GCENSG
MCID: GLY094
MIFTS: 25

Glycine Encephalopathy with Normal Serum Glycine (GCENSG)

Categories: Genetic diseases, Metabolic diseases, Neuronal diseases, Respiratory diseases

Aliases & Classifications for Glycine Encephalopathy with Normal Serum Glycine

MalaCards integrated aliases for Glycine Encephalopathy with Normal Serum Glycine:

Name: Glycine Encephalopathy with Normal Serum Glycine 57 72 36 29 6
Encephalopathy, Glycine, with Normal Serum Glycine 39
Gcensg 72

Characteristics:

OMIM®:

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

Miscellaneous:
onset in utero
early death may occur
three unrelated families have been reported (last curated january 2017)


HPO:

31
glycine encephalopathy with normal serum glycine:
Inheritance autosomal recessive inheritance
Onset and clinical course congenital onset


Classifications:



Summaries for Glycine Encephalopathy with Normal Serum Glycine

OMIM® : 57 Glycine encephalopathy with normal serum glycine is a severe metabolic disorder characterized by arthrogryposis multiplex congenita, joint hyperlaxity, lack of neonatal respiratory effort, axial hypotonia, hypertonia with pronounced clonus, and delayed psychomotor development. Some patients may have dysmorphic facial features and/or brain imaging abnormalities. Laboratory studies show increased CSF glycine and normal or only mildly increased serum glycine. Most patients die in infancy. The disorder is similar to, but distinct from, glycine encephalopathy (GCE; 605899) due to mutations in genes encoding the glycine cleavage system (summary by Kurolap et al., 2016). (617301) (Updated 05-Apr-2021)

MalaCards based summary : Glycine Encephalopathy with Normal Serum Glycine, is also known as encephalopathy, glycine, with normal serum glycine. An important gene associated with Glycine Encephalopathy with Normal Serum Glycine is SLC6A9 (Solute Carrier Family 6 Member 9), and among its related pathways/superpathways is Synaptic vesicle cycle. Related phenotypes are microcephaly and optic atrophy

KEGG : 36 Glycine encephalopathy [DS:H00191], also known as nonketotic hyperglycinemia (NKH), is characterized by severe neurologic dysfunctions. Recently, some individuals with NKH-like symptoms but lacking the typical elevation of serum glycine have been reported. They carry mutations in the SLC6A9 gene, that encodes glycine transporter (GLYT1). GLYT1 is located predominantly on astrocytes and is essential for the clearance of glycine from the extracellular space and termination of glycinergic neurotransmission.

UniProtKB/Swiss-Prot : 72 Glycine encephalopathy with normal serum glycine: An autosomal recessive, severe metabolic disorder characterized by arthrogryposis multiplex congenita, joint hyperlaxity, lack of neonatal respiratory effort, axial hypotonia, hypertonia with pronounced clonus, and delayed psychomotor development. Some patients may have dysmorphic facial features and/or brain imaging abnormalities. Laboratory studies show increased CSF glycine and normal or only mildly increased serum glycine. Most patients die in infancy.

Related Diseases for Glycine Encephalopathy with Normal Serum Glycine

Symptoms & Phenotypes for Glycine Encephalopathy with Normal Serum Glycine

Human phenotypes related to Glycine Encephalopathy with Normal Serum Glycine:

31 (show all 32)
# Description HPO Frequency HPO Source Accession
1 microcephaly 31 occasional (7.5%) HP:0000252
2 optic atrophy 31 occasional (7.5%) HP:0000648
3 clonus 31 HP:0002169
4 ptosis 31 HP:0000508
5 dysphagia 31 HP:0002015
6 global developmental delay 31 HP:0001263
7 depressed nasal bridge 31 HP:0005280
8 anteverted nares 31 HP:0000463
9 hypertonia 31 HP:0001276
10 genu recurvatum 31 HP:0002816
11 retrognathia 31 HP:0000278
12 low-set ears 31 HP:0000369
13 elbow flexion contracture 31 HP:0002987
14 joint laxity 31 HP:0001388
15 talipes equinovarus 31 HP:0001762
16 dolichocephaly 31 HP:0000268
17 ventriculomegaly 31 HP:0002119
18 hip dislocation 31 HP:0002827
19 apnea 31 HP:0002104
20 arthrogryposis multiplex congenita 31 HP:0002804
21 hip contracture 31 HP:0003273
22 respiratory failure 31 HP:0002878
23 long eyelashes 31 HP:0000527
24 trigonocephaly 31 HP:0000243
25 hypoplasia of the corpus callosum 31 HP:0002079
26 encephalopathy 31 HP:0001298
27 fetal distress 31 HP:0025116
28 hand clenching 31 HP:0001188
29 muscular hypotonia of the trunk 31 HP:0008936
30 overlapping toe 31 HP:0001845
31 exaggerated startle response 31 HP:0002267
32 myopathic facies 31 HP:0002058

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Head And Neck Nose:
depressed nasal bridge
upturned nose

Head And Neck Face:
retrognathia
myopathic facies

Skeletal:
joint laxity
arthrogryposis multiplex congenita

Head And Neck Head:
trigonocephaly
microcephaly (in some patients)

Head And Neck Eyes:
optic atrophy (in some patients)

Skeletal Limbs:
elbow contractures
hyperextension of the knees

Abdomen Gastrointestinal:
swallowing difficulties

Prenatal Manifestations:
nuchal translucency

Respiratory:
lack of respiratory drive, neonatal
apnea, recurrent

Muscle Soft Tissue:
hypertonia
hypotonia, profound, neonatal

Head And Neck Ears:
low-set ears

Skeletal Pelvis:
hip dislocation
hip contractures

Neurologic Central Nervous System:
encephalopathy
delayed psychomotor development
dilated ventricles
thin corpus callosum (in some patients)
hyperekplexia
more
Skeletal Feet:
foot deformities
club feet

Head And Neck Mouth:
tent-shaped mouth

Skeletal Hands:
clenched fists

Laboratory Abnormalities:
increased csf glycine
normal serum glycine
mildly increased serum glycine (1 patient)
increased urinary glycine
increased csf-to-plasma glycine ratio

Clinical features from OMIM®:

617301 (Updated 05-Apr-2021)

Drugs & Therapeutics for Glycine Encephalopathy with Normal Serum Glycine

Search Clinical Trials , NIH Clinical Center for Glycine Encephalopathy with Normal Serum Glycine

Genetic Tests for Glycine Encephalopathy with Normal Serum Glycine

Genetic tests related to Glycine Encephalopathy with Normal Serum Glycine:

# Genetic test Affiliating Genes
1 Glycine Encephalopathy with Normal Serum Glycine 29 SLC6A9

Anatomical Context for Glycine Encephalopathy with Normal Serum Glycine

Publications for Glycine Encephalopathy with Normal Serum Glycine

Articles related to Glycine Encephalopathy with Normal Serum Glycine:

# Title Authors PMID Year
1
Loss of Glycine Transporter 1 Causes a Subtype of Glycine Encephalopathy with Arthrogryposis and Mildly Elevated Cerebrospinal Fluid Glycine. 57 6
27773429 2016
2
Mutation in SLC6A9 encoding a glycine transporter causes a novel form of non-ketotic hyperglycinemia in humans. 6 57
27481395 2016
3
Gene knockout of glycine transporter 1: characterization of the behavioral phenotype. 57
15159536 2004
4
Inactivation of the glycine transporter 1 gene discloses vital role of glial glycine uptake in glycinergic inhibition. 57
14622582 2003
5
Glycine Transporter 1 Encephalopathy From Biochemical Pathway to Clinical Disease: Review. 61
30815509 2019

