MCID: CNG436
MIFTS: 40

Congenital Disorder of Deglycosylation

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

Aliases & Classifications for Congenital Disorder of Deglycosylation

MalaCards integrated aliases for Congenital Disorder of Deglycosylation:

Name: Congenital Disorder of Deglycosylation 53 12 71 28 69
Congenital Disorder of Glycosylation Type Iv 12 71
Deficiency of N-Glycanase 1 12 49
Ngly1-Deficiency 12 14
Ngly1-Cddg 12 55
Cddg 53 71
Congenital Disorder of Glycosylation, Type Iv, Formerly; Cdg1v, Formerly 53
Congenital Disorder of Glycosylation, Type Iv, Formerly 53
Alacrimia-Choreoathetosis-Liver Dysfunction Syndrome 55
Congenital Disorder of Glycosylation Type Iv; Cdg1v 49
Congenital Disorder of Deglycosylation;cddg 49
Congenital Disorder of Glycosylation 1v 71
Ngly1 Deficiency 55
Cdg1v, Formerly 53
N-Glycanase 1 13
Cdg1v 71
Cdgiv 71

Characteristics:

Orphanet epidemiological data:

55
alacrimia-choreoathetosis-liver dysfunction syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

53
Inheritance:
autosomal recessive


HPO:

31
congenital disorder of deglycosylation:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 55  
Inborn errors of metabolism


Summaries for Congenital Disorder of Deglycosylation

NIH Rare Diseases : 49 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-related congenital disorder of deglycosylation and ngly1-congenital disorder of deglycosylation, and has symptoms including fever, seizures and pain. 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.

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.

OMIM : 53 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)

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.

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 top 50) (show all 59)
# Related Disease Score Top Affiliating Genes
1 ngly1-related congenital disorder of deglycosylation 12.3
2 ngly1-congenital disorder of deglycosylation 11.4
3 fungal esophagitis 10.1 ATP12A ATP4A
4 bladder calculus 10.1 ATP12A ATP4A
5 gastrointestinal neuroendocrine benign tumor 10.1 ATP12A ATP4A
6 gastric neuroendocrine neoplasm 10.1 ATP12A ATP4A
7 neonatal candidiasis 10.1 ATP12A ATP4A
8 photoallergic dermatitis 10.1 ATP12A ATP4A
9 squamous papillomatosis 10.1 ATP12A ATP4A
10 acute laryngitis 10.1 ATP12A ATP4A
11 gastroduodenal crohn's disease 10.1 ATP12A ATP4A
12 toxic megacolon 10.1 ATP12A ATP4A
13 aspiration pneumonitis 10.1 ATP12A ATP4A
14 gastric antral vascular ectasia 10.1 ATP12A ATP4A
15 esophageal candidiasis 10.1 ATP12A ATP4A
16 postsurgical hypothyroidism 10.1 ATP12A ATP4A
17 rumination disorder 10.1 ATP12A ATP4A
18 laryngeal disease 10.1 ATP12A ATP4A
19 duodenitis 10.1 ATP12A ATP4A
20 bile reflux 10.1 ATP12A ATP4A
21 granulomatous gastritis 10.1 ATP12A ATP4A
22 active peptic ulcer disease 10.1 ATP12A ATP4A
23 dyskinesia of esophagus 10.0 ATP12A ATP4A
24 ischemic neuropathy 10.0 ATP12A ATP4A
25 anismus 10.0 ATP12A ATP4A
26 capillary disease 10.0 ATP12A ATP4A
27 peptic esophagitis 10.0 ATP12A ATP4A
28 duodenal disease 10.0 ATP12A ATP4A
29 hernia, hiatus 10.0 ATP12A ATP4A
30 esophageal atresia/tracheoesophageal fistula 10.0 ATP12A ATP4A
31 laryngitis 10.0 ATP12A ATP4A
32 laryngeal tuberculosis 10.0 ATP12A ATP4A
33 lymphocytic colitis 10.0 ATP12A ATP4A
34 chronic intestinal vascular insufficiency 10.0 ATP12A ATP4A
35 clostridium difficile colitis 10.0 ATP12A ATP4A
36 lower urinary tract calculus 10.0 ATP12A ATP4A
37 diarrhea 1, secretory chloride, congenital 10.0 ATP12A ATP4A
38 polyposis, skin pigmentation, alopecia, and fingernail changes 10.0 ATP12A ATP4A
39 aspiration pneumonia 10.0 ATP12A ATP4A
40 chronic laryngitis 10.0 ATP12A ATP4A
41 esophageal varix 10.0 ATP12A ATP4A
42 eosinophilic gastritis 10.0 ATP12A ATP4A
43 myopathy, x-linked, with excessive autophagy 10.0 ATP12A ATP4A
44 esophagus adenocarcinoma 10.0 ATP12A ATP4A
45 jejunoileitis 10.0 ATP12A ATP4A
46 pancreatic steatorrhea 10.0 ATP12A ATP4A
47 pneumatosis cystoides intestinalis 9.9 ATP12A ATP4A
48 superior mesenteric artery syndrome 9.9 ATP12A ATP4A
49 functional gastric disease 9.9 ATP12A ATP4A
50 lateral medullary syndrome 9.9 ATP12A ATP4A

