CDG1B
MCID: CNG189
MIFTS: 36

Congenital Disorder of Glycosylation, Type Ib (CDG1B)

Categories: Blood diseases, Bone diseases, Cardiovascular diseases, Ear diseases, Endocrine diseases, Eye diseases, Fetal diseases, Gastrointestinal diseases, Genetic diseases, Immune diseases, Liver diseases, Mental diseases, Metabolic diseases, Muscle diseases, Nephrological diseases, Neuronal diseases, Rare diseases, Skin diseases

Aliases & Classifications for Congenital Disorder of Glycosylation, Type Ib

MalaCards integrated aliases for Congenital Disorder of Glycosylation, Type Ib:

Name: Congenital Disorder of Glycosylation, Type Ib 58 13
Congenital Disorder of Glycosylation Type 1b 60 30 6 74
Cdg1b 58 60 76
Protein-Losing Enteropathy-Hepatic Fibrosis Syndrome 58 76
Congenital Disorder of Glycosylation Type Ib 60 76
Mannosephosphate Isomerase Deficiency 58 76
Saguenay-Lac Saint-Jean Syndrome 58 76
Mpi Deficiency 58 76
Slsj Syndrome 58 76
Cdg Ib 58 76
Cdg-Ib 60 76
Cdgib 58 76
Carbohydrate Deficient Glycoprotein Syndrome Type Ib 60
Carbohydrate-Deficient Glycoprotein Syndrome Type Ib 76
Glycosylation, Congenital Disorder of, Type Ib 41
Congenital Disorder of Glycosylation 1b 76
Phosphomannose Isomerase Deficiency 60
Cdg, Gastrointestinal Type 58
Mannosephosphate Isomerase 13
Cdg Gastrointestinal Type 76
Cdg Syndrome Type Ib 60
Cdg Ib; Cdgib 58
Mpi-Cdg 60
Cdgs1b 76
Pi M 6

Characteristics:

Orphanet epidemiological data:

60
mpi-cdg
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal; Age of death: early childhood,infantile,normal life expectancy;

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
onset of symptoms 2-12 months
responsive to oral mannose therapy


HPO:

33
congenital disorder of glycosylation, type ib:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Congenital Disorder of Glycosylation, Type Ib

OMIM : 58 Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of autosomal recessive disorders caused by enzymatic defects in the synthesis and processing of asparagine (N)-linked glycans or oligosaccharides on glycoproteins. Type I CDGs comprise defects in the assembly of the dolichol lipid-linked oligosaccharide (LLO) chain and its transfer to the nascent protein. These disorders can be identified by a characteristic abnormal isoelectric focusing profile of plasma transferrin (Leroy, 2006). For a discussion of the classification of CDGs, see CDG1A (212065). CDG Ib is clinically distinct from most other CDGs by the lack of significant central nervous system involvement. The predominant symptoms are chronic diarrhea with failure to thrive and protein-losing enteropathy with coagulopathy. Some patients develop hepatic fibrosis. CDG Ib is also different from other CDGs in that it can be treated effectively with oral mannose supplementation, but can be fatal if untreated (Marquardt and Denecke, 2003). Thus, CDG Ib should be considered in the differential diagnosis of patients with unexplained hypoglycemia, chronic diarrhea, liver disease, or coagulopathy in order to allow early diagnosis and effective therapy (Vuillaumier-Barrot et al., 2002) Freeze and Aebi (1999) reviewed CDG Ib and CDG Ic (603147). Marques-da-Silva et al. (2017) systematically reviewed the literature concerning liver involvement in CDG. (602579)

MalaCards based summary : Congenital Disorder of Glycosylation, Type Ib, also known as congenital disorder of glycosylation type 1b, is related to protein-losing enteropathy and congenital disorder of glycosylation, type ic, and has symptoms including vomiting and diarrhea. An important gene associated with Congenital Disorder of Glycosylation, Type Ib is MPI (Mannose Phosphate Isomerase), and among its related pathways/superpathways is Transport to the Golgi and subsequent modification. Affiliated tissues include liver and skin, and related phenotypes are malabsorption and congenital hepatic fibrosis

UniProtKB/Swiss-Prot : 76 Congenital disorder of glycosylation 1B: A form of congenital disorder of glycosylation, a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. CDG1B is clinically characterized by protein-losing enteropathy.

