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DPAGT1-congenital disorder of glycosylation(CDGIj; CDG1J)

MedGen UID:
419694
Concept ID:
C2931004
Disease or Syndrome
Synonyms: CDG 1J; CDG Ij; Congenital disorder of glycosylation type 1J; CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Ij; DPAGT1-CDG; DPAGT1-CDG (CDG-Ij)
SNOMED CT: Congenital disorder of glycosylation type 1j (725079003); Carbohydrate deficient glycoprotein syndrome type Ij (725079003); Congenital disorder of glycosylation type Ij (725079003); Dolichyl-phosphate N-acetylgalactosamine phosphotransferase deficiency (725079003); DPAGT1-CDG - dolichyl-phosphate n-acetylglucosamine phosphotransferase congenital disorder of glycosylation (725079003)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): DPAGT1 (11q23.3)
 
Monarch Initiative: MONDO:0011964
OMIM®: 608093
Orphanet: ORPHA86309

Definition

Like all CDGs, which are caused by a shortage of precursor monosaccharide phosphate or deficiencies in the glycosyltransferases required for lipid-linked oligosaccharide precursor (LLO) synthesis, CDG Ij is caused by a defect in the formation of DPAGT1, the first dolichyl-linked intermediate of the protein N-glycosylation pathway. For a general discussion of CDGs, see CDG1A (212065). [from OMIM]

