Management includes co-factor replacement where relevant (e.g. B6 for B6 responsive CBS deficiency [86], folate for MTHFR deficiency [87] and B12 for Cbl C disease [88]), betaine to enhance remethylation to methionine, and protein restriction if appropriate with provision of methionine–free amino acid supplementation [86]. Here, MTHFR is linked to homocystinuria.