Details of Disease

Disease Name

Congenital disorder of glycosylation

carbohydrate-deficient glycoprotein syndromes; congenital disorders of glycosylation; carbohydrate deficient glycoprotein syndrome; congenital disorder of glycosylation; CDG; carbohydrate-deficient glycoprotein syndrome

Definition

Congenital disorder of glycosylation (CDG) is a fast growing group of inborn errors of metabolism characterized by defective activity of enzymes that participate in glycosylation (modification of proteins and other macromolecules by adding and processing of oligosaccharide side chains). CDG is comprised of phenotypically diverse disorders affecting multiple systems including the central nervous system, muscle function, immunity, endocrine system, and coagulation. The numerous entities in this group are subdivided, based on the synthetic pathway affected, into disorder of protein N-glycosylation, disorder of protein O-glycosylation, disorder of multiple glycosylation, and disorder of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation.

Disease Hierarchy

DIS808M4: Disorder of glycosylation

DISO5FAY: Inborn error of metabolism

DIS400QP: Congenital disorder of glycosylation

Disease Identifiers

MONDO ID

MONDO_0015286

MESH ID

D018981

UMLS CUI

C0282577

MedGen ID

76469

Orphanet ID

137

SNOMED CT ID

238049009

General Information of Disease (ID: DIS400QP)

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 10 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
ALPI	TTHYMUV	Strong	Genetic Variation	[1]
APOC3	TTXOZQ1	Strong	Biomarker	[2]
ATP6AP1	TTWDM4U	Strong	Genetic Variation	[3]
ATXN3	TT6A17J	Strong	Altered Expression	[4]
F11	TTDM4ZU	Strong	Biomarker	[5]
IAPP	TTHN8EM	Strong	Genetic Variation	[1]
MGAM	TTXWASR	Strong	Genetic Variation	[6]
MGAT2	TTJOW1I	Strong	Genetic Variation	[7]
SERPINA6	TTJL8VG	Strong	Altered Expression	[8]
ST3GAL5	TTVF2BJ	Strong	Genetic Variation	[9]
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⏷ Show the Full List of 10 DTT(s)

This Disease Is Related to 6 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC35C1	DT3LZWR	Limited	Biomarker	[10]
SLC35A1	DTVZIRG	moderate	Biomarker	[11]
SLC26A3	DTN1FMD	Strong	Altered Expression	[12]
SLC35A2	DT0567K	Strong	Genetic Variation	[13]
SLC35A3	DTB930Q	Strong	Genetic Variation	[14]
SLC39A8	DTLPQGT	Strong	Biomarker	[15]
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⏷ Show the Full List of 6 DTP(s)