Clinical features

From HPO
Cryptorchidism
MedGen UID:
8192
Concept ID:
C0010417
Congenital Abnormality
Cryptorchidism, or failure of testicular descent, is a common human congenital abnormality with a multifactorial etiology that likely reflects the involvement of endocrine, environmental, and hereditary factors. Cryptorchidism can result in infertility and increases risk for testicular tumors. Testicular descent from abdomen to scrotum occurs in 2 distinct phases: the transabdominal phase and the inguinoscrotal phase (summary by Gorlov et al., 2002).
Single transverse palmar crease
MedGen UID:
96108
Concept ID:
C0424731
Finding
The distal and proximal transverse palmar creases are merged into a single transverse palmar crease.
Clinodactyly of the 5th finger
MedGen UID:
340456
Concept ID:
C1850049
Congenital Abnormality
Clinodactyly refers to a bending or curvature of the fifth finger in the radial direction (i.e., towards the 4th finger).
Jaundice
MedGen UID:
43987
Concept ID:
C0022346
Sign or Symptom
Yellow pigmentation of the skin due to bilirubin, which in turn is the result of increased bilirubin concentration in the bloodstream.
Aggressive behavior
MedGen UID:
1375
Concept ID:
C0001807
Individual Behavior
Behavior or an act aimed at harming a person, animal, or physical property (e.g., acts of physical violence; shouting, swearing, and using harsh language; slashing someone's tires).
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterised by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Tremor
MedGen UID:
21635
Concept ID:
C0040822
Sign or Symptom
An unintentional, oscillating to-and-fro muscle movement about a joint axis.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Hypsarrhythmia
MedGen UID:
195766
Concept ID:
C0684276
Finding
Hypsarrhythmia is abnormal interictal high amplitude waves and a background of irregular spikes. There is continuous (during wakefulness), high-amplitude (>200 Hz), generalized polymorphic slowing with no organized background and multifocal spikes demonstrated by electroencephalography (EEG).
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Infantile spasms
MedGen UID:
854616
Concept ID:
C3887898
Disease or Syndrome
Infantile spasms represent a subset of "epileptic spasms". Infantile Spasms are epileptic spasms starting in the first year of life (infancy).
Hereditary antithrombin deficiency
MedGen UID:
75781
Concept ID:
C0272375
Disease or Syndrome
Deficiency of antithrombin III is a major risk factor for venous thromboembolic disease. Two categories of AT-III deficiency have been defined on the basis of AT-III antigen levels in the plasma of affected individuals. The majority of AT-III deficiency families belong in the type I (classic) deficiency group and have a quantitatively abnormal phenotype in which antigen and heparin cofactor levels are both reduced to about 50% of normal. The second category of AT-III deficiency has been termed type II (functional) deficiency. Affected individuals from these kindreds produce dysfunctional AT-III molecules; they have reduced heparin cofactor activity levels (about 50% of normal) but levels of AT-III antigen are often normal or nearly normal (summary by Bock and Prochownik, 1987). The 2 categories of antithrombmin III deficiency have been classified further. Type I (low functional and immunologic antithrombin) has been subdivided into subtype Ia (reduced levels of normal antithrombin), and type Ib (reduced levels of antithrombin and the presence of low levels of a variant). Type II (low functional but normal immunologic antithrombin) has been subdivided into subtype IIa (functional abnormalities affecting both the reactive site and the heparin-binding site of AT3); subtype IIb (functional abnormalities limited to the reactive site); and subtype IIc (functional abnormalities limited to the heparin-binding site) (summary by Lane et al., 1992).
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Hypertonia
MedGen UID:
10132
Concept ID:
C0026826
Finding
A condition in which there is increased muscle tone so that arms or legs, for example, are stiff and difficult to move.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Flexion contracture
MedGen UID:
83069
Concept ID:
C0333068
Anatomical Abnormality
A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Apnea
MedGen UID:
2009
Concept ID:
C0003578
Sign or Symptom
Lack of breathing with no movement of the respiratory muscles and no exchange of air in the lungs. This term refers to a disposition to have recurrent episodes of apnea rather than to a single event.
Respiratory insufficiency
MedGen UID:
11197
Concept ID:
C0035229
Pathologic Function
Impairment of gas exchange within the lungs secondary to a disease process, neoplasm, or trauma, possibly resulting in hypoxia, hypercarbia, or both, but not requiring intubation or mechanical ventilation. Patients are normally managed with pharmaceutical therapy, supplemental oxygen, or both.
Hypoproteinemia
MedGen UID:
581229
Concept ID:
C0392692
Finding
A decreased concentration of protein in the blood.
Type I transferrin isoform profile
MedGen UID:
324900
Concept ID:
C1837899
Finding
Abnormal transferrin isoform profile consistent with a type I congenital disorder of glycosylation. In the traditional nomenclature for congenital disorders of glycosylation, absence of entire glycans was designated type I, and loss of one or more monosaccharides as type II.
Elevated hepatic transaminase
MedGen UID:
338525
Concept ID:
C1848701
Finding
Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage.
Skin dimple
MedGen UID:
661955
Concept ID:
C0578531
Finding
Skin dimples are cutaneous indentations that are the result of tethering of the skin to underlying structures (bone) causing an indentation.
Inversion of nipple
MedGen UID:
82844
Concept ID:
C0269269
Anatomical Abnormality
The presence of nipples that instead of pointing outward are retracted inwards.
Exotropia
MedGen UID:
4613
Concept ID:
C0015310
Disease or Syndrome
A form of strabismus with one or both eyes deviated outward.
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.
Cataract
MedGen UID:
39462
Concept ID:
C0086543
Disease or Syndrome
A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for DPAGT1-congenital disorder of glycosylation in Orphanet.

Professional guidelines

PubMed

Mueller AL, Payandeh Z, Mohammadkhani N, Mubarak SMH, Zakeri A, Alagheband Bahrami A, Brockmueller A, Shakibaei M
Cells 2021 Nov 4;10(11) doi: 10.3390/cells10113017. PMID: 34831240Free PMC Article
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Med Princ Pract 2021;30(3):223-235. Epub 2020 Oct 9 doi: 10.1159/000512142. PMID: 33040057Free PMC Article
Engel AG, Shen XM, Selcen D, Sine SM
Lancet Neurol 2015 Apr;14(4):420-34. doi: 10.1016/S1474-4422(14)70201-7. PMID: 25792100Free PMC Article

