Cerebral Folate Transport Deficiency

What else is it called?

  • Cerebral folate deficiency
  • FOLR1 deficiency
  • Neurodegeneration due to cerebral folate transport deficiency
  • Folate receptor alpha deficiency

Get in touch

Contact our caring team on 08452 412 173 for help and support. Our phone lines open 10am-4pm, Monday to Friday.

Prefer to email? Our email address is contact@metabolicsupportuk.org.

What causes it?

Cerebral folate deficiency can be caused by a fault in one of your inherited genes called the FOLR1 gene which codes for a receptor protein for folate. This protein (folate receptor alpha) is responsible for allowing Folate (Vitamin B9) entry into your body’s cells from the bloodstream. The Folate receptor alpha is mostly found within your brain and its role is for cognitive development and cognitive function.

Another way that cerebral folate deficiency is caused is by your body’s own antibodies blocking the receptor for folate to bind to. This would not allow folate to cross the cell membrane within your brain.

In the brain folate is necessary for making the fatty protective layer that surrounds nerves. This fatty protective layer is called myelin. Folate is also important for making the chemical messages that help our body respond to a stimulus, these chemical messages are an integral part of our nervous system, they are called neurotransmitters. Folate also plays a part in the production of protein and the repair of your body’s DNA.

When folate receptor alpha does not work correctly, your body cannot transport folate into the cells within your brain. This can lead to many neurological problems such as, speech difficulties and tremors.

How common is it?

It has been estimated that worldwide fewer than 20 cases of cerebral folate deficiency have been reported. Currently, there is no indication whether there is greater prevalence in any country or between males and females.

What are the signs and symptoms?

Symptoms of Cerebral folate deficiency can go unnoticed until late infancy, this is due to other mechanism that produce folate prior to birth. Your body can compensate for the lack of folate post birth due to this. Signs and symptoms, usually apparent after the second year of age include:

  • Movement disturbances
  • Loss of previously acquired mental and movement abilities
  • Poor muscle control (ataxia)
  • Epilepsy
  • Abnormally high muscle tone (hypertonia)
  • Loss of brain cells and connections between them (cerebral atrophy)
  • Loss of a type of brain tissue known as white matter (leukodystrophy)
  • Delayed cognitive development
  • Intellectual disability
  • Speech difficulties
  • Seizures

Treatment is required to prevent worsening of neurological problems over time.

How is it diagnosed?

A health care professional may take a sample of the cerebrospinal fluid from found your brain and spinal cord, this procedure is called a lumbar puncture. A lumbar puncture involves placing a very small needle in-between the bones in your spine to extract the cerebrospinal fluid. This sample is used to check the levels of the active form of folate (5-methyltetrahydrofolate) within your brain and spinal cord and to make a diagnosis of your condition if there are low levels of active folate in this fluid.

Levels of the inactive form of folate taken from the blood stream may remain constant within this fluid and your body. This may imply that folate is not getting converted into the active form to be used within the cells in your brain.

Can it be treated?

Current research suggests that symptoms of this condition has been shown to improve with the prolonged dosage of follinic acid. Dosage usually starts at 1.0mg per 1 kg of body weight per day. Dosage and treatment for this condition would all be fully explained by your health care professional.

Do my family need to be tested?

Cerebral folate deficiency can only be passed on to a child if both parents have a copy of the faulty gene. This is called autosomal recessive inheritance. A person who has a copy of the faulty gene is known as a carrier.

If both parents are carriers, their child has a one in four (25%) chance of inheriting the disorder, and a one in two chance (50%) of being a carrier. This is the same for each child the parents have.

If the child only inherits one copy of the faulty gene, they will be a carrier but will not have the disorder. In some rare cases, cerebral folate deficiency carriers have had mild symptoms of the disorder for which they carry the faulty gene.

Once you are diagnosed, you can speak to a genetic counsellor. They can explain how you may have inherited. They can also tell you about genetic testing for the rest of your family. They can provide advice and support if you go on to have children of your own.

If you have previously had a child with cerebral folate deficiency and go on to have further children, their Newborn Screening test should be carried out within 24-48 hours of birth.

Diagram showing the autosomal recessive inheritance pattern.

Relevant Organisations


References are available on request. Please contact us by phoning 0845 241 2173 or emailing contact@metabolicsupportuk.org [Resource Library No: CFKB10].

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