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Clinical and diagnostic approach in unsolved CDG patients with a type 2 transferrin pattern.
MedLine Citation:
PMID:  21362473     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
OBJECTIVE: 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. METHODS: 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 CDG-IIx. According to specific symptoms and laboratory results we initiated additional, targeted biochemical and genetic studies. RESULTS: We found a distinctive spectrum of CDG 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. CONCLUSION: Here we present unique CDG type 2-associated anomalies, including both ATPase-related and unrelated cutis laxa, and sensorineural hearing loss; a recently recognized symptom of CDG. Based on our findings we recommend clinicians to consider CDG in patients with cardiac rhythm disorders, spondylodysplasia and biochemical abnormalities of the copper and iron metabolism even in absence of intellectual disability.
Authors:
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
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-2-26
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  -     ISSN:  0006-3002     ISO Abbreviation:  -     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-3-2     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2010. Published by Elsevier B.V.
Affiliation:
Institute for Genetic and Metabolic Diseases at the Department of Pediatrics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; Laboratory of Genetic Endocrine and Metabolic Diseases at the Department of Laboratory Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
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