Recent clinical studies

Etiology

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Biochim Biophys Acta Rev Cancer 2021 Apr;1875(2):188409. Epub 2020 Aug 19 doi: 10.1016/j.bbcan.2020.188409. PMID: 32827580
Mammadova-Bach E, Jaeken J, Gudermann T, Braun A
Int J Mol Sci 2020 Aug 6;21(16) doi: 10.3390/ijms21165630. PMID: 32781578Free PMC Article
Altassan R, Péanne R, Jaeken J, Barone R, Bidet M, Borgel D, Brasil S, Cassiman D, Cechova A, Coman D, Corral J, Correia J, de la Morena-Barrio ME, de Lonlay P, Dos Reis V, Ferreira CR, Fiumara A, Francisco R, Freeze H, Funke S, Gardeitchik T, Gert M, Girad M, Giros M, Grünewald S, Hernández-Caselles T, Honzik T, Hutter M, Krasnewich D, Lam C, Lee J, Lefeber D, Marques-de-Silva D, Martinez AF, Moravej H, Õunap K, Pascoal C, Pascreau T, Patterson M, Quelhas D, Raymond K, Sarkhail P, Schiff M, Seroczyńska M, Serrano M, Seta N, Sykut-Cegielska J, Thiel C, Tort F, Vals MA, Videira P, Witters P, Zeevaert R, Morava E
J Inherit Metab Dis 2019 Jan;42(1):5-28. doi: 10.1002/jimd.12024. PMID: 30740725
Jaeken J, Péanne R
J Inherit Metab Dis 2017 Jul;40(4):569-586. Epub 2017 May 8 doi: 10.1007/s10545-017-0050-6. PMID: 28484880

Diagnosis

Qing L, Li Q, Dong Z
Bull Cancer 2022 Nov;109(11):1202-1216. Epub 2022 Sep 30 doi: 10.1016/j.bulcan.2022.08.001. PMID: 36184332
Luo G, Jin K, Deng S, Cheng H, Fan Z, Gong Y, Qian Y, Huang Q, Ni Q, Liu C, Yu X
Biochim Biophys Acta Rev Cancer 2021 Apr;1875(2):188409. Epub 2020 Aug 19 doi: 10.1016/j.bbcan.2020.188409. PMID: 32827580
Altassan R, Péanne R, Jaeken J, Barone R, Bidet M, Borgel D, Brasil S, Cassiman D, Cechova A, Coman D, Corral J, Correia J, de la Morena-Barrio ME, de Lonlay P, Dos Reis V, Ferreira CR, Fiumara A, Francisco R, Freeze H, Funke S, Gardeitchik T, Gert M, Girad M, Giros M, Grünewald S, Hernández-Caselles T, Honzik T, Hutter M, Krasnewich D, Lam C, Lee J, Lefeber D, Marques-de-Silva D, Martinez AF, Moravej H, Õunap K, Pascoal C, Pascreau T, Patterson M, Quelhas D, Raymond K, Sarkhail P, Schiff M, Seroczyńska M, Serrano M, Seta N, Sykut-Cegielska J, Thiel C, Tort F, Vals MA, Videira P, Witters P, Zeevaert R, Morava E
J Inherit Metab Dis 2019 Jan;42(1):5-28. doi: 10.1002/jimd.12024. PMID: 30740725
Jaeken J, Péanne R
J Inherit Metab Dis 2017 Jul;40(4):569-586. Epub 2017 May 8 doi: 10.1007/s10545-017-0050-6. PMID: 28484880
Stowell SR, Ju T, Cummings RD
Annu Rev Pathol 2015;10:473-510. doi: 10.1146/annurev-pathol-012414-040438. PMID: 25621663Free PMC Article

Therapy

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Aggarwal A, Bhatt M
Curr Opin Neurol 2020 Aug;33(4):534-542. doi: 10.1097/WCO.0000000000000837. PMID: 32657896
Mereiter S, Balmaña M, Campos D, Gomes J, Reis CA
Cancer Cell 2019 Jul 8;36(1):6-16. doi: 10.1016/j.ccell.2019.06.006. PMID: 31287993
Pereira NA, Chan KF, Lin PC, Song Z
MAbs 2018 Jul;10(5):693-711. doi: 10.1080/19420862.2018.1466767. PMID: 29733746Free PMC Article
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Prognosis

