2019 - present ReviewerASHG 2017 - present subcoordinatorMetabERN, European Metabolic reference Networks 2016 - present Board MemberSociety for the Study of Inborn Errors of Metabolism Council 2015 - present Editor in ChiefSSIEM 2015 - present Council [mayoclinic.org]

Both findings are consistently present and are required for the diagnosis. [pubs.rsna.org]

Affected individuals may also present with eye, skin, and cardiac disease, as well as facial dysmorphisms. [atm.amegroups.com]

Kyphoscoliosis was also present. In general, he showed poor growth with muscle atrophy and lack of pubertal development. A coagulopathy developed at age 9 years, which led to the correct diagnosis of CDG2A. [findzebra.com]

• Short Stature

  Genes related to Mgat2-cdg MGAT2 View recommended genes panels Clinical Features Top most frequent phenotypes and symptoms related to Mgat2-cdg Intellectual disability Seizures Global developmental delay Short stature Generalized hypotonia Hearing impairment [mendelian.co]

  stature, craniofacial dysmorphism, with or without congenital heart defects (JDSCD), B3GAT3-congenital disorder of glycosylation (B3GAT3-CDG) Peters-plus syndrome, B3GLCT-congenital disorder of glycosylation (B3GLCT-CDG) B4GALNT1-congenital disorder [invitae.com]

  Other features included mild to moderate bilateral sensorineural hearing loss, early hypotonia and late hypertonia, short terminal phalanges, and poor general growth with postnatal short stature. [findzebra.com]

  Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms). [ncbi.nlm.nih.gov]

  […] neck Decreased length of neck 0000470 Short stature Decreased body height Small stature [ more ] 0004322 Slender long bone Long bones slender Thin long bones [ more ] 0003100 Stereotypy Repetitive movements Repetitive or self-injurious behavior [ more [rarediseases.info.nih.gov]

• Recurrent Infection

  Fucose therapy can be beneficial in treating recurrent infections associated with this form of CDG and improving health. However, fucose therapy does not help with other symptoms of this disorder. [rarediseases.org]

  Therefore, clinical features such as syndromic fat pads and/or inverted nipples, chronic diarrhea, liver fibrosis, ichtiosis syndrome, different neurosyndomatic conditions (e.g. cataract, sensorineural deafness, radio-ulnar synostosis, recurrent infections [biochemia-medica.com]

  atypical, familial disseminated) STAT3 (Hyper-IgE recurrent infection syndrome) STAT5B (Growth hormone insensitivity with immunodeficiency) STIL (Microcephaly, primary autosomal recessive, 7) STIM1 (Immune dysfunction, with T-cell inactivation due to [de.praenatal-medizin.de]

  A typical feature was recurrent infections with marked leukocytosis. Neutrophils of these patients lack sialyl-Lewis x, a fucose-containing carbohydrate ligand of the selectin family of cell adhesion molecules. [nature.com]

• Ascites

  Ig N-glycosylation (assembly) Mannosyltransferase VIII deficiency Facial dysmorphism, psychomotor retardation, hypotonia, seizures, microcephaly Ih N-glycosylation (assembly) Glycosyltransferase II deficiency Hepatomegaly, protein-losing enteropathy, ascites [accessanesthesiology.mhmedical.com]

  […] absent psychomotor development, progressive microcephaly, and death in status epilepticus (40); oligohydramnion, dysmorphy, hypotonia, seizures, cerebellar hypoplasia, and severe thrombocytopenia (41); oligohydramnion, hypotonia, diarrhea, vomiting, ascites [nature.com]

• Lymphedema

  […] dilated, 1X) FLCN (Birt-Hogg-Dube syndrome) FLG (Ichthyosis vulgaris) FLJ14813 (Thrombocytopenia-2) FLJ22792 (Premature ovarian failure 2B) FLNA (FG syndrome 2) FLNB (Atelosteogenesis, type III) FLNC (Myopathy, myofibrillar, filamin C-related) FLT4 (Lymphedema [de.praenatal-medizin.de]

  Patients with autosomal recessive mutations in RELN typically present with microcephaly, seizures, marked cognitive impairment, and congenital lymphedema. The supratentorial brain shows a simplified gyration pattern in the majority of patients. [pubs.rsna.org]

