CDG1A
MCID: CNG415
MIFTS: 61

Congenital Disorder of Glycosylation, Type Ia (CDG1A)

Categories: Blood diseases, Bone diseases, Cardiovascular diseases, Ear diseases, Endocrine diseases, Eye diseases, Fetal diseases, Gastrointestinal diseases, Genetic diseases, Immune diseases, Infectious diseases, Liver diseases, Mental diseases, Metabolic diseases, Muscle diseases, Nephrological diseases, Neuronal diseases, Oral diseases, Rare diseases, Reproductive diseases, Skin diseases
Data Licensing
For inquiries, contact:

Aliases & Classifications for Congenital Disorder of Glycosylation, Type Ia

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

Name: Congenital Disorder of Glycosylation, Type Ia 57 12
Phosphomannomutase 2 Deficiency 57 42 58 73
Cdg Ia 57 42 73 53
Cdg1a 57 42 58 73
Congenital Disorder of Glycosylation Type Ia 42 58 73
Pmm2-Congenital Disorder of Glycosylation 11 42 28
Jaeken Syndrome 57 42 73
Carbohydrate-Deficient Glycoprotein Syndrome Type Ia 42 73
Congenital Disorder of Glycosylation Type 1a 58 71
Congenital Disorder of Glycosylation Ia 11 14
Congenital Disorder of Glycosylation 1a 11 73
Pmm2-Cdg 58 5
Cdgs1a 42 73
Cdg-Ia 58 73
Cdgia 57 73
Carbohydrate-Deficient Glycoprotein Syndrome, Type Ia, Formerly 57
Carbohydrate Deficient Glycoprotein Syndrome Type Ia 58
Glycosylation, Congenital Disorder of, Type Ia 38
Cdg Syndrome Type Ia 58
Cdg Syndrome Type 1a 75
Jaeken's Syndrome 73
Pmm2 Deficiency 73
Pmm Deficiency 42

Characteristics:


Inheritance:

Congenital Disorder of Glycosylation, Type Ia: Autosomal recessive 57
Pmm2-Cdg: Autosomal recessive 58

Prevelance:

Pmm2-Cdg: 1-9/100000 (Italy, Europe) 58

Age Of Onset:

Pmm2-Cdg: Infancy,Neonatal 58

Age Of Death:

Pmm2-Cdg: infantile,normal life expectancy 58

OMIM®:

57 (Updated 24-Oct-2022)
Miscellaneous:
two clinical presentations - solely neurologic form and a neurologic-multivisceral form
mortality approximately 20% in first 2 years


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare hepatic diseases
Rare skin diseases
Inborn errors of metabolism


External Ids:

Disease Ontology 11 DOID:0080552
OMIM® 57 212065
OMIM Phenotypic Series 57 PS212065
MeSH 43 D018981
ICD10 via Orphanet 32 E77.8
UMLS via Orphanet 72 C0349653
Orphanet 58 ORPHA79318
MedGen 40 C0349653
UMLS 71 C0349653

Summaries for Congenital Disorder of Glycosylation, Type Ia

MedlinePlus Genetics: 42 PMM2-congenital disorder of glycosylation (PMM2-CDG, also known as congenital disorder of glycosylation type Ia) is an inherited condition that affects many parts of the body. The type and severity of problems associated with PMM2-CDG vary widely among affected individuals, sometimes even among members of the same family.Individuals with PMM2-CDG typically develop signs and symptoms of the condition during infancy. Affected infants may have weak muscle tone (hypotonia), retracted (inverted) nipples, an abnormal distribution of fat, eyes that do not look in the same direction (strabismus), developmental delay, and a failure to gain weight and grow at the expected rate (failure to thrive). Infants with PMM2-CDG also frequently have an underdeveloped cerebellum, which is the part of the brain that coordinates movement. Distinctive facial features are sometimes present in affected individuals, including a high forehead, a triangular face, large ears, and a thin upper lip. Children with PMM2-CDG may also have elevated liver function test results, seizures, fluid around the heart (pericardial effusion), and blood clotting disorders. About 20 percent of affected infants do not survive the first year of life due to multiple organ failure.The most severe cases of PMM2-CDG are characterized by hydrops fetalis, a condition in which excess fluid builds up in the body before birth. Most babies with hydrops fetalis are stillborn or die soon after birth.People with PMM2-CDG who survive infancy may have moderate intellectual disability, and some are unable to walk independently. Affected individuals may also experience stroke-like episodes that involve an extreme lack of energy (lethargy) and temporary paralysis. Recovery from these episodes usually occurs over a period of a few weeks to several months.During adolescence or adulthood, individuals with PMM2-CDG have reduced sensation and weakness in their arms and legs (peripheral neuropathy), an abnormal curvature of the spine (kyphoscoliosis), impaired muscle coordination (ataxia), and joint deformities (contractures). Some affected individuals have an eye disorder called retinitis pigmentosa that causes vision loss. Females with PMM2-CDG have hypergonadotropic hypogonadism, which affects the production of hormones that direct sexual development. As a result, females with PMM2-CDG do not go through puberty. Affected males experience normal puberty but often have small testes.

