MTHFR and hyperinsulinemic hypoglycemia, familial, 4: Guidelines for diagnosis and management of the cobalamin-related re-methylation disorders and MTHFR deficiency strongly recommend to initiate treatment with parenteral hydroxocobalamin without delay in any suspected re-methylation disorder, and betaine treatment in individuals with MTHFR deficiency, as these approaches have been confirmed to improve survival and reduce the incidence of severe complications when provided early (33).