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Liver involvement in congenital disorders of glycosylation (CDG). A systematic review of the literature

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Journal of Inherited Metabolic Disease

Abstract

Congenital disorders of glycosylation (CDG) are a rapidly growing family of genetic diseases caused by defects in glycosylation. Nearly 100 CDG types are known so far. Patients present a great phenotypic diversity ranging from poly- to mono-organ/system involvement and from very mild to extremely severe presentation. In this literature review, we summarize the liver involvement reported in CDG patients. Although liver involvement is present in only a minority of the reported CDG types (22 %), it can be debilitating or even life-threatening. Sixteen of the patients we collated here developed cirrhosis, 10 had liver failure. We distinguish two main groups: on the one hand, the CDG types with predominant or isolated liver involvement including MPI-CDG, TMEM199-CDG, CCDC115-CDG, and ATP6AP1-CDG, and on the other hand, the CDG types associated with liver disease but not as a striking, unique or predominant feature, including PMM2-CDG, ALG1-CDG, ALG3-CDG, ALG6-CDG, ALG8-CDG, ALG9-CDG, PGM1-CDG, and COG-CDG. This review aims to facilitate CDG patient identification and to understand CDG liver involvement, hopefully leading to earlier diagnosis, and better management and treatment.

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Abbreviations

AF:

Alpha-fetoprotein

AP:

Alkaline phosphatase

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

AT:

Antithrombin

CDG:

Congenital disorder(s) of glycosylation

CK:

Creatine kinase

ER:

Endoplasmic reticulum

ERGIC:

Endoplasmic reticulum-Golgi intermediate compartment

γ-GT:

Gamma-glutamyl transferase

IEF:

Isoelectrofocusing

PT:

Prothrombin time

PTT:

Partial thromboplastin time

TA:

Transaminases

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Acknowledgements

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

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Authors and Affiliations

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

    D. Marques-da-Silva, M. Monticelli & P. A. Videira

  2. Portuguese Association for CDG, Lisboa, Portugal

    D. Marques-da-Silva, V. dos Reis Ferreira & P. A. Videira

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

    D. Marques-da-Silva, V. dos Reis Ferreira, P. A. Videira, P. Witters, J. Jaeken & D. Cassiman

  4. Dipartimento di Biologia, Università degli Studi di Napoli “Federico II”, Napoli, Italy

    M. Monticelli

  5. Departamento de Pediatria, Unidade de Doenças Metabólicas, CHLN, Hospital de Sta. Maria, Lisboa, Portugal

    P. Janeiro

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

    P. Witters, J. Jaeken & D. Cassiman

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  1. D. Marques-da-Silva
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  2. V. dos Reis Ferreira
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  3. M. Monticelli
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  4. P. Janeiro
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  5. P. A. Videira
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  7. J. Jaeken
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  8. D. Cassiman
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Correspondence to J. Jaeken or D. Cassiman.

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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.

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 Monticelli M. The authors confirmed independence from the sponsors, the content of the article has not been influenced by sponsors.

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Communicated by: Eva Morava

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Marques-da-Silva, D., dos Reis Ferreira, V., Monticelli, M. et al. Liver involvement in congenital disorders of glycosylation (CDG). A systematic review of the literature. J Inherit Metab Dis 40, 195–207 (2017). https://doi.org/10.1007/s10545-016-0012-4

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