MCID: CNG197
MIFTS: 35

Congenital Disorder of Glycosylation, Type Ih

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

Aliases & Classifications for Congenital Disorder of Glycosylation, Type Ih

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

Name: Congenital Disorder of Glycosylation, Type Ih 57 13
Congenital Disorder of Glycosylation Type 1h 59 29 6 73
Cdg1h 57 59 75
Congenital Disorder of Glycosylation Type Ih 59 75
Cdg Ih 57 75
Cdg-Ih 59 75
Cdgih 57 75
Carbohydrate Deficient Glycoprotein Syndrome Type Ih 59
Glycosylation, Congenital Disorder of, Type Ih 40
Congenital Disorder of Glycosylation 1h 75
Glucosyltransferase 2 Deficiency 59
Cdg Syndrome Type Ih 59
Cdg Ih; Cdgih 57
Alg8-Cdg 59

Characteristics:

Orphanet epidemiological data:

59
alg8-cdg
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal; Age of death: early childhood,infantile;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
onset in early infancy
death may occur in infancy
variable phenotype and severity
hepato/intestinal features are the most severe abnormalities
patient a had a mild disease course with survival and no neurologic involvement at age 3 years
four patients, including 2 sibs, have been reported (last curated january 2018)


Classifications:



External Ids:

OMIM 57 608104
Orphanet 59 ORPHA79325
ICD10 via Orphanet 34 E77.8
UMLS via Orphanet 74 C2931002
MeSH 44 D018981
UMLS 73 C2931002

Summaries for Congenital Disorder of Glycosylation, Type Ih

OMIM : 57 CDGs, previously called carbohydrate-deficient glycoprotein syndromes, grew from hereditary multisystem disorders first recognized by Jaeken et al. (1980). The characteristic biochemical abnormality of CDGs is the hypoglycosylation of glycoproteins, which is routinely determined by isoelectric focusing of serum transferrin. Type I CDG comprises those disorders in which there is a defect in the assembly of lipid-linked oligosaccharides or their transfer onto nascent glycoproteins, whereas type II CDG comprises defects of trimming, elongation, and processing of protein-bound glycans. For a general discussion of CDGs, see CDG1A (212065). CDG1H is a severe form of CDG. The majority of patients have brain involvement, liver pathology, gastrointestinal symptoms, dysmorphism (including brachydactyly), eye involvement (especially cataract), and skin symptoms. Most patients die within the first year of life (summary by Marques-da-Silva et al., 2017). (608104)

MalaCards based summary : Congenital Disorder of Glycosylation, Type Ih, also known as congenital disorder of glycosylation type 1h, is related to congenital disorder of glycosylation, type in. An important gene associated with Congenital Disorder of Glycosylation, Type Ih is ALG8 (ALG8, Alpha-1,3-Glucosyltransferase), and among its related pathways/superpathways are Transport to the Golgi and subsequent modification and Synthesis of substrates in N-glycan biosythesis. Affiliated tissues include liver, eye and brain, and related phenotypes are abnormality of the renal tubule and cataract

UniProtKB/Swiss-Prot : 75 Congenital disorder of glycosylation 1H: 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.

Related Diseases for Congenital Disorder of Glycosylation, Type Ih

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 Ih via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 congenital disorder of glycosylation, type in 10.2

Symptoms & Phenotypes for Congenital Disorder of Glycosylation, Type Ih

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
hypertelorism
retinal abnormalities, mild (patient a)

Head And Neck Neck:
short neck

Growth Other:
failure to thrive
intrauterine growth retardation

Abdomen Gastrointestinal:
vomiting
diarrhea
protein-losing enteropathy

Hematology:
anemia
thrombocytopenia
coagulation defects due to liver disease

Cardiovascular Heart:
patent ductus arteriosus
congenital heart defects (in some patients)
septal defects

Prenatal Manifestations Amniotic Fluid:
oligohydramnios

Skeletal Hands:
camptodactyly

Skeletal Feet:
club feet

Prenatal Manifestations Movement:
reduced fetal movements

Genitourinary Kidneys:
renal tubulopathy (in some patients)
renal microcysts

Head And Neck Ears:
low-set ears

Endocrine Features:
hypothyroidism

Abdomen Liver:
hepatomegaly
cholestasis
liver dysfunction
microcysts in the liver

