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Glycine N-Methyltransferase Deficiency: A Member of Dysmethylating Liver Disorders?

Case Report

Part of the JIMD Reports book series (JIMD,volume 31)

Abstract

Glycine N-methyltransferase deficiency is an inherited disorder of methionine metabolism, reported so far in only four patients and characterised by permanent hypermethioninemia. This disorder has been considered as probably benign because moderate hepatomegaly in two patients was the only obvious symptom and mild to moderate elevation of aminotransferases the only laboratory abnormality. Our experience with the current novel patient points out that this disease, due to very high hypermethioninemia, is not harmless and that there may be diagnostic pitfalls in interpretation of biochemical hallmarks of the disease. Since the first description of glycine N-methyltransferase deficiency, other disorders of this metabolic pathway affecting the liver have been reported pointing to dysmethylation as the common pathogenetic mechanism. Therefore, we suggest the whole group to be named dysmethylating liver diseases.

Keywords

  • Glycine-N-methyltransferase deficiency
  • Hypermethioninemia
  • Inherited liver disease
  • Methylation disorders

Competing interests: None declared

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Acknowledgements

The study was supported by the project “European Network and Registry for Homocystinurias and Methylation Defects (E-HOD)” which is co-funded by the European Union in the framework of the Health Program (No.2012_12_02). OV and RB were supported by FP7-REGPOT-2012-2013-1, Grant Agreement Number 316289-InnoMol.

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Correspondence to Ivo Barić .

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Additional information

Communicated by: Viktor Kožich

Take-Home Message

Glycine-N-methyltransferase deficiency does not seem a harmless disease and interpretation of diagnostic biochemical abnormalities requires caution.

Description of Authors’ Contributions to the Study

Ivo Barić- study design and supervision, writing of the manuscript; he contributed pertinent aspects of the planning, conducting and reporting of the work described in the article.

Sahin Erdol and Halil Saglam- diagnosis and follow-up of the patient, providing medical data of the patient for the manuscript and critical revision of the manuscript.

Mila Lovrić- biochemical analyses, contributing to the manuscript writing and critical revision of the manuscript.

Robert Belužić- gene analysis and expression studies, contributing to the manuscript writing and critical revision of the manuscript.

Oliver Vugrek- gene analysis and expression studies, contributing to the manuscript writing and critical revision of the manuscript.

Henk J. Blom- biochemical analyses, contributing to the manuscript writing and critical revision of the manuscript.

Ksenija Fumić- biochemical analyses, contributing to the manuscript writing and critical revision of the manuscript.

Guarantor for the Article

Ivo Barić

Conflict of Interest

Ivo Barić, Sahin Erdol, Halil Saglam, Mila Lovrić, Robert Belužić, Oliver Vugrek, Henk J. Blom, and Ksenija Fumić declare that they have no conflict of interest.

Details of Funding

The study was supported by the project “European Network and Registry for Homocystinurias and Methylation Defects (E-HOD)” which is co-funded by the European Union in the framework of the Health Program (No.2012_12_02). OV and RB were supported by FP7-REGPOT-2012-2013-1, Grant Agreement Number 316289-InnoMol. The author(s) confirm(s) independence from the sponsors; the content of the article has not been influenced by the sponsors.

Compliance with Ethics Guidelines

Ethics approval was not required for all research studies.

Informed Consent

All procedures followed were 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 the patient’s parents for investigations reported in this study.

Animal Rights

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

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Barić, I. et al. (2016). Glycine N-Methyltransferase Deficiency: A Member of Dysmethylating Liver Disorders?. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 31. JIMD Reports, vol 31. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2016_543

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  • DOI: https://doi.org/10.1007/8904_2016_543

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  • Print ISBN: 978-3-662-54118-0

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