We are currently receiving a high number of enquiries about MTHFR (methylenetetrahydrofolate reductase) and would like to provide some clarification. 

There are two very different situations that involve the MTHFR gene: 

1. Severe MTHFR deficiency (also known as N(5,10)-methylenetetrahydrofolate reductase deficiency) 

This is a rare inherited metabolic disorder caused by a severe deficiency of the MTHFR enzyme. It can lead to very high levels of homocysteine and low methionine levels and can cause significant cognitive decline, seizures, and a loss of motor function of the lower extremities (paraparesis). These symptoms are often present from infancy or early childhood with adult onset being rare. Individuals with this form of MTHFR deficiency are diagnosed and managed by specialised inherited metabolic disorder teams, requiring lifelong support.    

Metabolic Support UK supports those living with the severe form of MTHFR deficiency and their families. 

1. MTHFR gene polymorphisms (such as C677T or A1298C) 

These are common variants of the MTHFR gene which can be found in large numbers of the population. Some people may have slightly increased homocysteine levels, particularly if they have a folate deficiency or are taking certain medications. These variants do not cause inherited metabolic disorders and are not managed within specialised services for this group of conditions. If you have one of these variants and are concerned about your health, please speak to your GP who may be able to assist or refer you to the most appropriate service. 

Metabolic Support UK is unable to offer support to those with common variants (polymorphisms) of the MTHFR gene.  

We’d like to thank our healthcare colleagues within the inherited metabolic disorder specialty who have supported the development of this statement.