(Jaeken syndrome if type I, CDG syndrome)

Rare: 1/50,000 to 1/100,000 but a large number of cases are probably undiagnosed. Autosomal recessive transmission. Inborn errors of metabolism affecting the synthesis of glycoproteins in the endoplasmic reticulum and the Golgi apparatus. This step of protein synthesis is very important for stabilization, intracytoplasmic or transmembrane transport and the functionality of the proteins. Eight different modalities of glycosylation of proteins or lipids are known: the observed anomalies are therefore variable according to the chain of glycans (mannose, fucose, xylose, glucose, N-acetylgalactosamine), type of binding (N or O binding) or the defective protein type. This may result  in neurological injury associated with varied multivisceral impairments mimicking a mitochondrial cytopathy. Examples: the α-dystroglycanopathies (Fukuyama congenital myopathy, muscle-eye-brain syndrome and Walker-Warburg syndrome), paroxysmal nocturnal hemoglobinuria, some forms of congenital myasthenia gravis (GFPT1).

The most common sign is mental retardation. Other commonly associated signs include lipocutaneous abnormalities (orange peel), skeletal abnormalities, olivo-ponto-cerebellar atrophy, coagulation disorders, cytolysis and hepatic fibrosis. 

There are different types of CDG (Congenital Disorders of Glycosylation or Carbohydrate-Deficient Glycoprotein)

-         type Ia (70 %), , deficiency in phosphomannomutase (PMM2) (16p13) [MIM 212 065]: presentation predominantly either neurological or multivisceral. infant: susceptibility to infections, episodes of liver failure, bleeding or thrombosis, hypertrophic cardiomyopathy; childhood : facial dysmorphism (frontal bossing, almond-shaped eyes), abnormal eye movements, abnormal distribution of subcutaneous fat, inverted nipples, seizures, stroke (bleeding or thrombosis), ataxia, cerebellar hypoplasia in MRI; later: retinitis pigmentosa with progressive loss of vision; final stage (adolescence, adult): psychomotor retardation, kyphoscoliosis, hepatomegaly with moderate cytolysis (liver fibrosis), growth delay, cardiomyopathy, renal microcysts, hypothyroidism: early mortality caused by cardiac or liver failure, or status epilepticus.

-         type Ib, [MIM 602 579], phosphomannose isomerase deficiency (14q21): hypotonia, diarrhea and vomiting, hepatomegaly (fibrosis progressing to cirrhosis), thrombosis, hyperinsulinism, convulsions caused by hypoglycemia. Treatment: oral mannose to obtain a mannosemia around 150µmol/L;

-         type Ic, deficit in α-1,3-glucosyltransferase (ALG6) [MIM 603 147]: psychomotor retardation, sometimes seizures; complex abnormalities of hemostasis without hepatic failure with risk of bleeding and thrombosis; sometimes benign intracranial hypertension

-   type Iq [MIM 612 379],  or Al-Gazali syndrome: mutation of the SRD5A3 gene (4q12) resulting in type 3 steroid alpha-5-reductase deficiency. The phenotype is highly variable: visual impairment(coloboma, cataract, nystagmus, hypoplasia/optic nerve atrophy, glaucoma), ichthyosiform dermatitis, midline cerebral malformations (pituitary hypoplasia), endocrine abnormalities and mental retardation. Sometimes: abnormalities of clotting. A phenotype close to CHIME syndrome.

-         extremely rare types: Id [MIM 601 110], Ie [MIM 608 799], If [MIM 609 180], [MIM 607 143] Ig, Ih [MIM 608 104], Ii [MIM 607 906], Ij [MIM 608 903], Ik [MIM 608 540], he [MIM 608 776], Im [MIM 610 768], In [MIM 612 015], Io [MIM 612 937], I p [MIM 613 661], Iq [MIM 612 379], Ir [MIM 614 507 ]

-         type Ix: moderatepsychomotor retardation  with retinitis pigmentosa;

-         type IIa: severe deficiency in N - acetylglucosaminyltransferase II (MGAT2) [MIM 212 066] psychomotor retardation, facial dysmorphism (coarse features), digestive disorders; seizures and retinal damage

-         type IIb: deficit in α-1,2 glucosidase (GCS1) [MIM 606 056]

-         type IIc (or leukocyte adhesion deficit II): deficit of transport of fucose from the cytosol to the Golgi apparatus (FUCTI) (MIM 266 265); can be treated with oral fucose

-         type IId: α-1,4 galactosyltransferase of Golgi (B4GALTI) [MIM 607 091] deficiency

-         very rare types: IIe [MIM 608 779] IIR [MIM 603 585], IIg [MIM 611 209], IIh [MIM 611 182], IIi [MIM 613 612 ]

-         type III: very rare; convulsive encephalopathy with piriformis syndrome and abnormal pigmentation of the skin similar to incontinentia pigmenti

-         type IV: very rare; severe psychomotor retardation with hypsarrhythmia resistant to antiepileptic drugs.

A new classification of the CDG uses the gene name followed with -CDG: for example, CDG - Ia becomes PMM2-CDG.

Diagnosis: special electrophoresis of transferrin.

Anesthetic implications: 

anesthesia for an epileptic or polyhandicaped patient; monitor blood sugar levels; check hemostasis which is often abnormal because of liver damage; sometimes deficiency in factor XI and IX with APTT prolongation but also in protein C or S with thrombophilia. Check thyroid. Echocardiography.

References : 

-        de Lonlay P, Dormier-Daire V, Vuillaumier-Barrot S, Cuer M, Durand G, Munnich A, Saudubray JM, Seta N.
Syndrome d'hypoglycosylation des glycoprotéines sériques.
Arch Pédiatr 2000 ; 7 : 173-84.

-        Meaudre E, Meyrieux V, Suprano I, Camboulives J, Paut O.
Anesthesia considerations in carbohydrate-deficient glycoprotein syndrome type I.
Pediatr Anesth 2005 ; 15 : 905-6.

-        Lehavi A, Mandel H, Katz Y.
Anesthetic management of a boy with congenital disorder of glycosylation (CDG) I-x.
Int J Clin Med 2011; 2: 325-7.

-        Freeze HH, Eklund EA, Patterson MC.
Neurology of inherited glycosylation disorders.
Lancet Neurol 2012 ; 11 : 453-66.

-        Sakai W,Yoshikawa Y, Tokinaga Y, Yamakage M.
Anesthetic management of a child with phosphomannomutase-2 congenital disorder of glycosylation (PMM2-CDG).
JA Clinical Reports 2017;  3:8 DOI 10.1186/s40981-017-0080-y

Updated: July 2023