Muscle Soft Tissue:
ascites
hypotonia

Head And Neck Face:
long philtrum
dysmorphic facial features (in some patients)

Genitourinary External Genitalia Male:
cryptorchidism

Laboratory Abnormalities:
hypoalbuminemia
abnormal isoelectric focusing of serum transferrin, consistent with cdg type i
hypoglycosylation of serum glycoproteins
electrolyte disturbances

Head And Neck Head:
large fontanel

Skeletal Skull:
asymmetric skull

Abdomen External Features:
abdominal distension

Neurologic Central Nervous System:
no central nervous system abnormalities


Clinical features from OMIM:

608104

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

59 32
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 abnormality of the renal tubule 59 32 hallmark (90%) Very frequent (99-80%) HP:0000091
2 cataract 59 32 frequent (33%) Frequent (79-30%) HP:0000518
3 lymphedema 59 32 hallmark (90%) Very frequent (99-80%) HP:0001004
4 hepatic failure 59 32 hallmark (90%) Very frequent (99-80%) HP:0001399

Drugs & Therapeutics for Congenital Disorder of Glycosylation, Type Ih

Search Clinical Trials , NIH Clinical Center for Congenital Disorder of Glycosylation, Type Ih

Genetic Tests for Congenital Disorder of Glycosylation, Type Ih

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

# Genetic test Affiliating Genes
1 Congenital Disorder of Glycosylation Type 1h 29 ALG8

Anatomical Context for Congenital Disorder of Glycosylation, Type Ih

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

41
Liver, Eye, Brain, Skin, Heart

Publications for Congenital Disorder of Glycosylation, Type Ih

Articles related to Congenital Disorder of Glycosylation, Type Ih:

# Title Authors Year
1
Novel ALG8 mutations expand the clinical spectrum of congenital disorder of glycosylation type Ih. ( 19648040 )
2009
2
Clinical and molecular features of three patients with congenital disorders of glycosylation type Ih (CDG-Ih) (ALG8 deficiency). ( 15235028 )
2004

Variations for Congenital Disorder of Glycosylation, Type Ih

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

75
# Symbol AA change Variation ID SNP ID
1 ALG8 p.Thr47Pro VAR_023480 rs121908293
2 ALG8 p.Gly275Asp VAR_023482 rs121908294

