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]

• Epilepsy

  […] syndrome 605802 EPI Epilepsy Panel [lhsc.on.ca]

  The term epilepsy is used to describe chronic, recurrent seizures. [rarediseases.oscar.ncsu.edu]

  nocturnal frontal lobe, type 4) CHRNA4 (Epilepsy, nocturnal frontal lobe, 1) CHRNB1 (Myasthenic syndrome, congenital, associated with acetylcholine receptor deficiency) CHRNB2 (Epilepsy, nocturnal frontal lobe, 3) CHRND (Multiple pterygium syndrome, [de.praenatal-medizin.de]

  ALG6-CDG: A recognizable phenotype with epilepsy, proximal muscle weakness, ataxia and behavioral and limb anomalies. J Inherit Metab Dis. 2016;39(5):713–23.Google ScholarPubMed Morava, E, Vodopiutz, J, Lefeber, DJ, et al. [cambridge.org]

  II (I-cell disease, Pacman dysplasia) (ML II), Mucolipidosis type III (pseudo-Hurler polydystrophy) (ML III), Congenital disorders of glycosylation (GNPTAB-CDG) Geroderma osteodysplastica, Congenital disorders of glycosylation (GORAB-CDG) Myoclonic epilepsy [invitae.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]

• Jaundice

  The two sibling neonates recently described with a multi-systemic disorder had perinatal asphyxia, mild dysmorphic features, hypotonia, prolonged jaundice and hepatosplenomegaly with evidence of liver disease. [nature.com]

• Esotropia

  Ocular abnormalities of CDG-Ia include: myopia, infantile esotropia, delayed visual maturation, low vision, optic pallor, and reduced rod function on electroretinography.[11] Three subtypes of CDG I (a,b,d) can cause congenital hyperinsulinism with hyperinsulinemic [wikidoc.org]

  Esotropia, long philtrum, large, hypoplastic or dysplastic ears, hypotonic facies, and downslanting palpebral fissures are seen (top row). Profile view shows the prominent chin, which is more pronounced with age (bottom row). [atm.amegroups.com]

• 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]

• Muscle Weakness

  It has also been found that some patients with PCH type 1 develop the signs of muscle weakness or developmental delay at the age of several months. These late presenting patients have a milder form and may live up to four years. [rarediseases.org]

  Skelet Muscle. 2018;8(1):17.CrossRefGoogle ScholarPubMed Morava, E, Tiemes, V, Thiel, C, et al. ALG6-CDG: A recognizable phenotype with epilepsy, proximal muscle weakness, ataxia and behavioral and limb anomalies. [cambridge.org]

• Decrease in Height

  […] 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 ] 0000733 Thick [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]

• 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]

• 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]

• Seizure

  MGAT2-CDG is a form of congenital disorders of N-linked glycosylation characterized by facial dysmorphism (large, posteriorly rotated ears with prominent antihelices, convex nasal ridge, open mouth, large and crowded teeth), stereotypic hand movements, seizures [mendelian.co]

  The term epilepsy is used to describe chronic, recurrent seizures. [rarediseases.oscar.ncsu.edu]

  microcephaly If N-glycosylation (assembly) Lec35 deficiency Severe encephalopathy, dwarfism, erythematous skin disorder Ig N-glycosylation (assembly) Mannosyltransferase VIII deficiency Facial dysmorphism, psychomotor retardation, hypotonia, seizures [accessanesthesiology.mhmedical.com]

  Recurrent apnea, intractable seizures occur early in the course of this condition. [rarediseases.org]

  […] plus, type 2/Febrile seizures, familial, 3A/Migraine, familial hemiplegic, 3 182389 EPI Epilepsy Panel SCN1B Epilepsy, generalized, with febrile seizures plus, type 1/Atrial fibrillation, familial, 13/Brugada syndrome 5 600235 EPI Epilepsy Panel SCN2A [lhsc.on.ca]

• Convulsions

  […] intermittent abnormality of the central nervous system due to a sudden, excessive, disorderly discharge of cerebral neurons and characterized clinically by some combination of disturbance of sensation, loss of consciousness, impairment of psychic function, or convulsive [rarediseases.oscar.ncsu.edu]

  For example, anti-seizure medications (anti-convulsants) may be used to treat seizures, thyroid hormone may be used to treat hypothyroidism and surgery may be used to treat certain skeletal malformations. [rarediseases.org]

  (Omodysplasia 1) GPD1L (Brugada syndrome 2) GPHN (Hyperekplexia) GPI (Hemolytic anemia, nonspherocytic, due to glucose phosphate isomerase deficiency) GPR143 (Nystagmus 6, congenital, X-linked) GPR56 (Polymicrogyria, bilateral frontoparietal) GPR98 (Convulsions [de.praenatal-medizin.de]

  The recurrent episodes in infancy and early childhood may be associated with convulsions, apnea, decreased consciousness or coma. Patients may have generalized edema. [nature.com]

  […] lipofuscinosis, neuronal, 1 256730 LSD Lysosomal Storage Disorder PRICKLE1 Epilepsy, progressive myoclonic 1B 612437 EPI Epilepsy Panel PRKAR1A Carney complex, type 1 160980 HCPHereditary Cancer Panels PRPS1 CMTX5 311070 CMT Charcot-Marie-Tooth PRRT2 Convulsions [lhsc.on.ca]

• Chorea

  Victorian Clinical Genetics Services Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes Congenital disorder of glycosylation, type IIa, 212066 CONGENITAL DISORDER OF GLYCOSYLATION TYPE 2A (CDG2A) MGAT2 in Childhood onset dystonia or chorea [panelapp.genomicsengland.co.uk]

  Severe chorea occurs, and epilepsy is frequent, while signs of spinal anterior horn involvement are absent in PCH type 2. The main feature distinguishing PCH type 1 from PCH type 2 is that anterior horn cells are spared in PCH type 2. [rarediseases.org]

  […] combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation) NHLRC1 (Epilepsy, myoclonic, Lafora type) NHS (Cataract, congenital, X-linked) NIPA1 (Spastic paraplegia-6) NIPBL (Cornelia de Lange syndrome 1) NKX2-1 (Chorea [de.praenatal-medizin.de]

• Unstable Gait

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

• Cerebellar Sign

  Intellectual disability and cerebellar signs of visual impairment, nystagmus and ataxia follow the initial presentation. [rarediseases.org]

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]