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Congenital disorder of glycosylation with defective fucosylation(CDGF1)

MedGen UID:
1647704
Concept ID:
C4693905
Disease or Syndrome
Synonyms: CDGF; CDGF1; CONGENITAL DISORDER OF GLYCOSYLATION WITH DEFECTIVE FUCOSYLATION 1
 
Related genes: FCSK, FUT8
 
Monarch Initiative: MONDO:0060720
OMIM®: 602589; 618005
OMIM® Phenotypic series: PS618005

Definition

Congenital disorder of glycosylation with defective fucosylation is an autosomal recessive multisystem disorder apparent from birth. Affected infants have poor growth, failure to thrive, hypotonia, skeletal anomalies, and delayed psychomotor development with intellectual disability. Additional highly variable congenital defects may be observed (summary by Ng et al., 2018). Genetic Heterogeneity of Congenital Disorders of Glycosylation with Defective Fucosylation See also CDGF2 (618323), caused by mutation in the FCSK gene (608675) on chromosome 16q22. For an overview of congenital disorders of glycosylation (CDG), see CDG1A (212065) and CDG2A (212066). [from OMIM]

Clinical features

From HPO
Nephrocalcinosis
MedGen UID:
10222
Concept ID:
C0027709
Disease or Syndrome
Nephrocalcinosis is the deposition of calcium salts in renal parenchyma.
Limb undergrowth
MedGen UID:
116086
Concept ID:
C0239399
Finding
Limb shortening because of underdevelopment of one or more bones of the extremities.
Abnormal cardiac septum morphology
MedGen UID:
6752
Concept ID:
C0018816
Congenital Abnormality
An anomaly of the intra-atrial or intraventricular septum.
Fetal growth restriction
MedGen UID:
4693
Concept ID:
C0015934
Pathologic Function
An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. 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).
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Feeding difficulties
MedGen UID:
65429
Concept ID:
C0232466
Finding
Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterised by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Subnormal intellectual functioning which originates during the developmental period. Intellectual disability, previously referred to as mental retardation, has been defined as an IQ score below 70.
Hip dislocation
MedGen UID:
42455
Concept ID:
C0019554
Injury or Poisoning
Displacement of the femur from its normal location in the hip joint.
Osteopenia
MedGen UID:
18222
Concept ID:
C0029453
Disease or Syndrome
Osteopenia is a term to define bone density that is not normal but also not as low as osteoporosis. By definition from the World Health Organization osteopenia is defined by bone densitometry as a T score -1 to -2.5.
Retrognathia
MedGen UID:
19766
Concept ID:
C0035353
Congenital Abnormality
An abnormality in which the mandible is mislocalised posteriorly.
Flexion contracture
MedGen UID:
83069
Concept ID:
C0333068
Anatomical Abnormality
A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.
Kyphoscoliosis
MedGen UID:
154361
Concept ID:
C0575158
Anatomical Abnormality
An abnormal curvature of the spine in both a coronal (lateral) and sagittal (back-to-front) plane.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Respiratory insufficiency
MedGen UID:
11197
Concept ID:
C0035229
Pathologic Function
Impairment of gas exchange within the lungs secondary to a disease process, neoplasm, or trauma, possibly resulting in hypoxia, hypercarbia, or both, but not requiring intubation or mechanical ventilation. Patients are normally managed with pharmaceutical therapy, supplemental oxygen, or both.
Neutropenia
MedGen UID:
163121
Concept ID:
C0853697
Finding
An abnormally low number of neutrophils in the peripheral blood.
Hypoglycemia
MedGen UID:
6979
Concept ID:
C0020615
Disease or Syndrome
A decreased concentration of glucose in the blood.
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Abnormal facial shape
MedGen UID:
98409
Concept ID:
C0424503
Finding
An abnormal morphology (form) of the face or its components.
Narrow forehead
MedGen UID:
326956
Concept ID:
C1839758
Finding
Width of the forehead or distance between the frontotemporales is more than two standard deviations below the mean (objective); or apparently narrow intertemporal region (subjective).
Broad forehead
MedGen UID:
338610
Concept ID:
C1849089
Finding
Width of the forehead or distance between the frontotemporales is more than two standard deviations above the mean (objective); or apparently increased distance between the two sides of the forehead.
Wide nasal bridge
MedGen UID:
341441
Concept ID:
C1849367
Finding
Increased breadth of the nasal bridge (and with it, the nasal root).
Short nose
MedGen UID:
343052
Concept ID:
C1854114
Finding
Distance from nasion to subnasale more than two standard deviations below the mean, or alternatively, an apparently decreased length from the nasal root to the nasal tip.
Hirsutism
MedGen UID:
42461
Concept ID:
C0019572
Disease or Syndrome
Abnormally increased hair growth referring to a male pattern of body hair (androgenic hair).
Polyhydramnios
MedGen UID:
6936
Concept ID:
C0020224
Pathologic Function
The presence of excess amniotic fluid in the uterus during pregnancy.
Hypothyroidism
MedGen UID:
6991
Concept ID:
C0020676
Disease or Syndrome
Deficiency of thyroid hormone.
Glaucoma
MedGen UID:
42224
Concept ID:
C0017601
Disease or Syndrome
Glaucoma refers loss of retinal ganglion cells in a characteristic pattern of optic neuropathy usually associated with increased intraocular pressure.
Buphthalmos
MedGen UID:
1641795
Concept ID:
C4551507
Congenital Abnormality
Diffusely large eye (with megalocornea) associated with glaucoma.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Professional guidelines