MalaCards based summary: Congenital Disorder of Glycosylation, Type Ia, also known as phosphomannomutase 2 deficiency, is related to congenital disorder of glycosylation, type iid and congenital disorder of glycosylation, type ib, and has symptoms including ataxia, diarrhea and seizures. An important gene associated with Congenital Disorder of Glycosylation, Type Ia is PMM2 (Phosphomannomutase 2), and among its related pathways/superpathways are Metabolism of proteins and Transport to the Golgi and subsequent modification. The drugs Acetazolamide and Sorbitol have been mentioned in the context of this disorder. Affiliated tissues include liver, eye and skin, and related phenotypes are high palate and upslanted palpebral fissure

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. These glycoconjugates play critical roles in metabolism, cell recognition and adhesion, cell migration, protease resistance, host defense, and antigenicity, among others. CDGs are divided into 2 main groups: type I CDGs comprise defects in the assembly of the dolichol lipid-linked oligosaccharide (LLO) chain and its transfer to the nascent protein, whereas type II CDGs (see, e.g., CDG2A, 212066) refer to defects in the trimming and processing of the protein-bound glycans either late in the endoplasmic reticulum or the Golgi compartments. CDG1A is the most common form of CDG and was the first to be characterized at the molecular level (reviews by Marquardt and Denecke, 2003; Grunewald et al., 2002). Matthijs et al. (1997) noted that Jaeken syndrome (CDG1A) is a genetic multisystem disorder characterized by defective glycosylation of glycoconjugates. It usually presents as a severe disorder in the neonatal period. There is a severe encephalopathy with axial hypotonia, abnormal eye movement, and pronounced psychomotor retardation, as well as peripheral neuropathy, cerebellar hypoplasia, and retinitis pigmentosa. Patients show a peculiar distribution of subcutaneous fat, nipple retraction, and hypogonadism. There is a 20% lethality in the first year of life due to severe infections, liver insufficiency, or cardiomyopathy. Marques-da-Silva et al. (2017) noted that CDG1A is the most prevalent form of CDG, with more than 700 patients reported worldwide. (212065) (Updated 24-Oct-2022)

UniProtKB/Swiss-Prot: 73 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. CDG1A is an autosomal recessive disorder characterized by a severe encephalopathy with axial hypotonia, abnormal eye movement, and pronounced psychomotor retardation, as well as peripheral neuropathy, cerebellar hypoplasia, and retinitis pigmentosa. Patients show a peculiar distribution of subcutaneous fat, nipple retraction, and hypogonadism.

Orphanet: 58 PMM2-CDG is the most frequent form of congenital disorder of N-glycosylation and is characterized by cerebellar dysfunction, abnormal fat distribution, inverted nipples, strabismus and hypotonia. 3 forms of PMM2-CDG can be distinguished: the infantile multisystem type, late-infantile and childhood ataxia-intellectual disability type (3-10 yrs old), and the adult stable disability type. Infants usually develop ataxia, psychomotor delay and extraneurological manifestations including failure to thrive, enteropathy, hepatic dysfunction, coagulation abnormalities and cardiac and renal involvement. The phenotype is however highly variable and ranges from infants who die in the first year of life to mildly involved adults.

Disease Ontology: 11 A congenital disorder of glycosylation I that is characterized by a severe encephalopathy with axial hypotonia, abnormal eye movement, pronounced psychomotor retardation, peripheral neuropathy, cerebellar hypoplasia, and retinitis pigmentosa and has material basis in homozygous or compound heterozygous mutation in the gene encoding phosphomannomutase-2 on chromosome 16p13.

Wikipedia: 75 PMM2 deficiency or PMM2-CDG is a very rare genetic disorder caused by mutations in PMM2. It is an... more...

Related Diseases for Congenital Disorder of Glycosylation, Type Ia

Diseases in the Disorder of Multiple Glycosylation 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 Iir 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 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, Autosomal Recessive 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
Congenital Disorder of Glycosylation, Type Iit Congenital Disorder of Glycosylation, Type 2v
Congenital Disorder of Glycosylation, Type Iiw Congenital Disorder of Glycosylation, Type Iw, Autosomal Dominant
Congenital Disorder of Glycosylation Iw

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

(show top 50) (show all 168)
# Related Disease Score Top Affiliating Genes
1 congenital disorder of glycosylation, type iid 31.5 PMM2 MPI
2 congenital disorder of glycosylation, type ib 31.5 SERPINC1 MPI
3 congenital disorder of glycosylation, type iia 31.4 PMM2 MPI
4 congenital disorder of glycosylation, type ic 31.4 PMM2 ALG6
5 congenital disorder of glycosylation, type iik 31.4 PMM2 ALG6
6 congenital disorder of glycosylation, type iio 31.2 MPI ALG6
7 immunodeficiency 47 31.2 PMM2 MPI ALG6
8 factor xi deficiency 30.5 SERPINC1 F9
9 factor xii deficiency 30.3 SERPINC1 F9
10 nephrotic syndrome 30.1 TF SERPINC1 F9 CLU
11 intracranial hypertension 30.1 SERPINC1 F9
12 esotropia 30.0 PMM2 ALG6
13 deficiency anemia 29.8 TF SERPINC1 F9 ABCB7
14 thrombocytopenia 29.7 SERPINC1 PMM2 NEU1 F9
15 congenital disorder of glycosylation, type in 29.6 TF SERPINC1 PMM2 PMM1 MPI CLU
16 protein-losing enteropathy 29.6 SERPINC1 PMM2 MPI ALG6
17 congenital disorder of glycosylation, type if 11.2
18 phosphomannoisomerase deficiency 11.2
19 congenital disorder of glycosylation, type iic 10.9
20 congenital disorder of glycosylation, type iim 10.9
21 congenital disorder of glycosylation, type iir 10.9
22 congenital disorder of glycosylation, type id 10.9
23 congenital disorder of glycosylation, type ig 10.9
24 congenital disorder of glycosylation, type ij 10.9
25 congenital disorder of glycosylation, type ih 10.9
26 congenital disorder of glycosylation, type il 10.9
27 muscular dystrophy-dystroglycanopathy , type c, 15 10.9
28 congenital disorder of glycosylation, type ir 10.9
29 congenital disorder of glycosylation, type iil 10.9
30 congenital disorder of glycosylation, type it 10.9
31 congenital disorder of glycosylation, type iip 10.9
32 congenital disorder of glycosylation, type iit 10.9
33 congenital disorder of glycosylation, type iiw 10.9
34 developmental and epileptic encephalopathy 36 10.5
35 hypotonia 10.5
36 cardiomyopathy, familial hypertrophic, 1 10.4
37 hypertrophic cardiomyopathy 10.4
38 congenital disorders of n-linked glycosylation and multiple pathway 10.4
39 alacrima, achalasia, and mental retardation syndrome 10.3
40 hydrops fetalis, nonimmune 10.3
41 cerebellar hypoplasia 10.3
42 pericardial effusion 10.3
43 hypothyroidism 10.3
44 osteochondrodysplasia 10.3
45 ocular motor apraxia 10.2
46 apraxia 10.2
47 pathologic nystagmus 10.2
48 prothrombin deficiency 10.2 SERPINC1 F9
49 microvascular complications of diabetes 1 10.2
50 diabetic neuropathy 10.2

