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.

• MeSH
• Homocysteine genetics   MeSH
• Humans MeSH
• Methionine genetics   MeSH
• Methylenetetrahydrofolate Reductase (NADPH2) deficiency   MeSH
• Methylation drug effects   MeSH
• Proto-Oncogene Proteins c-cbl deficiency   MeSH
• Vitamin B 12 pharmacology   therapeutic use   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Homocysteine MeSH
• Methionine MeSH
• Methylenetetrahydrofolate Reductase (NADPH2) MeSH
• Proto-Oncogene Proteins c-cbl MeSH
• Vitamin B 12 MeSH