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

• Verfasst von: Barić, Ivo [VerfasserIn]
• Verfasst von: Staufner, Christian [VerfasserIn]
• Verfasst von: Opladen, Thomas [VerfasserIn]
• Titel: Consensus recommendations for the diagnosis, treatment and follow-up of inherited methylation disorders
• Verf.angabe: Ivo Barić, Christian Staufner, Persephone Augoustides-Savvopoulou, Yin-Hsiu Chien, Dries Dobbelaere, Sarah C. Grünert, Thomas Opladen, Danijela Petković Ramadža, Bojana Rakić, Anna Wedell, Henk J. Blom
• Jahr: 2017
• Jahr des Originals: 2016
• Umfang: 16 S.
• Teil: volume:40
• Teil: year:2017
• Teil: number:1
• Teil: pages:5-20
• Teil: extent:16
• Fussnoten: Published online: 26 September 2016 ; Gesehen am 20.09.2018
• Titel Quelle: Enthalten in: Journal of inherited metabolic disease
• Ort Quelle: Hoboken, NJ : Wiley, 1978
• Jahr Quelle: 2017
• Band/Heft Quelle: 40(2017), 1, Seite 5-20
• ISSN Quelle: 1573-2665
• DOI: doi:10.1007/s10545-016-9972-7
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: AdoMet
• Sach-SW: Methionine Level
• Sach-SW: Newborn Screening
• Sach-SW: Prenatal Diagnosis
• Sach-SW: Recurrent Hypoglycaemia
• K10plus-PPN: 158114833X

Abstract

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.