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COG4-congenital disorder of glycosylation(CDGIIj; CDG2J)

MedGen UID:
929221
Concept ID:
C4303552
Disease or Syndrome
Synonyms: CDG IIj; COG4-CDG; Congenital disorder of glycosylation type 2J; CONGENITAL DISORDER OF GLYCOSYLATION, TYPE IIj
SNOMED CT: Carbohydrate deficient glycoprotein syndrome type 2j (718751000); Carbohydrate deficient glycoprotein syndrome type IIj (718751000); CDG2J - carbohydrate deficient glycoprotein syndrome type 2J (718751000); Component of oligomeric golgi complex 4 congenital disorder of glycosylation (718751000); COG4 (component of oligomeric golgi complex 4) congenital disorder of glycosylation (718751000); COG4 congenital disorder of glycosylation (718751000)
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): COG4 (16q22.1)
 
Monarch Initiative: MONDO:0013281
OMIM®: 613489
Orphanet: ORPHA263501

Definition

An extremely rare form of carbohydrate deficient glycoprotein syndrome with, in the single reported case to date, seizures, some dysmorphic features, axial hypotonia, slight peripheral hypertonia and hyperreflexia. [from SNOMEDCT_US]

Clinical features

From HPO
Limb hypertonia
MedGen UID:
333083
Concept ID:
C1838391
Finding
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Cirrhosis of liver
MedGen UID:
7368
Concept ID:
C0023890
Disease or Syndrome
A chronic disorder of the liver in which liver tissue becomes scarred and is partially replaced by regenerative nodules and fibrotic tissue resulting in loss of liver function.
Liver failure
MedGen UID:
88444
Concept ID:
C0085605
Disease or Syndrome
A disorder characterized by the inability of the liver to metabolize chemicals in the body. Causes include cirrhosis and drug-induced hepatotoxicity. Signs and symptoms include jaundice and encephalopathy. Laboratory test results reveal abnormal plasma levels of ammonia, bilirubin, lactic dehydrogenase, and alkaline phosphatase.
Feeding difficulties
MedGen UID:
65429
Concept ID:
C0232466
Finding
Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.
Chronic diarrhea
MedGen UID:
96036
Concept ID:
C0401151
Finding
The presence of chronic diarrhea, which is usually taken to mean diarrhea that has persisted for over 4 weeks.
Recurrent infection of the gastrointestinal tract
MedGen UID:
343135
Concept ID:
C1854495
Disease or Syndrome
Recurrent infection of the gastrointestinal tract.
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Cerebral atrophy
MedGen UID:
116012
Concept ID:
C0235946
Disease or Syndrome
Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.
Hypoplasia of the corpus callosum
MedGen UID:
138005
Concept ID:
C0344482
Congenital Abnormality
Underdevelopment of the corpus callosum.
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.
Absent speech
MedGen UID:
340737
Concept ID:
C1854882
Finding
Complete lack of development of speech and language abilities.
Irritability
MedGen UID:
397841
Concept ID:
C2700617
Mental Process
A proneness to anger, i.e., a tendency to become easily bothered or annoyed.
Frontotemporal cerebral atrophy
MedGen UID:
867226
Concept ID:
C4021584
Disease or Syndrome
Atrophy (wasting, decrease in size of cells or tissue) affecting the frontotemporal cerebrum.
Axial hypotonia
MedGen UID:
342959
Concept ID:
C1853743
Finding
Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Recurrent respiratory infections
MedGen UID:
812812
Concept ID:
C3806482
Finding
An increased susceptibility to respiratory infections as manifested by a history of recurrent respiratory infections.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Elevated circulating alkaline phosphatase concentration
MedGen UID:
727252
Concept ID:
C1314665
Finding
Abnormally increased serum levels of alkaline phosphatase activity.
Elevated circulating hepatic transaminase concentration
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.
Type II transferrin isoform profile
MedGen UID:
892666
Concept ID:
C4021094
Finding
Abnormal transferrin isoform profile consistent with a type II congenital disorder of glycosylation.
Abnormal facial shape
MedGen UID:
98409
Concept ID:
C0424503
Finding
An abnormal morphology (form) of the face or its components.
Thick hair
MedGen UID:
892635
Concept ID:
C4073184
Finding
Increased density of hairs, i.e., and elevated number of hairs per unit area.
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.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