This Disease Is Related to 3 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
PGM1	DEA3VM1	Strong	Genetic Variation	[16]
PGM3	DER0EN5	Strong	Biomarker	[10]
SRD5A3	DEZGVDW	Strong	Genetic Variation	[17]
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This Disease Is Related to 54 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ALG1	OTVXPA9E	Limited	Genetic Variation	[7]
ALG14	OTBM7K28	Limited	Autosomal recessive	[18]
DPM3	OTSB4XO0	Limited	Biomarker	[19]
ST3GAL3	OTOORKUE	Limited	Genetic Variation	[20]
FCSK	OT4NTHYO	moderate	Biomarker	[21]
MOGS	OT99MBGB	moderate	Genetic Variation	[22]
AGA	OTNWT1WB	Strong	Biomarker	[23]
ALG11	OTTXM241	Strong	Genetic Variation	[24]
ALG12	OTVAT4OJ	Strong	Biomarker	[25]
ALG13	OTOH9PMY	Strong	Genetic Variation	[26]
ALG2	OT77B384	Strong	Genetic Variation	[27]
ALG3	OTPOL1QW	Strong	Genetic Variation	[28]
ALG8	OTMFG2YY	Strong	Genetic Variation	[7]
ALG9	OT5V9PIR	Strong	Genetic Variation	[7]
ALPP	OTZU4G9W	Strong	Genetic Variation	[1]
ATP6V0A2	OTJBDX0Y	Strong	Genetic Variation	[29]
B4GALT1	OTBCXEK7	Strong	Biomarker	[30]
CCDC115	OT04AZNZ	Strong	Biomarker	[31]
COG2	OTKQH4N4	Strong	Genetic Variation	[32]
COG5	OTZEG7K0	Strong	Genetic Variation	[33]
COG6	OTDLQITC	Strong	Genetic Variation	[7]
COG7	OTCV4JC1	Strong	Biomarker	[34]
COG8	OTDEA7YO	Strong	Biomarker	[35]
CSGALNACT1	OTBML9D9	Strong	Biomarker	[36]
DDOST	OT39PDMS	Strong	Genetic Variation	[37]
DHDDS	OTVLYBUS	Strong	Biomarker	[38]
DOLK	OT2HTIAN	Strong	Biomarker	[39]
DPAGT1	OTYEJAGZ	Strong	Genetic Variation	[40]
DPM1	OTXRRVGT	Strong	Biomarker	[41]
DPM2	OTDERBWM	Strong	Biomarker	[42]
FUT8	OTJJCVG1	Strong	Biomarker	[43]
GOLPH3	OTDLGYM3	Strong	Altered Expression	[34]
GRIN3A	OTQS9GYY	Strong	Genetic Variation	[44]
LAD1	OT6YGTVX	Strong	Biomarker	[45]
LEMD3	OTILAM4I	Strong	Genetic Variation	[46]
MAGT1	OTQSAV5C	Strong	Biomarker	[47]
MAN1A1	OT6LIGJP	Strong	Biomarker	[48]
MAN1B1	OTI780UB	Strong	Genetic Variation	[49]
MPDU1	OT27UPHN	Strong	Genetic Variation	[50]
MPI	OTBH6ZK1	Strong	Biomarker	[39]
NUS1	OT4DQ82L	Strong	Genetic Variation	[51]
PGAP1	OT1WQ55V	Strong	Biomarker	[52]
POFUT2	OT1MNJFZ	Strong	Genetic Variation	[53]
PYCR1	OTQHB52T	Strong	Biomarker	[54]
RAB1A	OTKPHRD0	Strong	Altered Expression	[34]
RFT1	OTW82NET	Strong	Biomarker	[55]
RNASE4	OTA5SZLC	Strong	Altered Expression	[34]
RXYLT1	OTQTO7VU	Strong	Biomarker	[38]
SSR3	OTJQP0IZ	Strong	Biomarker	[56]
SSR4	OTBWBGMR	Strong	Genetic Variation	[57]
STT3A	OTDPS6AV	Strong	Genetic Variation	[58]
STT3B	OTRLJTF0	Strong	Biomarker	[59]
TRAPPC11	OTPZYXGA	Strong	Genetic Variation	[60]
PGAP3	OTH9A75E	Definitive	Biomarker	[61]
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⏷ Show the Full List of 54 DOT(s)