PubMed

Etzioni A, Sturla L, Antonellis A, Green ED, Gershoni-Baruch R, Berninsone PM, Hirschberg CB, Tonetti M
Am J Med Genet 2002 Jun 15;110(2):131-5. doi: 10.1002/ajmg.10423. PMID: 12116250

Recent clinical studies

Etiology

Al Tuwaijri A, Alyafee Y, Umair M, Alsubait A, Alharbi M, AlEidi H, Ballow M, Aldrees M, Alam Q, Al Abdulrahman A, Alrifai MT, Alfadhel M
Mol Genet Genomic Med 2023 Apr;11(4):e2117. Epub 2022 Nov 24 doi: 10.1002/mgg3.2117. PMID: 36426412Free PMC Article
Abu Bakar N, Ashikov A, Brum JM, Smeets R, Kersten M, Huijben K, Keng WT, Speck-Martins CE, de Carvalho DR, de Rizzo IMPO, de Mello WD, Heiner-Fokkema R, Gorman K, Grunewald S, Michelakakis H, Moraitou M, Martinelli D, van Scherpenzeel M, Janssen M, de Boer L, van den Heuvel LP, Thiel C, Lefeber DJ
J Inherit Metab Dis 2022 Jul;45(4):769-781. Epub 2022 Mar 28 doi: 10.1002/jimd.12496. PMID: 35279850Free PMC Article
Özgün N, Şahin Y
Brain Dev 2022 Mar;44(3):239-243. Epub 2021 Nov 18 doi: 10.1016/j.braindev.2021.11.001. PMID: 34802815
Jansen JC, van Hoek B, Metselaar HJ, van den Berg AP, Zijlstra F, Huijben K, van Scherpenzeel M, Drenth JPH, Lefeber DJ
J Inherit Metab Dis 2020 Nov;43(6):1310-1320. Epub 2020 Jul 17 doi: 10.1002/jimd.12273. PMID: 32557671Free PMC Article
Ng BG, Rosenfeld JA, Emrick L, Jain M, Burrage LC, Lee B; Undiagnosed Diseases Network, Craigen WJ, Bearden DR, Graham BH, Freeze HH
Am J Hum Genet 2018 Dec 6;103(6):1030-1037. Epub 2018 Nov 29 doi: 10.1016/j.ajhg.2018.10.021. PMID: 30503518Free PMC Article

