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Classical Galactosaemia and CDG, the N-Glycosylation Interface. A Review

  • Research Report
  • Chapter
  • First Online:
JIMD Reports, Volume 34

Part of the book series: JIMD Reports ((JIMD,volume 34))

Abstract

Classical galactosaemia is a rare disorder of carbohydrate metabolism caused by galactose-1-phosphate uridyltransferase (GALT) deficiency (EC 2.7.7.12). The disease is life threatening if left untreated in neonates and the only available treatment option is a long-term galactose restricted diet. While this is lifesaving in the neonate, complications persist in treated individuals, and the cause of these, despite early initiation of treatment, and shared GALT genotypes remain poorly understood. Systemic abnormal glycosylation has been proposed to contribute substantially to the ongoing pathophysiology. The gross N-glycosylation assembly defects observed in the untreated neonate correct over time with treatment. However, N-glycosylation processing defects persist in treated children and adults.

Congenital disorders of glycosylation (CDG) are a large group of over 100 inherited disorders affecting largely N- and O-glycosylation.

In this review, we compare the clinical features observed in galactosaemia with a number of predominant CDG conditions.

We also summarize the N-glycosylation abnormalities, which we have described in galactosaemia adult and paediatric patients, using an automated high-throughput HILIC-UPLC analysis of galactose incorporation into serum IgG with analysis of the corresponding N-glycan gene expression patterns and the affected pathways.

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Acknowledgments

The authors acknowledge funding from the Irish Health Research Board (HRB-HRA POR award), and (MRCG/ TSCUH CFFH HRB award) which have supported this work.

Author information

Authors and Affiliations

  1. National Centre for Inherited Metabolic Disorders, Children’s University Hospital, Temple Street, Dublin, Ireland

    Ashwini Maratha, Ina Knerr & Eileen P. Treacy

  2. Department of Paediatrics, Trinity College, Dublin, Ireland

    Hugh-Owen Colhoun

  3. University College Dublin Clinical Research Centre, Eccles Street, Dublin, Ireland

    Ashwini Maratha, Peter Doran & Eileen P. Treacy

  4. Trinity College, Dublin, Ireland

    Eileen P. Treacy

  5. Faculty of Life Sciences and Medicine, Department of Infectious Diseases, King’s College London, Guy’s Hospital, London, UK

    Karen P. Coss

  6. Mater Misericordiae University Hospital, Eccles Street, Dublin, Ireland

    Eileen P. Treacy

Authors
  1. Ashwini Maratha
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  2. Hugh-Owen Colhoun
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  3. Ina Knerr
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  4. Karen P. Coss
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  5. Peter Doran
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  6. Eileen P. Treacy
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Correspondence to Eileen P. Treacy .

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Editors and Affiliations

  1. Tulane University Medical School, New Orleans, Louisiana, USA

    Eva Morava

  2. Division of Metabolism and Children’s Research Centre, University Children’s Hospital Zurich, Zurich, Switzerland

    Matthias Baumgartner

  3. Division of Child and Adolescent Neurology, Mayo Clinic, Rochester, Minnesota, USA

    Marc Patterson

  4. Clinical and Molecular Genetics Unit, UCL Institute of Child Health, London, United Kingdom

    Shamima Rahman

  5. Division of Human Genetics, Medical University Innsbruck, Innsbruck, Austria

    Johannes Zschocke

  6. Center for Child and Adolescent Medicine, Heidelberg University Hospital, Heidelberg, Germany

    Verena Peters

Additional information

Communicated by: Jaak Jaeken

Appendices

Synopsis

An understanding of the link between galactosaemia and CDG, with a focus on abnormal N-glycosylation.

Compliance with Ethics Guidelines

This article does not contain any studies with human or animal subjects performed by any of the authors.

Ashwini Maratha and Eileen Treacy have been involved in the planning, conception, writing, drafting and reviewing this review. Hugh-Owen Colhoun assisted in writing this review. Ina Knerr, Karen Coss and Peter Doran have assisted in reviewing this review.

Conflict of Interest

The authors Ashwini Maratha, Hugh-Owen Colhoun, Ina Knerr, Karen Coss, Peter Doran and Eileen Treacy declare that they have no conflict of interest.

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© 2016 SSIEM and Springer-Verlag Berlin Heidelberg

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Maratha, A., Colhoun, HO., Knerr, I., Coss, K.P., Doran, P., Treacy, E.P. (2016). Classical Galactosaemia and CDG, the N-Glycosylation Interface. A Review. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 34. JIMD Reports, vol 34. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2016_5

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  • DOI: https://doi.org/10.1007/8904_2016_5

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  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-55585-9

  • Online ISBN: 978-3-662-55586-6

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