Abstract
Congenital disorders of glycosylation (CDG) are a group of rare inherited metabolic
disorders caused by defects in various defects of protein or lipid glycosylation pathways.
The symptoms and signs of CDG usually develop in infancy. Epilepsy is commonly observed
in CDG individuals and is often a presenting symptom. These epilepsies can present
across the lifespan, share features of refractoriness to antiseizure medications,
and are often associated with comorbid developmental delay, psychomotor regression,
intellectual disability, and behavioral problems.
In this review, we discuss CDG and infantile epilepsy, focusing on an overview of
clinical manifestations and electroencephalographic features. Finally, we propose
a tiered approach that will permit a clinician to systematically investigate and identify
CDG earlier, and furthermore, to provide genetic counseling for the family.
Keywords
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References
- Incidence of unprovoked seizures and epilepsy in Iceland and assessment of the epilepsy syndrome classification: a prospective study.Lancet Neurol. 2005; 4: 627-634
- Incidence and classification of new-onset epilepsy and epilepsy syndromes in children in Olmsted County, Minnesota from 1980 to 2004: a population-based study.Epilepsy Res. 2011; 95: 110-118
- Incidence and outcome of epilepsy syndromes with onset in the first year of life: A retrospective population-based study.Epilepsia. 2016; 57: 1594-1601
- Early onset epilepsy and inherited metabolic disorders: Diagnosis and management.Can J Neurol Sci. 2010; 37: 350-358
- Congenital disorders of glycosylation from a neurological perspective.Brain Sci. 2021; 11: 88
- Perspectives on glycosylation and its congenital disorders.Trends Genet. 2018; 34: 466-476
- What is new in CDG?.J Inherit Metab Dis. 2017; 40: 569-586
- Neurological aspects of human glycosylation disorders.Annu Rev Neurosci. 2015; 38: 105-125
- Familial psychomotor retardation with markedly fluctuating serum prolactin, FSH and GH levels, partial TBG-deficiency, increased serum arylsulphatase A and increased CSF protein: a new syndrome?.Pediatr Res. 1980; 14: 179
- Congenital disorders of glycosylation: Prevalence, incidence and mutation spectrum in the Polish population.Mol Genet Metab Rep. 2021; 27100726
- Congenital disorders of glycosylation.Ann Transl Med. 2018; 6: 477
- CDG nomenclature: Time for a change!.BBA. 2009; 1792: 825-826
- Congenital disorders of glycosylation (CDG): Quo vadis?.Eur J Med Genet. 2018; 61: 643-663
- Therapeutic approaches in Congenital Disorders of Glycosylation (CDG) involving N-linked glycosylation: an update.Genet Med. 2020; 22: 268-279
- ALG3-CDG: a patient with novel variants and review of the genetic and ophthalmic findings.BMC Ophthalmol. 2021; 21: 249
- ALG6-CDG: a recognizable phenotype with epilepsy, proximal muscle weakness, ataxia and behavioral and limb anomalies.J Inherit Metab Dis. 2016; 39: 713-723
- SLC35A2-CDG: Novel variant and review.Mol Genet Metab Rep. 2021; 26100717
- NANS-CDG: Delineation of the Genetic, Biochemical, and Clinical spectrum.Front Neurol. 2021; 12668640
- SRD5A3-CDG: Emerging Phenotypic Features of an Ultrarare CDG Subtype.Front Genet. 2021; 12737094
- The challenge of CDG diagnosis.Mol Genet Metab. 2019; 126: 1-5
- Complex Phenotypes in Inborn Errors of Metabolism: Ooverlapping Presentations in Congenital Disorders of Glycosylation and Mitochondrial Disorders.Pediatr Clin N Am. 2018; 65: 375-388
- Electroclinical Features of Early-Onset Epileptic Encephalopathies in Congenital Disorders of Glycosylation (CDGs).JIMD Rep. 2016; 27: 93-99
- ALG13 participates in epileptogenesis via regulation of GABAA receptors in mouse models.Cell Death Discov. 2020; 6: 87