Related Diseases for Congenital Disorder of Glycosylation, Type Ib

Diseases in the Congenital Disorder of Glycosylation, Type Ii family:

Congenital Disorder of Glycosylation, Type Ia Congenital Disorder of Glycosylation, Type Iia
Congenital Disorder of Glycosylation, Type I/iix Congenital Disorder of Glycosylation, Type Iic
Congenital Disorder of Glycosylation, Type Iim Congenital Disorder of Glycosylation, Type Iy
Congenital Disorder of Glycosylation, Type Id Congenital Disorder of Glycosylation, Type Ib
Congenital Disorder of Glycosylation, Type Ic Congenital Disorder of Glycosylation, Type Iif
Congenital Disorder of Glycosylation, Type Iib Congenital Disorder of Glycosylation, Type Iid
Congenital Disorder of Glycosylation, Type Ig Congenital Disorder of Glycosylation, Type Ij
Congenital Disorder of Glycosylation, Type Ih Congenital Disorder of Glycosylation, Type Ik
Congenital Disorder of Glycosylation, Type Il Congenital Disorder of Glycosylation, Type Ie
Congenital Disorder of Glycosylation, Type if Congenital Disorder of Glycosylation, Type Im
Congenital Disorder of Glycosylation, Type Iih Congenital Disorder of Glycosylation, Type Iig
Congenital Disorder of Glycosylation, Type in Congenital Disorder of Glycosylation, Type Iq
Congenital Disorder of Glycosylation, Type Iij Congenital Disorder of Glycosylation, Type Iii
Congenital Disorder of Glycosylation, Type Ip Congenital Disorder of Glycosylation, Type Ir
Congenital Disorder of Glycosylation, Type Iil Congenital Disorder of Glycosylation, Type Iik
Congenital Disorder of Glycosylation, Type It Congenital Disorder of Glycosylation, Type Iu
Congenital Disorder of Glycosylation, Type Iw Congenital Disorder of Glycosylation, Type Ix
Congenital Disorder of Glycosylation, Type Iin Congenital Disorder of Glycosylation, Type Iio
Congenital Disorder of Glycosylation, Type Iip Congenital Disorder of Glycosylation, Type Iiq

Diseases related to Congenital Disorder of Glycosylation, Type Ib via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 protein-losing enteropathy 29.4 MPI SERPINA1
2 congenital disorder of glycosylation, type ic 11.3
3 congenital disorder of glycosylation, type ie 11.3
4 congenital disorder of glycosylation, type if 11.3
5 congenital disorder of glycosylation, type ig 11.1
6 congenital hepatic fibrosis 10.4
7 congenital disorder of glycosylation, type in 10.2
8 hyperinsulinemic hypoglycemia 10.2
9 hypoglycemia 10.2
10 alpha-1-antitrypsin deficiency 9.8

Graphical network of the top 20 diseases related to Congenital Disorder of Glycosylation, Type Ib:



Diseases related to Congenital Disorder of Glycosylation, Type Ib

Symptoms & Phenotypes for Congenital Disorder of Glycosylation, Type Ib

Human phenotypes related to Congenital Disorder of Glycosylation, Type Ib:

60 33 (show all 23)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 malabsorption 60 33 hallmark (90%) Very frequent (99-80%) HP:0002024
2 congenital hepatic fibrosis 60 33 hallmark (90%) Very frequent (99-80%) HP:0002612
3 hepatic failure 60 33 hallmark (90%) Very frequent (99-80%) HP:0001399
4 hypoglycemia 60 33 frequent (33%) Frequent (79-30%) HP:0001943
5 lymphedema 60 33 frequent (33%) Frequent (79-30%) HP:0001004
6 muscular hypotonia 33 HP:0001252
7 failure to thrive 33 HP:0001508
8 hepatomegaly 33 HP:0002240
9 vomiting 33 HP:0002013
10 abnormal bleeding 33 HP:0001892
11 abnormal thrombosis 33 HP:0001977
12 hepatic fibrosis 33 HP:0001395
13 cirrhosis 33 HP:0001394
14 hyperinsulinemic hypoglycemia 33 HP:0000825
15 diarrhea 33 HP:0002014
16 generalized hypotonia 33 HP:0001290
17 hypoalbuminemia 33 HP:0003073
18 protein-losing enteropathy 33 HP:0002243
19 villous atrophy 33 HP:0011473
20 reduced factor xi activity 33 HP:0001929
21 type i transferrin isoform profile 33 HP:0003642
22 reduced antithrombin iii activity 33 HP:0001976
23 lymphangiectasis 33 HP:0031842

Symptoms via clinical synopsis from OMIM:

58
Growth Other:
failure to thrive

Abdomen Gastrointestinal:
vomiting
diarrhea
protein-losing enteropathy
villous atrophy
lymphangiectasia