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

6
(show all 26)
# Gene Variation Type Significance SNP ID Assembly Location
1 ALG8 NM_024079.4(ALG8): c.413delC (p.Thr138Lysfs) deletion Pathogenic rs387906277 GRCh37 Chromosome 11, 77832176: 77832176
2 ALG8 NM_024079.4(ALG8): c.413delC (p.Thr138Lysfs) deletion Pathogenic rs387906277 GRCh38 Chromosome 11, 78121130: 78121130
3 ALG8 NM_024079.4(ALG8): c.396dup (p.Val133Serfs) duplication Pathogenic GRCh37 Chromosome 11, 77832193: 77832193
4 ALG8 NM_024079.4(ALG8): c.396dup (p.Val133Serfs) duplication Pathogenic GRCh38 Chromosome 11, 78121147: 78121147
5 ALG8 NM_024079.4(ALG8): c.96-2A> G single nucleotide variant Pathogenic GRCh38 Chromosome 11, 78127438: 78127438
6 ALG8 NM_024079.4(ALG8): c.96-2A> G single nucleotide variant Pathogenic GRCh37 Chromosome 11, 77838484: 77838484
7 ALG8 NM_024079.4(ALG8): c.139A> C (p.Thr47Pro) single nucleotide variant Pathogenic rs121908293 GRCh37 Chromosome 11, 77838439: 77838439
8 ALG8 NM_024079.4(ALG8): c.139A> C (p.Thr47Pro) single nucleotide variant Pathogenic rs121908293 GRCh38 Chromosome 11, 78127393: 78127393
9 ALG8 NM_024079.4(ALG8): c.673+4A> G single nucleotide variant Pathogenic GRCh38 Chromosome 11, 78114262: 78114262
10 ALG8 NM_024079.4(ALG8): c.673+4A> G single nucleotide variant Pathogenic GRCh37 Chromosome 11, 77825308: 77825308
11 ALG8 NM_024079.4(ALG8): c.824G> A (p.Gly275Asp) single nucleotide variant Pathogenic rs121908294 GRCh37 Chromosome 11, 77823770: 77823770
12 ALG8 NM_024079.4(ALG8): c.824G> A (p.Gly275Asp) single nucleotide variant Pathogenic rs121908294 GRCh38 Chromosome 11, 78112724: 78112724
13 ALG8 NM_024079.4(ALG8): c.121C> T (p.Arg41Ter) single nucleotide variant Pathogenic rs200888240 GRCh37 Chromosome 11, 77838457: 77838457
14 ALG8 NM_024079.4(ALG8): c.121C> T (p.Arg41Ter) single nucleotide variant Pathogenic rs200888240 GRCh38 Chromosome 11, 78127411: 78127411
15 ALG8 NM_001007027.2(ALG8): c.1316T> C (p.Ile439Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs17825668 GRCh37 Chromosome 11, 77815059: 77815059
16 ALG8 NM_001007027.2(ALG8): c.1316T> C (p.Ile439Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs17825668 GRCh38 Chromosome 11, 78104013: 78104013
17 ALG8 NM_024079.4(ALG8): c.856T> G (p.Trp286Gly) single nucleotide variant Conflicting interpretations of pathogenicity rs794727931 GRCh37 Chromosome 11, 77823738: 77823738
18 ALG8 NM_024079.4(ALG8): c.856T> G (p.Trp286Gly) single nucleotide variant Conflicting interpretations of pathogenicity rs794727931 GRCh38 Chromosome 11, 78112692: 78112692
19 ALG8 NM_001007027.2(ALG8): c.96-6G> C single nucleotide variant Conflicting interpretations of pathogenicity rs199911532 GRCh37 Chromosome 11, 77838488: 77838488
20 ALG8 NM_001007027.2(ALG8): c.96-6G> C single nucleotide variant Conflicting interpretations of pathogenicity rs199911532 GRCh38 Chromosome 11, 78127442: 78127442
21 ALG8 NM_024079.4(ALG8): c.1090C> T (p.Arg364Ter) single nucleotide variant Pathogenic rs376161880 GRCh37 Chromosome 11, 77817941: 77817941
22 ALG8 NM_024079.4(ALG8): c.1090C> T (p.Arg364Ter) single nucleotide variant Pathogenic rs376161880 GRCh38 Chromosome 11, 78106895: 78106895
23 ALG8 NM_024079.4(ALG8): c.896T> C (p.Ile299Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs61995922 GRCh38 Chromosome 11, 78112652: 78112652
24 ALG8 NM_024079.4(ALG8): c.896T> C (p.Ile299Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs61995922 GRCh37 Chromosome 11, 77823698: 77823698
25 ALG8 NM_024079.4(ALG8): c.1285A> G (p.Ile429Val) single nucleotide variant Uncertain significance rs200068321 GRCh38 Chromosome 11, 78104044: 78104044
26 ALG8 NM_024079.4(ALG8): c.1285A> G (p.Ile429Val) single nucleotide variant Uncertain significance rs200068321 GRCh37 Chromosome 11, 77815090: 77815090

Expression for Congenital Disorder of Glycosylation, Type Ih

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

Pathways for Congenital Disorder of Glycosylation, Type Ih

GO Terms for Congenital Disorder of Glycosylation, Type Ih

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

# Name GO ID Score Top Affiliating Genes
1 endoplasmic reticulum membrane GO:0005789 8.62 ALG2 ALG8

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

# Name GO ID Score Top Affiliating Genes
1 protein glycosylation GO:0006486 9.26 ALG2 ALG8
2 mannosylation GO:0097502 9.16 ALG2 ALG8
3 dolichol-linked oligosaccharide biosynthetic process GO:0006488 8.96 ALG2 ALG8
4 oligosaccharide-lipid intermediate biosynthetic process GO:0006490 8.62 ALG2 ALG8

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

# Name GO ID Score Top Affiliating Genes
1 transferase activity, transferring glycosyl groups GO:0016757 8.96 ALG2 ALG8
2 alpha-1,3-mannosyltransferase activity GO:0000033 8.62 ALG2 ALG8

Sources for Congenital Disorder of Glycosylation, Type Ih

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74 UMLS via Orphanet
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