- Congenital disorders of glycosylation presenting as epileptic encephalopathy with migrating partial seizures in infancy.Dev Med Child Neurol. 2016; 58: 1085-1091
- Epileptic spasms in congenital disorders of glycosylation.Epileptic Disord. 2017; 19: 15-23
- Congenital disorders of glycosylation type IIb with MOGS mutations cause early infantile epileptic encephalopathy, dysmorphic features, and hepatic dysfunction.Brain Dev. 2021; 43: 402-410
- 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. 2003; 278: 22498-224505
- Wide clinical spectrum in ALG8-CDG: clues from molecular findings suggest an explanation for a milder phenotype in the first-described patient.Pediatr Res. 2019; 85: 384-389
- Further Delineation of the ALG9-CDG Phenotype.JIMD Rep. 2016; 27: 107-112
- Early and lethal neurodegeneration with myasthenic and myopathic features: A new ALG14-CDG.Neurology. 2017; 89: 657-664
- Pathogenic Variants in Fucokinase Cause a Congenital Disorder of Glycosylation.Am J Hum Genet. 2018; 103: 1030-1037
- Biallelic Mutations in FUT8 Cause a Congenital Disorder of Gglycosylation with Defective Fucosylation.Am J Hum Genet. 2018; 102: 188-195
- Siblings with MAN1B1-CDG Showing Novel Biochemical Profiles.Cells. 2021; 10: 3117
- Immune dysfunction in MGAT2-CDG: A clinical report and review of the literature.Am J Med Genet A. 2021; 185: 213-218
- Epilepsy and movement disorders in CDG: Report on the oldest-known MOGS-CDG patient.Am J Med Genet. 2021; 185A: 219-222
- Oligosaccharyltransferase complex-congenital disorders of glycosylation: A novel congenital disorder of glycosylation.Am J Med Genet. 2020; 182A: 1460-1465
- Long-term evolution of eight Spanish patients with CDG type Ia: typical and atypical manifestations.Eur J Paediatr Neurol. 2009; 13: 444-451
- A new congenital disorder of glycosylation caused by a mutation in SSR4, the signal sequence receptor 4 protein of the TRAP complex.Hum Mol Genet. 2014; 23: 1602-1605
- Phenotypic Heterogeneity in a Congenital Disorder of Glycosylation Caused by Mutations in STT3A.J Child Neurol. 2017; 32: 560-565
- Two Argentinean Siblings with CDG-Ix: A Novel Type of Congenital Disorder of Glycosylation?.JIMD Rep. 2011; 1: 65-72
- Adams-Oliver syndrome caused by mutations of the EOGT gene.Am J Med Genet. 2019; 179A: 2246-2251
- B3GALNT2 mutations associated with non-syndromic autosomal recessive intellectual disability reveal a lack of genotype–phenotype associations in the muscular dystrophy-dystroglycanopathies.Genome Med. 2017; 9: 118
- Seizure-genotype relationship in Fukuyama-type congenital muscular dystrophy.Brain Dev. 2008; 30: 59-67
- Novel congenital disorder of O-linked glycosylation caused by GALNT2 loss of function.Brain. 2020; 143: 1114-1126
- 160 kb deletion in ISPD unmasking a recessive mutation in a patient with Walker-Warburg syndrome.Eur J Med Genet. 2013; 56: 689-694
- POMGnT1 Mutations in Congenital Muscular Dystrophy: Genotype-Phenotype Correlation and Expanded Clinical Spectrum.Arch Neurol. 2006; 63: 1491-1495
- POMK mutations disrupt muscle development leading to a spectrum of neuromuscular presentations.Hum Mol Genet. 2014; 23: 5781-5792
- Clinical long-time course, novel mutations and genotype-phenotype correlation in a cohort of 27 families with POMT1-related disorders.Orphanet J Rare Dis. 2019; 14: 179
- Hyperphosphatasia with mental retardation syndrome, expanded phenotype of PIGL related disorders.Mol Genet Metab Rep. 2018; 15: 46-49
- PIGO mutations in intractable epilepsy and severe developmental delay with mild elevation of alkaline phosphatase levels.Epilepsia. 2014; 55: e13-e17
