MCID: CNG436
MIFTS: 41

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 57 12 75 29 6 73
Alacrimia-Choreoathetosis-Liver Dysfunction Syndrome 53 59
Congenital Disorder of Glycosylation Type Iv 12 75
Deficiency of N-Glycanase 1 12 53
Ngly1-Deficiency 12 15
Ngly1-Cddg 12 59
Cddg 57 75
Congenital Disorder of Glycosylation, Type Iv, Formerly; Cdg1v, Formerly 57
Congenital Disorder of Glycosylation, Type Iv, Formerly 57
Congenital Disorder of Glycosylation Type Iv; Cdg1v 53
Glycosylation, Congenital Disorder of, Type Iv 40
Congenital Disorder of Deglycosylation;cddg 53
Congenital Disorder of Glycosylation 1v 75
Ngly1 Deficiency 59
Cdg1v, Formerly 57
N-Glycanase 1 13
Cdg1v 75
Cdgiv 75

Characteristics:

Orphanet epidemiological data:

59
alacrimia-choreoathetosis-liver dysfunction syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal recessive


HPO:

32
congenital disorder of deglycosylation:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 59  
Inborn errors of metabolism


Summaries for Congenital Disorder of Deglycosylation

NIH Rare Diseases : 53 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.

MalaCards based summary : Congenital Disorder of Deglycosylation, also known as alacrimia-choreoathetosis-liver dysfunction syndrome, is related to ngly1-related congenital disorder of deglycosylation and ngly1-congenital disorder of deglycosylation, and has symptoms including involuntary movements 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 brain, and related phenotypes are hypertelorism and ptosis

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 : 57 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 : 75 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 in the Congenital Disorder of Deglycosylation family:

Ngly1-Related 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 60)
# Related Disease Score Top Affiliating Genes
1 ngly1-related congenital disorder of deglycosylation 12.1
2 ngly1-congenital disorder of deglycosylation 11.5
3 fungal esophagitis 10.1 ATP12A ATP4A
4 bladder calculus 10.1 ATP12A ATP4A
5 gastrointestinal neuroendocrine benign tumor 10.1 ATP12A ATP4A
6 neonatal candidiasis 10.1 ATP12A ATP4A
7 photoallergic dermatitis 10.1 ATP12A ATP4A
8 squamous papillomatosis 10.1 ATP12A ATP4A
9 acute laryngitis 10.1 ATP12A ATP4A
10 gastroduodenal crohn's disease 10.1 ATP12A ATP4A
11 gastric neuroendocrine neoplasm 10.1 ATP12A ATP4A
12 toxic megacolon 10.1 ATP12A ATP4A
13 aspiration pneumonitis 10.1 ATP12A ATP4A
14 postsurgical hypothyroidism 10.1 ATP12A ATP4A
15 gastric antral vascular ectasia 10.1 ATP12A ATP4A
16 esophageal candidiasis 10.1 ATP12A ATP4A
17 duodenitis 10.1 ATP12A ATP4A
18 rumination disorder 10.1 ATP12A ATP4A
19 bile reflux 10.1 ATP12A ATP4A
20 granulomatous gastritis 10.1 ATP12A ATP4A
21 active peptic ulcer disease 10.1 ATP12A ATP4A
22 laryngeal disease 10.1 ATP12A ATP4A
23 ischemic neuropathy 10.1 ATP12A ATP4A
24 capillary disease 10.1 ATP12A ATP4A
25 peptic esophagitis 10.1 ATP12A ATP4A
26 duodenal disease 10.1 ATP12A ATP4A
27 dyskinesia of esophagus 10.1 ATP12A ATP4A
28 hernia, hiatus 10.1 ATP12A ATP4A
29 anismus 10.1 ATP12A ATP4A
30 esophageal atresia/tracheoesophageal fistula 10.1 ATP12A ATP4A
31 laryngitis 10.1 ATP12A ATP4A
32 laryngeal tuberculosis 10.0 ATP12A ATP4A
33 lymphocytic colitis 10.0 ATP12A ATP4A
34 clostridium difficile colitis 10.0 ATP12A ATP4A
35 lower urinary tract calculus 10.0 ATP12A ATP4A
36 aspiration pneumonia 10.0 ATP12A ATP4A
37 diarrhea 1, secretory chloride, congenital 10.0 ATP12A ATP4A
38 chronic laryngitis 10.0 ATP12A ATP4A
39 chronic intestinal vascular insufficiency 10.0 ATP12A ATP4A
40 eosinophilic gastritis 10.0 ATP12A ATP4A
41 polyposis, skin pigmentation, alopecia, and fingernail changes 10.0 ATP12A ATP4A
42 esophageal varix 10.0 ATP12A ATP4A
43 esophagus adenocarcinoma 10.0 ATP12A ATP4A
44 myopathy, x-linked, with excessive autophagy 10.0 ATP12A ATP4A
45 gastric lymphoma 10.0 ATP12A ATP4A
46 pancreatic steatorrhea 9.9 ATP12A ATP4A
47 pneumatosis cystoides intestinalis 9.9 ATP12A ATP4A
48 superior mesenteric artery syndrome 9.9 ATP12A ATP4A
49 jejunoileitis 9.9 ATP12A ATP4A
50 functional gastric disease 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:

57
Neurologic Peripheral Nervous System:
peripheral neuropathy

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 Central Nervous System:
involuntary movements
developmental delay
hypotonia
regression of motor development
epilepsy, multifocal, intractable
more
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 37)
# Description HPO Frequency HPO Source Accession
1 hypertelorism 32 very rare (1%) HP:0000316
2 ptosis 32 very rare (1%) HP:0000508
3 hyperhidrosis 32 very rare (1%) HP:0000975
4 seizures 32 very rare (1%) HP:0001250
5 muscular hypotonia 32 very rare (1%) HP:0001252
6 scoliosis 32 very rare (1%) HP:0002650
7 global developmental delay 32 very rare (1%) HP:0001263
8 recurrent respiratory infections 32 very rare (1%) HP:0002205
9 hepatomegaly 32 very rare (1%) HP:0002240
10 corneal opacity 32 very rare (1%) HP:0007957
11 microcephaly 32 very rare (1%) HP:0000252
12 fever 32 HP:0001945
13 osteoporosis 32 very rare (1%) HP:0000939
14 strabismus 32 very rare (1%) HP:0000486
15 respiratory distress 32 very rare (1%) HP:0002098
16 short foot 32 HP:0001773
17 elevated hepatic transaminases 32 very rare (1%) HP:0002910
18 small hand 32 HP:0200055
19 pain 32 HP:0012531
20 involuntary movements 32 very rare (1%) HP:0004305
21 hyporeflexia 32 very rare (1%) HP:0001265
22 anhidrosis 32 very rare (1%) HP:0000970
23 restlessness 32 very rare (1%) HP:0000711
24 single transverse palmar crease 32 very rare (1%) HP:0000954
25 polyneuropathy 32 HP:0001271
26 alacrima 32 HP:0000522
27 generalized hypotonia 32 HP:0001290
28 hyperkinesis 32 very rare (1%) HP:0002487
29 oral-pharyngeal dysphagia 32 very rare (1%) HP:0200136
30 pain insensitivity 32 very rare (1%) HP:0007021
31 decreased sensory nerve conduction velocity 32 very rare (1%) HP:0003448
32 delayed myelination 32 very rare (1%) HP:0012448
33 high myoinositol in brain by mrs 32 HP:0025460
34 intrinsic hand muscle atrophy 32 very rare (1%) HP:0008954
35 decreased csf 5-hydroxyindolacetic acid 32 HP:0025455
36 decreased csf albumin 32 HP:0025458
37 decreased csf/serum albumin ratio 32 very rare (1%) HP:0030978

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 29 NGLY1

Anatomical Context for Congenital Disorder of Deglycosylation

MalaCards organs/tissues related to Congenital Disorder of Deglycosylation:

41
Liver, Eye, Brain, 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
3
<i>NGLY1</i>-Related Congenital Disorder of Deglycosylation ( 29419975 )
1993

Variations for Congenital Disorder of Deglycosylation

ClinVar genetic disease variations for Congenital Disorder of Deglycosylation:

6
(show top 50) (show all 124)
# 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.1891delC (p.Gln631Serfs) deletion Pathogenic/Likely pathogenic rs587776982 GRCh38 Chromosome 3, 25719534: 25719534
3 NGLY1 NM_018297.3(NGLY1): c.1201A> T (p.Arg401Ter) single nucleotide variant Pathogenic rs201337954 GRCh37 Chromosome 3, 25775422: 25775422
4 NGLY1 NM_018297.3(NGLY1): c.1201A> T (p.Arg401Ter) single nucleotide variant Pathogenic rs201337954 GRCh38 Chromosome 3, 25733931: 25733931
5 NGLY1 NM_018297.3(NGLY1): c.1370dupG (p.Arg458Lysfs) duplication Pathogenic rs587777265 GRCh37 Chromosome 3, 25773865: 25773865
6 NGLY1 NM_018297.3(NGLY1): c.1370dupG (p.Arg458Lysfs) duplication Pathogenic rs587777265 GRCh38 Chromosome 3, 25732374: 25732374
7 NGLY1 NM_001145294.1(NGLY1): c.1079_1081delGAA (p.Arg360del) deletion Pathogenic rs587777266 GRCh37 Chromosome 3, 25775416: 25775418
8 NGLY1 NM_001145294.1(NGLY1): c.1079_1081delGAA (p.Arg360del) deletion Pathogenic rs587777266 GRCh38 Chromosome 3, 25733925: 25733927
9 NGLY1 NM_018297.3(NGLY1): c.1624C> T (p.Arg542Ter) single nucleotide variant Pathogenic rs528583612 GRCh37 Chromosome 3, 25761670: 25761670
10 NGLY1 NM_018297.3(NGLY1): c.1624C> T (p.Arg542Ter) single nucleotide variant Pathogenic rs528583612 GRCh38 Chromosome 3, 25720179: 25720179
11 NGLY1 NM_018297.3(NGLY1): c.930C> T (p.Gly310=) single nucleotide variant Pathogenic rs745814294 GRCh38 Chromosome 3, 25737407: 25737407
12 NGLY1 NM_018297.3(NGLY1): c.881+5G> T single nucleotide variant Pathogenic rs1135401731 GRCh37 Chromosome 3, 25781063: 25781063
13 NGLY1 NM_018297.3(NGLY1): c.1910delT (p.Leu637Terfs) deletion Pathogenic rs1135401730 GRCh37 Chromosome 3, 25761006: 25761006
14 NGLY1 NM_018297.3(NGLY1): c.1910delT (p.Leu637Terfs) deletion Pathogenic rs1135401730 GRCh38 Chromosome 3, 25719515: 25719515
15 NGLY1 NM_018297.3(NGLY1): c.1604G> A (p.Trp535Ter) single nucleotide variant Pathogenic rs767388144 GRCh37 Chromosome 3, 25770631: 25770631
16 NGLY1 NM_018297.3(NGLY1): c.1604G> A (p.Trp535Ter) single nucleotide variant Pathogenic rs767388144 GRCh38 Chromosome 3, 25729140: 25729140
17 NGLY1 NM_018297.3(NGLY1): c.1169G> C (p.Arg390Pro) single nucleotide variant Pathogenic rs1135401728 GRCh37 Chromosome 3, 25775454: 25775454
18 NGLY1 NM_018297.3(NGLY1): c.1169G> C (p.Arg390Pro) single nucleotide variant Pathogenic rs1135401728 GRCh38 Chromosome 3, 25733963: 25733963
19 NGLY1 NM_018297.3(NGLY1): c.931G> A (p.Glu311Lys) single nucleotide variant Pathogenic rs201791209 GRCh37 Chromosome 3, 25778897: 25778897
20 NGLY1 NM_018297.3(NGLY1): c.931G> A (p.Glu311Lys) single nucleotide variant Pathogenic rs201791209 GRCh38 Chromosome 3, 25737406: 25737406
21 NGLY1 NM_018297.3(NGLY1): c.930C> T (p.Gly310=) single nucleotide variant Pathogenic rs745814294 GRCh37 Chromosome 3, 25778898: 25778898
22 NGLY1 NM_018297.3(NGLY1): c.881+5G> T single nucleotide variant Pathogenic rs1135401731 GRCh38 Chromosome 3, 25739572: 25739572
23 NGLY1 NM_018297.3(NGLY1): c.730T> C (p.Trp244Arg) single nucleotide variant Pathogenic rs1135401729 GRCh37 Chromosome 3, 25781219: 25781219
24 NGLY1 NM_018297.3(NGLY1): c.730T> C (p.Trp244Arg) single nucleotide variant Pathogenic rs1135401729 GRCh38 Chromosome 3, 25739728: 25739728
25 NGLY1 NM_018297.3(NGLY1): c.622C> T (p.Gln208Ter) single nucleotide variant Pathogenic rs200561967 GRCh37 Chromosome 3, 25792625: 25792625
26 NGLY1 NM_018297.3(NGLY1): c.622C> T (p.Gln208Ter) single nucleotide variant Pathogenic rs200561967 GRCh38 Chromosome 3, 25751134: 25751134
27 NGLY1 NM_018297.3(NGLY1): c.347C> G (p.Ser116Ter) single nucleotide variant Pathogenic rs907852687 GRCh37 Chromosome 3, 25805702: 25805702
28 NGLY1 NM_018297.3(NGLY1): c.347C> G (p.Ser116Ter) single nucleotide variant Pathogenic rs907852687 GRCh38 Chromosome 3, 25764211: 25764211
29 NGLY1 NM_018297.3(NGLY1): c.1869T> C (p.Gly623=) single nucleotide variant Benign/Likely benign rs73155397 GRCh37 Chromosome 3, 25761047: 25761047