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:

53
Neurologic Central Nervous System:
involuntary movements
developmental delay
hypotonia
regression of motor development
epilepsy, multifocal, intractable
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:

31 (show all 33)
# Description HPO Frequency HPO Source Accession
1 fever 31 HP:0001945
2 seizures 31 very rare (1%) HP:0001250
3 pain 31 HP:0012531
4 respiratory distress 31 very rare (1%) HP:0002098
5 involuntary movements 31 very rare (1%) HP:0004305
6 restlessness 31 very rare (1%) HP:0000711
7 hypertelorism 31 very rare (1%) HP:0000316
8 ptosis 31 very rare (1%) HP:0000508
9 hyperhidrosis 31 very rare (1%) HP:0000975
10 muscular hypotonia 31 very rare (1%) HP:0001252
11 scoliosis 31 very rare (1%) HP:0002650
12 global developmental delay 31 very rare (1%) HP:0001263
13 recurrent respiratory infections 31 very rare (1%) HP:0002205
14 hepatomegaly 31 very rare (1%) HP:0002240
15 corneal opacity 31 very rare (1%) HP:0007957
16 microcephaly 31 very rare (1%) HP:0000252
17 osteoporosis 31 very rare (1%) HP:0000939
18 strabismus 31 very rare (1%) HP:0000486
19 short foot 31 HP:0001773
20 elevated hepatic transaminases 31 very rare (1%) HP:0002910
21 small hand 31 HP:0200055
22 hyporeflexia 31 very rare (1%) HP:0001265
23 anhidrosis 31 very rare (1%) HP:0000970
24 single transverse palmar crease 31 very rare (1%) HP:0000954
25 polyneuropathy 31 HP:0001271
26 alacrima 31 HP:0000522
27 generalized hypotonia 31 HP:0001290
28 hyperkinesis 31 very rare (1%) HP:0002487
29 oral-pharyngeal dysphagia 31 very rare (1%) HP:0200136
30 pain insensitivity 31 very rare (1%) HP:0007021
31 decreased sensory nerve conduction velocity 31 very rare (1%) HP:0003448
32 delayed myelination 31 very rare (1%) HP:0012448
33 intrinsic hand muscle atrophy 31 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:

# Genetic test Affiliating Genes
1 Congenital Disorder of Deglycosylation 28 NGLY1

Anatomical Context for Congenital Disorder of Deglycosylation

MalaCards organs/tissues related to Congenital Disorder of Deglycosylation:

38
Liver, Eye, Testes

Publications for Congenital Disorder of Deglycosylation

Articles related to Congenital Disorder of Deglycosylation:

# Title Authors Year
1
Prospective phenotyping of NGLY1-CDDG, the first congenital disorder of deglycosylation. ( 27388694 )
2017
2
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 15)
# Gene Variation Type Significance SNP ID Assembly Location
1 NGLY1 NM_018297.3(NGLY1): c.1891delC (p.Gln631Serfs) deletion Pathogenic/Likely 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.1604G> A (p.Trp535Ter) single nucleotide variant Pathogenic rs767388144 GRCh38 Chromosome 3, 25729140: 25729140
7 NGLY1 NM_018297.3(NGLY1): c.1169G> C (p.Arg390Pro) single nucleotide variant Pathogenic rs1135401728 GRCh37 Chromosome 3, 25775454: 25775454
8 NGLY1 NM_018297.3(NGLY1): c.1910delT (p.Leu637Terfs) deletion Pathogenic rs1135401730 GRCh37 Chromosome 3, 25761006: 25761006
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
15 NGLY1 NM_018297.3(NGLY1): c.871C> T (p.Arg291Ter) single nucleotide variant Pathogenic rs772994617 GRCh38 Chromosome 3, 25739587: 25739587

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:

# 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:

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

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

# 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
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 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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