U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

TMEM199-CDG(CDGIIp; CDG2P)

MedGen UID:
895025
Concept ID:
C4225190
Disease or Syndrome
Synonyms: CDG IIp; CONGENITAL DISORDER OF GLYCOSYLATION, TYPE IIp
SNOMED CT: Transmembrane protein 199 congenital disorder of glycosylation (1208738002); TMEM199 congenital disorder of glycosylation (1208738002); Congenital disorder of glycosylation type IIp (1208738002); TMEM199-CDG - transmembrane protein 199 congenital disorder of glycosylation (1208738002); CDG (congenital disorder of glycosylation) syndrome type IIp (1208738002); Carbohydrate deficient glycoprotein syndrome type IIp (1208738002)
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): TMEM199 (17q11.2)
 
Monarch Initiative: MONDO:0014790
OMIM®: 616829
Orphanet: ORPHA466703

Definition

Congenital disorder of glycosylation type IIp (CDG2P) is an autosomal recessive metabolic disorder characterized by mild liver dysfunction, which may be found incidentally during adolescence. Laboratory abnormalities include elevated liver enzymes and alkaline phosphatase, 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 an overview of congenital disorders of glycosylation, see CDG1A (212065) and CDG2A (212066). [from OMIM]

Clinical features

From HPO
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Decreased liver function
MedGen UID:
65430
Concept ID:
C0232744
Finding
Reduced ability of the liver to perform its functions.
Hepatic fibrosis
MedGen UID:
116093
Concept ID:
C0239946
Disease or Syndrome
The presence of excessive fibrous connective tissue in the liver. Fibrosis is a reparative or reactive process.
Hepatic steatosis
MedGen UID:
398225
Concept ID:
C2711227
Disease or Syndrome
Steatosis is a term used to denote lipid accumulation within hepatocytes.
Copper accumulation in liver
MedGen UID:
910570
Concept ID:
C3672035
Finding
An anomalous build up of copper (Cu) in the liver.
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.
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.
Hypercholesterolemia
MedGen UID:
5687
Concept ID:
C0020443
Disease or Syndrome
An increased concentration of cholesterol in the blood.
Elevated circulating aspartate aminotransferase concentration
MedGen UID:
57497
Concept ID:
C0151904
Finding
The concentration of aspartate aminotransferase (AST) in the blood circulation is above the upper limit of normal.
Elevated circulating alanine aminotransferase concentration
MedGen UID:
57740
Concept ID:
C0151905
Finding
An abnormally high concentration in the circulation of alanine aminotransferase (ALT).
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.
Decreased circulating copper concentration
MedGen UID:
488831
Concept ID:
C0268070
Disease or Syndrome
A reduced concentration of copper in the blood.
Increased LDL cholesterol concentration
MedGen UID:
154289
Concept ID:
C0549399
Finding
An elevated concentration of low-density lipoprotein cholesterol in the blood.
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 protein O-linked glycosylation
MedGen UID:
868534
Concept ID:
C4022933
Anatomical Abnormality
An anomaly of protein O-linked glycosylation, i.e., of the process in which a carbohydrate or carbohydrate derivative unit is added to a protein via the hydroxyl group of a serine or threonine residue.
Abnormal protein N-linked glycosylation
MedGen UID:
868545
Concept ID:
C4022944
Finding
An anomaly of protein N-linked glycosylation, i.e., an abnormality of the protein glycosylation process in which a carbohydrate or carbohydrate derivative unit is added to a protein via a nitrogen atom in an amino acid residue in a protein.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVTMEM199-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

Messina A, Palmigiano A, Esposito F, Fiumara A, Bordugo A, Barone R, Sturiale L, Jaeken J, Garozzo D
Glycoconj J 2021 Apr;38(2):201-211. Epub 2020 Sep 11 doi: 10.1007/s10719-020-09947-7. PMID: 32915358
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
Vajro P, Zielinska K, Ng BG, Maccarana M, Bengtson P, Poeta M, Mandato C, D'Acunto E, Freeze HH, Eklund EA
Orphanet J Rare Dis 2018 Jan 10;13(1):4. doi: 10.1186/s13023-017-0757-3. PMID: 29321044Free 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
Vajro P, Zielinska K, Ng BG, Maccarana M, Bengtson P, Poeta M, Mandato C, D'Acunto E, Freeze HH, Eklund EA
Orphanet J Rare Dis 2018 Jan 10;13(1):4. doi: 10.1186/s13023-017-0757-3. PMID: 29321044Free PMC Article

Clinical prediction guides

Fiumara A, Sapuppo A, Ferri L, Arena A, Prato A, Garozzo D, Sturiale L, Morrone A, Barone R
Eur J Med Genet 2023 Mar;66(3):104709. Epub 2023 Jan 24 doi: 10.1016/j.ejmg.2023.104709. PMID: 36706865

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