References

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2	MALDI-MS profiling of serum O-glycosylation and N-glycosylation in COG5-CDG.J Mass Spectrom. 2017 Jun;52(6):372-377. doi: 10.1002/jms.3936.
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5	Hypoglycosylation is a common finding in antithrombin deficiency in the absence of a SERPINC1 gene defect.J Thromb Haemost. 2016 Aug;14(8):1549-60. doi: 10.1111/jth.13372. Epub 2016 Jun 29.
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15	SLC39A8 deficiency: biochemical correction and major clinical improvement by manganese therapy.Genet Med. 2018 Feb;20(2):259-268. doi: 10.1038/gim.2017.106. Epub 2017 Jul 27.
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17	Review of SRD5A3 Disease-Causing Sequence Variants and Ocular Findings in Steroid 5-Reductase Type 3 Congenital Disorder of Glycosylation, and a Detailed New Case.Folia Biol (Praha). 2019;65(3):134-141.
18	Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
19	Toward understanding tissue-specific symptoms in dolichol-phosphate-mannose synthesis disorders; insight from DPM3-CDG.J Inherit Metab Dis. 2019 Sep;42(5):984-992. doi: 10.1002/jimd.12095. Epub 2019 Apr 23.
20	A novel nonsense and inactivating variant of ST3GAL3 in two infant siblings suffering severe epilepsy and expressing circulating CA19.9.Glycobiology. 2020 Jan 28;30(2):95-104. doi: 10.1093/glycob/cwz079.
21	Pathogenic Variants in Fucokinase Cause a Congenital Disorder of Glycosylation. Am J Hum Genet. 2018 Dec 6;103(6):1030-1037. doi: 10.1016/j.ajhg.2018.10.021. Epub 2018 Nov 29.
22	Compound heterozygous variants in MOGS inducing congenital disorders of glycosylation (CDG) IIb.J Hum Genet. 2019 Mar;64(3):265-268. doi: 10.1038/s10038-018-0552-6. Epub 2018 Dec 26.
23	Elevation of plasma aspartylglucosaminidase is a useful marker for the congenital disorders of glycosylation type I (CDG I).J Inherit Metab Dis. 2005;28(6):1197-8. doi: 10.1007/s10545-005-0157-z.
24	Arrest of Fetal Brain Development in ALG11-Congenital Disorder of Glycosylation.Pediatr Neurol. 2019 May;94:64-69. doi: 10.1016/j.pediatrneurol.2018.12.009. Epub 2018 Dec 24.
25	Ocular abnormalities in a patient with congenital disorder of glycosylation type Ig.Ophthalmic Genet. 2019 Dec;40(6):549-552. doi: 10.1080/13816810.2019.1692361. Epub 2019 Nov 19.
26	X chromosome exome sequencing reveals a novel ALG13 mutation in a nonsyndromic intellectual disability family with multiple affected male siblings. Am J Med Genet A. 2014 Jan;164A(1):164-9. doi: 10.1002/ajmg.a.36233.
27	Ten years of screening for congenital disorders of glycosylation in Argentina: case studies and pitfalls.Pediatr Res. 2018 Dec;84(6):837-841. doi: 10.1038/s41390-018-0206-6. Epub 2018 Oct 18.
28	Novel variants and clinical symptoms in four new ALG3-CDG patients, review of the literature, and identification of AAGRP-ALG3 as a novel ALG3 variant with alanine and glycine-rich N-terminus. Hum Mutat. 2019 Jul;40(7):938-951. doi: 10.1002/humu.23764. Epub 2019 May 8.
29	Phenotypic and genotypic spectrum of congenital disorders of glycosylation type I and type II.Mol Genet Metab. 2017 Mar;120(3):235-242. doi: 10.1016/j.ymgme.2016.12.014. Epub 2017 Jan 3.
30	B4GALT1-congenital disorders of glycosylation presents as a non-neurologic glycosylation disorder with hepatointestinal involvement. J Pediatr. 2011 Dec;159(6):1041-3.e2. doi: 10.1016/j.jpeds.2011.08.007. Epub 2011 Sep 13.
31	CCDC115-CDG: A new rare and misleading inherited cause of liver disease.Mol Genet Metab. 2018 Jul;124(3):228-235. doi: 10.1016/j.ymgme.2018.05.002. Epub 2018 May 9.
32	Mutations in COG2 encoding a subunit of the conserved oligomeric golgi complex cause a congenital disorder of glycosylation. Clin Genet. 2015 May;87(5):455-60. doi: 10.1111/cge.12417. Epub 2014 May 24.
