Details of Disease

General Information of Disease (ID: DISZRBCA)

• Disease Name: PMM2-congenital disorder of glycosylation
• Synonyms: carbohydrate-deficient glycoprotein syndrome, type Ia; carbohydrate-deficient glycoprotein syndrome, type Ia, formerly; carbohydrate-deficient glycoprotein syndrome type 1A; Jaeken syndrome; carbohydrate-deficient glycoprotein syndrome type 1A (formerly); congenital disorder of glycosylation, type Ia; PMM2-CDG (CDG-Ia); congenital disorder of glycosylation type Ia; PMM2-CDG; carbohydrate deficient glycoprotein syndrome type Ia; PMM2-congenital disorder of glycosylation; CDG syndrome type Ia; CDG1A; CDG-IA; phosphomannomutase 2 deficiency; CDG 1A; congenital disorder of glycosylation type 1a
• Definition: The most frequent form of congenital disorder of N-glycosylation and is characterized by cerebellar dysfunction, abnormal fat distribution, inverted nipples, strabismus and hypotonia. 3 forms of PMM2-CDG can be distinguished: the infantile multisystem type, late-infantile and childhood ataxia-intellectual disability type (3-10 yrs old), and the adult stable disability type. Infants usually develop ataxia, psychomotor delay and extraneurological manifestations including failure to thrive, enteropathy, hepatic dysfunction, coagulation abnormalities and cardiac and renal involvement. The phenotype is however highly variable and ranges from infants who die in the first year of life to mildly involved adults.
• Disease Hierarchy:
  DISBHHT1: Congenital disorder of glycosylation type I
  DIST8BQR: Disorder of protein N-glycosylation
  DISZRBCA: PMM2-congenital disorder of glycosylation
• Disease Identifiers:
  MONDO ID: MONDO_0008907
  MESH ID: C535739
  UMLS CUI: C0349653
  OMIM ID: 212065
  MedGen ID: 138111
  Orphanet ID: 79318
  SNOMED CT ID: 277893002

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 1 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
AHCY	TTE2KUJ	Limited	Biomarker	[1]

This Disease Is Related to 3 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
PMM2	DEBRX3L	Limited	Genetic Variation	[2]
PMM1	DEJFMQ8	Strong	Biomarker	[3]
PMM2	DEBRX3L	Definitive	Autosomal recessive	[4]

This Disease Is Related to 4 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
LEMD3	OTILAM4I	Strong	Genetic Variation	[5]
ALG6	OTZRVUH4	Definitive	Biomarker	[6]
MPI	OTBH6ZK1	Definitive	Altered Expression	[7]
PMM2	OTBXEB91	Definitive	Autosomal recessive	[4]

References

• [1] Clinical picture of S-adenosylhomocysteine hydrolase deficiency resembles phosphomannomutase 2 deficiency.Mol Genet Metab. 2012 Nov;107(3):611-3. doi: 10.1016/j.ymgme.2012.08.014. Epub 2012 Aug 23.
• [2] Unsuccessful intravenous D-mannose treatment in PMM2-CDG.Orphanet J Rare Dis. 2019 Oct 22;14(1):231. doi: 10.1186/s13023-019-1213-3.
• [3] The X-ray crystal structures of human alpha-phosphomannomutase 1 reveal the structural basis of congenital disorder of glycosylation type 1a. J Biol Chem. 2006 May 26;281(21):14918-26.
• [4] 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.
• [5] 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.
• [6] N-Glycosylation Defects in Humans Lower Low-Density Lipoprotein Cholesterol Through Increased Low-Density Lipoprotein Receptor Expression.Circulation. 2019 Jul 23;140(4):280-292. doi: 10.1161/CIRCULATIONAHA.118.036484. Epub 2019 May 23.
• [7] Phosphomannose isomerase inhibitors improve N-glycosylation in selected phosphomannomutase-deficient fibroblasts.J Biol Chem. 2011 Nov 11;286(45):39431-8. doi: 10.1074/jbc.M111.285502. Epub 2011 Sep 26.