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Congenital Disorders of Glycosylation and Their Effects on the Liver

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Fibrocystic Diseases of the Liver

Part of the book series: Clinical Gastroenterology ((CG))

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Summary

Glycoprotein synthesis is one of the major duties of the liver. During the last decade a large number of inherited disorders in protein glycosylation have been identified that alter the architecture and function of the liver. Many congenital disorders of glycosylation (CDG) compromise the synthesis of a host of membrane and secreted glycoproteins often leading to steatosis, hepatic fibrosis, and abnormal bile duct architecture. Misfolded glycoproteins accumulate in the endoplasmic reticulum (ER) and improperly glycosylated plasma proteins are frequently unstable, leading to pro- or anti-coagulant status. CDG patients with liver pathology often present with a host of abnormalities in other systems, including the gastrointestinal tract causing protein-losing enteropathy, hypotonia, hypoglycemia, developmental delay, and seizures. In some cases, pathology is primarily confined to the liver. Effective therapy is available for only one of the more than 20 types of CDG. A simple and inexpensive serum transferrin glycosylation test can suggest a glycosylation disorder and should be used early on in a diagnostic workup of any patients with unknown liver-related pathology, especially if it occurs in combination with abnormalities in other organ systems. Many CDG patients probably remain undiagnosed.

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Acknowledgment

This work was supported by R01 DK55615 and the March of Dimes Foundation grants to HF. The authors wish to dedicate this work to the memory of John “Rocket” Williams who succumbed to complications of CDG-Ia at age 2.

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  1. Children’s Hospital, Lund University Hospital, Lund, Sweden

    Erik A. Eklund MD, PhD

  2. Burnham Institute for Medical Research, Sanford Children’s Health Research Center, La Jolla, CA, USA

    Hudson H. Freeze PhD

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  1. Erik A. Eklund MD, PhD
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  1. School of Medicine, Children's Hospital & Regional, University of Washington, Sand Point Way NE. 4800, Seattle, 98105, USA

    Karen F. Murray

  2. St. Paul University Hospital, Harry Hines Blvd. 5939, Dallas, 75390-9258, USA

    Anne M. Larson

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Eklund, E.A., Freeze, H.H. (2010). Congenital Disorders of Glycosylation and Their Effects on the Liver. In: Murray, K., Larson, A. (eds) Fibrocystic Diseases of the Liver. Clinical Gastroenterology. Humana Press. https://doi.org/10.1007/978-1-60327-524-8_12

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