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Cardiac complications of congenital disorders of glycosylation (CDG): a systematic review of the literature

  • Review
  • Published:
Journal of Inherited Metabolic Disease

Abstract

Congenital disorders of glycosylation (CDG) are inborn errors of metabolism due to protein and lipid hypoglycosylation. This rapidly growing family of genetic diseases comprises 103 CDG types, with a broad phenotypic diversity ranging from mild to severe poly-organ -system dysfunction. This literature review summarizes cardiac involvement, reported in 20% of CDG. CDG with cardiac involvement were divided according to the associated type of glycosylation: N-glycosylation, O-glycosylation, dolichol synthesis, glycosylphosphatidylinositol (GPI)-anchor biosynthesis, COG complex, V-ATPase complex, and other glycosylation pathways. The aim of this review was to document and interpret the incidence of heart disease in CDG patients. Heart disorders were grouped into cardiomyopathies, structural defects, and arrhythmogenic disorders. This work may contribute to improved early management of cardiac complications in CDG.

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Abbreviations

A:

Arrhythmia

AD:

Aortic dilation

AI:

Aorta insufficiency

ASD:

Atrial septal defect

ASH:

Atrial septal hypertrophy

B:

Bradycardia

BAV:

Bicuspid aortic valve

BF:

Biventricular function

BVD:

Biventricular dilation

BVH:

Biventricular hypertrophy

CD:

Cardiac dilation

CDG:

Congenital disorder(s) of glycosylation

CHD:

Congenital heart disease

CM:

Cardiomegaly

CVD:

Cardiac valve defects

DCM:

Dilated cardiomyopathy

ER:

Endoplasmic reticulum

GPI:

Glycosylphosphatidylinositol

HCM:

Hypertrophic cardiomyopathy

HF:

Heart failure

LGE:

Late gadolinium enhancement

LV:

Left ventricle

LDCM:

Dilated ventricular cardiomyopathy

LRHCM:

Left/right HCM

LRVHCM:

Left/right ventricular HCM

LVD:

Left ventricular dilation

LVEF:

Left ventricular ejection fraction

LVH:

Left ventricular hypertrophy

LVRWMA:

Left ventricular regional wall motion abnormality (defined as a left ventricular segment in which the systolic motion score is below normal)

MP:

Mitral prolapse

MRI:

Magnetic resonance imaging

PDA:

Patent ductus arteriosus

PFO:

Patent foramen ovale

PH:

Pulmonary hypertension

PMV:

Parachute mitral valve

PPS:

Peripheral pulmonary stenosis

PVSD:

Perimembranous ventricular septal defect

QRS:

Q wave, R wave, and S wave

RAD:

Right atrial dilation

RBBB:

Right bundle branch block

RHHS:

Right hypoplastic heart syndrome

RVD:

Right ventricular dilation

RVDe:

Right ventricular defect

RVEF:

Right ventricular ejection fraction

RVH:

Right ventricular hypertrophy

SAI:

Small aortic isthmus

SD:

Septal defect

SR:

Sarcoplasmic reticulum

T:

Tachycardia

TI:

Tricuspid insufficiency

TR:

Tricuspid regurgitation

VD:

Ventricular dysfunction

VH:

Ventricular hypertrophy

VLD:

Valvular defects

VSD:

Ventricular septal defect

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Acknowledgments

Dorinda Marques da Silva and Rita Francisco acknowledge support from the Liliana Scientific Scholarship 2016. We also thank the CDG & Allies—Professionals and Patient Associations International Network (CDG & Allies PPAIN), whose network expertise greatly helped with this manuscript. We are grateful to Diogo Sampaio (http://www.diogosampaio.pt/), who helped to design Fig. 1 of this publication.

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Author notes

  1. D. Marques-da-Silva, R. Francisco equally contributed to this work and should be considered first authors.

Authors and Affiliations

  1. UCIBIO, Departamento Ciências da Vida, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, Lisbon, Portugal

    D. Marques-da-Silva & R. Francisco

  2. Portuguese Association for CDG, Lisbon, Portugal

    D. Marques-da-Silva, R. Francisco & V. dos Reis Ferreira

  3. CDG & Allies – Professionals and Patient Associations International Network (CDG & Allies – PPAIN), Caparica, Portugal

    D. Marques-da-Silva, R. Francisco, V. dos Reis Ferreira & J. Jaeken

  4. Division of Infectious Diseases, Department of Medicine, Saint John Regional Hospital, Dalhousie University, Saint John, NB, Canada

    D. Webster

  5. Center for Metabolic Diseases, UZ and KU Leuven, Leuven, Belgium

    J. Jaeken

  6. Department of Biochemistry and Molecular Biology, Faculty of Medicine, Dalhousie University, Dalhousie Medicine New Brunswick, 100 Tucker Park Road, Saint John, NB, E2L 4L5, Canada

    T. Pulinilkunnil

Authors
  1. D. Marques-da-Silva
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  2. R. Francisco
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  3. D. Webster
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  4. V. dos Reis Ferreira
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  5. J. Jaeken
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  6. T. Pulinilkunnil
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Corresponding author

Correspondence to T. Pulinilkunnil.

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Conflict of interests

Vanessa dos Reis Ferreira is president and founder of the Portuguese Association for CDG and Other Rare Metabolic Diseases (APCDG-DMR). All other authors declare no competing financial interests.

Human and animal rights and informed consent

This review does not contain any data from human or animal studies performed by any of the listed authors.

Funding

This work was supported by the CDG Professionals and Patient Associations International Network (CDG & Allies—PPAIN) and Liliana Fellowships from APCDG attributed to Marques-da-Silva D. and Francisco R. Figure 1 was supported by Foundation Glycosylation. The authors confirmed independence from sponsors, the content of the article has not been influenced by sponsors. This work was supported by the Natural Sciences and Engineering Research Council of Canada (RGPIN-2014-03687) grant to TP.

Additional information

Communicated by: Eva Morava

Note

This study is a result of a collaborative study between patient advocacy groups, families, and professionals (CDG Professionals and Patient Associations International Network; CDG & Allies—PPAIN).

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Marques-da-Silva, D., Francisco, R., Webster, D. et al. Cardiac complications of congenital disorders of glycosylation (CDG): a systematic review of the literature. J Inherit Metab Dis 40, 657–672 (2017). https://doi.org/10.1007/s10545-017-0066-y

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  • DOI: https://doi.org/10.1007/s10545-017-0066-y

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