54 articles
ALG-pathway congenital disorders of glycosylation
ALG-pathway congenital disorders of glycosylation are inherited metabolic diseases in which defective ALG-family genes disrupt assembly of lipid-linked oligosaccharides in the endoplasmic reticulum, causing type I CDG; ALG6-CDG is the most common subtype.
ALG11-CDG
ALG11-CDG (CDG-Ip) is a rare autosomal recessive N-glycosylation disorder caused by ALG11 mutations, causing epilepsy, developmental disability, microcephaly, and sensorineural deafness, with no specific treatment.
ALG13-CDG
ALG13-CDG (CDG type Is, EIEE36) is a rare X-linked congenital disorder of glycosylation caused by ALG13 gene variants, presenting in infancy with epileptic spasms, hypotonia, and developmental delay; transferrin tests are usually normal, so genetic sequencing confirms it.
ALG2-CDG
ALG2-CDG (CDG-Ii, CDG1I, mannosyltransferase 2 deficiency) is an ultra-rare autosomal recessive congenital disorder of glycosylation from ALG2 loss-of-function variants, causing infantile spasms, iris coloboma, cataract, developmental delay, and coagulopathy.
ALG3-CDG
ALG3-CDG (CDG-Id, OMIM 601110) is a rare autosomal recessive congenital disorder of glycosylation caused by ALG3 alpha-1,3-mannosyltransferase deficiency, causing truncated N-glycans, severe epilepsy, microcephaly, hypotonia, and multisystem disease.
ALG6-CDG
ALG6-CDG, also called congenital disorder of glycosylation type Ic (CDG-Ic), is an inherited autosomal recessive metabolic disease causing hypotonia, seizures, and developmental delay in infants, first reported in 1998.
ALG8-CDG
ALG8-CDG (CDG-Ih, glucosyltransferase 2 deficiency) is a rare autosomal recessive congenital disorder of N-linked glycosylation from ALG8 (11q14.1) mutations, causing severe hepatic, gastrointestinal, neurologic, and coagulation symptoms with poor prognosis.
ALG9-CDG
ALG9-CDG (CDG-IL, CDG1L) is a rare autosomal recessive N-glycosylation disorder from ALG9 (11q23) mannosyltransferase 7-9 deficiency, causing infantile epilepsy, hypotonia, cysts, or lethal fetal skeletal dysplasia.
ATP6AP1-CDG
ATP6AP1-CDG (CDG-IIs, Immunodeficiency 47, OMIM 300972) is a rare X-linked recessive congenital disorder of glycosylation causing hepatopathy, immunodeficiency, cutis laxa, and type II transferrin glycosylation defects, first described in 2016.
Autism spectrum disorder-epilepsy-arthrogryposis syndrome
Autism spectrum disorder-epilepsy-arthrogryposis syndrome (SLC35A3-CDG, AMRS, OMIM 615553) is an ultra-rare autosomal recessive N-linked glycosylation disorder from SLC35A3 variants, causing autism, epilepsy, intellectual disability, arthrogryposis, and microcephaly.
CCDC115-CDG
CCDC115-CDG (CDG-IIo, CDG2O, MIM 616828) is an ultra-rare autosomal recessive congenital disorder of glycosylation caused by CCDC115 variants, causing a Golgi homeostasis defect with infantile hepatosplenomegaly, liver failure, hypotonia, and combined N- and O-glycosylation abnormalities.
CHIME syndrome
CHIME syndrome (Zunich neuroectodermal syndrome, OMIM 280000) is an extremely rare autosomal recessive PIGL-related congenital disorder of glycosylation marked by colobomas, heart defects, migratory ichthyosiform dermatosis, intellectual disability, and conductive hearing loss.
COG1-CDG
COG1-CDG (CDG-IIg, OMIM 611209) is an extremely rare autosomal recessive congenital disorder of glycosylation caused by COG1 gene variants, with growth retardation, microcephaly, psychomotor delay, dysmorphism, and type 2 transferrin IEF; only a handful of patients reported.
COG6-CGD
COG6-CGD (CDG2L, congenital disorder of glycosylation type IIl, OMIM 614576) is an autosomal recessive COG6-gene Golgi glycosylation disorder with neonatal multisystem disease, under 1 per million prevalence, and no interventional trials.
