What Are the Symptoms of Cerebral Folate Deficiency?

Cerebral Folate Deficiency

Cerebral Folate Deficiency (CFD) is a recently identified neurometabolic disorder showing low concentrations of 5-MTHF (5-methyltetrahydrofolate) in the cerebrospinal fluid (CSF); however, in these cases, the folate levels in the bloodstream may remain unaffected. This implies that the 5-MTHF may not be getting converted/generated from folate for proper absorption into the cells. (1)(2)

It is important to know that supplementing with folic acid can in no way bring a solution, but rather it tends to worsen the problem. Folic acid is a synthetic, man-made form of folate that does not properly convert into 5-MTHF (bioavailable folate) for most people. What most people need is the active form of folate, 5-MTHF or methylfolate for short. The unavailability or scarcity of this nutrient in the body can lead to developmental delays.

Besides developmental delays, there are other symptoms that include seizures, gross motor problems and poor sleep. Cerebral Folate Deficiency is commonly associated with mitochondrial dysfunction in a subset of children. Although this does not occur all the time, these kids often develop with a smaller head circumference. (1)(2)

In such situations, it is very important to consider eating dairy-free, as folate receptor autoantibodies (FRAs) can often be regulated by reducing the intake of cow’s milk. Folate receptor autoantibodies are found in children with autism at an alarming rate. These folate receptor autoantibodies (FRAs) are responsible for blocking the process of transporting folate into the Cerebral Spinal Fluid. But CFD does not only occur due to the effects of FRAs, dairy, and mitochondrial dysfunction, as there are also several genetic mutations that can affect folate metabolism. (2)(3)(4)

CFD can affect a child at an early age (as early as 4 months old). This disorder is believed to occur due to the disruption of the transport of folates within the blood-brain barrier. Severe neurodevelopmental symptoms can even be experienced together with other symptoms, like developmental regression, acquired microcephaly, seizures, dyskinesia, cerebellar ataxia, and spastic paraplegia during the first cases of CFD. In some cases, hearing loss and central visual disturbances such as blindness and optic atrophy can manifest after age of 3 and 6, respectively. (3)(4)

Major symptoms and signs of Cerebral Folate Deficiency (CFD) occur in a progressive manner. While agitation and insomnia may be the initial manifestations of the condition, hypotonia, psychomotor retardation, and deceleration of head growth, often follow in time. Then, epilepsy, speech, gait disturbances, dyskinesia, ataxia, and spasticity will begin to manifest. These are the symptoms that can be commonly observed from 4 months to 3 years of age including some autistic symptoms. (3)(4)

The decline in 5-methyltetrahydrofolate can be observed despite normal folate levels in red blood cells and blood serum. While frontotemporal atrophy may begin to manifest from 18 months with signs of subcortical and periventricular demyelination, MRI of the brain can still be normal. (3)(4)



4 Responses to “What Are the Symptoms of Cerebral Folate Deficiency?”

  1. rosabelle says :

    I learned a new condition from this post. I have seen kids with smaller head circumference, but I don’t think that they have cerebral folate deficiency because they play and learn normally. Does newborn screening could detect it that early? Are the kids with such condition could still live normally?

  2. Monica says :

    Thanks, this is awesome! This is so helpful. My son had a lumbar puncture for severe paediatric epileptic encephalopathy. He also has autistic traits. His cerebral folate levels were 38. Low. In your research, what dose of Leucovorin Calcium is appropriate? I’m wondering if the 5mg/day my son was prescribed is sufficient.

  3. jerome says :

    “It is important to know that supplementing with folic acid can in no way bring a solution, but rather it tends to worsen the problem. Folic acid is a synthetic, man-made form of folate that does not properly convert into 5-MTHF (bioavailable folate”

    This is extremely crucial for people to know this that these kind of issues cannot be fixed through man made supplements.

  4. Alexa says :

    It seems that folic acid is rarely the good solution to almost any problem. Would methylated folate work better or would that also not be as effective in such cases? I wonder why there isn’t much more information available for people with such problems. I know you can search online for this but shouldn’t you hear this from a doctor or at least be led in the right direction? It just seems to me that many doctors nowadays just want to take your money without having to do much.

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