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



Diseases related to Congenital Disorder of Glycosylation, Type Ia

Symptoms & Phenotypes for Congenital Disorder of Glycosylation, Type Ia

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

58 30 (show top 50) (show all 133)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 high palate 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0000218
2 upslanted palpebral fissure 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0000582
3 osteopenia 58 30 Frequent (33%) Frequent (79-30%)
HP:0000938
4 global developmental delay 58 30 Very rare (1%) Frequent (79-30%)
HP:0001263
5 hypertelorism 58 30 Frequent (33%) Frequent (79-30%)
HP:0000316
6 mandibular prognathia 58 30 Frequent (33%) Frequent (79-30%)
HP:0000303
7 delayed speech and language development 58 30 Very rare (1%) Frequent (79-30%)
HP:0000750
8 pes planus 58 30 Frequent (33%) Frequent (79-30%)
HP:0001763
9 anteverted nares 58 30 Frequent (33%) Frequent (79-30%)
HP:0000463
10 vomiting 58 30 Very rare (1%) Frequent (79-30%)
HP:0002013
11 prominent forehead 58 30 Frequent (33%) Frequent (79-30%)
HP:0011220
12 osteoporosis 58 30 Frequent (33%) Frequent (79-30%)
HP:0000939
13 retrognathia 58 30 Frequent (33%) Frequent (79-30%)
HP:0000278
14 epicanthus 58 30 Frequent (33%) Frequent (79-30%)
HP:0000286
15 inverted nipples 58 30 Frequent (33%) Frequent (79-30%)
HP:0003186
16 lipodystrophy 58 30 Frequent (33%) Frequent (79-30%)
HP:0009125
17 joint laxity 58 30 Frequent (33%) Frequent (79-30%)
HP:0001388
18 kyphoscoliosis 58 30 Frequent (33%) Frequent (79-30%)
HP:0002751
19 thin upper lip vermilion 58 30 Frequent (33%) Frequent (79-30%)
HP:0000219
20 long face 58 30 Frequent (33%) Frequent (79-30%)
HP:0000276
21 long philtrum 58 30 Frequent (33%) Frequent (79-30%)
HP:0000343
22 wide mouth 58 30 Frequent (33%) Frequent (79-30%)
HP:0000154
23 hyporeflexia 58 30 Frequent (33%) Frequent (79-30%)
HP:0001265
24 feeding difficulties 58 30 Frequent (33%) Frequent (79-30%)
HP:0011968
25 prominent nose 58 30 Frequent (33%) Frequent (79-30%)
HP:0000448
26 abnormal subcutaneous fat tissue distribution 58 30 Frequent (33%) Frequent (79-30%)
HP:0007552
27 long fingers 58 30 Frequent (33%) Frequent (79-30%)
HP:0100807
28 esotropia 58 30 Frequent (33%) Frequent (79-30%)
HP:0000565
29 delayed myelination 58 30 Frequent (33%) Frequent (79-30%)
HP:0012448
30 seizure 30 Frequent (33%) HP:0001250
31 axial hypotonia 30 Frequent (33%) HP:0008936
32 intellectual disability 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0001249
33 failure to thrive 58 30 Very rare (1%) Occasional (29-5%)
HP:0001508
34 ataxia 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0001251
35 cataract 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000518
36 macrotia 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000400
37 proteinuria 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000093
38 fever 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0001945
39 elevated hepatic transaminase 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0002910
40 myopia 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000545
41 hyperinsulinemia 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000842
42 hepatic fibrosis 58 30 Very rare (1%) Occasional (29-5%)
HP:0001395
43 multiple joint contractures 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0002828
44 abnormal renal tubule morphology 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000091
45 nephrotic syndrome 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000100
46 multiple renal cysts 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0005562
47 prominent nasal bridge 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000426
48 peripheral neuropathy 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0009830
49 decreased testicular size 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0008734
50 hypoalbuminemia 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0003073

Symptoms via clinical synopsis from OMIM®:

57 (Updated 24-Oct-2022)
Neurologic Central Nervous System:
seizures
ataxia
hyporeflexia
psychomotor retardation
olivopontocerebellar hypoplasia
more
Head And Neck Eyes:
nystagmus
retinitis pigmentosa
abnormal eye movements
internal strabismus

