"Incidence and Consequences of Disorders of Glycosylation in Patients With Conotruncal and Septal Heart Defects"

NCT ID: NCT02503267

Last Updated: 2017-03-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

300 participants

Study Classification

OBSERVATIONAL

Study Start Date

2015-07-31

Study Completion Date

2017-06-30

Brief Summary

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The objective of the study is to investigate congenital disorders of glycosylation in congenital heart diseases without a clear molecular or genetic basis.

Detailed Description

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Congenital disorders of glycosylation (CDG) are a family of inherited disorders caused by defects in the synthesis of glycans, glycoproteins or other glycoconjugates. Congenital disorders of glycosylation (CDG) are a family of inherited disorders caused by defects in the synthesis of glycans, glycoproteins or other glycoconjugates. Glycosylation of proteins is crucial for a proper organ morphogenesis and for an appropriate coagulation system functioning. The neurological system is commonly affected in this type of disorders but cases of CDG with normal neurological development have been recently described. The group of Experimental Hematology and Clinic Oncology of the University of Murcia (Spain) recently described a rare disorder of glycosylation (ALG12-CDG) as the cause of antithrombin deficiency in a patient of 19 years with a history of repaired ventricular septal defect.

On the other hand, population studies have shown an increased incidence of thromboembolic events in patients with congenital heart disease when compared to the general population. The identified genetic defects involved in the development of congenital heart diseases have variable or incomplete penetrance and in most cases the molecular basis is completely unknown.

The investigators postulate that a CDG might be behind the development of some forms of congenital heart disease and contribute to the greater prevalence of thromboembolic events in this patient population.

Conditions

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Congenital Heart Diseases Conotruncal Defects Congenital Disorder of Glycosylation Antithrombin III Deficiency

Study Design

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Observational Model Type

CASE_ONLY

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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patients with congenital heart disease

patients with congenital heart disease

none intervention

Intervention Type OTHER

Interventions

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none intervention

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Adult with a congenital heart disease with most probability to present a congenital disorder of glycosylation of proteins

Exclusion Criteria

* Denial of informed consent.
Minimum Eligible Age

18 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Universidad de Murcia

OTHER

Sponsor Role collaborator

Hospital Universitari Vall d'Hebron Research Institute

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Vall d'Hebron Hospital

Barcelona, Barcelona, Spain

Site Status RECRUITING

Countries

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Spain

Central Contacts

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Berta Miranda, MD

Role: CONTACT

+34934894038 ext. 4038

Facility Contacts

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Berta Miranda, MD

Role: primary

+34932743164

Laura Dos, MD,PhD

Role: backup

+34932743164

References

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Footitt EJ, Karimova A, Burch M, Yayeh T, Dupre T, Vuillaumier-Barrot S, Chantret I, Moore SE, Seta N, Grunewald S. Cardiomyopathy in the congenital disorders of glycosylation (CDG): a case of late presentation and literature review. J Inherit Metab Dis. 2009 Dec;32 Suppl 1:S313-9. doi: 10.1007/s10545-009-1262-1. Epub 2009 Sep 7.

Reference Type BACKGROUND
PMID: 19757145 (View on PubMed)

Gehrmann J, Sohlbach K, Linnebank M, Bohles HJ, Buderus S, Kehl HG, Vogt J, Harms E, Marquardt T. Cardiomyopathy in congenital disorders of glycosylation. Cardiol Young. 2003 Aug;13(4):345-51.

Reference Type BACKGROUND
PMID: 14694955 (View on PubMed)

Romano S, Bajolle F, Valayannopoulos V, Lyonnet S, Colomb V, de Barace C, Vouhe P, Pouard P, Vuillaumier-Barrot S, Dupre T, de Keyzer Y, Sidi D, Seta N, Bonnet D, de Lonlay P. Conotruncal heart defects in three patients with congenital disorder of glycosylation type Ia (CDG Ia). J Med Genet. 2009 Apr;46(4):287-8. doi: 10.1136/jmg.2008.057620. No abstract available.

Reference Type BACKGROUND
PMID: 19357119 (View on PubMed)

Mitra N, Sinha S, Ramya TN, Surolia A. N-linked oligosaccharides as outfitters for glycoprotein folding, form and function. Trends Biochem Sci. 2006 Mar;31(3):156-63. doi: 10.1016/j.tibs.2006.01.003. Epub 2006 Feb 10.

Reference Type BACKGROUND
PMID: 16473013 (View on PubMed)

Lin YS, Liu PH, Wu LS, Chen YM, Chang CJ, Chu PH. Major adverse cardiovascular events in adult congenital heart disease: a population-based follow-up study from Taiwan. BMC Cardiovasc Disord. 2014 Mar 21;14:38. doi: 10.1186/1471-2261-14-38.

Reference Type BACKGROUND
PMID: 24655794 (View on PubMed)

de la Morena-Barrio ME, Hernandez-Caselles T, Corral J, Garcia-Lopez R, Martinez-Martinez I, Perez-Duenas B, Altisent C, Sevivas T, Kristensen SR, Guillen-Navarro E, Minano A, Vicente V, Jaeken J, Lozano ML. GPI-anchor and GPI-anchored protein expression in PMM2-CDG patients. Orphanet J Rare Dis. 2013 Oct 20;8:170. doi: 10.1186/1750-1172-8-170.

Reference Type BACKGROUND
PMID: 24139637 (View on PubMed)

Martinez-Martinez I, Ordonez A, Navarro-Fernandez J, Perez-Lara A, Gutierrez-Gallego R, Giraldo R, Martinez C, Llop E, Vicente V, Corral J. Antithrombin Murcia (K241E) causing antithrombin deficiency: a possible role for altered glycosylation. Haematologica. 2010 Aug;95(8):1358-65. doi: 10.3324/haematol.2009.015487. Epub 2010 Apr 30.

Reference Type BACKGROUND
PMID: 20435622 (View on PubMed)

Aguila S, Martinez-Martinez I, Dichiara G, Gutierrez-Gallego R, Navarro-Fernandez J, Vicente V, Corral J. Increased N-glycosylation efficiency by generation of an aromatic sequon on N135 of antithrombin. PLoS One. 2014 Dec 8;9(12):e114454. doi: 10.1371/journal.pone.0114454. eCollection 2014.

Reference Type BACKGROUND
PMID: 25485983 (View on PubMed)

Dorn C, Grunert M, Sperling SR. Application of high-throughput sequencing for studying genomic variations in congenital heart disease. Brief Funct Genomics. 2014 Jan;13(1):51-65. doi: 10.1093/bfgp/elt040. Epub 2013 Oct 3.

Reference Type BACKGROUND
PMID: 24095982 (View on PubMed)

Other Identifiers

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CARDIoG

Identifier Type: -

Identifier Source: org_study_id

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