MCID: CNG436
MIFTS: 38

Congenital Disorder of Deglycosylation

Categories: Genetic diseases, Rare diseases, Metabolic diseases, Liver diseases

Aliases & Classifications for Congenital Disorder of Deglycosylation

MalaCards integrated aliases for Congenital Disorder of Deglycosylation:

Name: Congenital Disorder of Deglycosylation 54 12 71 29 69
Congenital Disorder of Glycosylation Type Iv 12 71
Deficiency of N-Glycanase 1 12 50
Ngly1-Deficiency 12 14
Ngly1-Cddg 12 56
Alacrimia-Choreoathetosis-Liver Dysfunction Syndrome 56
Congenital Disorder of Glycosylation Type Iv; Cdg1v 50
Congenital Disorder of Deglycosylation;cddg 50
Congenital Disorder of Glycosylation 1v 71
Ngly1 Deficiency 56
N-Glycanase 1 13
Cdg1v 71
Cdgiv 71
Cddg 71

Characteristics:

Orphanet epidemiological data:

56
alacrimia-choreoathetosis-liver dysfunction syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

54
Inheritance:
autosomal recessive


HPO:

32
congenital disorder of deglycosylation:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 56  
Inborn errors of metabolism


Summaries for Congenital Disorder of Deglycosylation

NIH Rare Diseases : 50 deficiency of n-glycanase 1 (ngly1 deficiency) is a complex neurological syndrome in which there is a deficiency of an enzyme  known as n-glycanase 1 (ngly1). this enzyme normally helps the body remove proteins that are not functioning properly. the typical features of ngly1 deficiency include abnormal tear production, a movement disorder (choreoathetosis), and liver disease. additional features may include developmental delay, hypotonia (weak muscle tone), peripheral neuropathy , eeg abnormalities, and a small head size (microcephaly). the condition is caused by mutations in the n-glycanase 1 gene (ngly1 gene) and is inherited in an autosomal recessive manner. last updated: 9/9/2015

MalaCards based summary : Congenital Disorder of Deglycosylation, also known as congenital disorder of glycosylation type iv, is related to ngly1-cdg and ngly1-congenital disorder of deglycosylation, and has symptoms including scoliosis, involuntary movements and recurrent respiratory infections. An important gene associated with Congenital Disorder of Deglycosylation is NGLY1 (N-Glycanase 1), and among its related pathways/superpathways is Calnexin/calreticulin cycle. Affiliated tissues include liver, eye and testes.

UniProtKB/Swiss-Prot : 71 Congenital disorder of deglycosylation: A multisystem disorder characterized by developmental delay, hypotonia, abnormal involuntary movements and alacrima or poor tear production. Other features include microcephaly, intractable seizures, abnormal eye movements and evidence of liver dysfunction, probably due to cytoplasmic accumulation of storage material in vacuoles.

OMIM : 54
Congenital disorder of deglycosylation is an autosomal recessive multisystem disorder characterized by global developmental delay, hypotonia, abnormal involuntary movements, and alacrima or poor tear production. Other common features include microcephaly, intractable seizures, abnormal eye movements, and evidence of liver dysfunction. Liver biopsy shows cytoplasmic accumulation of storage material in vacuoles (summary by Enns et al., 2014). For a discussion of the classification of congenital disorders of glycosylation, see CDG1A (212065). (615273)

Disease Ontology : 12 A carbohydrate metabolic disorder that has material basis in homozygous or compound heterozygous mutation in the NGLY1 gene on chromosome 1p24. It is characterized by global developmental delay, hypotonia, abnormal involuntary movements, and alacrima or poor tear production.

