findings of a confirmed asparagine synthetase deficiency case. 61
32564386 2020
19
A novel compound heterozygous missense mutation in ASNS broadens the spectrum of asparagine synthetase deficiency. 61
32255274 2020
20
Congenital microcephaly with early onset epileptic encephalopathy caused by ASNS gene mutation: A case report. 61
32481472 2020
21
Generation of four induced pluripotent stem cell lines, GZWWTi001-A, GZWTZi001-A, GZWXYi001-A, and GZWXDi001-A, derived from peripheral blood mononuclear cells from a family with asparagine synthetase deficiency. 61
31698190 2019
22
Asparagine synthetase deficiency: A novel case with an unusual molecular mechanism. 61
31720226 2019
23
Epileptic encephalopathy with microcephaly in a patient with asparagine synthetase deficiency: a video-EEG report. 61
31617495 2019
24
Cyst-Peritoneal Shunt for the Treatment of a Progressive Intracerebral Cyst Associated with ASNS Mutation: Case Report and Literature Review. 61
30844524 2019
25
Clinical outcomes of two patients with a novel pathogenic variant in ASNS: response to asparagine supplementation and review of the literature. 61
31123592 2019
26
Asparagine Synthetase Deficiency 61
30234940 2018
27
Asparagine synthetase: Function, structure, and role in disease. 61
29084849 2017
28
Erratum to: Asparagine synthetase deficiency-report of a novel mutation and review of literature. 61
28875262 2017
29
Antenatal manifestations of inborn errors of metabolism: autopsy findings suggestive of a metabolic disorder. 61
27106218 2016

Variations for Asparagine Synthetase Deficiency

ClinVar genetic disease variations for Asparagine Synthetase Deficiency:

6 (show all 43)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 CZ1P-ASNS , ASNS NM_001673.5(ASNS):c.601del (p.Met201fs) Deletion Pathogenic 545474 rs1481539409 GRCh37: 7:97488597-97488597
GRCh38: 7:97859285-97859285
2 CZ1P-ASNS , ASNS NM_001673.5(ASNS):c.569T>G (p.Leu190Ter) SNV Pathogenic 623341 rs1562817048 GRCh37: 7:97488629-97488629
GRCh38: 7:97859317-97859317
3 CZ1P-ASNS , ASNS NM_001673.5(ASNS):c.728T>C (p.Val243Ala) SNV Pathogenic 377002 rs148111963 GRCh37: 7:97488213-97488213
GRCh38: 7:97858901-97858901
4 CZ1P-ASNS , ASNS NM_001673.5(ASNS):c.1476+1G>A SNV Pathogenic 870425 GRCh37: 7:97482371-97482371
GRCh38: 7:97853059-97853059
5 CZ1P-ASNS , ASNS NM_001673.5(ASNS):c.1019G>A (p.Arg340His) SNV Pathogenic 635970 rs1360484422 GRCh37: 7:97486013-97486013
GRCh38: 7:97856701-97856701
6 CZ1P-ASNS , ASNS NM_001673.5(ASNS):c.1097G>A (p.Gly366Glu) SNV Pathogenic 635971 rs1584459666 GRCh37: 7:97484705-97484705
GRCh38: 7:97855393-97855393
7 CZ1P-ASNS , ASNS NM_001673.5(ASNS):c.1138G>T (p.Ala380Ser) SNV Pathogenic 635973 rs758183057 GRCh37: 7:97483992-97483992
GRCh38: 7:97854680-97854680
8 CZ1P-ASNS , ASNS NM_001673.5(ASNS):c.413A>T (p.Asp138Val) SNV Pathogenic 210338 rs797045306 GRCh37: 7:97493645-97493645
GRCh38: 7:97864333-97864333
9 CZ1P-ASNS , ASNS NM_001673.5(ASNS):c.17C>A (p.Ala6Glu) SNV Pathogenic 91842 rs398122975 GRCh37: 7:97498452-97498452
GRCh38: 7:97869140-97869140
10 CZ1P-ASNS , ASNS NM_001673.5(ASNS):c.478del (p.Glu160fs) Deletion Pathogenic 210339 rs797045307 GRCh37: 7:97493580-97493580
GRCh38: 7:97864268-97864268
11 CZ1P-ASNS , ASNS NM_001673.5(ASNS):c.1439C>T (p.Ser480Phe) SNV Pathogenic 242550 rs754043007 GRCh37: 7:97482409-97482409
GRCh38: 7:97853097-97853097
12 CZ1P-ASNS , ASNS NM_001673.5(ASNS):c.1084T>G (p.Phe362Val) SNV Pathogenic 91840 rs398122973 GRCh37: 7:97484718-97484718
GRCh38: 7:97855406-97855406
13 CZ1P-ASNS , ASNS NM_001673.5(ASNS):c.1137+1G>A SNV Pathogenic 993020 GRCh37: 7:97484664-97484664
GRCh38: 7:97855352-97855352
14 CZ1P-ASNS , ASNS NM_001673.5(ASNS):c.1648C>T (p.Arg550Cys) SNV Likely pathogenic 91841 rs398122974 GRCh37: 7:97481609-97481609
GRCh38: 7:97852297-97852297
15 CZ1P-ASNS , ASNS NM_001673.5(ASNS):c.1649G>A (p.Arg550His) SNV Likely pathogenic 800534 rs552452349 GRCh37: 7:97481608-97481608
GRCh38: 7:97852296-97852296
16 CZ1P-ASNS , ASNS NM_001673.5(ASNS):c.1030+1G>A SNV Likely pathogenic 434401 rs780288372 GRCh37: 7:97486001-97486001
GRCh38: 7:97856689-97856689
17 CZ1P-ASNS , ASNS NM_001673.5(ASNS):c.1213G>A (p.Ala405Thr) SNV Likely pathogenic 802339 rs749406391 GRCh37: 7:97483917-97483917
GRCh38: 7:97854605-97854605
18 CZ1P-ASNS , ASNS NM_001673.5(ASNS):c.883G>A (p.Asp295Asn) SNV Likely pathogenic 802340 rs781581679 GRCh37: 7:97487610-97487610
GRCh38: 7:97858298-97858298
19 CZ1P-ASNS , ASNS NM_001673.5(ASNS):c.119A>G (p.Tyr40Cys) SNV Likely pathogenic 977852 GRCh37: 7:97498350-97498350
GRCh38: 7:97869038-97869038
20 CZ1P-ASNS , ASNS NM_001673.5(ASNS):c.1393C>T (p.Arg465Ter) SNV Likely pathogenic 836319 GRCh37: 7:97482455-97482455
GRCh38: 7:97853143-97853143
21 CZ1P-ASNS , ASNS NM_001673.5(ASNS):c.437T>C (p.Phe146Ser) SNV Likely pathogenic 977917 GRCh37: 7:97493621-97493621
GRCh38: 7:97864309-97864309
22 CZ1P-ASNS , ASNS NM_001673.5(ASNS):c.666_667del (p.Phe223fs) Microsatellite Likely pathogenic 984946 GRCh37: 7:97488531-97488532
GRCh38: 7:97859219-97859220
23 CZ1P-ASNS , ASNS NM_001673.5(ASNS):c.1160A>G (p.Glu387Gly) SNV Likely pathogenic 800982 rs1584458744 GRCh37: 7:97483970-97483970