Diagnosis

Abu Bakar N, Ashikov A, Brum JM, Smeets R, Kersten M, Huijben K, Keng WT, Speck-Martins CE, de Carvalho DR, de Rizzo IMPO, de Mello WD, Heiner-Fokkema R, Gorman K, Grunewald S, Michelakakis H, Moraitou M, Martinelli D, van Scherpenzeel M, Janssen M, de Boer L, van den Heuvel LP, Thiel C, Lefeber DJ
J Inherit Metab Dis 2022 Jul;45(4):769-781. Epub 2022 Mar 28 doi: 10.1002/jimd.12496. PMID: 35279850Free PMC Article
Özgün N, Şahin Y
Brain Dev 2022 Mar;44(3):239-243. Epub 2021 Nov 18 doi: 10.1016/j.braindev.2021.11.001. PMID: 34802815
Jansen JC, van Hoek B, Metselaar HJ, van den Berg AP, Zijlstra F, Huijben K, van Scherpenzeel M, Drenth JPH, Lefeber DJ
J Inherit Metab Dis 2020 Nov;43(6):1310-1320. Epub 2020 Jul 17 doi: 10.1002/jimd.12273. PMID: 32557671Free PMC Article
Guillard M, Morava E, van Delft FL, Hague R, Körner C, Adamowicz M, Wevers RA, Lefeber DJ
Clin Chem 2011 Apr;57(4):593-602. Epub 2011 Jan 27 doi: 10.1373/clinchem.2010.153635. PMID: 21273509
Hess D, Keusch JJ, Oberstein SA, Hennekam RC, Hofsteenge J
J Biol Chem 2008 Mar 21;283(12):7354-60. Epub 2008 Jan 16 doi: 10.1074/jbc.M710251200. PMID: 18199743

Therapy

Hüllen A, Falkenstein K, Weigel C, Huidekoper H, Naumann-Bartsch N, Spenger J, Feichtinger RG, Schaefers J, Frenz S, Kotlarz D, Momen T, Khoshnevisan R, Riedhammer KM, Santer R, Herget T, Rennings A, Lefeber DJ, Mayr JA, Thiel C, Wortmann SB
J Inherit Metab Dis 2021 Nov;44(6):1441-1452. Epub 2021 Sep 15 doi: 10.1002/jimd.12426. PMID: 34389986

Prognosis

Abu Bakar N, Ashikov A, Brum JM, Smeets R, Kersten M, Huijben K, Keng WT, Speck-Martins CE, de Carvalho DR, de Rizzo IMPO, de Mello WD, Heiner-Fokkema R, Gorman K, Grunewald S, Michelakakis H, Moraitou M, Martinelli D, van Scherpenzeel M, Janssen M, de Boer L, van den Heuvel LP, Thiel C, Lefeber DJ
J Inherit Metab Dis 2022 Jul;45(4):769-781. Epub 2022 Mar 28 doi: 10.1002/jimd.12496. PMID: 35279850Free PMC Article
Zhang A, Berardinelli SJ, Leonhard-Melief C, Vasudevan D, Liu TW, Taibi A, Giannone S, Apte SS, Holdener BC, Haltiwanger RS
J Biol Chem 2020 Nov 13;295(46):15742-15753. Epub 2020 Sep 10 doi: 10.1074/jbc.RA120.014557. PMID: 32913123Free PMC Article
Ng BG, Xu G, Chandy N, Steyermark J, Shinde DN, Radtke K, Raymond K, Lebrilla CB, AlAsmari A, Suchy SF, Powis Z, Faqeih EA, Berry SA, Kronn DF, Freeze HH
Am J Hum Genet 2018 Jan 4;102(1):188-195. doi: 10.1016/j.ajhg.2017.12.009. PMID: 29304374Free PMC Article

Clinical prediction guides

Abu Bakar N, Ashikov A, Brum JM, Smeets R, Kersten M, Huijben K, Keng WT, Speck-Martins CE, de Carvalho DR, de Rizzo IMPO, de Mello WD, Heiner-Fokkema R, Gorman K, Grunewald S, Michelakakis H, Moraitou M, Martinelli D, van Scherpenzeel M, Janssen M, de Boer L, van den Heuvel LP, Thiel C, Lefeber DJ
J Inherit Metab Dis 2022 Jul;45(4):769-781. Epub 2022 Mar 28 doi: 10.1002/jimd.12496. PMID: 35279850Free PMC Article
Zhang A, Berardinelli SJ, Leonhard-Melief C, Vasudevan D, Liu TW, Taibi A, Giannone S, Apte SS, Holdener BC, Haltiwanger RS
J Biol Chem 2020 Nov 13;295(46):15742-15753. Epub 2020 Sep 10 doi: 10.1074/jbc.RA120.014557. PMID: 32913123Free PMC Article
Sturla L, Fruscione F, Noda K, Miyoshi E, Taniguchi N, Contini P, Tonetti M
Glycobiology 2005 Oct;15(10):924-34. Epub 2005 May 25 doi: 10.1093/glycob/cwi081. PMID: 15917429
Becker DJ, Lowe JB
Glycobiology 2003 Jul;13(7):41R-53R. Epub 2003 Mar 19 doi: 10.1093/glycob/cwg054. PMID: 12651883

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