Related Diseases for Congenital Disorder of Deglycosylation

Diseases related to Congenital Disorder of Deglycosylation via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 43)
id Related Disease Score Top Affiliating Genes
1 ngly1-cdg 11.1
2 ngly1-congenital disorder of deglycosylation 11.0
3 scrotum melanoma 10.2 ATP12A ATP4A
4 congenital aphakia 10.2 ATP12A ATP4A
5 shwartzman phenomenon 10.2 ATP12A ATP4A
6 primary syphilis 10.2 ATP12A ATP4A
7 bone giant cell sarcoma 10.2 ATP12A ATP4A
8 urethral calculus 10.2 ATP12A ATP4A
9 breast ductal adenoma 10.2 ATP12A ATP4A
10 hypopituitarism 10.2 ATP12A ATP4A
11 amyotrophic lateral sclerosis type 5 10.2 ATP12A ATP4A
12 abnormal pupillary function 10.2 ATP12A ATP4A
13 atheroembolism of kidney 10.2 ATP12A ATP4A
14 synostosis 10.2 ATP12A ATP4A
15 muscle cancer 10.2 ATP12A ATP4A
16 adult xanthogranuloma 10.2 ATP12A ATP4A
17 polysyndactyly with cardiac malformation 10.2 ATP12A ATP4A
18 focal hand dystonia 10.2 ATP12A ATP4A
19 cloacal exstrophy 10.2 ATP12A ATP4A
20 thrombocytopenia due to platelet alloimmunization 10.2 ATP12A ATP4A
21 proliferative fasciitis 10.2 ATP12A ATP4A
22 hodgkin's paragranuloma 10.2 ATP12A ATP4A
23 bladder neck cancer 10.2 ATP12A ATP4A
24 spinocerebellar ataxia 18 10.1 ATP12A ATP4A
25 intracranial sinus thrombosis 10.1 ATP12A ATP4A
26 fungal gastritis 10.1 ATP12A ATP4A
27 cubitus valgus with mental retardation and unusual facies 10.1 ATP12A ATP4A
28 villous adenocarcinoma 10.1 ATP12A ATP4A
29 ileocolitis 10.1 ATP12A ATP4A
30 allergic urticaria 10.1 ATP12A ATP4A
31 mesenteric vascular occlusion 10.1 ATP12A ATP4A
32 scleral staphyloma 10.1 ATP12A ATP4A
33 anterior cerebral artery infarction 10.0 ATP12A ATP4A
34 pediatric infratentorial ependymoblastoma 10.0 ATP12A ATP4A
35 hepatic veno-occlusive disease 10.0 ATP12A ATP4A
36 frontal sinus schneiderian papilloma 10.0 ATP12A ATP4A
37 prostatic cyst 9.9 ATP12A ATP4A
38 gnathomiasis 9.9 ATP12A ATP4A
39 fibrosarcomatous osteosarcoma 9.8 ATP12A ATP4A
40 tuberculum sellae meningioma 9.8 ATP12A ATP4A
41 lymphoma, malt, somatic 9.7 ATP12A ATP4A
42 farber lipogranulomatosis 9.5 ATP12A ATP4A
43 microphthalmia, syndromic 12 7.9 ATP12A ATP4A ENGASE FAF1 MED19 NGLY1

Graphical network of the top 20 diseases related to Congenital Disorder of Deglycosylation:



Diseases related to Congenital Disorder of Deglycosylation

Symptoms & Phenotypes for Congenital Disorder of Deglycosylation

Symptoms via clinical synopsis from OMIM:

54

Neurologic- Central Nervous System:
hypotonia
involuntary movements
developmental delay
epilepsy, multifocal, intractable
regression of motor development
more
Skeletal- Hands:
small hands

Head And Neck- Eyes:
congenital absence of tears

Metabolic Features:
abnormal urine oligosaccharides (keratan sulfate, heparan sulfate, and chondroitin sulfate)
normal transferrin isoelectric focusing test
normal n-glycan analysis

Neurologic- Peripheral Nervous System:
peripheral neuropathy

Skeletal- Feet:
small feet

Abdomen- Liver:
abnormal liver function
inflammatory liver changes
amorphous substance in the cytoplasm


Clinical features from OMIM:

615273

Human phenotypes related to Congenital Disorder of Deglycosylation:

32 (show all 32)
id Description HPO Frequency HPO Source Accession
1 scoliosis 32 very rare (1%) HP:0002650
2 involuntary movements 32 very rare (1%) HP:0004305
3 recurrent respiratory infections 32 very rare (1%) HP:0002205
4 strabismus 32 very rare (1%) HP:0000486
5 hyporeflexia 32 very rare (1%) HP:0001265
6 hepatomegaly 32 very rare (1%) HP:0002240
7 seizures 32 very rare (1%) HP:0001250
8 ptosis 32 very rare (1%) HP:0000508
9 microcephaly 32 very rare (1%) HP:0000252
10 hypertelorism 32 very rare (1%) HP:0000316
11 anhidrosis 32 very rare (1%) HP:0000970
12 osteoporosis 32 very rare (1%) HP:0000939
13 global developmental delay 32 very rare (1%) HP:0001263
14 respiratory distress 32 very rare (1%) HP:0002098
15 delayed myelination 32 very rare (1%) HP:0012448
16 fever 32 HP:0001945
17 muscular hypotonia 32 very rare (1%) HP:0001252
18 pain insensitivity 32 very rare (1%) HP:0007021
19 polyneuropathy 32 HP:0001271
20 hyperhidrosis 32 very rare (1%) HP:0000975
21 alacrima 32 HP:0000522
22 restlessness 32 very rare (1%) HP:0000711
23 single transverse palmar crease 32 very rare (1%) HP:0000954
24 corneal opacity 32 very rare (1%) HP:0007957
25 hyperkinesis 32 very rare (1%) HP:0002487
26 pain 32 HP:0012531
27 elevated hepatic transaminases 32 very rare (1%) HP:0002910
28 oral-pharyngeal dysphagia 32 very rare (1%) HP:0200136
29 small hand 32 HP:0200055
30 short foot 32 HP:0001773
31 decreased sensory nerve conduction velocity 32 very rare (1%) HP:0003448
32 intrinsic hand muscle atrophy 32 very rare (1%) HP:0008954

UMLS symptoms related to Congenital Disorder of Deglycosylation:


involuntary movements

Drugs & Therapeutics for Congenital Disorder of Deglycosylation

Search Clinical Trials , NIH Clinical Center for Congenital Disorder of Deglycosylation