Laboratory Abnormalities:
hypoalbuminemia
abnormal isoelectric focusing of serum transferrin, type i pattern
phosphomannose isomerase deficiency in leukocytes, fibroblasts, or liver

Hematology:
thrombosis
factor xi deficiency
anti-thrombin iii deficiency
bleeding episodes

Abdomen Liver:
hepatomegaly
hepatic fibrosis
cirrhosis
hepatic failure

Endocrine Features:
hyperinsulinemic hypoglycemia

Neurologic Central Nervous System:
hypotonia

Clinical features from OMIM:

602579

UMLS symptoms related to Congenital Disorder of Glycosylation, Type Ib:


vomiting, diarrhea

Drugs & Therapeutics for Congenital Disorder of Glycosylation, Type Ib

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Study of ORL-1M (D-mannose) in Patients With CDG-Ib Recruiting NCT03404869 Phase 1, Phase 2 ORL-1M - D-mannose

Search NIH Clinical Center for Congenital Disorder of Glycosylation, Type Ib

Genetic Tests for Congenital Disorder of Glycosylation, Type Ib

Genetic tests related to Congenital Disorder of Glycosylation, Type Ib:

# Genetic test Affiliating Genes
1 Congenital Disorder of Glycosylation Type 1b 30 MPI

Anatomical Context for Congenital Disorder of Glycosylation, Type Ib

MalaCards organs/tissues related to Congenital Disorder of Glycosylation, Type Ib:

42
Liver, Skin

Publications for Congenital Disorder of Glycosylation, Type Ib

Articles related to Congenital Disorder of Glycosylation, Type Ib:

# Title Authors Year
1
[Congenital disorder of glycosylation type 1b. Experience with mannose treatment]. ( 18928705 )
2008
2
Protein losing enteropathy-hepatic fibrosis syndrome in Saguenay-Lac St-Jean, Quebec is a congenital disorder of glycosylation type Ib. ( 12414827 )
2002
3
Genetic and metabolic analysis of the first adult with congenital disorder of glycosylation type Ib: long-term outcome and effects of mannose supplementation. ( 11350186 )
2001

Variations for Congenital Disorder of Glycosylation, Type Ib

UniProtKB/Swiss-Prot genetic disease variations for Congenital Disorder of Glycosylation, Type Ib:

76 (show all 13)
# Symbol AA change Variation ID SNP ID
1 MPI p.Ser102Leu VAR_012338 rs104894494
2 MPI p.Met138Thr VAR_012339 rs104894495
3 MPI p.Arg219Gln VAR_012340 rs104894489
4 MPI p.Ile140Thr VAR_012345 rs773678732
5 MPI p.Met51Thr VAR_022516 rs764835081
6 MPI p.Tyr129Cys VAR_022517 rs887249336
7 MPI p.Asp131Asn VAR_022518 rs566620411
8 MPI p.Arg152Gln VAR_022519 rs766458792
9 MPI p.Gly250Ser VAR_022520 rs748090636
10 MPI p.Tyr255Cys VAR_022521
11 MPI p.Arg295His VAR_022522 rs28928906
12 MPI p.Ile398Thr VAR_022523 rs369326210
13 MPI p.Arg418His VAR_022524 rs863225087

ClinVar genetic disease variations for Congenital Disorder of Glycosylation, Type Ib:

6 (show top 50) (show all 109)
# Gene Variation Type Significance SNP ID Assembly Location
1 MPI NM_002435.2(MPI): c.684C> T (p.Asn228=) single nucleotide variant Benign/Likely benign rs139190144 GRCh38 Chromosome 15, 74896165: 74896165
2 MPI NM_002435.2(MPI): c.684C> T (p.Asn228=) single nucleotide variant Benign/Likely benign rs139190144 GRCh37 Chromosome 15, 75188506: 75188506
3 MPI NM_002435.2(MPI): c.166dupC (p.Arg56Profs) duplication Likely pathogenic rs786204593 GRCh38 Chromosome 15, 74891400: 74891400
4 MPI NM_002435.2(MPI): c.166dupC (p.Arg56Profs) duplication Likely pathogenic rs786204593 GRCh37 Chromosome 15, 75183741: 75183741
5 MPI NM_002435.2(MPI): c.1205A> G (p.Glu402Gly) single nucleotide variant Pathogenic rs863225086 GRCh38 Chromosome 15, 74897663: 74897663
6 MPI NM_002435.2(MPI): c.1205A> G (p.Glu402Gly) single nucleotide variant Pathogenic rs863225086 GRCh37 Chromosome 15, 75190004: 75190004
7 MPI NM_002435.2(MPI): c.1253G> A (p.Arg418His) single nucleotide variant Pathogenic rs863225087 GRCh38 Chromosome 15, 74897711: 74897711
8 MPI NM_002435.2(MPI): c.1253G> A (p.Arg418His) single nucleotide variant Pathogenic rs863225087 GRCh37 Chromosome 15, 75190052: 75190052
9 MPI NM_002435.2(MPI): c.656G> A (p.Arg219Gln) single nucleotide variant Pathogenic/Likely pathogenic rs104894489 GRCh37 Chromosome 15, 75185647: 75185647
10 MPI NM_002435.2(MPI): c.656G> A (p.Arg219Gln) single nucleotide variant Pathogenic/Likely pathogenic rs104894489 GRCh38 Chromosome 15, 74893306: 74893306
11 MPI NM_002435.2(MPI): c.305C> T (p.Ser102Leu) single nucleotide variant Pathogenic rs104894494 GRCh37 Chromosome 15, 75183880: 75183880
12 MPI NM_002435.2(MPI): c.305C> T (p.Ser102Leu) single nucleotide variant Pathogenic rs104894494 GRCh38 Chromosome 15, 74891539: 74891539
13 MPI NM_002435.2(MPI): c.413T> C (p.Met138Thr) single nucleotide variant Pathogenic rs104894495 GRCh37 Chromosome 15, 75185069: 75185069
14 MPI NM_002435.2(MPI): c.413T> C (p.Met138Thr) single nucleotide variant Pathogenic rs104894495 GRCh38 Chromosome 15, 74892728: 74892728
15 MPI MPI, 1-BP INS, 166C insertion Pathogenic
16 MPI NM_002435.2(MPI): c.884G> A (p.Arg295His) single nucleotide variant Pathogenic rs28928906 GRCh37 Chromosome 15, 75189391: 75189391
17 MPI NM_002435.2(MPI): c.884G> A (p.Arg295His) single nucleotide variant Pathogenic rs28928906 GRCh38 Chromosome 15, 74897050: 74897050
18 SERPINA1 NM_001127701.1(SERPINA1): c.1178C> T (p.Pro393Leu) single nucleotide variant Pathogenic/Likely pathogenic rs199422209 GRCh37 Chromosome 14, 94844865: 94844865
19 SERPINA1 NM_001127701.1(SERPINA1): c.1178C> T (p.Pro393Leu) single nucleotide variant Pathogenic/Likely pathogenic rs199422209 GRCh38 Chromosome 14, 94378528: 94378528
20 SERPINA1 NM_001127701.1(SERPINA1): c.272G> A (p.Gly91Glu) single nucleotide variant Pathogenic rs28931568 GRCh37 Chromosome 14, 94849303: 94849303
21 SERPINA1 NM_001127701.1(SERPINA1): c.272G> A (p.Gly91Glu) single nucleotide variant Pathogenic rs28931568 GRCh38 Chromosome 14, 94382966: 94382966
22 SERPINA1 NM_001127701.1(SERPINA1): c.194T> C (p.Leu65Pro) single nucleotide variant Pathogenic/Likely pathogenic rs28931569 GRCh37 Chromosome 14, 94849381: 94849381
23 SERPINA1 NM_001127701.1(SERPINA1): c.194T> C (p.Leu65Pro) single nucleotide variant Pathogenic/Likely pathogenic rs28931569 GRCh38 Chromosome 14, 94383044: 94383044
24 SERPINA1 NM_000295.4(SERPINA1): c.514G> A (p.Gly172Arg) single nucleotide variant Uncertain significance rs112030253 GRCh37 Chromosome 14, 94849061: 94849061
25 SERPINA1 NM_000295.4(SERPINA1): c.514G> A (p.Gly172Arg) single nucleotide variant Uncertain significance rs112030253 GRCh38 Chromosome 14, 94382724: 94382724
26 MPI NM_002435.2(MPI): c.1049C> T (p.Thr350Met) single nucleotide variant Conflicting interpretations of pathogenicity rs116933453 GRCh37 Chromosome 15, 75189556: 75189556