30 NGLY1 NM_018297.3(NGLY1): c.1869T> C (p.Gly623=) single nucleotide variant Benign/Likely benign rs73155397 GRCh38 Chromosome 3, 25719556: 25719556
31 NGLY1 NM_018297.3(NGLY1): c.1722A> G (p.Gln574=) single nucleotide variant Benign/Likely benign rs74650888 GRCh37 Chromosome 3, 25761572: 25761572
32 NGLY1 NM_018297.3(NGLY1): c.1722A> G (p.Gln574=) single nucleotide variant Benign/Likely benign rs74650888 GRCh38 Chromosome 3, 25720081: 25720081
33 NGLY1 NM_018297.3(NGLY1): c.596C> T (p.Pro199Leu) single nucleotide variant Uncertain significance rs760530009 GRCh38 Chromosome 3, 25751160: 25751160
34 NGLY1 NM_018297.3(NGLY1): c.596C> T (p.Pro199Leu) single nucleotide variant Uncertain significance rs760530009 GRCh37 Chromosome 3, 25792651: 25792651
35 NGLY1 NM_018297.3(NGLY1): c.1875C> G (p.Val625=) single nucleotide variant Likely benign rs117889176 GRCh37 Chromosome 3, 25761041: 25761041
36 NGLY1 NM_018297.3(NGLY1): c.1875C> G (p.Val625=) single nucleotide variant Likely benign rs117889176 GRCh38 Chromosome 3, 25719550: 25719550
37 NGLY1 NM_018297.3(NGLY1): c.1300C> G (p.Leu434Val) single nucleotide variant Uncertain significance rs761035118 GRCh37 Chromosome 3, 25773935: 25773935
38 NGLY1 NM_018297.3(NGLY1): c.1300C> G (p.Leu434Val) single nucleotide variant Uncertain significance rs761035118 GRCh38 Chromosome 3, 25732444: 25732444
39 NGLY1 NM_018297.3(NGLY1): c.881+8C> T single nucleotide variant Benign/Likely benign rs143998271 GRCh37 Chromosome 3, 25781060: 25781060
40 NGLY1 NM_018297.3(NGLY1): c.881+8C> T single nucleotide variant Benign/Likely benign rs143998271 GRCh38 Chromosome 3, 25739569: 25739569
41 NGLY1 NM_018297.3(NGLY1): c.717A> C (p.Glu239Asp) single nucleotide variant Uncertain significance rs754083716 GRCh38 Chromosome 3, 25739741: 25739741
42 NGLY1 NM_018297.3(NGLY1): c.717A> C (p.Glu239Asp) single nucleotide variant Uncertain significance rs754083716 GRCh37 Chromosome 3, 25781232: 25781232
43 NGLY1 NM_018297.3(NGLY1): c.629A> C (p.Lys210Thr) single nucleotide variant Uncertain significance GRCh37 Chromosome 3, 25792618: 25792618
44 NGLY1 NM_018297.3(NGLY1): c.629A> C (p.Lys210Thr) single nucleotide variant Uncertain significance GRCh38 Chromosome 3, 25751127: 25751127
45 NGLY1 NM_018297.3(NGLY1): c.492+4A> T single nucleotide variant Likely benign rs181461044 GRCh38 Chromosome 3, 25764062: 25764062
46 NGLY1 NM_018297.3(NGLY1): c.492+4A> T single nucleotide variant Likely benign rs181461044 GRCh37 Chromosome 3, 25805553: 25805553
47 NGLY1 NM_018297.3(NGLY1): c.1918C> T (p.His640Tyr) single nucleotide variant Uncertain significance rs529998714 GRCh38 Chromosome 3, 25719507: 25719507
48 NGLY1 NM_018297.3(NGLY1): c.1918C> T (p.His640Tyr) single nucleotide variant Uncertain significance rs529998714 GRCh37 Chromosome 3, 25760998: 25760998
49 NGLY1 NM_018297.3(NGLY1): c.1889C> A (p.Thr630Asn) single nucleotide variant Uncertain significance rs891240035 GRCh38 Chromosome 3, 25719536: 25719536
50 NGLY1 NM_018297.3(NGLY1): c.1889C> A (p.Thr630Asn) single nucleotide variant Uncertain significance rs891240035 GRCh37 Chromosome 3, 25761027: 25761027

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 potassium ion import GO:0010107 9.4 ATP12A ATP4A
2 ATP hydrolysis coupled proton transport GO:0015991 9.37 ATP12A ATP4A
3 cellular sodium ion homeostasis GO:0006883 9.32 ATP12A ATP4A
4 cellular potassium ion homeostasis GO:0030007 9.26 ATP12A ATP4A
5 sodium ion export across plasma membrane GO:0036376 9.16 ATP12A ATP4A
6 establishment or maintenance of transmembrane electrochemical gradient GO:0010248 8.96 ATP12A ATP4A
7 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 sodium:potassium-exchanging ATPase activity GO:0005391 8.96 ATP12A ATP4A
2 potassium:proton exchanging ATPase activity GO:0008900 8.62 ATP12A ATP4A

Sources for Congenital Disorder of Deglycosylation

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