Genetic Tests for Congenital Disorder of Deglycosylation

Genetic tests related to Congenital Disorder of Deglycosylation:

id Genetic test Affiliating Genes
1 Congenital Disorder of Deglycosylation 29

Anatomical Context for Congenital Disorder of Deglycosylation

MalaCards organs/tissues related to Congenital Disorder of Deglycosylation:

39
Liver, Eye, Testes

Publications for Congenital Disorder of Deglycosylation

Articles related to Congenital Disorder of Deglycosylation:

id Title Authors Year
1
A congenital disorder of deglycosylation: Biochemical characterization of N-glycanase 1 deficiency in patient fibroblasts. ( 25900930 )
2015

Variations for Congenital Disorder of Deglycosylation

ClinVar genetic disease variations for Congenital Disorder of Deglycosylation:

6 (show all 14)
id Gene Variation Type Significance SNP ID Assembly Location
1 NGLY1 NM_018297.3(NGLY1): c.1891delC (p.Gln631Serfs) deletion Pathogenic rs587776982 GRCh37 Chromosome 3, 25761025: 25761025
2 NGLY1 NM_018297.3(NGLY1): c.1201A> T (p.Arg401Ter) single nucleotide variant Pathogenic rs201337954 GRCh37 Chromosome 3, 25775422: 25775422
3 NGLY1 NM_018297.3(NGLY1): c.1370dupG (p.Arg458Lysfs) duplication Pathogenic rs587777265 GRCh37 Chromosome 3, 25773865: 25773865
4 NGLY1 NM_001145294.1(NGLY1): c.1079_1081delGAA (p.Arg360del) deletion Pathogenic rs587777266 GRCh37 Chromosome 3, 25775416: 25775418
5 NGLY1 NM_001145293.1(NGLY1): c.1570C> T (p.Arg524Ter) single nucleotide variant Pathogenic rs528583612 GRCh37 Chromosome 3, 25761670: 25761670
6 NGLY1 NM_018297.3(NGLY1): c.1910delT (p.Leu637Terfs) deletion Pathogenic rs1135401730 GRCh37 Chromosome 3, 25761006: 25761006
7 NGLY1 NM_018297.3(NGLY1): c.1604G> A (p.Trp535Ter) single nucleotide variant Pathogenic rs767388144 GRCh37 Chromosome 3, 25770631: 25770631
8 NGLY1 NM_018297.3(NGLY1): c.1169G> C (p.Arg390Pro) single nucleotide variant Pathogenic rs1135401728 GRCh37 Chromosome 3, 25775454: 25775454
9 NGLY1 NM_018297.3(NGLY1): c.931G> A (p.Glu311Lys) single nucleotide variant Pathogenic rs201791209 GRCh37 Chromosome 3, 25778897: 25778897
10 NGLY1 NM_018297.3(NGLY1): c.930C> T (p.Gly310=) single nucleotide variant Pathogenic rs745814294 GRCh37 Chromosome 3, 25778898: 25778898
11 NGLY1 NM_018297.3(NGLY1): c.881+5G> T single nucleotide variant Pathogenic rs1135401731 GRCh37 Chromosome 3, 25781063: 25781063
12 NGLY1 NM_018297.3(NGLY1): c.730T> C (p.Trp244Arg) single nucleotide variant Pathogenic rs1135401729 GRCh37 Chromosome 3, 25781219: 25781219
13 NGLY1 NM_018297.3(NGLY1): c.622C> T (p.Gln208Ter) single nucleotide variant Pathogenic rs200561967 GRCh37 Chromosome 3, 25792625: 25792625
14 NGLY1 NM_018297.3(NGLY1): c.347C> G (p.Ser116Ter) single nucleotide variant Pathogenic rs907852687 GRCh37 Chromosome 3, 25805702: 25805702

Expression for Congenital Disorder of Deglycosylation

Search GEO for disease gene expression data for Congenital Disorder of Deglycosylation.

Pathways for Congenital Disorder of Deglycosylation

Pathways related to Congenital Disorder of Deglycosylation according to GeneCards Suite gene sharing:

id Super pathways Score Top Affiliating Genes
1
Show member pathways
10.55 ENGASE NGLY1

GO Terms for Congenital Disorder of Deglycosylation

Biological processes related to Congenital Disorder of Deglycosylation according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 potassium ion transport GO:0006813 9.32 ATP12A ATP4A
2 sodium ion transport GO:0006814 9.26 ATP12A ATP4A
3 proton transport GO:0015992 9.16 ATP12A ATP4A
4 establishment or maintenance of transmembrane electrochemical gradient GO:0010248 8.96 ATP12A ATP4A
5 protein deglycosylation GO:0006517 8.62 ENGASE NGLY1

Molecular functions related to Congenital Disorder of Deglycosylation according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 hydrolase activity GO:0016787 9.46 ATP12A ATP4A ENGASE NGLY1
2 sodium:potassium-exchanging ATPase activity GO:0005391 8.96 ATP12A ATP4A
3 hydrogen:potassium-exchanging ATPase activity GO:0008900 8.62 ATP12A ATP4A

Sources for Congenital Disorder of Deglycosylation

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 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 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 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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