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Abnormal isoelectric focusing of serum transferrin

MedGen UID:
413671
Concept ID:
C2749688
Finding
Synonyms: Abnormal isoelectric focusing of transferrin; Abnormal transferrin isoelectric focusing
 
HPO: HP:0003160

Definition

Glycosylated transferrin concentrations can be measured in serum as a marker of N-linked glycosylation fidelity. In the traditional nomenclature for congenital disorders of glycosylation, absence of entire glycans was designated type I, and loss of one or more monosaccharides as type II. These terms are retained for historical reasons but for new annotations the precise glycosylation defect should be recorded. [from HPO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVAbnormal isoelectric focusing of serum transferrin

Conditions with this feature

Cutis laxa with osteodystrophy
MedGen UID:
82795
Concept ID:
C0268355
Disease or Syndrome
ATP6V0A2-related cutis laxa is characterized by generalized cutis laxa, findings associated with generalized connective tissue disorder, developmental delays, and a variety of neurologic findings including abnormality on brain MRI. At birth, hypotonia, overfolded skin, and distinctive facial features are present and enlarged fontanelles are often observed. During childhood, the characteristic facial features and thick or coarse hair may become quite pronounced. The skin findings decrease with age, although easy bruising and Ehlers-Danlos-like scars have been described in some. In most (not all) affected individuals, cortical and cerebellar malformations are observed on brain MRI. Nearly all affected individuals have developmental delays, seizures, and neurologic regression.
Wrinkly skin syndrome
MedGen UID:
98030
Concept ID:
C0406587
Disease or Syndrome
ATP6V0A2-related cutis laxa is characterized by generalized cutis laxa, findings associated with generalized connective tissue disorder, developmental delays, and a variety of neurologic findings including abnormality on brain MRI. At birth, hypotonia, overfolded skin, and distinctive facial features are present and enlarged fontanelles are often observed. During childhood, the characteristic facial features and thick or coarse hair may become quite pronounced. The skin findings decrease with age, although easy bruising and Ehlers-Danlos-like scars have been described in some. In most (not all) affected individuals, cortical and cerebellar malformations are observed on brain MRI. Nearly all affected individuals have developmental delays, seizures, and neurologic regression.
Geroderma osteodysplastica
MedGen UID:
98149
Concept ID:
C0432255
Disease or Syndrome
Geroderma osteodysplasticum (GO) is an autosomal recessive disorder characterized by skin wrinkling limited to the dorsa of hands and feet and to the abdomen, bowed long bones, and osteopenia with frequent fractures. There is a distinctive facial appearance with droopy skin at the cheeks, maxillary hypoplasia, and large ears. Adult patients appear prematurely aged (summary by Rajab et al., 2008).
PGM1-congenital disorder of glycosylation
MedGen UID:
414536
Concept ID:
C2752015
Disease or Syndrome