27 MPI NM_002435.2(MPI): c.1049C> T (p.Thr350Met) single nucleotide variant Conflicting interpretations of pathogenicity rs116933453 GRCh38 Chromosome 15, 74897215: 74897215
28 MPI NM_002435.2(MPI): c.1131A> G (p.Val377=) single nucleotide variant Benign rs1130741 GRCh37 Chromosome 15, 75189930: 75189930
29 MPI NM_002435.2(MPI): c.1131A> G (p.Val377=) single nucleotide variant Benign rs1130741 GRCh38 Chromosome 15, 74897589: 74897589
30 MPI NM_002435.2(MPI): c.345+15G> A single nucleotide variant Benign rs11638130 GRCh37 Chromosome 15, 75183935: 75183935
31 MPI NM_002435.2(MPI): c.345+15G> A single nucleotide variant Benign rs11638130 GRCh38 Chromosome 15, 74891594: 74891594
32 MPI NM_002435.2(MPI): c.345+16C> T single nucleotide variant Benign rs143242949 GRCh37 Chromosome 15, 75183936: 75183936
33 MPI NM_002435.2(MPI): c.345+16C> T single nucleotide variant Benign rs143242949 GRCh38 Chromosome 15, 74891595: 74891595
34 MPI NM_002435.2(MPI): c.670+9A> G single nucleotide variant Benign rs7495739 GRCh37 Chromosome 15, 75185670: 75185670
35 MPI NM_002435.2(MPI): c.670+9A> G single nucleotide variant Benign rs7495739 GRCh38 Chromosome 15, 74893329: 74893329
36 MPI NM_002435.2(MPI): c.762C> T (p.Ile254=) single nucleotide variant Benign/Likely benign rs12440159 GRCh37 Chromosome 15, 75188584: 75188584
37 MPI NM_002435.2(MPI): c.762C> T (p.Ile254=) single nucleotide variant Benign/Likely benign rs12440159 GRCh38 Chromosome 15, 74896243: 74896243
38 MPI NM_002435.2(MPI): c.982C> T (p.Arg328Trp) single nucleotide variant Conflicting interpretations of pathogenicity rs117089191 GRCh37 Chromosome 15, 75189489: 75189489
39 MPI NM_002435.2(MPI): c.982C> T (p.Arg328Trp) single nucleotide variant Conflicting interpretations of pathogenicity rs117089191 GRCh38 Chromosome 15, 74897148: 74897148
40 MPI NM_002435.2(MPI): c.10C> T (p.Pro4Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs143982014 GRCh37 Chromosome 15, 75182424: 75182424
41 MPI NM_002435.2(MPI): c.10C> T (p.Pro4Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs143982014 GRCh38 Chromosome 15, 74890083: 74890083
42 SERPINA1 NM_001127701.1(SERPINA1): c.227_229delTCT (p.Phe76del) deletion Pathogenic/Likely pathogenic rs775982338 GRCh37 Chromosome 14, 94849346: 94849348
43 SERPINA1 NM_001127701.1(SERPINA1): c.227_229delTCT (p.Phe76del) deletion Pathogenic/Likely pathogenic rs775982338 GRCh38 Chromosome 14, 94383009: 94383011
44 MPI NM_002435.2(MPI): c.1178G> C (p.Gly393Ala) single nucleotide variant Uncertain significance rs201815588 GRCh38 Chromosome 15, 74897636: 74897636
45 MPI NM_002435.2(MPI): c.1178G> C (p.Gly393Ala) single nucleotide variant Uncertain significance rs201815588 GRCh37 Chromosome 15, 75189977: 75189977
46 MPI NM_002435.2(MPI): c.120delC (p.Ile40Metfs) deletion Likely pathogenic rs1057516466 GRCh38 Chromosome 15, 74890630: 74890630
47 MPI NM_002435.2(MPI): c.120delC (p.Ile40Metfs) deletion Likely pathogenic rs1057516466 GRCh37 Chromosome 15, 75182971: 75182971
48 MPI NM_002435.2(MPI): c.145-1G> A single nucleotide variant Likely pathogenic rs1057516573 GRCh38 Chromosome 15, 74891378: 74891378
49 MPI NM_002435.2(MPI): c.145-1G> A single nucleotide variant Likely pathogenic rs1057516573 GRCh37 Chromosome 15, 75183719: 75183719
50 MPI NM_002435.2(MPI): c.487+2delT deletion Likely pathogenic rs1057516550 GRCh38 Chromosome 15, 74892804: 74892804

Expression for Congenital Disorder of Glycosylation, Type Ib

Search GEO for disease gene expression data for Congenital Disorder of Glycosylation, Type Ib.

Pathways for Congenital Disorder of Glycosylation, Type Ib

GO Terms for Congenital Disorder of Glycosylation, Type Ib

Sources for Congenital Disorder of Glycosylation, Type Ib

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
Content
Loading form....