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
Dashti HM, Mathew TC, Al-Zaid NS
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

He M, Zhou X, Wang X
Signal Transduct Target Ther 2024 Aug 5;9(1):194. doi: 10.1038/s41392-024-01886-1. PMID: 39098853Free PMC Article
Llop E, Ardá A, Zacco E, O'Flaherty R, García-Ayllón MS, Aureli M, Frenkel-Pinter M, Reis CA, Greiner-Tollersrud OK, Cuchillo-Ibáñez I
Glycoconj J 2022 Oct;39(5):579-586. Epub 2022 Aug 24 doi: 10.1007/s10719-022-10078-4. PMID: 36001187Free PMC Article
Trbojević-Akmačić I, Petrović T, Lauc G
Glycoconj J 2021 Oct;38(5):611-623. Epub 2021 Sep 20 doi: 10.1007/s10719-021-10021-z. PMID: 34542788Free PMC Article
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

Diagnosis

He M, Zhou X, Wang X
Signal Transduct Target Ther 2024 Aug 5;9(1):194. doi: 10.1038/s41392-024-01886-1. PMID: 39098853Free 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
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
Stowell SR, Ju T, Cummings RD
Annu Rev Pathol 2015;10:473-510. doi: 10.1146/annurev-pathol-012414-040438. PMID: 25621663Free PMC Article
Rivinoja A, Pujol FM, Hassinen A, Kellokumpu S
Ann Med 2012 Sep;44(6):542-54. Epub 2011 May 17 doi: 10.3109/07853890.2011.579150. PMID: 21585247

Therapy

Zheng W, Li H, Go Y, Chan XHF, Huang Q, Wu J
Nutrients 2022 Nov 1;14(21) doi: 10.3390/nu14214588. PMID: 36364850Free PMC Article
McQuiston A, Emtiazjoo A, Angel P, Machuca T, Christie J, Atkinson C
Front Immunol 2021;12:711102. Epub 2021 Aug 11 doi: 10.3389/fimmu.2021.711102. PMID: 34456920Free PMC Article
Pleass RJ
MAbs 2021 Jan-Dec;13(1):1953220. doi: 10.1080/19420862.2021.1953220. PMID: 34288809Free PMC Article
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

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
McEwen JM, Fraser S, Guir ALS, Dave J, Scheck RA
Nat Commun 2021 Jun 3;12(1):3316. doi: 10.1038/s41467-021-23625-8. PMID: 34083524Free PMC Article
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

Clinical prediction guides

Lee HF, Chi CS
Epilepsy Behav 2023 May;142:109214. Epub 2023 Apr 21 doi: 10.1016/j.yebeh.2023.109214. PMID: 37086590
Radovani B, Gudelj I
Front Immunol 2022;13:893365. Epub 2022 Jun 27 doi: 10.3389/fimmu.2022.893365. PMID: 35833138Free PMC Article
Sánchez-Navarro A, Murillo-de-Ozores AR, Pérez-Villalva R, Linares N, Carbajal-Contreras H, Flores ME, Gamba G, Castañeda-Bueno M, Bobadilla NA
FASEB J 2022 Mar;36(3):e22190. doi: 10.1096/fj.202101912R. PMID: 35147994
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
Offersen R, Yu WH, Scully EP, Julg B, Euler Z, Sadanand S, Garcia-Dominguez D, Zheng L, Rasmussen TA, Jennewein MF, Linde C, Sassic J, Lofano G, Vigano S, Stephenson KE, Fischinger S, Suscovich TJ, Lichterfeld M, Lauffenburger D, Rosenberg ES, Allen T, Altfeld M, Charles RC, Østergaard L, Tolstrup M, Barouch DH, Søgaard OS, Alter G
Cell Rep 2020 Dec 15;33(11):108502. doi: 10.1016/j.celrep.2020.108502. PMID: 33326789

Recent systematic reviews

Conte F, Sam JE, Lefeber DJ, Passier R
Int J Mol Sci 2023 May 11;24(10) doi: 10.3390/ijms24108632. PMID: 37239976Free PMC Article
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
Xue M, Xu W, Ou YN, Cao XP, Tan MS, Tan L, Yu JT
Ageing Res Rev 2019 Nov;55:100944. Epub 2019 Aug 17 doi: 10.1016/j.arr.2019.100944. PMID: 31430566
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

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