Congenital muscular dystrophy with intellectual disability and severe epilepsy
Congenital muscular dystrophy with intellectual disability and severe epilepsy, also DPM2-CDG or CDG type Iu (MIM 615042), is an ultra-rare autosomal recessive DPM2 glycosylation disorder first described by Barone in 2012, causing hypotonia, intractable epilepsy, microcephaly, and early death.
Congenital rubella syndrome
Congenital rubella syndrome, or congenital rubella, is a group of birth defects caused by maternal rubella infection during pregnancy, most commonly cataracts, heart disease, and hearing loss.
DDOST-CDG
DDOST-CDG (CDG-Ir, OMIM 614507) is an ultra-rare autosomal recessive congenital disorder of N-linked glycosylation caused by DDOST mutations, with hypotonia, developmental delay, and hepatic dysfunction.
Diagnosis of congenital disorders of glycosylation
Diagnosis of congenital disorders of glycosylation (CDG) proceeds from transferrin isoelectric focusing screening through enzyme assays to gene sequencing, since over 160 CDG types are recognized.
DK1-CDG
DK1-CDG (dolichol kinase deficiency, CDG type Im) is an autosomal recessive glycosylation disorder from DOLK mutations at 9q34.11, causing dilated cardiomyopathy, hypotonia, and ichthyosis, prevalence under 1 in a million.
DPM1-CDG
DPM1-CDG (CDG-Ie, OMIM 608799) is an ultra-rare autosomal recessive congenital disorder of glycosylation caused by DPM1 gene variants, with developmental delay, hypotonia, seizures, microcephaly, elevated CK, and fewer than 20 reported cases.
Genetic disorder
Genetic disorder: health condition caused by gene, chromosome, or multifactorial genetic abnormalities; inherited or somatic variants; diagnosed by exam, family history, and genetic testing; managed with counseling, screening, and emerging gene therapy.
Germ cell tumor
Germ cell tumor: a benign or malignant neoplasm arising from sperm- or egg-precursor cells, occurring in the gonads or extragonadal sites. Classified by WHO into GCNIS-derived and non-GCNIS groups; includes seminoma, teratoma, yolk sac tumor, choriocarcinoma.
GM3 synthase deficiency
GM3 synthase deficiency, also called Amish infantile epilepsy syndrome, salt & pepper syndrome, or ST3GAL5-CDG, is an autosomal recessive congenital disorder of glycosylation causing infantile refractory epilepsy, developmental stagnation, deafness, and skin pigment changes.
Hayley Okines
Hayley Leanne Okines (1997-2015), English progeria campaigner known as the 100-year-old teenager; wrote Old Before My Time and Young at Heart, joined Boston drug trials, died at 17 of pneumonia.
History and classification of congenital disorders of glycosylation
Congenital disorders of glycosylation, first described by Jaak Jaeken in 1980 as CDGS, were renamed at a 1999 workshop and have grown to about 200 inherited disorders.
Intellectual disability-seizures-hypophosphatasia-ophthalmic-skeletal anomalies syndrome
Intellectual disability-seizures-hypophosphatasia-ophthalmic-skeletal anomalies syndrome, also called MCAHS3 or PIGT-CDG, is an autosomal recessive GPI-anchor defect caused by biallelic PIGT variants, presenting in infancy with hypotonia, seizures, intellectual disability, and low alkaline phosphatase.
Kabuki syndrome
Kabuki syndrome (Niikawa–Kuroki syndrome), a rare congenital histone-modification disorder caused by KMT2D or KDM6A variants, with distinctive facies, fetal fingertip pads, growth and developmental delay, and emerging targeted therapies.
MAN1B1-CDG
MAN1B1-CDG, also called congenital disorder of glycosylation type II due to MAN1B1 deficiency, is a rare autosomal recessive Golgi glycosylation disorder (MAN1B1, 9q34.3) causing intellectual disability, hypotonia, truncal obesity, facial dysmorphism, and a type 2 transferrin IEF pattern.
Management and treatment of congenital disorders of glycosylation
Treatment of congenital disorders of glycosylation (CDG) relies on targeted supplements like mannose, galactose, fucose, and manganese for a few subtypes, with supportive care for the rest.
MGAT2-CDG
MGAT2-CDG (formerly CDG-IIa, Alkuraya syndrome) is an autosomal recessive congenital disorder of glycosylation caused by MGAT2 loss-of-function mutations at 14q21, causing facial dysmorphism, seizures, developmental delay, and bleeding tendency.