Clinical and diagnostic approach in unsolved CDG patients with a type 2 transferrin pattern

M. Mohamed, M. Guillard, S. B. Wortmann, S. Cirak, E. Marklova, H. Michelakakis, E. Korsch, M. Adamowicz, B. Koletzko, F. J. van Spronsen, K. E. Niezen-Koning, G. Matthijs, T. Gardeitchik, D. Kouwenberg, B. Chan Lim, R. Zeevaert, R. A. Wevers, D. J. Lefeber, Eva Morava-Kozicz

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Dysmorphic features, multisystem disease, and central nervous system involvement are common symptoms in congenital disorders of glycosylation, including several recently discovered Golgi-related glycosylation defects. In search for discriminative features, we assessed eleven children suspected with a Golgi-related inborn error of glycosylation. We evaluated all genetically unsolved patients, diagnosed with a type 2 transferrin isofocusing pattern in the period of 1999-2009. By combining biochemical results with characteristic clinical symptoms, we used a diagnostic flow chart to approach the underlying defect in patients with congenital disorders of glycosylation-IIx. According to specific symptoms and laboratory results, we initiated additional, targeted biochemical and genetic studies. We found a distinctive spectrum of congenital disorders of glycosylation type 2-associated anomalies including sudden hearing loss, brain malformations, wrinkled skin, and epilepsy in combination with skeletal dysplasia, dilated cardiomyopathy, sudden cardiac arrest, abnormal copper and iron metabolism, and endocrine abnormalities in our patients. One patient with severe cortical malformations and mild skin abnormalities was diagnosed with a known genetic syndrome, due to an ATP6V0A2 defect. Here, we present unique congenital disorders of glycosylation type 2-associated anomalies, including both ATPase-related and unrelated cutis laxa and sensorineural hearing loss, a recently recognized symptom of congenital disorders of glycosylation. Based on our findings, we recommend clinicians to consider congenital disorders of glycosylation in patients with cardiac rhythm disorders, spondylodysplasia and biochemical abnormalities of the copper and iron metabolism even in absence of intellectual disability.

Original languageEnglish (US)
Pages (from-to)691-698
Number of pages8
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1812
Issue number6
DOIs
StatePublished - Jun 1 2011
Externally publishedYes

Fingerprint

Congenital Disorders of Glycosylation
Transferrin
Glycosylation
Copper
Iron
Cutis Laxa
Skin Abnormalities
Sudden Hearing Loss
Sensorineural Hearing Loss
Central Nervous System Diseases
Sudden Cardiac Death
Dilated Cardiomyopathy
Intellectual Disability
Adenosine Triphosphatases
Molecular Biology
Epilepsy
Skin
Brain

Keywords

  • CDG type 2
  • CDG-IIx
  • Copper metabolism
  • Golgi-system
  • Hearing loss
  • Seizure
  • TIEF

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

Cite this

Clinical and diagnostic approach in unsolved CDG patients with a type 2 transferrin pattern. / Mohamed, M.; Guillard, M.; Wortmann, S. B.; Cirak, S.; Marklova, E.; Michelakakis, H.; Korsch, E.; Adamowicz, M.; Koletzko, B.; van Spronsen, F. J.; Niezen-Koning, K. E.; Matthijs, G.; Gardeitchik, T.; Kouwenberg, D.; Lim, B. Chan; Zeevaert, R.; Wevers, R. A.; Lefeber, D. J.; Morava-Kozicz, Eva.

In: Biochimica et Biophysica Acta - Molecular Basis of Disease, Vol. 1812, No. 6, 01.06.2011, p. 691-698.