Endocrine Features:
hypothyroidism
hypergonadotropic hypogonadism
decreased thyroxine
decreased thyroxine-binding globulin
adrenal insufficiency (in some patients)

Abdomen Liver:
hepatomegaly
liver fibrosis
steatosis

Abdomen Gastrointestinal:
vomiting
diarrhea
feeding problems

Chest Breasts:
inverted nipples

Neurologic Peripheral Nervous System:
peripheral neuropathy

Cardiovascular Heart:
cardiomyopathy
pericardial effusion

Muscle Soft Tissue:
abnormal subcutaneous fat tissue distribution
weakness

Head And Neck Mouth:
thin upper lip

Head And Neck Ears:
large ears

Head And Neck Head:
microcephaly (50% of patients)

Prenatal Manifestations:
hydrops fetalis, nonimmune

Growth Weight:
failure to thrive

Skeletal Spine:
kyphosis

Skeletal:
osteopenia

Laboratory Abnormalities:
proteinuria
hypoalbuminemia
hypocholesterolemia
elevated transaminases
abnormal isoelectric focusing of serum transferrin (type 1 pattern)
more
Head And Neck Face:
prominent forehead

Genitourinary Kidneys:
nephrotic syndrome
proximal tubulopathy
renal cysts

Hematology:
prolonged prothrombin time
thrombocytosis
factor xi deficiency
antithrombin iii deficiency

Skin Nails Hair Skin:
abnormal subcutaneous fat tissue distribution
fat pads
'orange peel' skin

Genitourinary Internal Genitalia Female:
primary ovarian failure

Head And Neck Nose:
flat nasal bridge

Skeletal Limbs:
joint contractures

Immunology:
decreased immunoglobulin a (iga)
decreased immunoglobulin g (igg)

Clinical features from OMIM®:

212065 (Updated 24-Oct-2022)

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


ataxia; diarrhea; seizures; vomiting; weakness

MGI Mouse Phenotypes related to Congenital Disorder of Glycosylation, Type Ia:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 embryo MP:0005380 9.43 ABCB7 ALG6 F9 MPI PMM2 TF
2 cardiovascular system MP:0005385 9.28 ABCB7 CLU F9 MPI NEU1 PMM2

Drugs & Therapeutics for Congenital Disorder of Glycosylation, Type Ia

Drugs for Congenital Disorder of Glycosylation, Type Ia (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 6)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Acetazolamide Approved, Vet_approved Phase 2, Phase 3 59-66-5, 1424-27-7 1986
2
Sorbitol Approved, Investigational Phase 3 69-65-8, 50-70-4 453 6251 5780
3
Epalrestat Investigational Phase 3 82159-09-9 1549120
4 Carbonic Anhydrase Inhibitors Phase 2, Phase 3
5 Anticonvulsants Phase 2, Phase 3
6 diuretics Phase 2, Phase 3

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Randomized, Double-blind, Placebo-controlled Study Evaluating Acetazolamide Efficacy in Ataxia in PMM2-CDG Active, not recruiting NCT04679389 Phase 2, Phase 3 Placebo;Acetazolamide
2 A Prospective, Randomized, Double-Blind, Placebo-Controlled, Single-Center Study of Oral Epalrestat Therapy in Pediatric Subjects With Phosphomannomutase 2-congenital Disorder of Glycosylation (PMM2-CDG) Not yet recruiting NCT04925960 Phase 3 Epalrestat;Placebo
3 A Phase 2, Randomized, Open-Label, 12-Week Study to Assess the Pharmacodynamics, Safety, Tolerability, and Pharmacokinetics of Multiple Doses of GLM101 Administered Intravenously to Adult Participants With PMM2-CDG Not yet recruiting NCT05549219 Phase 2 GLM101
4 Clinical and Basic Investigations Into Phosphomannomutase Deficiency (PMM2-CDG) Active, not recruiting NCT03173300

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

Genetic Tests for Congenital Disorder of Glycosylation, Type Ia

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

# Genetic test Affiliating Genes
1 Pmm2-Congenital Disorder of Glycosylation 28 PMM2

Anatomical Context for Congenital Disorder of Glycosylation, Type Ia

Organs/tissues related to Congenital Disorder of Glycosylation, Type Ia:

MalaCards : Liver, Eye, Skin, Testes, Cerebellum, Brain, Heart
ODiseA: Blood And Bone Marrow, Brain, Kidney

Publications for Congenital Disorder of Glycosylation, Type Ia

Articles related to Congenital Disorder of Glycosylation, Type Ia:

(show top 50) (show all 397)
# Title Authors PMID Year
1
Biochemical and molecular studies in 26 Spanish patients with congenital disorder of glycosylation type Ia. 53 62 57 5
12705494 2002
2
Characterization of the 415G>A (E139K) PMM2 mutation in carbohydrate-deficient glycoprotein syndrome type Ia disrupting a splicing enhancer resulting in exon 5 skipping. 53 62 57 5
10571956 1999
3
Mutations in PMM2, a phosphomannomutase gene on chromosome 16p13, in carbohydrate-deficient glycoprotein type I syndrome (Jaeken syndrome). 53 62 57 5
9140401 1997
4
Sorbitol Is a Severity Biomarker for PMM2-CDG with Therapeutic Implications. 62 57 5
34652821 2021
5
Mitotic Intragenic Recombination: A Mechanism of Survival for Several Congenital Disorders of Glycosylation. 62 57 5
26805780 2016
6
Clinical phenotype correlates to glycoprotein phenotype in a sib pair with CDG-Ia. 62 57 5
18629883 2008
7
Primary skeletal dysplasia as a major manifesting feature in an infant with congenital disorder of glycosylation type Ia. 62 57 5
18203160 2008
8
Congenital disorder of glycosylation type Ia presenting with hydrops fetalis. 62 57 5
17158594 2007
9
Congenital disorder of glycosylation type 1a in a macrosomic 16-month-old boy with an atypical phenotype and homozygosity of the N216I mutation. 62 57 5
12905014 2003
10
Hyperinsulinaemic hypoglycaemia--leading symptom in a patient with congenital disorder of glycosylation Ia (phosphomannomutase deficiency). 62 57 5
11916319 2001
11
A broad spectrum of clinical presentations in congenital disorders of glycosylation I: a series of 26 cases. 62 57 5
11134235 2001
12
Phosphomannomutase deficiency: the molecular basis of the classical Jaeken syndrome (CDGS type Ia). 62 57 5
10527672 1999
13
Carbohydrate-deficient glycoprotein syndrome type IA (phosphomannomutase-deficiency). 62 57 5
10571009 1999
14
Deep sequencing reveals 50 novel genes for recessive cognitive disorders. 57 5
21937992 2011
15
Hair changes in congenital disorders of glycosylation (CDG type 1). 57 5
12607543 2003
16
Genotypes and phenotypes of patients in the UK with carbohydrate-deficient glycoprotein syndrome type 1. 57 5
10801058 2000
17
Congenital disorder of glycosylation type Ia in a 6-year-old girl with a mild intellectual phenotype: two novel PMM2 mutations. 53 62 5
16435227 2005
18
Congenital disorders of glycosylation type Ia and IIa are associated with different primary haemostatic complications. 53 62 57
11596651 2001
19
PMM2 mutation spectrum, including 10 novel mutations, in a large CDG type 1A family material with a focus on Scandinavian families. 53 62 5
11058896 2000
20
Identification of four novel PMM2 mutations in congenital disorders of glycosylation (CDG) Ia French patients. 53 62 5
10922383 2000
21
Effect of mutations found in carbohydrate-deficient glycoprotein syndrome type IA on the activity of phosphomannomutase 2. 53 62 5
10386614 1999
22
Should patients with Phosphomannomutase 2-CDG (PMM2-CDG) be screened for adrenal insufficiency? 62 57
34140212 2021
23
Congenital disorders of glycosylation: Prevalence, incidence and mutational spectrum in the Polish population. 62 5
33643843 2021
24
Congenital Disorders of Glycosylation in Portugal-Two Decades of Experience. 62 5
33340551 2021
25
Liver manifestations in a cohort of 39 patients with congenital disorders of glycosylation: pin-pointing the characteristics of liver injury and proposing recommendations for follow-up. 62 5
33413482 2021
26
Identification through exome sequencing of the first PMM2-CDG individual of Mexican mestizo origin. 62 5
32874916 2020
27
New Insights into Immunological Involvement in Congenital Disorders of Glycosylation (CDG) from a People-Centric Approach. 62 5
32635232 2020
28
Novel PMM2 missense mutation in a Chinese family with non-syndromic premature ovarian insufficiency. 62 5
31902100 2020
29
N-Glycosylation Defects in Humans Lower Low-Density Lipoprotein Cholesterol Through Increased Low-Density Lipoprotein Receptor Expression. 62 5
31117816 2019
30
Multifactorial hypercoagulable state associated with a thrombotic phenotype in phosphomannomutase-2 congenital disorder of glycosylation (PMM2-CDG): Case report and brief review of the literature. 62 5
30991241 2019
31
From gestalt to gene: early predictive dysmorphic features of PMM2-CDG. 62 57
30464053 2019
32
The Analysis of Variants in the General Population Reveals That PMM2 Is Extremely Tolerant to Missense Mutations and That Diagnosis of PMM2-CDG Can Benefit from the Identification of Modifiers. 62 5
30061496 2018
33
Renal involvement in PMM2-CDG, a mini-review. 62 57
29229467 2018
34
Stroke-Like Episodes and Cerebellar Syndrome in Phosphomannomutase Deficiency (PMM2-CDG): Evidence for Hypoglycosylation-Driven Channelopathy. 62 5
29470411 2018
35
Atrial septal defect in a patient with congenital disorder of glycosylation type 1a: a case report. 62 5
29361989 2018
36
A novel PMCA3 mutation in an ataxic patient with hypomorphic phosphomannomutase 2 (PMM2) heterozygote mutations: Biochemical characterization of the pump defect. 62 5
28807751 2017
37
A quantitative assessment of the evolution of cerebellar syndrome in children with phosphomannomutase-deficiency (PMM2-CDG). 62 5
28915903 2017
38
Polycystic Kidney Disease with Hyperinsulinemic Hypoglycemia Caused by a Promoter Mutation in Phosphomannomutase 2. 62 5
28373276 2017
39
Three families with mild PMM2-CDG and normal cognitive development. 62 5
28425223 2017
40
A Population-Based Study on Congenital Disorders of Protein N- and Combined with O-Glycosylation Experience in Clinical and Genetic Diagnosis. 62 5
28139241 2017
41
Phenotypic and genotypic spectrum of congenital disorders of glycosylation type I and type II. 62 5
28122681 2017
42
Liver involvement in congenital disorders of glycosylation (CDG). A systematic review of the literature. 62 57
28108845 2017
43
A mouse model of a human congenital disorder of glycosylation caused by loss of PMM2. 62 5
27053713 2016
44
Natural Killer Cell Receptors and Cytotoxic Activity in Phosphomannomutase 2 Deficiency (PMM2-CDG). 62 5
27415628 2016
45
Phosphomannomutase deficiency (PMM2-CDG): ataxia and cerebellar assessment. 62 5
26502900 2015
46
The Effects of PMM2-CDG-Causing Mutations on the Folding, Activity, and Stability of the PMM2 Protein. 62 5
26014514 2015
47
Application of whole exome sequencing to a rare inherited metabolic disease with neurological and gastrointestinal manifestations: a congenital disorder of glycosylation mimicking glycogen storage disease. 62 5
25681648 2015
48
A nationwide survey of PMM2-CDG in Italy: high frequency of a mild neurological variant associated with the L32R mutation. 62 5
25355454 2015
49
Heterodimerization of Two Pathological Mutants Enhances the Activity of Human Phosphomannomutase2. 62 5
26488408 2015
50
29 French adult patients with PMM2-congenital disorder of glycosylation: outcome of the classical pediatric phenotype and depiction of a late-onset phenotype. 62 5
25497157 2014