GRCh38: 7:97854658-97854658
24 CZ1P-ASNS , ASNS NM_001673.5(ASNS):c.202C>A (p.Pro68Thr) SNV Likely pathogenic 522653 rs1554350554 GRCh37: 7:97498267-97498267
GRCh38: 7:97868955-97868955
25 CZ1P-ASNS , ASNS NM_001673.5(ASNS):c.1165G>C (p.Glu389Gln) SNV Likely pathogenic 545473 rs948326794 GRCh37: 7:97483965-97483965
GRCh38: 7:97854653-97854653
26 CZ1P-ASNS , ASNS NM_001673.5(ASNS):c.146G>A (p.Arg49Gln) SNV Conflicting interpretations of pathogenicity 383733 rs769236847 GRCh37: 7:97498323-97498323
GRCh38: 7:97869011-97869011
27 CZ1P-ASNS , ASNS NM_001673.5(ASNS):c.1465G>A (p.Val489Ile) SNV Uncertain significance 445433 rs772079299 GRCh37: 7:97482383-97482383
GRCh38: 7:97853071-97853071
28 CZ1P-ASNS , ASNS NM_001673.5(ASNS):c.203C>T (p.Pro68Leu) SNV Uncertain significance 635034 rs774187768 GRCh37: 7:97498266-97498266
GRCh38: 7:97868954-97868954
29 CZ1P-ASNS , ASNS NM_001673.5(ASNS):c.1616C>T (p.Pro539Leu) SNV Uncertain significance 453130 rs1182799813 GRCh37: 7:97481641-97481641
GRCh38: 7:97852329-97852329
30 CZ1P-ASNS , ASNS NM_001673.5(ASNS):c.250-10G>A SNV Uncertain significance 730793 rs202126429 GRCh37: 7:97493818-97493818
GRCh38: 7:97864506-97864506
31 CZ1P-ASNS , ASNS NM_001673.5(ASNS):c.153G>A (p.Ala51=) SNV Uncertain significance 745738 rs143288271 GRCh37: 7:97498316-97498316
GRCh38: 7:97869004-97869004
32 CZ1P-ASNS , ASNS NM_001673.5(ASNS):c.1570C>A (p.Arg524Ser) SNV Uncertain significance 991203 GRCh37: 7:97481687-97481687
GRCh38: 7:97852375-97852375
33 CZ1P-ASNS , ASNS NM_001673.5(ASNS):c.613C>T (p.His205Tyr) SNV Uncertain significance 991204 GRCh37: 7:97488585-97488585
GRCh38: 7:97859273-97859273
34 CZ1P-ASNS , ASNS NM_001673.5(ASNS):c.29G>A (p.Ser10Asn) SNV Uncertain significance 634631 rs1562823595 GRCh37: 7:97498440-97498440
GRCh38: 7:97869128-97869128
35 CZ1P-ASNS , ASNS NM_001673.5(ASNS):c.1193A>G (p.Tyr398Cys) SNV Uncertain significance 800997 rs1166271142 GRCh37: 7:97483937-97483937
GRCh38: 7:97854625-97854625
36 CZ1P-ASNS , ASNS NM_001673.5(ASNS):c.1587G>A (p.Arg529=) SNV Uncertain significance 728953 rs140975053 GRCh37: 7:97481670-97481670
GRCh38: 7:97852358-97852358
37 CZ1P-ASNS , ASNS NM_001673.5(ASNS):c.1364C>T (p.Ser455Phe) SNV Uncertain significance 729858 rs61733327 GRCh37: 7:97482484-97482484
GRCh38: 7:97853172-97853172
38 CZ1P-ASNS , ASNS NM_001673.5(ASNS):c.224A>T (p.Asn75Ile) SNV Uncertain significance 1029362 GRCh37: 7:97498245-97498245
GRCh38: 7:97868933-97868933
39 CZ1P-ASNS , ASNS NM_001673.5(ASNS):c.1112C>T (p.Thr371Met) SNV Uncertain significance 1031113 GRCh37: 7:97484690-97484690
GRCh38: 7:97855378-97855378
40 CZ1P-ASNS , ASNS NM_001673.5(ASNS):c.591A>C (p.Ala197=) SNV Likely benign 707980 rs141969298 GRCh37: 7:97488607-97488607
GRCh38: 7:97859295-97859295
41 CZ1P-ASNS , ASNS NM_001673.5(ASNS):c.594C>T (p.Ser198=) SNV Likely benign 797303 rs527301530 GRCh37: 7:97488604-97488604
GRCh38: 7:97859292-97859292
42 CZ1P-ASNS , ASNS NM_001673.5(ASNS):c.629T>A (p.Val210Glu) SNV Benign 667997 rs1049674 GRCh37: 7:97488569-97488569
GRCh38: 7:97859257-97859257
43 CZ1P-ASNS , ASNS NM_001673.5(ASNS):c.18G>A (p.Ala6=) SNV Benign 771726 rs76996735 GRCh37: 7:97498451-97498451
GRCh38: 7:97869139-97869139

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

72
# 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:

36
# 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
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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