Congenital disorder of glycosylation type It (CDG1T) is an autosomal recessive disorder characterized by a wide range of clinical manifestations and severity. The most common features include cleft lip and bifid uvula, apparent at birth, followed by hepatopathy, intermittent hypoglycemia, short stature, and exercise intolerance, often accompanied by increased serum creatine kinase. Less common features include rhabdomyolysis, dilated cardiomyopathy, and hypogonadotropic hypogonadism (summary by Tegtmeyer et al., 2014). For a discussion of the classification of CDGs, see CDG1A (212065).
B4GALT1-congenital disorder of glycosylation
MedGen UID:
419310
Concept ID:
C2931009
Disease or Syndrome
Congenital disorders of glycosylation (CDG) are a group of hereditary multisystem disorders that are commonly associated with severe psychomotor and mental retardation. The characteristic biochemical abnormality of CDGs is the hypoglycosylation of glycoproteins, which is routinely determined by isoelectric focusing (IEF) of serum transferrin. Type I CDG comprises those disorders in which there is a defect in the assembly of lipid-linked oligosaccharides or their transfer onto nascent glycoproteins, whereas type II CDG comprises defects of trimming, elongation, and processing of protein-bound glycans (summary by Hansske et al., 2002). For a general discussion of CDGs, see CDG1A (212065).
SLC35A2-congenital disorder of glycosylation
MedGen UID:
813018
Concept ID:
C3806688
Disease or Syndrome
Congenital disorder of glycosylation type IIm, or developmental and epileptic encephalopathy-22 (DEE22), is an X-linked dominant severe neurologic disorder characterized by infantile-onset seizures, hypsarrhythmia on EEG, hypotonia, and developmental delay associated with severe intellectual disability and lack of speech. These features are consistent with developmental and epileptic encephalopathy (DEE). Brain malformations usually include cerebral and cerebellar atrophy. Additionally, some patients may have dysmorphic features or coarse facies (Ng et al., 2013; Kodera et al., 2013). For a general discussion of CDGs, see CDG1A (212065) and CDG2A (212066). For a general phenotypic description and a discussion of genetic heterogeneity of DEE, see 308350.
Congenital muscular dystrophy with intellectual disability and severe epilepsy
MedGen UID:
1682844
Concept ID:
C5190603
Disease or Syndrome
A rare fatal inborn error of metabolism disorder with characteristics of respiratory distress and severe hypotonia at birth, severe global developmental delay, early-onset intractable seizures, myopathic facies with craniofacial dysmorphism (trigonocephaly/progressive microcephaly, low anterior hairline, arched eyebrows, hypotelorism, strabismus, small nose, prominent philtrum, thin upper lip, high-arched palate, micrognathia, malocclusion), severe, congenital flexion joint contractures and elevated serum creatine kinase levels. Scoliosis, optic atrophy, mild hepatomegaly, and hypoplastic genitalia may also be associated. There is evidence the disease is caused by homozygous or compound heterozygous mutation in the DPM2 gene on chromosome 9q34.
Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalities
MedGen UID:
1824058
Concept ID:
C5774285
Disease or Syndrome
Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalities (NEDHFS) is an autosomal recessive disorder characterized by severe global developmental delay with impaired intellectual development and poor or absent speech. Affected individuals have dysmorphic facies, including large abnormally shaped ears and strabismus, hypotonia, and dry skin with keratosis pilaris. Some patients develop seizures. Metabolic studies are unremarkable (Morava et al., 2021).

