Guidelines for diagnosis and management of the cobalamin-related remethylation disorders and MTHFR deficiency

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. Based on a systematic review, evaluation and discussion of the medical literature following the GRADE methodology we present recommendations for the diagnosis and management of these severe disorders.

We strongly recommend measuring plasma total homocysteine in any patient presenting with the combination of neurological and/or visual and/or haematological symptoms, spinal cord impairment, atypical haemolytic uraemic syndrome, or thromboembolic events. Treatment with parenteral hydroxocobalamin and oral betaine should be initiated without delay in any suspected remethylation disorder.

This guideline will soon be published in the Journal of Intherited Metabolic Diseases and may contribute to the harmonisation of diagnosis, treatment and management in this group of rare disorders.