How does Folate Deficiency in Infants and Toddlers relate to CFD and FRAAs?

Folate, a generic term for Vitamin B9, is a critical water-soluble vitamin. Folate is often used to describe the naturally occurring nutrient found in food, although there are many forms that include both natural and synthetic. The synthetic form, generally found in supplements or fortified foods, is called folic acid. Beginning in 1998, the US government mandated the fortification of various foods with folic acid in an attempt to combat neural tube defects.

In general, folate is very important for many bodily functions. These include:

1. Prevention of Neural Tube Defects: Adequate folate intake before and during early pregnancy can significantly reduce the risk of neural tube defects in babies, such as spina bifida and anencephaly. Neural tube defects occur very early in pregnancy, often before a woman knows she’s pregnant, so it’s essential for women of childbearing age to ensure they get enough folate.
2. Cell Division and Growth: Folate plays a vital role in DNA synthesis and repair, which are critical processes during cell division and growth. This is especially important during periods of rapid growth, such as infancy, adolescence, and pregnancy.
3. Red Blood Cell Formation: Folate is essential for the production of red blood cells. A deficiency in folate can lead to a type of anemia called megaloblastic anemia, where red blood cells are larger than normal and don’t function properly.
4. Homocysteine Regulation: Folate helps metabolize homocysteine, an amino acid. Elevated levels of homocysteine in the blood are associated with an increased risk of cardiovascular disease. Folate, along with vitamins B6 and B12, helps keep homocysteine levels in check.
5. Supports Mental Health: Folate is involved in the production of neurotransmitters like serotonin, which plays a role in mood regulation. It is thought that folate deficiency may exacerbate certain mental illnesses such as depression and schizophrenia.
6. Supports Digestive Health: Folate is involved in the synthesis of digestive enzymes, supporting the breakdown and absorption of nutrients from food.
7. Healthy Skin and Hair: Folate plays a role in the synthesis of DNA and RNA, which are essential for the growth and repair of skin and hair cells.

Vitamin B9 is crucial for overall health, particularly for proper growth and development, maintenance of healthy blood cells, and supporting mental and cardiovascular health.

That being said, folate continues to be important for newborns and toddlers after birth. Although there are no specific guidelines for folate consumption, breastmilk and formula can generally provide sufficient folate needed for infants under the age 1 year.

Listed below are some Recommended Daily Allowances (RDA) for folate based on the age of the child:

• Birth to 6 months: 65 mcg
• 7 to 12 months: 80 mcg
• 1 to 3 years: 150 mcg

Breastfed and formula fed babies typically do not need folic acid supplementation unless recommended by their healthcare provider. Once a child begins eating solid foods, it is highly recommended that their diet includes foods rich in folate. This should be continued throughout their growth and development. Many foods have folate, and having a varied diet is important so that your child meets all their developmental needs.

Besides consumption of folate, it is important that it is also reduced (by particular enzymes) and transported to the corresponding cells that require it. Remarkably, in 2004 a distinct condition was discovered in young children that had some very peculiar symptoms which were highlighted as such:

1. Developmental delays, including delays in motor skills, speech, and cognitive development.
2. Movement disorders, such as ataxia (difficulty with coordination and balance) or spasticity.
3. Seizures or epilepsy.
4. Behavioral problems, such as irritability, hyperactivity, or autistic-like behaviors.
5. Hypotonia (decreased muscle tone) or hypertonia (increased muscle tone)

In these cases, folate serum levels in the children were presented as normal, however, 5mthf levels in their cerebrospinal fluid were exceedingly low. 5mthf represents the reduced form of folate that is able to cross the blood brain barrier, enter the choroid plexus and into the cerebrospinal fluid (CSF). This is critical for proper neurological function. Could it be that there was a certain blockage of folate causing these peculiar symptoms? Further investigation of this led to the discovery of folate receptor autoantibodies and the condition now known as Cerebral Folate Deficiency (CFD). It turns out that these autoantibodies were attacking the main folate transporter, known as folate receptor alpha, and preventing reduced folate (5mthf) in reaching the CSF.

Besides identifying these autoantibodies, the other exciting part to this was that a treatment was also identified. This treatment was the use of high dose folinic acid, which was able to restore regular CSF levels in many of these cases, with marked improvement in symptoms as well. It is important to screen for folate receptor autoantibodies if you suspect any of the above symptoms in young children. FRAT^® is a diagnostic tool that screens for folate receptor autoantibodies. As with any medical diagnosis and treatment you should always contact your physician for information and guidance.