Congenital disorders of glycosylation (CDG) type I

Congenital disorders of glycosylation (CDGs) are a group of autosomal recessive disorders caused by defects in various genes for N-glycan biosynthesis. CDG type I is caused by one of the enzyme genes involved in the synthesis of dolichol bound N-glycan precursor.

Inherited metabolic disease

(CDG-Ia) PMM2; phosphomannomutase 2 [HSA:5373] [KO:K01840]
(CDG-Ib) MPI; mannose phosphate isomerase [HSA:4351] [KO:K01809]
(CDG-Ic) ALG6; a1-3 glucosyltransferase [HSA:29929] [KO:K03848]
(CDG-Id) ALG3; a1-3 mannosyltransferase [HSA:10195] [KO:K03845]
(CDG-Ie) DPM1; P-dolichol mannosyltransferase [HSA:8813] [KO:K00721]
(CDG-If) MPDU1; mannose-P-dolichol utilization defect 1 [HSA:9526] [KO:K09660]
(CDG-Ig) ALG12; a1-6 mannosyltransferase [HSA:79087] [KO:K03847]
(CDG-Ih) ALG8; a1-3 glucosyltransferase [HSA:79053] [KO:K03849]
(CDG-Ii) ALG2; a1-3/6 mannosyltransferase [HSA:85365] [KO:K03843]
(CDG-Ij) DPAGT1, ALG7; P-dolichol N-acetylglucosaminephosphotransferase [HSA:1798] [KO:K01001]
(CDG-Ik) ALG1; b1-4 mannosyltransferase [HSA:56052] [KO:K03842]
(CDG-IL) ALG9; a1-2 mannosyltransferase [HSA:79796] [KO:K03846]
(CDG-Im) DOLK; dolichol kinase [HSA:22845] [KO:K00902]
(CDG-In) RFT1; oligosaccharidyl-lipid flippase [HSA:91869] [KO:K06316]
(CDG-Io) DPM3 [HSA:54344] [KO:K09659]
(CDG-Ip) ALG11 [HSA:440138] [KO:K03844]
(CDG-Iq) SRD5A3 [HSA:79644] [KO:K12345]

PMID:16511948

Sparks SE

Inherited disorders of glycosylation.

Mol Genet Metab 87:1-7 (2006)

PMID:12756558

Marquardt T, Denecke J

Congenital disorders of glycosylation: review of their molecular bases, clinical presentations and specific therapies.

Eur J Pediatr 162:359-79 (2003)

PMID:12905014 (CDG type Ia)

Neumann LM, von Moers A, Kunze J, Blankenstein O, Marquardt T

Congenital disorder of glycosylation type 1a in a macrosomic 16-month-old boy with an atypical phenotype and homozygosity of the N216I mutation.

Eur J Pediatr 162:710-3 (2003)

PMID:12414827 (CDG type Ib)

Vuillaumier-Barrot S, Le Bizec C, de Lonlay P, Barnier A, Mitchell G, Pelletier V, Prevost C, Saudubray JM, Durand G, Seta N

Protein losing enteropathy-hepatic fibrosis syndrome in Saguenay-Lac St-Jean, Quebec is a congenital disorder of glycosylation type Ib.

J Med Genet 39:849-51 (2002)

PMID:10359825 (CDG type Ic)

Imbach T, Burda P, Kuhnert P, Wevers RA, Aebi M, Berger EG, Hennet T

A mutation in the human ortholog of the Saccharomyces cerevisiae ALG6 gene causes carbohydrate-deficient glycoprotein syndrome type-Ic.

Proc Natl Acad Sci U S A 96:6982-7 (1999)

PMID:15108280 (CDG type Id)

Denecke J, Kranz C, Kemming D, Koch HG, Marquardt T

An activated 5' cryptic splice site in the human ALG3 gene generates a premature termination codon insensitive to nonsense-mediated mRNA decay in a new case of congenital disorder of glycosylation type Id (CDG-Id).

