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IgG N-Glycosylation Galactose Incorporation Ratios for the Monitoring of Classical Galactosaemia

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JIMD Reports, Volume 27

Part of the book series: JIMD Reports ((JIMD,volume 27))

Abstract

Classical galactosaemia (OMIM #230400) is a rare disorder of carbohydrate metabolism caused by deficiency of the galactose-1-phosphate uridyltransferase enzyme (EC 2.7.7.12). The cause of the long-term complications, including neurological, cognitive and fertility problems in females, remains poorly understood. The relatively small number of patients with galactosaemia and the lack of validated biomarkers pose a substantial challenge for determining prognosis and monitoring disease progression and responses to new therapies. We report an improved method of automated robotic hydrophilic interaction ultra-performance liquid chromatography N-glycan analysis for the measurement of IgG N-glycan galactose incorporation ratios applied to the monitoring of adult patients with classical galactosaemia. We analysed 40 affected adult patients and 81 matched healthy controls. Significant differences were noted between the G0/G1 and G0/G2 incorporation ratios between galactosaemia patients and controls (p < 0.001 and <0.01, respectively). Our data indicate that the use of IgG N-glycosylation galactose incorporation analysis may be now applicable for monitoring patient dietary compliance, determining prognosis and the evaluation of potential new therapies.

Competing interests: None declared

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Abbreviations

G0:

Agalactosylated

G1:

Monogalactosylated

G2:

Digalactosylated

Gal-1-P:

Galactose-1-phosphate

GALT:

Galactose-1-phosphate uridyltransferase

HILIC-UPLC:

Hydrophilic interaction ultra-performance liquid chromatography

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Acknowledgements

Funding for these studies was granted by the Irish Medical Research Charities Group (CFFH/TSCUH)/Health Research Board (No 2) was supported by the EU FP7 Research Framework Program ‘HighGlycan’ (Grant Reference No. 278535).

Author information

Authors and Affiliations

  1. National Institute for Bioprocessing Research and Training (NIBRT), Glycoscience Group, Mount Merrion, Blackrock, Dublin University College, Dublin, Ireland

    Henning Stockmann & Pauline Rudd

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

    Karen P. Coss

  3. Maastricht University Medical Centre, Minderbroedersberg 4, Maastricht, The Netherlands

    M. Estela Rubio-Gozalbo

  4. National Centre for Inherited Metabolic Disorders, Childrens University Hospital, Dublin, Ireland

    Ina Knerr

  5. Mater Misericordiae University Hospital, Eccles St, Dublin, Ireland

    Maria Fitzgibbon & Eileen P. Treacy

  6. University College Dublin Clinical Research Centre, Eccles St, Dublin, Ireland

    Ashwini Maratha & Eileen P. Treacy

  7. Centre for Population Health Sciences, Medical School, Teviot Place, Edinburgh, EH8 9AG, Scotland

    James Wilson

  8. Trinity College, Dublin, Ireland

    Eileen P. Treacy

Authors
  1. Henning Stockmann
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  2. Karen P. Coss
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  3. M. Estela Rubio-Gozalbo
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  4. Ina Knerr
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  5. Maria Fitzgibbon
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  6. Ashwini Maratha
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  7. James Wilson
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  8. Pauline Rudd
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  9. Eileen P. Treacy
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Corresponding author

Correspondence to Eileen P. Treacy .

Editor information

Editors and Affiliations

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

    Eva Morava

  2. Division of Metabolism and Children’s Re, University Children's Hospital Zurich, Zurich, Switzerland

    Matthias Baumgartner

  3. Division of Child and Adolescent Neurolo, 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, Baden-Württemberg, Germany

    Verena Peters

Additional information

Communicated by: Jaak Jaeken

Appendices

Synopsis

The use of IgG N-glycosylation galactose incorporation analysis by HILIC-UPLC analysis can be applied for monitoring of optimum metabolic control for individuals with classical galactosaemia.

Compliance with Ethics Guidelines

Conflict of Interest

The authors, Henning Stockmann, Karen P. Coss, M. Estela Rubio-Gozalbo, Ina Knerr, Maria Fitzgibbon, Ashwini Maratha, James Wilson, Pauline Rudd and Eileen P. Treacy, declare that they have no conflict of interest.

All procedures regarding the galactosaemia patient studies and sampling were followed in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study.

All authors listed above have been involved in the conception or design of this study and in drafting/revising the submitted article. Henning Stockmann and Karen Coss were involved in the direct planning and conduct of the study and experiments. The other authors were involved in interpreting the results, drafting and revising the manuscript.

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© 2015 SSIEM and Springer-Verlag Berlin Heidelberg

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Stockmann, H. et al. (2015). IgG N-Glycosylation Galactose Incorporation Ratios for the Monitoring of Classical Galactosaemia. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 27. JIMD Reports, vol 27. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2015_490

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  • DOI: https://doi.org/10.1007/8904_2015_490

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  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-50408-6

  • Online ISBN: 978-3-662-50409-3

  • eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)

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