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, E. Morava

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


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
Issue number6
StatePublished - Jun 2011


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

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology


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