Research output: Contribution to journalArticle

Mohamed, M, Guillard, M, Wortmann, SB, Cirak, S, Marklova, E, Michelakakis, H, Korsch, E, Adamowicz, M, Koletzko, B, van Spronsen, FJ, Niezen-Koning, KE, Matthijs, G, Gardeitchik, T, Kouwenberg, D, Lim, BC, Zeevaert, R, Wevers, RA, Lefeber, DJ & Morava-Kozicz, E 2011, 'Clinical and diagnostic approach in unsolved CDG patients with a type 2 transferrin pattern', Biochimica et Biophysica Acta - Molecular Basis of Disease, vol. 1812, no. 6, pp. 691-698. https://doi.org/10.1016/j.bbadis.2011.02.011
Mohamed, M. ; Guillard, M. ; Wortmann, S. B. ; Cirak, S. ; Marklova, E. ; Michelakakis, H. ; Korsch, E. ; Adamowicz, M. ; Koletzko, B. ; van Spronsen, F. J. ; Niezen-Koning, K. E. ; Matthijs, G. ; Gardeitchik, T. ; Kouwenberg, D. ; Lim, B. Chan ; Zeevaert, R. ; Wevers, R. A. ; Lefeber, D. J. ; Morava-Kozicz, Eva. / Clinical and diagnostic approach in unsolved CDG patients with a type 2 transferrin pattern. In: Biochimica et Biophysica Acta - Molecular Basis of Disease. 2011 ; Vol. 1812, No. 6. pp. 691-698.
@article{d9bd9f3bf88941f793c2887083a8aac1,
title = "Clinical and diagnostic approach in unsolved CDG patients with a type 2 transferrin pattern",
abstract = "Dysmorphic features, multisystem disease, and central nervous system involvement are common symptoms in congenital disorders of glycosylation, including several recently discovered Golgi-related glycosylation defects. In search for discriminative features, we assessed eleven children suspected with a Golgi-related inborn error of glycosylation. We evaluated all genetically unsolved patients, diagnosed with a type 2 transferrin isofocusing pattern in the period of 1999-2009. By combining biochemical results with characteristic clinical symptoms, we used a diagnostic flow chart to approach the underlying defect in patients with congenital disorders of glycosylation-IIx. According to specific symptoms and laboratory results, we initiated additional, targeted biochemical and genetic studies. We found a distinctive spectrum of congenital disorders of glycosylation type 2-associated anomalies including sudden hearing loss, brain malformations, wrinkled skin, and epilepsy in combination with skeletal dysplasia, dilated cardiomyopathy, sudden cardiac arrest, abnormal copper and iron metabolism, and endocrine abnormalities in our patients. One patient with severe cortical malformations and mild skin abnormalities was diagnosed with a known genetic syndrome, due to an ATP6V0A2 defect. Here, we present unique congenital disorders of glycosylation type 2-associated anomalies, including both ATPase-related and unrelated cutis laxa and sensorineural hearing loss, a recently recognized symptom of congenital disorders of glycosylation. Based on our findings, we recommend clinicians to consider congenital disorders of glycosylation in patients with cardiac rhythm disorders, spondylodysplasia and biochemical abnormalities of the copper and iron metabolism even in absence of intellectual disability.",
keywords = "CDG type 2, CDG-IIx, Copper metabolism, Golgi-system, Hearing loss, Seizure, TIEF",
author = "M. Mohamed and M. Guillard and Wortmann, {S. B.} and S. Cirak and E. Marklova and H. Michelakakis and E. Korsch and M. Adamowicz and B. Koletzko and {van Spronsen}, {F. J.} and Niezen-Koning, {K. E.} and G. Matthijs and T. Gardeitchik and D. Kouwenberg and Lim, {B. Chan} and R. Zeevaert and Wevers, {R. A.} and Lefeber, {D. J.} and Eva Morava-Kozicz",
year = "2011",
month = "6",
day = "1",
doi = "10.1016/j.bbadis.2011.02.011",
language = "English (US)",
volume = "1812",
pages = "691--698",
journal = "Biochimica et Biophysica Acta - Molecular Basis of Disease",
issn = "0925-4439",
publisher = "Elsevier",
number = "6",

}

TY - JOUR

T1 - Clinical and diagnostic approach in unsolved CDG patients with a type 2 transferrin pattern

AU - Mohamed, M.

AU - Guillard, M.

AU - Wortmann, S. B.

AU - Cirak, S.

AU - Marklova, E.

AU - Michelakakis, H.

AU - Korsch, E.

AU - Adamowicz, M.

AU - Koletzko, B.

AU - van Spronsen, F. J.

AU - Niezen-Koning, K. E.

AU - Matthijs, G.

