Consensus recommendations for the diagnosis, treatment and follow-up of inherited methylation disorders

Barić, Ivo and Staufner, Christian and Augoustides-Savvopoulou, Persephone and Chien, Yin-Hsiu and Dobbelaere, Dries and Grünert, Sarah C. and Opladen, Thomas and Petković Ramadža, Danijela and Rakić, Bojana and Wedell, Anna and Blom, Henk J. (2017) Consensus recommendations for the diagnosis, treatment and follow-up of inherited methylation disorders. Journal of Inherited Metabolic Disease, 40 (1). pp. 5-20. ISSN 0141-8955

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Inherited methylation disorders are a group of rarely reported, probably largely underdiagnosed disorders affecting transmethylation processes in the metabolic pathway between methionine and homocysteine. These are methionine adenosyltransferase I/III, glycine N-methyltransferase, S-adenosylhomocysteine hydrolase and adenosine kinase deficiencies. This paper provides the first consensus recommendations for the diagnosis and management of methylation disorders. Following search of the literature and evaluation according to the SIGN-methodology of all reported patients with methylation defects, graded recommendations are provided in a structured way comprising diagnosis (clinical presentation, biochemical abnormalities, differential diagnosis, newborn screening, prenatal diagnosis), therapy and follow-up. Methylation disorders predominantly affect the liver, central nervous system and muscles, but clinical presentation can vary considerably between and within disorders. Although isolated hypermethioninemia is the biochemical hallmark of this group of disorders, it is not always present, especially in early infancy. Plasma S-adenosylmethionine and S-adenosylhomocysteine are key metabolites for the biochemical clarification of isolated hypermethioninemia. Mild hyperhomocysteinemia can be present in all methylation disorders. Methylation disorders do not qualify as primary targets of newborn screening. A low-methionine diet can be beneficial in patients with methionine adenosyltransferase I/III deficiency if plasma methionine concentrations exceed 800 μmol/L. There is some evidence that this diet may also be beneficial in patients with S-adenosylhomocysteine hydrolase and adenosine kinase deficiencies. S-adenosylmethionine supplementation may be useful in patients with methionine adenosyltransferase I/III deficiency. Recommendations given in this article are based on general principles and in practice should be adjusted individually according to patient's age, severity of the disease, clinical and laboratory findings.

Item Type: Article
Additional Information: Open Access This article is distributed under the terms of the Creative Commons At tribution 4.0 International License (http:/ /, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
MeSH: Consensus ; Homocysteine / metabolism ; Humans ; Infant, Newborn ; Metabolism, Inborn Errors / diagnosis ; Metabolism, Inborn Errors / metabolism ; Methionine / metabolism ; Methionine Adenosyltransferase / deficiency ; Methylation ; Neonatal Screening / methods ; S-Adenosylhomocysteine / metabolism ; S-Adenosylmethionine / metabolism
Departments: Katedra za pedijatriju
Depositing User: Martina Žužak
Status: Published
Staufner, ChristianUNSPECIFIED
Augoustides-Savvopoulou, PersephoneUNSPECIFIED
Dobbelaere, DriesUNSPECIFIED
Grünert, Sarah C.UNSPECIFIED
Opladen, ThomasUNSPECIFIED
Petković Ramadža, DanijelaUNSPECIFIED
Date: January 2017
Date Deposited: 12 Sep 2017 14:00
Last Modified: 17 Aug 2020 08:08
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