• Poor Feeding

  Pontocerebellar Hypoplasia Type 6 (PCH type 6): PCH type 6 manifests as early as the first day of life or within the first month of life as infantile encephalopathy, with generalized hypotonia, lethargic, poor sucking and poor feeding. [rarediseases.org]

• Anhidrosis

  NRAMP2 (Anemia, hypochromic microcytic) NRAS (Colorectal cancer) NSD1 (Beckwith-Wiedemann syndrome) NSDHL (CHILD syndrome) NT5C3 (Anemia, hemolytic, due to UMPH1 deficiency) NTF4 (Glaucoma 1, open angle, 1O) NTRK1 (Insensitivity to pain, congenital, with anhidrosis [de.praenatal-medizin.de]

• Coxa Valga

  Coxa valga MedGen UID: 116080 •Concept ID: C0239137 • Finding Coxa valga is a deformity of the hip in which the angle between the femoral shaft and the femoral neck is increased compared to age-adjusted values (about 150 degrees in newborns gradually [ncbi.nlm.nih.gov]

  […] the dentition Abnormal dentition Abnormal teeth Dental abnormality [ more ] 0000164 Aggressive behavior Aggression Aggressive behaviour Aggressiveness [ more ] 0000718 Autosomal recessive inheritance 0000007 Brachycephaly Short and broad skull 0000248 Coxa [rarediseases.info.nih.gov]

• Beaked Nose

  Convex nasal ridge Beaked nose, Polly beak nasal deformity, Hooked nose, Convex dorsum of nose, Convex nasal dorsum, Beaklike protrusion [more] Nasal ridge curving anteriorly to an imaginary line that connects the nasal root and tip. [rarediseases.oscar.ncsu.edu]

  Dysmorphic features were mentioned in all cases and appeared distinctive with a beaked nose, long philtrum, thin vermilion border of the upper lip, large ears, gum hypertrophy, and thoracic deformity. [jmg.bmj.com]

  Cormier-Daire et al. (2000) described a child with CDG IIa who had severe mental retardation, chronic feeding problems with severe diarrhea, growth retardation, distinctive dysmorphic features including a beaked nose, long philtrum, thin vermilion border [findzebra.com]

  He developed a beaked nose and an abnormal fat distribution around the hips by a continuous improvement of the cutis laxa (Figure 1i). [nature.com]

• Short Neck

  He had thin lips, gum hypertrophy, large and posteriorly rotated ears, hook nose, large mouth, retrognathia, short neck, and distal limb anomalies. He also showed severe developmental delay. [findzebra.com]

  neck Decreased length of neck 0000470 Short stature Decreased body height Small stature [ more ] 0004322 Slender long bone Long bones slender Thin long bones [ more ] 0003100 Stereotypy Repetitive movements Repetitive or self-injurious behavior [ more [rarediseases.info.nih.gov]

  Short neck MedGen UID: 99267 •Concept ID: C0521525 • Finding Diminished length of the neck. [ncbi.nlm.nih.gov]

• Thin Lips

  Affected individuals had small head circumference, retrognathia, long eyelashes, thick eyebrows, prominent columella, prominent nasal bridge, thin upper lip, everted lower lip, diastema, and an open mouth due to the combination of retrognathia and an [findzebra.com]

  […] volume of lip Thin lips [ more ] 0000233 Thoracolumbar kyphoscoliosis 0003423 Type II transferrin isoform profile 0012301 Unsteady gait Unsteady walk 0002317 Ventricular septal defect Hole in heart wall separating two lower heart chambers 0001629 Wide [rarediseases.info.nih.gov]

  lips, wide set nipples and anteposition of the anus were noted at birth. [nature.com]

• Unstable Gait

  On examination, he had severe mental retardation with no speech and an unstable gait. [jmg.bmj.com]

• Hypoalbuminemia

  The consistent hypoalbuminemia in CDG-Ia may be related to liver dysfunction, to protein-losing enteropathy and other unknown factors. [nature.com]

  Epilepsy Panel AP3B2 Developmental and epileptic encephalopathy 48 617276 EPI Epilepsy Panel APC(incl. 5’UTR) Adenomatous polyposis coli Gastric cancer, somatic 175100 613659 HCPHereditary Cancer Panels APTX Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia [lhsc.on.ca]

  Infants with CDG may present with fulminant multi-organ disease, intractable seizures, or severe hypoalbuminemia progressing to anasarca. Some patients respond to aggressive diuresis and albumin replacement while others are refractive to treatment. [atm.amegroups.com]