33	Novel compound heterozygous COG5 mutations in a Chinese male patient with severe clinical symptoms and type IIi congenital disorder of glycosylation: A case report.Exp Ther Med. 2019 Oct;18(4):2695-2700. doi: 10.3892/etm.2019.7834. Epub 2019 Jul 30.
34	COG7 deficiency in Drosophila generates multifaceted developmental, behavioral and protein glycosylation phenotypes.J Cell Sci. 2017 Nov 1;130(21):3637-3649. doi: 10.1242/jcs.209049. Epub 2017 Sep 7.
35	The first case of antenatal presentation in COG8-congenital disorder of glycosylation with a novel splice site mutation and an extended phenotype.Am J Med Genet A. 2019 Mar;179(3):480-485. doi: 10.1002/ajmg.a.61030. Epub 2019 Jan 28.
36	CSGALNACT1-congenital disorder of glycosylation: A mild skeletal dysplasia with advanced bone age.Hum Mutat. 2020 Mar;41(3):655-667. doi: 10.1002/humu.23952. Epub 2019 Dec 3.
37	DDOST mutations identified by whole-exome sequencing are implicated in congenital disorders of glycosylation. Am J Hum Genet. 2012 Feb 10;90(2):363-8. doi: 10.1016/j.ajhg.2011.12.024. Epub 2012 Feb 2.
38	What is new in CDG?.J Inherit Metab Dis. 2017 Jul;40(4):569-586. doi: 10.1007/s10545-017-0050-6. Epub 2017 May 8.
39	CDG Therapies: From Bench to Bedside.Int J Mol Sci. 2018 Apr 27;19(5):1304. doi: 10.3390/ijms19051304.
40	Congenital glycosylation disorder: a novel presentation of coexisting anterior and posterior segment pathology and its implications in pediatric cataract management.J AAPOS. 2019 Oct;23(5):297-300. doi: 10.1016/j.jaapos.2019.05.004. Epub 2019 May 30.
41	Structural basis for dolichylphosphate mannose biosynthesis.Nat Commun. 2017 Jul 25;8(1):120. doi: 10.1038/s41467-017-00187-2.
42	DPM2-CDG: a muscular dystrophy-dystroglycanopathy syndrome with severe epilepsy. Ann Neurol. 2012 Oct;72(4):550-8. doi: 10.1002/ana.23632.
43	Childhood glaucoma in association with congenital disorder of glycosylation caused by mutations in fucosyltransferase 8.J AAPOS. 2019 Dec;23(6):351-352. doi: 10.1016/j.jaapos.2019.08.272. Epub 2019 Sep 30.
44	N-Glycosylation Regulates the Trafficking and Surface Mobility of GluN3A-Containing NMDA Receptors.Front Mol Neurosci. 2018 Jun 4;11:188. doi: 10.3389/fnmol.2018.00188. eCollection 2018.
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46	N-glycosylation deficiency reduces ICAM-1 induction and impairs inflammatory response.Glycobiology. 2014 Apr;24(4):392-8. doi: 10.1093/glycob/cwu006. Epub 2014 Jan 28.
47	Mutations in MAGT1 lead to a glycosylation disorder with a variable phenotype.Proc Natl Acad Sci U S A. 2019 May 14;116(20):9865-9870. doi: 10.1073/pnas.1817815116. Epub 2019 Apr 29.
48	Novel ALG8 mutations expand the clinical spectrum of congenital disorder of glycosylation type Ih.Mol Genet Metab. 2009 Nov;98(3):305-9. doi: 10.1016/j.ymgme.2009.06.010. Epub 2009 Jun 24.
49	MAN1B-CDG: Novel variants with a distinct phenotype and review of literature.Eur J Med Genet. 2019 Feb;62(2):109-114. doi: 10.1016/j.ejmg.2018.06.011. Epub 2018 Jun 14.
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56	Mutations in the translocon-associated protein complex subunit SSR3 cause a novel congenital disorder of glycosylation.J Inherit Metab Dis. 2019 Sep;42(5):993-997. doi: 10.1002/jimd.12091. Epub 2019 Apr 16.
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59	Construction of green fluorescence protein mutant to monitor STT3B-dependent N-glycosylation.FEBS J. 2018 Mar;285(5):915-928. doi: 10.1111/febs.14375. Epub 2018 Jan 11.
60	Mutations in TRAPPC11 are associated with a congenital disorder of glycosylation.Hum Mutat. 2017 Feb;38(2):148-151. doi: 10.1002/humu.23145. Epub 2016 Nov 26.
61	Mutations in PGAP3 impair GPI-anchor maturation, causing a subtype of hyperphosphatasia with mental retardation. Am J Hum Genet. 2014 Feb 6;94(2):278-87. doi: 10.1016/j.ajhg.2013.12.012. Epub 2014 Jan 16.