Variations for Glycine Encephalopathy with Normal Serum Glycine

ClinVar genetic disease variations for Glycine Encephalopathy with Normal Serum Glycine:

6 (show all 30)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 SLC6A9 NM_001024845.3(SLC6A9):c.709_713del (p.Lys237fs) Deletion Pathogenic 374988 rs1057519315 GRCh37: 1:44468535-44468539
GRCh38: 1:44002863-44002867
2 SLC6A9 NM_001024845.3(SLC6A9):c.832C>T (p.Gln278Ter) SNV Pathogenic 568191 rs201437896 GRCh37: 1:44468210-44468210
GRCh38: 1:44002538-44002538
3 SLC6A9 NM_001024845.3(SLC6A9):c.31-6251A>G SNV Pathogenic 998231 GRCh37: 1:44482805-44482805
GRCh38: 1:44017133-44017133
4 SLC6A9 NM_001024845.3(SLC6A9):c.1000A>G (p.Ser334Gly) SNV Pathogenic 374986 rs1057519313 GRCh37: 1:44467262-44467262
GRCh38: 1:44001590-44001590
5 SLC6A9 NM_001024845.3(SLC6A9):c.1498C>T (p.Gln500Ter) SNV Pathogenic 374987 rs1057519314 GRCh37: 1:44466477-44466477
GRCh38: 1:44000805-44000805
6 SLC6A9 NM_001024845.3(SLC6A9):c.962G>A (p.Arg321Gln) SNV Uncertain significance 1031818 GRCh37: 1:44467985-44467985
GRCh38: 1:44002313-44002313
7 SLC6A9 NM_001024845.3(SLC6A9):c.31-6241del Deletion Uncertain significance 1031819 GRCh37: 1:44482795-44482795
GRCh38: 1:44017123-44017123
8 SLC6A9 NM_001024845.3(SLC6A9):c.407C>T (p.Ser136Leu) SNV Uncertain significance 1031820 GRCh37: 1:44474208-44474208
GRCh38: 1:44008536-44008536
9 SLC6A9 NM_001024845.3(SLC6A9):c.1602C>T (p.Gly534=) SNV Uncertain significance 1007399 GRCh37: 1:44463632-44463632
GRCh38: 1:43997960-43997960
10 SLC6A9 NM_001024845.3(SLC6A9):c.1435G>A (p.Gly479Arg) SNV Uncertain significance 1011843 GRCh37: 1:44466628-44466628
GRCh38: 1:44000956-44000956
11 SLC6A9 NM_001024845.3(SLC6A9):c.1381T>G (p.Phe461Val) SNV Uncertain significance 1015814 GRCh37: 1:44466682-44466682
GRCh38: 1:44001010-44001010
12 SLC6A9 NM_001024845.3(SLC6A9):c.1003G>A (p.Val335Ile) SNV Uncertain significance 598735 rs149105213 GRCh37: 1:44467259-44467259
GRCh38: 1:44001587-44001587
13 SLC6A9 NM_001024845.3(SLC6A9):c.64G>A (p.Asp22Asn) SNV Uncertain significance 853225 GRCh37: 1:44476521-44476521
GRCh38: 1:44010849-44010849
14 SLC6A9 NM_001024845.3(SLC6A9):c.754G>A (p.Val252Met) SNV Uncertain significance 969939 GRCh37: 1:44468288-44468288
GRCh38: 1:44002616-44002616
15 SLC6A9 NM_001024845.3(SLC6A9):c.461A>G (p.His154Arg) SNV Uncertain significance 848719 GRCh37: 1:44474154-44474154
GRCh38: 1:44008482-44008482
16 SLC6A9 NM_001024845.3(SLC6A9):c.664G>A (p.Gly222Ser) SNV Uncertain significance 651556 rs143087050 GRCh37: 1:44468584-44468584
GRCh38: 1:44002912-44002912
17 SLC6A9 NM_001024845.3(SLC6A9):c.535T>C (p.Ser179Pro) SNV Uncertain significance 660073 rs201636712 GRCh37: 1:44474080-44474080