Variations for Congenital Disorder of Glycosylation, Type Ia

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

5 (show top 50) (show all 422)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 PMM2 NM_000303.3(PMM2):c.193G>T (p.Asp65Tyr) SNV Pathogenic
7710 rs104894527 GRCh37: 16:8898638-8898638
GRCh38: 16:8804781-8804781
2 PMM2 NM_000303.3(PMM2):c.669C>G (p.Asp223Glu) SNV Pathogenic
7714 rs104894531 GRCh37: 16:8941610-8941610
GRCh38: 16:8847753-8847753
3 PMM2 PMM2, 28-KB DEL DEL Pathogenic
7726 GRCh37:
GRCh38:
4 PMM2 NM_000303.3(PMM2):c.355T>C (p.Phe119Leu) SNV Pathogenic
371231 rs1057517110 GRCh37: 16:8904943-8904943
GRCh38: 16:8811086-8811086
5 overlap with 3 genes NC_000016.10:g.(?_8779459)_(8847845_?)del DEL Pathogenic
661750 GRCh37: 16:8873316-8941702
GRCh38: 16:8779459-8847845
6 PMM2 NM_000303.3(PMM2):c.394A>T (p.Ile132Phe) SNV Pathogenic
818203 rs753632453 GRCh37: 16:8904982-8904982
GRCh38: 16:8811125-8811125
7 PMM2 NC_000016.10:g.(?_8804742)_(8813116_?)del DEL Pathogenic
830598 GRCh37: 16:8898599-8906973
GRCh38:
8 PMM2 NC_000016.10:g.(?_8797873)_(8813116_?)del DEL Pathogenic
639371 GRCh37: 16:8891730-8906973
GRCh38: 16:8797873-8813116
9 PMM2 NC_000016.9:g.(?_8895646)_(8895777_?)del DEL Pathogenic
1074658 GRCh37: 16:8895646-8895777
GRCh38:
10 PMM2 NM_000303.3(PMM2):c.451G>T (p.Glu151Ter) SNV Pathogenic
1358766 GRCh37: 16:8905498-8905498
GRCh38: 16:8811641-8811641
11 PMM2 NC_000016.9:g.(?_8891573)_(8895787_?)del DEL Pathogenic
1363954 GRCh37: 16:8891573-8895787
GRCh38:
12 PMM2 NM_000303.3(PMM2):c.59del (p.Pro20fs) DEL Pathogenic
1367452 GRCh37: 16:8891795-8891795
GRCh38: 16:8797938-8797938
13 PMM2 NC_000016.9:g.(?_8891730)_(8926102_?)del DEL Pathogenic
1457401 GRCh37: 16:8891730-8926102
GRCh38:
14 PMM2 NM_000303.3(PMM2):c.16_22del (p.Pro6fs) DEL Pathogenic
1393525 GRCh37: 16:8891753-8891759
GRCh38: 16:8797896-8797902
15 PMM2 NM_000303.3(PMM2):c.377_381del (p.Met126fs) DEL Pathogenic
1072362 GRCh37: 16:8904964-8904968
GRCh38: 16:8811107-8811111
16 PMM2 NM_000303.3(PMM2):c.73dup (p.Thr25fs) DUP Pathogenic
1072807 GRCh37: 16:8895661-8895662
GRCh38: 16:8801804-8801805
17 PMM2 NM_000303.3(PMM2):c.457dup (p.Ile153fs) DUP Pathogenic
1073046 GRCh37: 16:8905503-8905504
GRCh38: 16:8811646-8811647
18 PMM2 NM_000303.3(PMM2):c.66+1G>A SNV Pathogenic
1073938 GRCh37: 16:8891806-8891806
GRCh38: 16:8797949-8797949
19 PMM2 NM_000303.3(PMM2):c.264_265del (p.His90fs) DEL Pathogenic
1075469 GRCh37: 16:8900180-8900181
GRCh38: 16:8806323-8806324
20 PMM2 NM_000303.3(PMM2):c.256-1G>C SNV Pathogenic
7727 rs757394782 GRCh37: 16:8900172-8900172
GRCh38: 16:8806315-8806315
21 PMM2 NM_000303.3(PMM2):c.95_96delinsGC (p.Leu32Arg) INDEL Pathogenic
92807 rs398123312 GRCh37: 16:8895684-8895685
GRCh38: 16:8801827-8801828
22 PMM2 NM_000303.3(PMM2):c.488_491del (p.Lys163fs) DEL Pathogenic
970523 rs2060678732 GRCh37: 16:8905533-8905536
GRCh38: 16:8811676-8811679
23 PMM2 NC_000016.10:g.(?_8804742)_(8813126_?)del DEL Pathogenic
530391 GRCh37: 16:8898599-8906983
GRCh38: 16:8804742-8813126
24 PMM2 NM_000303.3(PMM2):c.463C>T (p.Gln155Ter) SNV Pathogenic
656436 rs754407762 GRCh37: 16:8905510-8905510
GRCh38: 16:8811653-8811653
25 PMM2 NM_000303.3(PMM2):c.-167G>T SNV Pathogenic