Hum Mutat 23:477-86 (2004)

PMID:12736397 (CDG type Ig)

Zdebska E, Bader-Meunier B, Schischmanoff PO, Dupre T, Seta N, Tchernia G, Koscielak J, Delaunay J

Abnormal glycosylation of red cell membrane band 3 in the congenital disorder of glycosylation Ig.

Pediatr Res 54:224-9 (2003)

PMID:15235028 (CDG type Ih)

Schollen E, Frank CG, Keldermans L, Reyntjens R, Grubenmann CE, Clayton PT, Winchester BG, Smeitink J, Wevers RA, Aebi M, Hennet T, Matthijs G

Clinical and molecular features of three patients with congenital disorders of glycosylation type Ih (CDG-Ih) (ALG8 deficiency).

J Med Genet 41:550-6 (2004)

PMID:12684507 (CDG type Ii)

Thiel C, Schwarz M, Peng J, Grzmil M, Hasilik M, Braulke T, Kohlschutter A, von Figura K, Lehle L, Korner C.

A new type of congenital disorders of glycosylation (CDG-Ii) provides new insights into the early steps of dolichol-linked oligosaccharide biosynthesis.

J Biol Chem 278:22498-505 (2003)

PMID:12872255 (CDG type Ij)

Wu X, Rush JS, Karaoglu D, Krasnewich D, Lubinsky MS, Waechter CJ, Gilmore R, Freeze HH

Deficiency of UDP-GlcNAc:Dolichol Phosphate N-Acetylglucosamine-1 Phosphate Transferase (DPAGT1) causes a novel congenital disorder of Glycosylation Type Ij.

Hum Mutat 22:144-50 (2003)

PMID:17273964 (CDG type Im)

Kranz C, Jungeblut C, Denecke J, Erlekotte A, Sohlbach C, Debus V, Kehl HG, Harms E, Reith A, Reichel S, Grobe H, Hammersen G, Schwarzer U, Marquardt T

A defect in dolichol phosphate biosynthesis causes a new inherited disorder with death in early infancy.

Am J Hum Genet 80:433-40 (2007)

PMID:18313027 (CDG type In)

Haeuptle MA, Pujol FM, Neupert C, Winchester B, Kastaniotis AJ, Aebi M, Hennet T

Human RFT1 deficiency leads to a disorder of N-linked glycosylation.

Am J Hum Genet 82:600-6 (2008)

PMID:19576565

Lefeber DJ, Schonberger J, Morava E, Guillard M, Huyben KM, Verrijp K, Grafakou O, Evangeliou A, Preijers FW, Manta P, Yildiz J, Grunewald S, Spilioti M, van den Elzen C, Klein D, Hess D, Ashida H, Hofsteenge J, Maeda Y, van den Heuvel L, Lammens M, Lehle L, Wevers RA

Deficiency of Dol-P-Man synthase subunit DPM3 bridges the congenital disorders of glycosylation with the dystroglycanopathies.

Am J Hum Genet 85:76-86 (2009)

PMID:20080937

Rind N, Schmeiser V, Thiel C, Absmanner B, Lubbehusen J, Hocks J, Apeshiotis N, Wilichowski E, Lehle L, Korner C

A severe human metabolic disease caused by deficiency of the endoplasmatic mannosyltransferase hALG11 leads to congenital disorder of glycosylation-Ip.

Hum Mol Genet 19:1413-24 (2010)

PMID:20637498

Cantagrel V, Lefeber DJ, Ng BG, Guan Z, Silhavy JL, Bielas SL, Lehle L, Hombauer H, Adamowicz M, Swiezewska E, De Brouwer AP, Blumel P, Sykut-Cegielska J, Houliston S, Swistun D, Ali BR, Dobyns WB, Babovic-Vuksanovic D, van Bokhoven H, Wevers RA, Raetz CR, Freeze HH, Morava E, Al-Gazali L, Gleeson JG

SRD5A3 is required for converting polyprenol to dolichol and is mutated in a congenital glycosylation disorder.

Cell 142:203-17 (2010)