GRCh38: 1:44008408-44008408
18 SLC6A9 NM_001024845.3(SLC6A9):c.120C>T (p.Ser40=) SNV Likely benign 712931 rs571004944 GRCh37: 1:44476465-44476465
GRCh38: 1:44010793-44010793
19 SLC6A9 NM_001024845.3(SLC6A9):c.1810G>A (p.Gly604Ser) SNV Likely benign 719042 rs61733177 GRCh37: 1:44463309-44463309
GRCh38: 1:43997637-43997637
20 SLC6A9 NM_001024845.3(SLC6A9):c.468C>T (p.Cys156=) SNV Likely benign 733549 rs777756958 GRCh37: 1:44474147-44474147
GRCh38: 1:44008475-44008475
21 SLC6A9 NM_001024845.3(SLC6A9):c.1653C>T (p.Ile551=) SNV Likely benign 735203 rs202054416 GRCh37: 1:44463581-44463581
GRCh38: 1:43997909-43997909
22 SLC6A9 NM_001024845.3(SLC6A9):c.528C>T (p.Ser176=) SNV Likely benign 784655 rs139332952 GRCh37: 1:44474087-44474087
GRCh38: 1:44008415-44008415
23 SLC6A9 NM_001024845.3(SLC6A9):c.517G>A (p.Ala173Thr) SNV Likely benign 788180 rs142642003 GRCh37: 1:44474098-44474098
GRCh38: 1:44008426-44008426
24 SLC6A9 NM_001024845.3(SLC6A9):c.705G>C (p.Gly235=) SNV Benign 791709 rs72890664 GRCh37: 1:44468543-44468543
GRCh38: 1:44002871-44002871
25 SLC6A9 NM_001024845.3(SLC6A9):c.472G>A (p.Gly158Ser) SNV Benign 791710 rs61741712 GRCh37: 1:44474143-44474143
GRCh38: 1:44008471-44008471
26 SLC6A9 NM_001024845.3(SLC6A9):c.654T>C (p.Leu218=) SNV Benign 784947 rs140091591 GRCh37: 1:44468594-44468594
GRCh38: 1:44002922-44002922
27 SLC6A9 NM_001024845.3(SLC6A9):c.31-697C>G SNV Benign 786870 rs187474842 GRCh37: 1:44477251-44477251
GRCh38: 1:44011579-44011579
28 SLC6A9 NM_001024845.3(SLC6A9):c.1146G>A (p.Pro382=) SNV Benign 774154 rs76354303 GRCh37: 1:44467116-44467116
GRCh38: 1:44001444-44001444
29 SLC6A9 NM_001024845.3(SLC6A9):c.1537-6G>A SNV Benign 476371 rs113184612 GRCh37: 1:44463703-44463703
GRCh38: 1:43998031-43998031
30 SLC6A9 NM_001024845.3(SLC6A9):c.960C>T (p.Tyr320=) SNV Benign 476370 rs61733181 GRCh37: 1:44467987-44467987
GRCh38: 1:44002315-44002315

UniProtKB/Swiss-Prot genetic disease variations for Glycine Encephalopathy with Normal Serum Glycine:

72
# Symbol AA change Variation ID SNP ID
1 SLC6A9 p.Ser407Gly VAR_078074 rs105751931

Expression for Glycine Encephalopathy with Normal Serum Glycine

Search GEO for disease gene expression data for Glycine Encephalopathy with Normal Serum Glycine.

Pathways for Glycine Encephalopathy with Normal Serum Glycine

Pathways related to Glycine Encephalopathy with Normal Serum Glycine according to KEGG:

36
# Name Kegg Source Accession
1 Synaptic vesicle cycle hsa04721

GO Terms for Glycine Encephalopathy with Normal Serum Glycine

Sources for Glycine Encephalopathy with Normal Serum Glycine

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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