Professional guidelines

PubMed

Marklová E, Albahri Z
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Recent clinical studies

Etiology

Raynor A, Bruneel A, Vermeersch P, Cholet S, Friedrich S, Eckenweiler M, Schumann A, Hengst S, Tuncel AT, Fenaille F, Thiel C, Rymen D
Proteomics Clin Appl 2024 Mar;18(2):e2300040. Epub 2023 Oct 24 doi: 10.1002/prca.202300040. PMID: 37876147
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
Babovic-Vuksanovic D, O'Brien JF
Mol Diagn Ther 2007;11(5):303-11. doi: 10.1007/BF03256251. PMID: 17963418
Marklová E, Albahri Z
Clin Chim Acta 2007 Oct;385(1-2):6-20. Epub 2007 Jul 13 doi: 10.1016/j.cca.2007.07.002. PMID: 17716641
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Glycobiology 1993 Oct;3(5):423-8. doi: 10.1093/glycob/3.5.423. PMID: 8286854

Diagnosis

Gardeitchik T, Wyckmans J, Morava E
Pediatr Clin North Am 2018 Apr;65(2):375-388. doi: 10.1016/j.pcl.2017.11.012. PMID: 29502919
Palmigiano A, Bua RO, Barone R, Rymen D, Régal L, Deconinck N, Dionisi-Vici C, Fung CW, Garozzo D, Jaeken J, Sturiale L
J Mass Spectrom 2017 Jun;52(6):372-377. doi: 10.1002/jms.3936. PMID: 28444691
Babovic-Vuksanovic D, O'Brien JF
Mol Diagn Ther 2007;11(5):303-11. doi: 10.1007/BF03256251. PMID: 17963418
Marklová E, Albahri Z
Clin Chim Acta 2007 Oct;385(1-2):6-20. Epub 2007 Jul 13 doi: 10.1016/j.cca.2007.07.002. PMID: 17716641
Stibler H
Clin Chem 1991 Dec;37(12):2029-37. PMID: 1764777

Therapy

Harms HK, Zimmer KP, Kurnik K, Bertele-Harms RM, Weidinger S, Reiter K
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Prognosis

Arai Y, Okanishi T, Kanai S, Okazaki T, Koshimizu E, Miyatake S, Maeoka Y, Fujimoto A, Matsumoto N, Maegaki Y
Brain Dev 2022 Nov;44(10):732-736. Epub 2022 Jul 27 doi: 10.1016/j.braindev.2022.07.005. PMID: 35907674
Makhamreh MM, Cottingham N, Ferreira CR, Berger S, Al-Kouatly HB
J Inherit Metab Dis 2020 Mar;43(2):223-233. Epub 2019 Nov 8 doi: 10.1002/jimd.12162. PMID: 31420886
Höck M, Wegleiter K, Ralser E, Kiechl-Kohlendorfer U, Scholl-Bürgi S, Fauth C, Steichen E, Pichler K, Lefeber DJ, Matthjis G, Keldermans L, Maurer K, Zschocke J, Karall D
Orphanet J Rare Dis 2015 Jun 12;10:73. doi: 10.1186/s13023-015-0289-7. PMID: 26066342Free PMC Article
Asada-Senju M, Maeda T, Sakata T, Hayashi A, Suzuki T
J Hum Genet 2002;47(7):355-9. doi: 10.1007/s100380200049. PMID: 12111369
Grünewald S, Imbach T, Huijben K, Rubio-Gozalbo ME, Verrips A, de Klerk JB, Stroink H, de Rijk-van Andel JF, Van Hove JL, Wendel U, Matthijs G, Hennet T, Jaeken J, Wevers RA
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Clinical prediction guides

Ziburová J, Nemčovič M, Šesták S, Bellová J, Pakanová Z, Siváková B, Šalingová A, Šebová C, Ostrožlíková M, Lekka DE, Brucknerová J, Brucknerová I, Skokňová M, Mc Cullough A, Hrčková G, Hlavatá A, Bzdúch V, Mucha J, Baráth P
Am J Med Genet A 2021 Nov;185(11):3494-3501. Epub 2021 Sep 1 doi: 10.1002/ajmg.a.62474. PMID: 34467644Free PMC Article
Papazoglu GM, Cubilla M, Pereyra M, de Kremer RD, Pérez B, Sturiale L, Asteggiano CG
Glycoconj J 2021 Apr;38(2):191-200. Epub 2021 Mar 1 doi: 10.1007/s10719-021-09976-w. PMID: 33644825
Babovic-Vuksanovic D, O'Brien JF
Mol Diagn Ther 2007;11(5):303-11. doi: 10.1007/BF03256251. PMID: 17963418
Jaeken J, Carchon H, Stibler H
Glycobiology 1993 Oct;3(5):423-8. doi: 10.1093/glycob/3.5.423. PMID: 8286854
Stibler H, Borg S, Allgulander C
Acta Med Scand 1979;206(4):275-81. doi: 10.1111/j.0954-6820.1979.tb13510.x. PMID: 116481

Recent systematic reviews

Makhamreh MM, Cottingham N, Ferreira CR, Berger S, Al-Kouatly HB
J Inherit Metab Dis 2020 Mar;43(2):223-233. Epub 2019 Nov 8 doi: 10.1002/jimd.12162. PMID: 31420886

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