- PGAP2 Mutations, Affecting the GPI-Anchor-Synthesis Pathway, Cause Hyperphosphatasia with Mental Retardation Syndrome.Am J Hum Genet. 2013; 92: 584-589
- Compound Heterozygous PIGS Variants Associated With Infantile Spasm, Global Developmental Delay, Hearing Loss, Visual Impairment, and Hypotonia.Front Genet. 2020; 11: 564
- PIGT-CDG, a disorder of the glycosylphosphatidylinositol anchor: description of 13 novel patients and expansion of the clinical characteristics.Genet Med. 2019; 21: 2216-2223
- COG1-congenital disorders of glycosylation: Milder presentation and review.Clin Genet. 2021; 100: 318-323
- Mutations in COG2 encoding a subunit of the conserved oligomeric golgi complex cause a congenital disorder of glycosylation.Clin Genet. 2015; 87: 455-460
- Golgi function and dysfunction in the first COG4-deficient CDG type II patient.Hum Mol Genet. 2009; 18: 3244-3256
- COG5-CDG: expanding the clinical spectrum.Orphanet J Rare Dis. 2012; 7: 94
- Fatal outcome due to deficiency of subunit 6 of the conserved oligomeric Golgi complex leading to a new type of congenital disorders of glycosylation.Hum Mol Genet. 2010; 19: 3623-3633
- Mutation of the COG complex subunit gene COG7 causes a lethal congenital disorder.Nat Med. 2004; 10: 518-523
- A case of fatal Type I congenital disorders of glycosylation (CDG I) associated with low dehydrodolichol diphosphate synthase (DHDDS) activity.Orphanet J Rare Dis. 2016; 11: 84
- DPM2-CDG: A Muscular Dystrophy-Dystroglycanopathy Syndrome with Severe Epilepsy.Ann Neurol. 2012; 72: 550-558
- GMPPB-Associated Dystroglycanopathy: Emerging Common Variants with Phenotype Correlation.Hum Mutat. 2015; 36: 1159-1163
- Mutation of NgBR, a subunit of cis-prenyltransferase, causes a congenital disorder of glycosylation.Cell Metab. 2014; 20: 448-457
- Encephalopathy caused by Novel Mutations in the CMP-Sialic Acid Transporter, SLC35A1.Am J Med Genet A. 2017; 173: 2906-2911
- Recessive mutations in SLC35A3 cause early onset epileptic encephalopathy with skeletal defects.Am J Med Genet. 2017; 173: 1119-1123
- SLC39A8 deficiency: biochemical correction and major clinical improvement by manganese therapy.Genet Med. 2018; 20: 259-268
- SRD5A3-CDG: Expanding the phenotype of a congenital disorder of glycosylation with emphasis on adult onset features.Am J Med Genet A. 2016; 170: 3165-3171
- TRAPPC11 and GOSR2 mutations associate with hypoglycosylation of α-dystroglycan and muscular dystrophy.Skelet Muscle. 2018; 8: 17
- Successful treatment of intractable epilepsy with ketogenic diet therapy in twins with ALG3-CDG.Brain Dev. 2020; 42: 539-545
- Rapid determination of transferrin isoforms by immunoaffinity liquid chromatography and electrospray mass spectrometry.Clin Chem. 2001; 47: 513-518
- Congenital disorders of glycosylation: a rapidly expanding disease family.Annu Rev Genomics Hum Genet. 2007; 8: 261-278
- Solving glycosylation disorders: fundamental approaches reveal complicated pathways.Am J Hum Genet. 2014; 94: 161-175
- RFT1-congenital disorder of glycosylation (CDG) syndrome: a cause of early-onset severe epilepsy.Epileptic Disord. 2016; 18: 92-96
- Congenital Disorders of Glycosylation: What Clinicians Need to Know?.Front Pediatr. 2021; 9715151
- Congenital disorders of glycosylation with emphasis on cerebellar involvement.Semin Neurol. 2014; 34: 357-366
- Congenital Disorders of Glycosylation.Adv Neonatal Care. 2012; 12: 90-95
- Nutritional Therapies in Congenital Disorders of Glycosylation (CDG).Nutrients. 2017; 9: 1222
Article info
Publication history
Published online: April 20, 2023
Accepted:
April 4,
2023
Received in revised form:
April 1,
2023
Received:
June 18,
2022
Identification
Copyright
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