  (Hyperchylomicronemia, late-onset) APOB (Hypercholesterolemia, due to ligand-defective apo B) APOC2 (Hyperlipoproteinemia, type Ib) APOE (Alzheimer disease-2) APP (Alzheimer disease 1, familial) APTX (Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia [de.praenatal-medizin.de]

• Neutrophilia

  Cataract, congenital nuclear, autosomal recessive 3) CRYBB2 (Cataract, cerulean, type 2) CRYBB3 (Cataract, congenital nuclear, 2) CRYGC (Cataract, Coppock-like) CRYGD (Cataract, congenital, cerulean type, 3) CSF2RA (Pulmonary alveolar proteinosis) CSF3R (Neutrophilia [de.praenatal-medizin.de]

• Leukocytosis

  Lack thereof leads to leukocytosis and increase sensitivity to infections as seen in SLC35C1-CDG(CDG-IIc); caused by a GDP-fucose (Fuc) transporter deficiency. [wikidoc.org]

  A typical feature was recurrent infections with marked leukocytosis. Neutrophils of these patients lack sialyl-Lewis x, a fucose-containing carbohydrate ligand of the selectin family of cell adhesion molecules. [nature.com]

Galactose treatment in PGM1-CDG led to treatment trials and successful dietary treatment in other types of CDGs as well. [mayoclinic.org]

In flow cytometry, the binding of Ricinus communis lectin (reactive with β‐galactose primarily) to control platelets increased after neuraminidase treatment: this increase was smaller (p < 0.01) in CDG Ia patients (3.1 ± 0.08 times) than in control platelets [onlinelibrary.wiley.com]

Treatment for glycosylation defects is mainly supportive, although targeted therapies are available for MPI-CDG, SLC35C1-CDG, PIGM-CDG, and PGM1-CDG. Details about these treatments are under the “Targeted Therapies and Prognosis” section below. [atm.amegroups.com]

Standard Therapies Treatment The treatment of most forms of CDG is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. [rarediseases.org]

Affected individuals should talk to their physician and medical team about their specific case, associated symptoms and overall prognosis. [rarediseases.org]

In the absence of shunt-related complications, the prognosis is generally favorable. [pubs.rsna.org]

Details about these treatments are under the “Targeted Therapies and Prognosis” section below. [atm.amegroups.com]

PMID: 30345709Free PMC Article Prognosis Pascoal C, Ferreira I, Teixeira C, Almeida E, Slade A, Brasil S, Francisco R, Ligezka AN, Morava E, Plotkin H, Jaeken J, Videira PA, Barros L, Dos Reis Ferreira V Orphanet J Rare Dis 2022 Oct 29;17(1):398. doi: [ncbi.nlm.nih.gov]

Clinical features and genetic etiology of more common CDG by pathway is summarized in Table S1. [atm.amegroups.com]

Congenital pontocerebellar atrophy in three patients: clinical, radiologic and etiologic considerations. Neuroradiology. 1996;38(7):684-7. Barth PG, Blennow G, Lenard HG, et al. [rarediseases.org]

[…] stereotypy Seizure Self-mutilation Unsteady gait Ear malformation Macrotia Posteriorly rotated ears Sensorineural hearing loss disorder Growth abnormality Failure to thrive Postnatal growth retardation Short stature Neoplasm Midfrontal capillary hemangioma Etiology [ncbi.nlm.nih.gov]

In addition, several CDGs of so far unknown etiology (CDG-x) have been recognized. [biochemia-medica.com]

Epidemiology The incidence and prevalence of all types of CDG in aggregate have not been well established, although patients have been reported worldwide from almost every ethnic background and both sexes are equally affected. [atm.amegroups.com]

Although the pathophysiology of multitude symptoms remains to be elucidated, the relationship between certain glycosylation pathways and specific clinical symptoms has been clarified. [atm.amegroups.com]

Gastrostomy tube may be required for feeding; fundoplication may be needed to prevent aspiration. [rarediseases.org]

As to symptomatic treatment, we have obtained efficient prevention of stroke-like events by using 0.5 mg/kg per day acetylsalicylic acid (C. Van Geet and J. Jaeken, in preparation). [nature.com]

For example, N-acetylgalactosaminyltransferase 3 (GALNT3) O-glycosylates the phosphaturic hormone, FGF23, preventing proteolytic cleavage and allowing its intact secretion. [atm.amegroups.com]