AU - Gardeitchik, T.

AU - Kouwenberg, D.

AU - Lim, B. Chan

AU - Zeevaert, R.

AU - Wevers, R. A.

AU - Lefeber, D. J.

AU - Morava-Kozicz, Eva

PY - 2011/6/1

Y1 - 2011/6/1

N2 - Dysmorphic features, multisystem disease, and central nervous system involvement are common symptoms in congenital disorders of glycosylation, including several recently discovered Golgi-related glycosylation defects. In search for discriminative features, we assessed eleven children suspected with a Golgi-related inborn error of glycosylation. We evaluated all genetically unsolved patients, diagnosed with a type 2 transferrin isofocusing pattern in the period of 1999-2009. By combining biochemical results with characteristic clinical symptoms, we used a diagnostic flow chart to approach the underlying defect in patients with congenital disorders of glycosylation-IIx. According to specific symptoms and laboratory results, we initiated additional, targeted biochemical and genetic studies. We found a distinctive spectrum of congenital disorders of glycosylation type 2-associated anomalies including sudden hearing loss, brain malformations, wrinkled skin, and epilepsy in combination with skeletal dysplasia, dilated cardiomyopathy, sudden cardiac arrest, abnormal copper and iron metabolism, and endocrine abnormalities in our patients. One patient with severe cortical malformations and mild skin abnormalities was diagnosed with a known genetic syndrome, due to an ATP6V0A2 defect. Here, we present unique congenital disorders of glycosylation type 2-associated anomalies, including both ATPase-related and unrelated cutis laxa and sensorineural hearing loss, a recently recognized symptom of congenital disorders of glycosylation. Based on our findings, we recommend clinicians to consider congenital disorders of glycosylation in patients with cardiac rhythm disorders, spondylodysplasia and biochemical abnormalities of the copper and iron metabolism even in absence of intellectual disability.

AB - Dysmorphic features, multisystem disease, and central nervous system involvement are common symptoms in congenital disorders of glycosylation, including several recently discovered Golgi-related glycosylation defects. In search for discriminative features, we assessed eleven children suspected with a Golgi-related inborn error of glycosylation. We evaluated all genetically unsolved patients, diagnosed with a type 2 transferrin isofocusing pattern in the period of 1999-2009. By combining biochemical results with characteristic clinical symptoms, we used a diagnostic flow chart to approach the underlying defect in patients with congenital disorders of glycosylation-IIx. According to specific symptoms and laboratory results, we initiated additional, targeted biochemical and genetic studies. We found a distinctive spectrum of congenital disorders of glycosylation type 2-associated anomalies including sudden hearing loss, brain malformations, wrinkled skin, and epilepsy in combination with skeletal dysplasia, dilated cardiomyopathy, sudden cardiac arrest, abnormal copper and iron metabolism, and endocrine abnormalities in our patients. One patient with severe cortical malformations and mild skin abnormalities was diagnosed with a known genetic syndrome, due to an ATP6V0A2 defect. Here, we present unique congenital disorders of glycosylation type 2-associated anomalies, including both ATPase-related and unrelated cutis laxa and sensorineural hearing loss, a recently recognized symptom of congenital disorders of glycosylation. Based on our findings, we recommend clinicians to consider congenital disorders of glycosylation in patients with cardiac rhythm disorders, spondylodysplasia and biochemical abnormalities of the copper and iron metabolism even in absence of intellectual disability.

KW - CDG type 2

KW - CDG-IIx

KW - Copper metabolism

KW - Golgi-system

KW - Hearing loss

KW - Seizure

KW - TIEF

UR - http://www.scopus.com/inward/record.url?scp=79954618927&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79954618927&partnerID=8YFLogxK

U2 - 10.1016/j.bbadis.2011.02.011

DO - 10.1016/j.bbadis.2011.02.011

M3 - Article

C2 - 21362473

AN - SCOPUS:79954618927

VL - 1812

SP - 691

EP - 698

JO - Biochimica et Biophysica Acta - Molecular Basis of Disease

JF - Biochimica et Biophysica Acta - Molecular Basis of Disease

SN - 0925-4439

IS - 6

ER -