656718 rs1596481676 GRCh37: 16:8891573-8891573
GRCh38: 16:8797716-8797716
26 PMM2 NM_000303.3(PMM2):c.55del (p.Ala19fs) DEL Pathogenic
659079 rs1596481889 GRCh37: 16:8891794-8891794
GRCh38: 16:8797937-8797937
27 PMM2 NC_000016.10:g.(?_8847701)_(8847835_?)del DEL Pathogenic
662283 GRCh37: 16:8941558-8941692
GRCh38: 16:8847701-8847835
28 PMM2 NC_000016.10:g.(?_8811069)_(8832245_?)del DEL Pathogenic
666215 GRCh37: 16:8904926-8926102
GRCh38: 16:8811069-8832245
29 PMM2 NM_000303.3(PMM2):c.97C>T (p.Gln33Ter) SNV Pathogenic
803211 rs149530060 GRCh37: 16:8895686-8895686
GRCh38: 16:8801829-8801829
30 PMM2 NC_000016.10:g.(?_8797873)_(8797958_?)del DEL Pathogenic
830581 GRCh37: 16:8891730-8891815
GRCh38:
31 PMM2 NC_000016.10:g.(?_8804742)_(8806417_?)del DEL Pathogenic
830700 GRCh37: 16:8898599-8900274
GRCh38:
32 PMM2 NC_000016.10:g.(?_8804742)_(8804853_?)del DEL Pathogenic
830707 GRCh37: 16:8898599-8898710
GRCh38:
33 PMM2 NC_000016.10:g.(?_8797873)_(8847835_?)del DEL Pathogenic
832784 GRCh37: 16:8891730-8941692
GRCh38:
34 PMM2 NM_000303.3(PMM2):c.561G>A (p.Trp187Ter) SNV Pathogenic
854121 rs201855351 GRCh37: 16:8906885-8906885
GRCh38: 16:8813028-8813028
35 PMM2 NM_000303.3(PMM2):c.72del (p.Thr25fs) DEL Pathogenic
1070199 GRCh37: 16:8895660-8895660
GRCh38: 16:8801803-8801803
36 PMM2 NM_000303.3(PMM2):c.201_202del (p.Phe68fs) MICROSAT Pathogenic
1076104 GRCh37: 16:8898643-8898644
GRCh38: 16:8804786-8804787
37 PMM2 NM_000303.3(PMM2):c.255+2T>C SNV Pathogenic
321216 rs139716296 GRCh37: 16:8898702-8898702
GRCh38: 16:8804845-8804845
38 PMM2 NM_000303.3(PMM2):c.556G>A (p.Gly186Arg) SNV Pathogenic
1693595 GRCh37: 16:8906880-8906880
GRCh38: 16:8813023-8813023
39 PMM2 NM_000303.3(PMM2):c.324del (p.Ile110fs) DEL Pathogenic
503676 rs1555449314 GRCh37: 16:8900241-8900241
GRCh38: 16:8806384-8806384
40 PMM2 NM_000303.3(PMM2):c.548T>C (p.Phe183Ser) SNV Pathogenic
651739 rs780581250 GRCh37: 16:8906872-8906872
GRCh38: 16:8813015-8813015
41 PMM2 NM_000303.3(PMM2):c.367C>T (p.Arg123Ter) SNV Pathogenic
429981 rs191295403 GRCh37: 16:8904955-8904955
GRCh38: 16:8811098-8811098
42 PMM2 NM_000303.3(PMM2):c.160dup (p.Glu54fs) DUP Pathogenic
929131 rs753122961 GRCh37: 16:8895747-8895748
GRCh38: 16:8801890-8801891
43 PMM2 NM_000303.3(PMM2):c.385G>T (p.Val129Leu) SNV Pathogenic
1068915 GRCh37: 16:8904973-8904973
GRCh38: 16:8811116-8811116
44 PMM2 NM_000303.3(PMM2):c.243_244del (p.Leu82fs) MICROSAT Pathogenic
1069079 GRCh37: 16:8898686-8898687
GRCh38: 16:8804829-8804830
45 PMM2 NM_000303.3(PMM2):c.458_462del (p.Ile153fs) DEL Pathogenic
1072868 GRCh37: 16:8905504-8905508
GRCh38: 16:8811647-8811651
46 PMM2 NM_000303.3(PMM2):c.523+1del DEL Pathogenic
1440145 GRCh37: 16:8905570-8905570
GRCh38: 16:8811713-8811713
47 PMM2 NM_000303.3(PMM2):c.696del (p.Ala233fs) DEL Pathogenic
1342149 GRCh37: 16:8941637-8941637
GRCh38: 16:8847780-8847780
48 PMM2 NM_000303.3(PMM2):c.422G>A (p.Arg141His) SNV Pathogenic
7706 rs28936415 GRCh37: 16:8905010-8905010
GRCh38: 16:8811153-8811153
49 PMM2 NM_000303.3(PMM2):c.357C>A (p.Phe119Leu) SNV Pathogenic
7711 rs80338701 GRCh37: 16:8904945-8904945
GRCh38: 16:8811088-8811088
50 PMM2 NM_000303.3(PMM2):c.722G>C (p.Cys241Ser) SNV Pathogenic
7717 rs80338709 GRCh37: 16:8941663-8941663
GRCh38: 16:8847806-8847806

