Huemer, MartinaDiodato, DariaSchwahn, BerndSchiff, ManuelBandeira, AnabelaBenoist, Jean-FrancoisBurlina, AlbertoCerone, RobertoCouce, Maria L.Garcia-Cazorla, Angelesla Marca, GiancarloPasquini, ElisabettaVilarinho, LauraWeisfeld-Adams, James D.Kožich, ViktorBlom, HenkBaumgartner, Matthias R.Dionisi-Vici, Carlo2017-03-242017-03-242016-11-30J Inherit Metab Dis. 2017 Jan;40(1):21-48. doi: 10.1007/s10545-016-9991-4. Epub 2016 Nov 300141-8955http://hdl.handle.net/10400.18/4697PMC Free: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5203859/Background: Remethylation defects are rare inherited disorders in which impaired remethylation of homocysteine to methionine leads to accumulation of homocysteine and perturbation of numerous methylation reactions. Objective: To summarise clinical and biochemical characteristics of these severe disorders and to provide guidelines on diagnosis and management. Data sources: Review, evaluation and discussion of the medical literature (Medline, Cochrane databases) by a panel of experts on these rare diseases following the GRADE approach. Key recommendations: We strongly recommend measuring plasma total homocysteine in any patient presenting with the combination of neurological and/or visual and/or haematological symptoms, subacute spinal cord degeneration, atypical haemolytic uraemic syndrome or unexplained vascular thrombosis. We strongly recommend to initiate treatment with parenteral hydroxocobalamin without delay in any suspected remethylation disorder; it significantly improves survival and incidence of severe complications. We strongly recommend betaine treatment in individuals with MTHFR deficiency; it improves the outcome and prevents disease when given early.engRemethylation DisordersRare Inherited DisordersDoenças Genéticasjournal article10.1007/s10545-016-9991-4