cerebral folate deficiency in low-functioning autism: milk-free diet downregulates folate receptor autoimmunity

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Folate receptor autoimmunity and cerebral folate deficiency in

low-functioning autism with neurological deficits.

<http://www.ncbi.nlm.nih.gov/pubmed/18461502>

Ramaekers VT, Blau N, Sequeira JM, Nassogne MC, Quadros EV.

Neuropediatrics. 2007 Dec;38(6):276-81.

Reduced folate transport to the CNS was identified in two autism

spectrum disorders, i.e., Rett syndrome and infantile low-functioning

autism with neurological abnormalities. Twenty-five patients with

early-onset low-functioning autism with or without neurological

deficits, were evaluated for serum folate, cerebrospinal fluid (CSF)

5-methyltetrahydrofolate (5MTHF), and serum FR autoantibodies of the

blocking type to determine the significance of folate receptor (FR)

autoantibodies with respect to folate transport across the blood-CSF

barrier. In spite of normal serum folate, CSF 5MTHF was low in 23 of 25

patients. The reduced CSF folate in 19 of these 23 patients could be

explained by serum FR autoantibodies blocking the folate binding site of

the membrane-attached FR on the choroid epithelial cells. Oral folinic

acid supplements led to normal CSF 5MTHF and partial or complete

clinical recovery after 12 months. Serum FR autoimmunity appears to

represent an important factor in the pathogenesis of reduced folate

transport to the nervous system among children with early-onset

low-functioning autism associated with or without neurological deficits.

Early detection of FR autoantibodies may be a key factor in the

prevention and therapeutic intervention among this subgroup of patients

with autism.

A milk-free diet downregulates folate receptor autoimmunity in cerebral

folate deficiency syndrome. <http://www.ncbi.nlm.nih.gov/pubmed/18355335>

Ramaekers VT, Sequeira JM, Blau N, Quadros EV.

Dev Med Child Neurol. 2008 May;50(5):346-52

In cerebral folate deficiency syndrome, the presence of autoantibodies

against the folate receptor (FR) explains decreased folate transport to

the central nervous system and the clinical response to folinic acid.

Autoantibody crossreactivity with milk FR from different species

prompted us to test the effect of a milk-free diet. Intervention with a

milkfree diet in 12 children (nine males, three females; mean age 6y [sD

4y 11mo], range 1-19y), decreased autoantibody titer significantly from

2.08pmol of FR blocked per ml of serum (SD 2.1; range 0.24-8.35) to

0.35pmol (SD 0.49; range 0-1.32; p=0.012) over 3 to 13 months, whereas

FR autoantibody titer increased significantly to 6.53 (SD 6.08; range

0.54-14.07; p=0.013) in nine children who were reexposed to milk for 6

to 14 weeks. In 12 children on a normal diet (eight males, four females;

mean age 5y 5mo [sD 4y 1mo], range 1y 6mo-16y 4mo), the antibody titer

increased significantly from 0.84pmol of FR blocked per ml (SD 0.39;

range 0.24-1.44) to 3.04pmol (SD 1.42; range 0.84-6.01; p=0.001) over 10

to 24 months. Decreasing the autoantibody titer with a milk-free diet in

conjunction with folinic acid therapy may be advocated for these patients.

Cerebral folate deficiency. <http://www.ncbi.nlm.nih.gov/pubmed/19260931>

Gordon N.

Dev Med Child Neurol. 2009 Mar;51(3):180-2.

Cerebral folate deficiency (CFD) is associated with low levels of

5-methyltetrahydrofolate in the cerebrospinal fluid (CSF) with normal

folate levels in the plasma and red blood cells. The onset of symptoms

caused by the deficiency of folates in the brain is at around 4 to 6

months of age. This is followed by delayed development, with

deceleration of head growth, hypotonia, and ataxia, followed in

one-third of children by dyskinesias (choreo-athetosis, hemiballismus),

spasticity, speech difficulties, and epilepsy. The low level of

5-methyltetrahydrofolate in the CSF can result from decreased transport

across the blood-brain barrier, which is most probably because of the

blocking of folate transport into the CSF by the binding of folate

receptor antibodies to the folate receptors in the choroid plexus.

Treatment of the condition with folinic acid for prolonged periods can

result in significant improvement of clinical symptoms and a return of

5-methyltetrahydrofolate levels in the CSF to normal. In view of this

response to treatment in CFD and allied conditions, a case can be made

for screening the CSF of patients with neurological disorders of unknown

origin.