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

73 (show top 50) (show all 66)
# Symbol AA change Variation ID SNP ID
1 PMM2 p.Val44Ala VAR_006093 rs104894534
2 PMM2 p.Asp65Tyr VAR_006094 rs104894527
3 PMM2 p.Asn101Lys VAR_006095 rs769839273
4 PMM2 p.Tyr106Cys VAR_006096 rs387906824
5 PMM2 p.Ala108Val VAR_006097 rs200503569
6 PMM2 p.Pro113Leu VAR_006098 rs80338700
7 PMM2 p.Gly117Arg VAR_006099 rs104894530
8 PMM2 p.Phe119Leu VAR_006100 rs80338701
9 PMM2 p.Arg123Gln VAR_006101 rs141498002
10 PMM2 p.Val129Met VAR_006102 rs104894525
11 PMM2 p.Pro131Ala VAR_006103 rs1274547742
12 PMM2 p.Ile132Thr VAR_006104 rs80338702
13 PMM2 p.Arg141His VAR_006105 rs28936415
14 PMM2 p.Arg162Trp VAR_006106 rs104894526
15 PMM2 p.Gly175Arg VAR_006107 rs941830625
16 PMM2 p.Asp188Gly VAR_006108 rs80338704
17 PMM2 p.Gly208Ala VAR_006109 rs398123309
18 PMM2 p.Asn216Ile VAR_006110 rs78290141
19 PMM2 p.Asp223Glu VAR_006111 rs104894531
20 PMM2 p.Tyr229Ser VAR_006112 rs398123311
21 PMM2 p.Val231Met VAR_006113 rs80338707
22 PMM2 p.Thr237Met VAR_006115 rs80338708
23 PMM2 p.Arg238Pro VAR_006116 rs151319324
24 PMM2 p.Glu139Lys VAR_009232 rs80338703
25 PMM2 p.Leu104Val VAR_012344 rs770458492
26 PMM2 p.Cys9Tyr VAR_022469 rs104894532
27 PMM2 p.Phe11Cys VAR_022470
28 PMM2 p.Gly15Glu VAR_022471
29 PMM2 p.Pro20Ser VAR_022472 rs949271895
30 PMM2 p.Leu32Arg VAR_022473 rs398123312
31 PMM2 p.Gln37His VAR_022474
32 PMM2 p.Tyr64Cys VAR_022476
33 PMM2 p.Val67Met VAR_022477 rs1318611010
34 PMM2 p.Pro69Ser VAR_022478 rs769648248
35 PMM2 p.Tyr76Cys VAR_022479 rs1440183322
36 PMM2 p.Glu93Ala VAR_022480
37 PMM2 p.Cys103Phe VAR_022481
38 PMM2 p.Ile120Thr VAR_022482 rs368582085
39 PMM2 p.Ile132Phe VAR_022483 rs753632453
40 PMM2 p.Ile132Asn VAR_022484
41 PMM2 p.Arg141Cys VAR_022485 rs746610168
42 PMM2 p.Phe144Leu VAR_022486 rs150719105
43 PMM2 p.Asp148Asn VAR_022487 rs148032587
44 PMM2 p.Glu151Gly VAR_022488
45 PMM2 p.Ile153Thr VAR_022489 rs150577656
46 PMM2 p.Phe157Ser VAR_022490 rs190521996
47 PMM2 p.Phe172Val VAR_022491
48 PMM2 p.Gly176Val VAR_022492
49 PMM2 p.Gln177His VAR_022493
50 PMM2 p.Phe183Ser VAR_022494 rs780581250

Expression for Congenital Disorder of Glycosylation, Type Ia

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

Pathways for Congenital Disorder of Glycosylation, Type Ia

Pathways related to Congenital Disorder of Glycosylation, Type Ia according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.29 TF SERPINC1 PMM2 PMM1 NEU1 MPI
2
Show member pathways
12.53 PMM2 PMM1 NEU1 MPI ALG6
3
Show member pathways
12.27 PMM2 NEU1 MPI ALG6
4
Show member pathways
12 SERPINC1 F9 CLU
5
Show member pathways
11.34 PMM2 PMM1 NEU1 MPI ALG6

GO Terms for Congenital Disorder of Glycosylation, Type Ia

Cellular components related to Congenital Disorder of Glycosylation, Type Ia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular exosome GO:0070062 9.8 TF SERPINC1 SERPINA7 NEU1 MPI F9
2 blood microparticle GO:0072562 9.1 TF SERPINC1 CLU

Biological processes related to Congenital Disorder of Glycosylation, Type Ia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 positive regulation of receptor-mediated endocytosis GO:0048260 9.56 TF CLU
2 mannose metabolic process GO:0006013 9.46 PMM2 PMM1
3 protein N-linked glycosylation GO:0006487 9.43 PMM2 PMM1 ALG6
4 hemostasis GO:0007599 9.32 SERPINC1 F9
5 GDP-mannose biosynthetic process GO:0009298 9.1 PMM2 PMM1 MPI

Molecular functions related to Congenital Disorder of Glycosylation, Type Ia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 isomerase activity GO:0016853 9.13 PMM2 PMM1 MPI
2 phosphomannomutase activity GO:0004615 8.92 PMM2 PMM1

Sources for Congenital Disorder of Glycosylation, Type Ia

2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 24-Oct-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
Content
Loading form....