Stanczak MA, Rodrigues Mantuano N, Kirchhammer N, Sanin DE, Jacob F, Coelho R, Everest-Dass AV, Wang J, Trefny MP, Monaco G, Bärenwaldt A, Gray MA, Petrone A, Kashyap AS, Glatz K, Kasenda B, Normington K, Broderick J, Peng L, Pearce OMT, Pearce EL, Bertozzi CR, Zippelius A, Läubli H
Sci Transl Med 2022 Nov 2;14(669):eabj1270. doi: 10.1126/scitranslmed.abj1270. PMID: 36322632Free PMC Article
Qing L, Li Q, Dong Z
Bull Cancer 2022 Nov;109(11):1202-1216. Epub 2022 Sep 30 doi: 10.1016/j.bulcan.2022.08.001. PMID: 36184332
Mueller AL, Payandeh Z, Mohammadkhani N, Mubarak SMH, Zakeri A, Alagheband Bahrami A, Brockmueller A, Shakibaei M
Cells 2021 Nov 4;10(11) doi: 10.3390/cells10113017. PMID: 34831240Free PMC Article
Dotz V, Visconti A, Lomax-Browne HJ, Clerc F, Hipgrave Ederveen AL, Medjeral-Thomas NR, Cook HT, Pickering MC, Wuhrer M, Falchi M
J Am Soc Nephrol 2021 Oct;32(10):2455-2465. Epub 2021 Jun 14 doi: 10.1681/ASN.2020081208. PMID: 34127537Free PMC Article
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Biochim Biophys Acta Rev Cancer 2021 Apr;1875(2):188409. Epub 2020 Aug 19 doi: 10.1016/j.bbcan.2020.188409. PMID: 32827580

Clinical prediction guides

Radovani B, Gudelj I
Front Immunol 2022;13:893365. Epub 2022 Jun 27 doi: 10.3389/fimmu.2022.893365. PMID: 35833138Free PMC Article
Dashti H, Pabon Porras MA, Mora S
Adv Exp Med Biol 2021;1325:307-319. doi: 10.1007/978-3-030-70115-4_15. PMID: 34495542
Luo G, Jin K, Deng S, Cheng H, Fan Z, Gong Y, Qian Y, Huang Q, Ni Q, Liu C, Yu X
Biochim Biophys Acta Rev Cancer 2021 Apr;1875(2):188409. Epub 2020 Aug 19 doi: 10.1016/j.bbcan.2020.188409. PMID: 32827580
Groux-Degroote S, Cavdarli S, Uchimura K, Allain F, Delannoy P
Adv Protein Chem Struct Biol 2020;119:111-156. Epub 2019 Nov 26 doi: 10.1016/bs.apcsb.2019.08.008. PMID: 31997767
Vogt G, Vogt B, Chuzhanova N, Julenius K, Cooper DN, Casanova JL
Curr Opin Genet Dev 2007 Jun;17(3):245-51. Epub 2007 Apr 30 doi: 10.1016/j.gde.2007.04.008. PMID: 17467977

Recent systematic reviews

Simpson TC, Clarkson JE, Worthington HV, MacDonald L, Weldon JC, Needleman I, Iheozor-Ejiofor Z, Wild SH, Qureshi A, Walker A, Patel VA, Boyers D, Twigg J
Cochrane Database Syst Rev 2022 Apr 14;4(4):CD004714. doi: 10.1002/14651858.CD004714.pub4. PMID: 35420698Free PMC Article
Peer N, Balakrishna Y, Durao S
Cochrane Database Syst Rev 2020 May 29;5(5):CD005266. doi: 10.1002/14651858.CD005266.pub2. PMID: 32470201Free PMC Article
Lin X, Zhang X, Guo J, Roberts CK, McKenzie S, Wu WC, Liu S, Song Y
J Am Heart Assoc 2015 Jun 26;4(7) doi: 10.1161/JAHA.115.002014. PMID: 26116691Free PMC Article
Yang Z, Scott CA, Mao C, Tang J, Farmer AJ
Sports Med 2014 Apr;44(4):487-99. doi: 10.1007/s40279-013-0128-8. PMID: 24297743
Leach MJ, Kumar S
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