MCID: CNG189
MIFTS: 36

Congenital Disorder of Glycosylation, Type Ib

Categories: Genetic diseases, Cardiovascular diseases, Gastrointestinal diseases, Liver diseases, Skin diseases, Metabolic diseases, Fetal diseases, Rare diseases, Neuronal diseases, Mental diseases, Blood diseases, Nephrological diseases, Ear diseases, Bone diseases, Muscle diseases, Endocrine 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 57 13
Congenital Disorder of Glycosylation Type 1b 59 29 6 73
Cdg1b 57 59 75
Protein-Losing Enteropathy-Hepatic Fibrosis Syndrome 57 75
Congenital Disorder of Glycosylation Type Ib 59 75
Mannosephosphate Isomerase Deficiency 57 75
Saguenay-Lac Saint-Jean Syndrome 57 75
Mpi Deficiency 57 75
Slsj Syndrome 57 75
Cdg Ib 57 75
Cdg-Ib 59 75
Cdgib 57 75
Carbohydrate Deficient Glycoprotein Syndrome Type Ib 59
Carbohydrate-Deficient Glycoprotein Syndrome Type Ib 75
Glycosylation, Congenital Disorder of, Type Ib 40
Congenital Disorder of Glycosylation 1b 75
Phosphomannose Isomerase Deficiency 59
Cdg, Gastrointestinal Type 57
Mannosephosphate Isomerase 13
Cdg Gastrointestinal Type 75
Cdg Syndrome Type Ib 59
Cdg Ib; Cdgib 57
Mpi-Cdg 59
Cdgs1b 75
Pi M 6

Characteristics:

Orphanet epidemiological data:

59
mpi-cdg
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal; Age of death: early childhood,infantile,normal life expectancy;

OMIM:

57
Inheritance:
autosomal recessive

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


HPO:

32
congenital disorder of glycosylation, type ib:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Congenital Disorder of Glycosylation, Type Ib

OMIM : 57 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 diarrhea and vomiting. 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 hypoglycemia

CDC : 3 The Performance Improvement Managers Network (PIM Network) is a community of practice that connects performance improvement managers (PIMs) working on the National Public Health Improvement Initiative (NPHII). PIMs are a vital part of NPHII, which supports state, tribal, local, and territorial health agencies and is strongly focused on performance management and continuous quality improvement, as well as improving jurisdictions’ abilities to meet national public health standards. The PIM Network was created by CDC in the Office for State, Tribal, Local and Territorial Support (OSTLTS) and includes PIMs and performance management and quality improvement experts and practitioners who receive NPHII support.

UniProtKB/Swiss-Prot : 75 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 in 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 Ii
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 Iq
Congenital Disorder of Glycosylation, Type Io 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 28.4 MPI SERPINA1
2 congenital disorder of glycosylation, type ic 11.1
3 congenital disorder of glycosylation, type ie 11.1
4 congenital disorder of glycosylation, type if 11.1
5 congenital disorder of glycosylation, type ig 10.9
6 congenital disorder of glycosylation, type in 10.2
7 congenital disorders of n-linked glycosylation and multiple pathway 10.0
8 hepatitis 10.0
9 alpha-1-antitrypsin deficiency 9.7

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

Symptoms via clinical synopsis from OMIM:

57
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

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

59 32 (show all 22)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 malabsorption 59 32 hallmark (90%) Very frequent (99-80%) HP:0002024
2 hypoglycemia 59 32 frequent (33%) Frequent (79-30%) HP:0001943
3 lymphedema 59 32 frequent (33%) Frequent (79-30%) HP:0001004
4 congenital hepatic fibrosis 59 32 hallmark (90%) Very frequent (99-80%) HP:0002612
5 hepatic failure 59 32 hallmark (90%) Very frequent (99-80%) HP:0001399
6 muscular hypotonia 32 HP:0001252
7 failure to thrive 32 HP:0001508
8 hepatomegaly 32 HP:0002240
9 vomiting 32 HP:0002013
10 abnormal bleeding 32 HP:0001892
11 abnormal thrombosis 32 HP:0001977
12 hepatic fibrosis 32 HP:0001395
13 cirrhosis 32 HP:0001394
14 hyperinsulinemic hypoglycemia 32 HP:0000825
15 diarrhea 32 HP:0002014
16 generalized hypotonia 32 HP:0001290
17 hypoalbuminemia 32 HP:0003073
18 protein-losing enteropathy 32 HP:0002243
19 villous atrophy 32 HP:0011473
20 reduced factor xi activity 32 HP:0001929
21 type i transferrin isoform profile 32 HP:0003642
22 reduced antithrombin iii activity 32 HP:0001976

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


diarrhea, vomiting

Drugs & Therapeutics for Congenital Disorder of Glycosylation, Type Ib

Interventional clinical trials:


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

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 29 MPI

Anatomical Context for Congenital Disorder of Glycosylation, Type Ib

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

41
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
4
Genomic organization of the human phosphomannose isomerase (MPI) gene and mutation analysis in patients with congenital disorders of glycosylation type Ib (CDG-Ib). ( 10980531 )
2000

Variations for Congenital Disorder of Glycosylation, Type Ib

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

75 (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 all 49)
# Gene Variation Type Significance SNP ID Assembly Location
1 MPI NM_002435.2(MPI): c.656G> A (p.Arg219Gln) single nucleotide variant Pathogenic/Likely pathogenic rs104894489 GRCh37 Chromosome 15, 75185647: 75185647
2 MPI NM_002435.2(MPI): c.656G> A (p.Arg219Gln) single nucleotide variant Pathogenic/Likely pathogenic rs104894489 GRCh38 Chromosome 15, 74893306: 74893306
3 MPI NM_002435.2(MPI): c.305C> T (p.Ser102Leu) single nucleotide variant Pathogenic rs104894494 GRCh37 Chromosome 15, 75183880: 75183880
4 MPI NM_002435.2(MPI): c.305C> T (p.Ser102Leu) single nucleotide variant Pathogenic rs104894494 GRCh38 Chromosome 15, 74891539: 74891539
5 MPI NM_002435.2(MPI): c.413T> C (p.Met138Thr) single nucleotide variant Pathogenic rs104894495 GRCh37 Chromosome 15, 75185069: 75185069
6 MPI NM_002435.2(MPI): c.413T> C (p.Met138Thr) single nucleotide variant Pathogenic rs104894495 GRCh38 Chromosome 15, 74892728: 74892728
7 MPI MPI, 1-BP INS, 166C insertion Pathogenic
8 MPI NM_002435.2(MPI): c.884G> A (p.Arg295His) single nucleotide variant Pathogenic rs28928906 GRCh37 Chromosome 15, 75189391: 75189391
9 MPI NM_002435.2(MPI): c.884G> A (p.Arg295His) single nucleotide variant Pathogenic rs28928906 GRCh38 Chromosome 15, 74897050: 74897050
10 SERPINA1 NM_001127701.1(SERPINA1): c.1178C> T (p.Pro393Leu) single nucleotide variant Pathogenic/Likely pathogenic rs199422209 GRCh37 Chromosome 14, 94844865: 94844865
11 SERPINA1 NM_001127701.1(SERPINA1): c.1178C> T (p.Pro393Leu) single nucleotide variant Pathogenic/Likely pathogenic rs199422209 GRCh38 Chromosome 14, 94378528: 94378528
12 SERPINA1 NM_001127701.1(SERPINA1): c.272G> A (p.Gly91Glu) single nucleotide variant Pathogenic rs28931568 GRCh37 Chromosome 14, 94849303: 94849303
13 SERPINA1 NM_001127701.1(SERPINA1): c.272G> A (p.Gly91Glu) single nucleotide variant Pathogenic rs28931568 GRCh38 Chromosome 14, 94382966: 94382966
14 SERPINA1 NM_001127701.1(SERPINA1): c.194T> C (p.Leu65Pro) single nucleotide variant Pathogenic rs28931569 GRCh37 Chromosome 14, 94849381: 94849381
15 SERPINA1 NM_001127701.1(SERPINA1): c.194T> C (p.Leu65Pro) single nucleotide variant Pathogenic rs28931569 GRCh38 Chromosome 14, 94383044: 94383044
16 MPI NM_002435.2(MPI): c.684C> T (p.Asn228=) single nucleotide variant Benign/Likely benign rs139190144 GRCh37 Chromosome 15, 75188506: 75188506
17 MPI NM_002435.2(MPI): c.684C> T (p.Asn228=) single nucleotide variant Benign/Likely benign rs139190144 GRCh38 Chromosome 15, 74896165: 74896165
18 MPI NM_002435.2(MPI): c.166dupC (p.Arg56Profs) duplication Likely pathogenic rs786204593 GRCh38 Chromosome 15, 74891400: 74891400
19 MPI NM_002435.2(MPI): c.166dupC (p.Arg56Profs) duplication Likely pathogenic rs786204593 GRCh37 Chromosome 15, 75183741: 75183741
20 MPI NM_002435.2(MPI): c.1205A> G (p.Glu402Gly) single nucleotide variant Pathogenic rs863225086 GRCh37 Chromosome 15, 75190004: 75190004
21 MPI NM_002435.2(MPI): c.1205A> G (p.Glu402Gly) single nucleotide variant Pathogenic rs863225086 GRCh38 Chromosome 15, 74897663: 74897663
22 MPI NM_002435.2(MPI): c.1253G> A (p.Arg418His) single nucleotide variant Pathogenic rs863225087 GRCh38 Chromosome 15, 74897711: 74897711
