16 June 2016

MTHFR gene variants rarely linked to pathology

Genetics

Increasing patient demand for a common and usually harmless genetic mutation has prompted criticism from experts, who say the mutation is rarely associated with significant pathology.

About 60% to 70% of the population have at least one genetic variant of the MTHFR gene, which encodes the enzyme methylenetetrahydrofolate reductase, said genetic counsellor Ms Sarah Long, from Genetic Services of Western Australia.

And although many naturopaths claim a mutation in the gene can lead to a myriad of medical conditions, including anxiety and depression, the evidence that a MTHFR gene mutation is linked to these conditions is extremely weak, Ms Long told TMR.

Natural practitioners also claim the enzyme, important in the metabolism of folate, can cause cardiovascular disease, miscarriage, autism, diabetes, cancer and neural tube defects.

However, Ms Long said her own review of the scientific evidence found the data, “large, varied and often conflicting”.

And testing for the gene was potentially harmful to patients.

“Bipolar and schizophrenia are very complicated disorders, and saying it’s down to one polymorphism, when 70% of population will have that is simplifying the issue, it’s not good science and it isn’t helping anyone,” she said.

Suggesting MTHFR variations were to blame for miscarriages or other medical conditions risked overlooking other serious underlying conditions, and telling people the mutation was the answer to their problem was “a bit deceitful, and can also raise anxiety unnecessarily”, she said.

Meanwhile, GPs report that patients are presenting with requests for the test, convinced they have symptoms caused by the gene.

Founder of MTHFR Support Australia, naturopath Carolyn Ledowsky, said identifying the mutation and supplementing accordingly would help people who have often spent decades trying to treat their anxiety and depression with no luck.

Ms Ledowsky said there was a “lack of awareness and a lack of knowledge” about the MTHFR mutation among the medical fraternity, but that its impacts could be “absolutely profound”.

Some patients with severe and long-standing mental illness have seen significant a turn-around in their health after only eight-weeks of proper supplementation with a form of folate, she said.

Every month had seen increasing numbers of patients seeking services at her Sydney clinic in the 2.5 years since it opened, she said.

Around 60% of these patients suffered from anxiety or depression, and 20-25% visited for those reasons specifically, she said.

“Patients with a family history of miscarriage, family history of spina bifida or cleft palate, family history of anxiety or depression or cardiovascular disease [are] certainly when you want to be thinking about whether the gene is implicated in this,” she said.

Douglass Hanly Moir and Laverty offer the gene testing, as does MTHFR Support for $90.

But the Centre for Genetics Education said testing attracts a rebate only if there is a proven DVT/PE or a known mutation in a first degree relative.

A number of variants had been identified in the MTHFR gene, most commonly C677T and A1298C, according to the centre’s recent fact sheet.

While having one or both these variants could possibly reduce a person’s ability to metabolise folate, it was unlikely to have any impact on health in the absence of low red blood cell folate or high homocysteine.

Low folate levels were unlikely in countries such as Australia that have folic acid fortification programs, the fact sheet says, and a woman’s MTHFR status did not change the routine recommendation for them to begin folate at least one month before conception.

“There are currently no recommended changes in clinical management based on a MTHFR test result”.

A spokeswoman for the Federal Department of Health confirmed the item number for the MTHFR gene test, 73308, was restricted to people, “who have had a proven venous thrombosis or pulmonary embolism”.

“And first degree relatives of people who are found to have an abnormal genotype under item 73308, may claim item 73311,” she said.