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CCDC115-CDG(CDGIIo; CDG2O)

MedGen UID:
906792
Concept ID:
C4225191
Disease or Syndrome
Synonyms: CDG IIo; CONGENITAL DISORDER OF GLYCOSYLATION, TYPE IIo
SNOMED CT: Coiled-coil domain containing 115 congenital disorder of glycosylation (1187174002); CCDC115-CDG - coiled-coil domain containing 115 congenital disorder of glycosylation (1187174002); Congenital disorder of glycosylation type 2o (1187174002); Congenital disorder of glycosylation type IIo (1187174002); Carbohydrate deficient glycoprotein syndrome type IIo (1187174002); CCDC115 congenital disorder of glycosylation (1187174002)
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): CCDC115 (2q21.1)
 
Monarch Initiative: MONDO:0014789
OMIM®: 616828
Orphanet: ORPHA468684

Definition

Congenital disorder of glycosylation type IIo (CDG2O) is an autosomal recessive metabolic disorder characterized by infantile onset of progressive liver failure, hypotonia, and delayed psychomotor development. Laboratory abnormalities include elevated liver enzymes, coagulation factor deficiencies, hypercholesterolemia, and low ceruloplasmin. Serum isoelectric focusing of proteins shows a combined defect of N- and O-glycosylation, suggestive of a Golgi defect (summary by Jansen et al., 2016). For a general discussion of CDGs, see CDG1A (212065). [from OMIM]

Clinical features

From HPO
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Hepatosplenomegaly
MedGen UID:
9225
Concept ID:
C0019214
Sign or Symptom
Simultaneous enlargement of the liver and spleen.
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.
Cholestatic liver disease
MedGen UID:
163651
Concept ID:
C0860204
Disease or Syndrome
Prolonged neonatal jaundice
MedGen UID:
347108
Concept ID:
C1859236
Finding
Neonatal jaundice refers to a yellowing of the skin and other tissues of a newborn infant as a result of increased concentrations of bilirubin in the blood. Neonatal jaundice affects over half of all newborns to some extent in the first week of life. Prolonged neonatal jaundice is said to be present if the jaundice persists for longer than 14 days in term infants and 21 days in preterm infants.
Copper accumulation in liver
MedGen UID:
910570
Concept ID:
C3672035
Finding
An anomalous build up of copper (Cu) in the liver.
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.
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.
Muscular atrophy
MedGen UID:
892680
Concept ID:
C0541794
Pathologic Function
The presence of skeletal muscular atrophy (which is also known as amyotrophy).
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Hypercholesterolemia
MedGen UID:
5687
Concept ID:
C0020443
Disease or Syndrome
An increased concentration of cholesterol in the blood.
Elevated circulating hepatic transaminase concentration
MedGen UID:
116013
Concept ID:
C0235996
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.
Decreased circulating ceruloplasmin concentration
MedGen UID:
472980
Concept ID:
C0240997
Finding
Decreased concentration of ceruloplasmin in the blood.
Elevated circulating creatine kinase concentration
MedGen UID:
69128
Concept ID:
C0241005
Finding
An elevation of the level of the enzyme creatine kinase (also known as creatine phosphokinase (CK; EC 2.7.3.2) in the blood. CK levels can be elevated in a number of clinical disorders such as myocardial infarction, rhabdomyolysis, and muscular dystrophy.
Increased LDL cholesterol concentration
MedGen UID:
154289
Concept ID:
C0549399
Finding
An elevated concentration of low-density lipoprotein cholesterol in the blood.
Elevated alkaline phosphatase of bone origin
MedGen UID:
318930
Concept ID:
C1833667
Finding
An abnormally increased level of bone isoforms of alkaline phosphatase, tissue-nonspecific isozyme in the blood.
Abnormal glycosylation
MedGen UID:
868547
Concept ID:
C4022946
Finding
An anomaly of a glycosylation process, i.e., a process involved in the covalent attachment of a glycosyl residue to a substrate molecule.
Downslanted palpebral fissures
MedGen UID:
98391
Concept ID:
C0423110
Finding
The palpebral fissure inclination is more than two standard deviations below the mean.
Abnormal facial shape
MedGen UID:
98409
Concept ID:
C0424503
Finding
An abnormal morphology (form) of the face or its components.
Long face
MedGen UID:
324419
Concept ID:
C1836047
Finding
Facial height (length) is more than 2 standard deviations above the mean (objective); or, an apparent increase in the height (length) of the face (subjective).
Ptosis
MedGen UID:
2287
Concept ID:
C0005745
Disease or Syndrome
The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVCCDC115-CDG

Recent clinical studies

Etiology

Marques-da-Silva D, Dos Reis Ferreira V, Monticelli M, Janeiro P, Videira PA, Witters P, Jaeken J, Cassiman D
J Inherit Metab Dis 2017 Mar;40(2):195-207. Epub 2017 Jan 20 doi: 10.1007/s10545-016-0012-4. PMID: 28108845

Diagnosis

Haouari W, Dubail J, Lounis-Ouaras S, Prada P, Bennani R, Roseau C, Huber C, Afenjar A, Colin E, Vuillaumier-Barrot S, Seta N, Foulquier F, Poüs C, Cormier-Daire V, Bruneel A
J Inherit Metab Dis 2020 Nov;43(6):1349-1359. Epub 2020 Aug 7 doi: 10.1002/jimd.12291. PMID: 32700771
Girard M, Poujois A, Fabre M, Lacaille F, Debray D, Rio M, Fenaille F, Cholet S, Ruel C, Caussé E, Selves J, Bridoux-Henno L, Woimant F, Dupré T, Vuillaumier-Barrot S, Seta N, Alric L, de Lonlay P, Bruneel A
Mol Genet Metab 2018 Jul;124(3):228-235. Epub 2018 May 9 doi: 10.1016/j.ymgme.2018.05.002. PMID: 29759592
Abu Bakar N, Lefeber DJ, van Scherpenzeel M
J Inherit Metab Dis 2018 May;41(3):499-513. Epub 2018 Mar 1 doi: 10.1007/s10545-018-0144-9. PMID: 29497882Free PMC Article
Marques-da-Silva D, Dos Reis Ferreira V, Monticelli M, Janeiro P, Videira PA, Witters P, Jaeken J, Cassiman D
J Inherit Metab Dis 2017 Mar;40(2):195-207. Epub 2017 Jan 20 doi: 10.1007/s10545-016-0012-4. PMID: 28108845

Prognosis

Girard M, Poujois A, Fabre M, Lacaille F, Debray D, Rio M, Fenaille F, Cholet S, Ruel C, Caussé E, Selves J, Bridoux-Henno L, Woimant F, Dupré T, Vuillaumier-Barrot S, Seta N, Alric L, de Lonlay P, Bruneel A
Mol Genet Metab 2018 Jul;124(3):228-235. Epub 2018 May 9 doi: 10.1016/j.ymgme.2018.05.002. PMID: 29759592

Recent systematic reviews

Marques-da-Silva D, Dos Reis Ferreira V, Monticelli M, Janeiro P, Videira PA, Witters P, Jaeken J, Cassiman D
J Inherit Metab Dis 2017 Mar;40(2):195-207. Epub 2017 Jan 20 doi: 10.1007/s10545-016-0012-4. PMID: 28108845

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