23 MPI NM_002435.2(MPI): c.1253G> A (p.Arg418His) single nucleotide variant Pathogenic rs863225087 GRCh37 Chromosome 15, 75190052: 75190052
24 MPI NM_002435.2(MPI): c.10C> T (p.Pro4Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs143982014 GRCh37 Chromosome 15, 75182424: 75182424
25 MPI NM_002435.2(MPI): c.10C> T (p.Pro4Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs143982014 GRCh38 Chromosome 15, 74890083: 74890083
26 SERPINA1 NM_001127701.1(SERPINA1): c.227_229delTCT (p.Phe76del) deletion Pathogenic rs775982338 GRCh37 Chromosome 14, 94849346: 94849348
27 SERPINA1 NM_001127701.1(SERPINA1): c.227_229delTCT (p.Phe76del) deletion Pathogenic rs775982338 GRCh38 Chromosome 14, 94383009: 94383011
28 MPI NM_002435.2(MPI): c.1178G> C (p.Gly393Ala) single nucleotide variant Uncertain significance rs201815588 GRCh38 Chromosome 15, 74897636: 74897636
29 MPI NM_002435.2(MPI): c.1178G> C (p.Gly393Ala) single nucleotide variant Uncertain significance rs201815588 GRCh37 Chromosome 15, 75189977: 75189977
30 MPI NM_002435.2(MPI): c.120delC (p.Ile40Metfs) deletion Likely pathogenic rs1057516466 GRCh38 Chromosome 15, 74890630: 74890630
31 MPI NM_002435.2(MPI): c.120delC (p.Ile40Metfs) deletion Likely pathogenic rs1057516466 GRCh37 Chromosome 15, 75182971: 75182971
32 MPI NM_002435.2(MPI): c.145-1G> A single nucleotide variant Likely pathogenic rs1057516573 GRCh38 Chromosome 15, 74891378: 74891378
33 MPI NM_002435.2(MPI): c.145-1G> A single nucleotide variant Likely pathogenic rs1057516573 GRCh37 Chromosome 15, 75183719: 75183719
34 MPI NM_002435.2(MPI): c.487+2delT deletion Likely pathogenic rs1057516550 GRCh38 Chromosome 15, 74892804: 74892804
35 MPI NM_002435.2(MPI): c.487+2delT deletion Likely pathogenic rs1057516550 GRCh37 Chromosome 15, 75185145: 75185145
36 MPI NM_002435.2(MPI): c.488-1G> A single nucleotide variant Likely pathogenic rs759579169 GRCh37 Chromosome 15, 75185478: 75185478
37 MPI NM_002435.2(MPI): c.488-1G> A single nucleotide variant Likely pathogenic rs759579169 GRCh38 Chromosome 15, 74893137: 74893137
38 MPI NM_002435.2(MPI): c.488-1G> C single nucleotide variant Likely pathogenic rs759579169 GRCh37 Chromosome 15, 75185478: 75185478
39 MPI NM_002435.2(MPI): c.488-1G> C single nucleotide variant Likely pathogenic rs759579169 GRCh38 Chromosome 15, 74893137: 74893137
40 MPI NM_002435.2(MPI): c.652A> T (p.Lys218Ter) single nucleotide variant Likely pathogenic rs1057516424 GRCh38 Chromosome 15, 74893302: 74893302
41 MPI NM_002435.2(MPI): c.652A> T (p.Lys218Ter) single nucleotide variant Likely pathogenic rs1057516424 GRCh37 Chromosome 15, 75185643: 75185643
42 MPI NM_002435.2(MPI): c.727C> T (p.Gln243Ter) single nucleotide variant Likely pathogenic rs749911553 GRCh37 Chromosome 15, 75188549: 75188549
43 MPI NM_002435.2(MPI): c.727C> T (p.Gln243Ter) single nucleotide variant Likely pathogenic rs749911553 GRCh38 Chromosome 15, 74896208: 74896208
44 MPI NM_002435.2(MPI): c.740delG (p.Gly247Valfs) deletion Likely pathogenic rs1057517115 GRCh38 Chromosome 15, 74896221: 74896221
45 MPI NM_002435.2(MPI): c.740delG (p.Gly247Valfs) deletion Likely pathogenic rs1057517115 GRCh37 Chromosome 15, 75188562: 75188562
46 MPI NM_002435.2(MPI): c.1096T> C (p.Ser366Pro) single nucleotide variant Uncertain significance GRCh37 Chromosome 15, 75189895: 75189895
47 MPI NM_002435.2(MPI): c.1096T> C (p.Ser366Pro) single nucleotide variant Uncertain significance GRCh38 Chromosome 15, 74897554: 74897554
48 MPI NM_002435.2(MPI): c.7G> A (p.Ala3Thr) single nucleotide variant Uncertain significance rs770421382 GRCh38 Chromosome 15, 74890080: 74890080
49 MPI NM_002435.2(MPI): c.7G> A (p.Ala3Thr) single nucleotide variant Uncertain significance rs770421382 GRCh37 Chromosome 15, 75182421: 75182421

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

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